WorldWideScience

Sample records for bone diseases

  1. Bone Diseases

    Science.gov (United States)

    Your bones help you move, give you shape and support your body. They are living tissues that rebuild constantly ... childhood and your teens, your body adds new bone faster than it removes old bone. After about ...

  2. Bone Marrow Diseases

    Science.gov (United States)

    Bone marrow is the spongy tissue inside some of your bones, such as your hip and thigh bones. It contains stem cells. The stem cells can ... the platelets that help with blood clotting. With bone marrow disease, there are problems with the stem ...

  3. [Bone disease in Gaucher's disease].

    Science.gov (United States)

    Roca Espiau, Mercedes

    2011-09-01

    The exposition aims, is to review the pathophysiological mechanisms of bone marrow involvement and the patterns of marrow infiltration by Gaucher cells. We have reviewed the different methods of assessment of bone marrow infiltration and its temporal development. Qualitative methods include simple radiography, magnetic resonance imaging (MRI), computed tomography (CT) and radioisotope. The simple radiography is the basic element, but its sensitivity is limited and only allows for assessing changes and trabecular bone remodeling MRI allows us to appreciate the bone marrow infiltration, detection of complications and response to therapy. Radioisotopes can contribute to the differential diagnosis of osteomyelitis and bone crises. Among the quantitative methods are the QCSI (quantitative chemical shift imaging) and the dual-energy X-ray absorptiometry (DEXA), as well as new quantitative techniques of CT, MRI and ultrasound densitometry. The QCSI performed an assessment of fat content of bone marrow in the spine. DEXA quantifies bone density by measuring the attenuation coefficient. The semiquantitative methods have various "scores" to establish criteria for generalized bone disease endpoints of disease progression and response to therapy.

  4. Osteopetrosis (marble bone disease

    Directory of Open Access Journals (Sweden)

    Alexey Nikolayevich Kalyagin

    2014-01-01

    Full Text Available We report the data of the history of describing osteopetrosis (marble bone disease, its clinical features, diagnosis, and possible therapy approaches. Our own clinical case is presented.

  5. Metastatic Bone Disease

    Science.gov (United States)

    ... begin in bone are much less common in adults older than 45 years. Other diseases, such as Paget’s sarcoma, post-radiation sarcoma, hyperparathyroidism, and fractures due to osteoporosis, are also possibilities. Additional tests will likely be ...

  6. Hypercalciuric Bone Disease

    Science.gov (United States)

    Favus, Murray J.

    2008-09-01

    Hypercalciuria plays an important causal role in many patients with calcium oxalate (CaOx) stones. The source of the hypercalciuria includes increased intestinal Ca absorption and decreased renal tubule Ca reabsorption. In CaOx stone formers with idiopathic hypercalciuria (IH), Ca metabolic balance studies have revealed negative Ca balance and persistent hypercalciuria in the fasting state and during low dietary Ca intake. Bone resorption may also contribute to the high urine Ca excretion and increase the risk of bone loss. Indeed, low bone mass by DEXA scanning has been discovered in many IH patients. Thiazide diuretic agents reduce urine Ca excretion and may increase bone mineral density (BMD), thereby reducing fracture risk. Dietary Ca restriction that has been used unsuccessfully in the treatment of CaOx nephrolithiasis in the past may enhance negative Ca balance and accelerate bone loss. DEXA scans may demonstrate low BMD at the spine, hip, or forearm, with no predictable pattern. The unique pattern of bone histologic changes in IH differs from other causes of low DEXA bone density including postmenopausal osteoporosis, male hypogonadal osteoporosis, and glucocorticoid-induced osteoporosis. Hypercalciuria appears to play an important pathologic role in the development of low bone mass, and therefore correction of urine Ca losses should be a primary target for treatment of the bone disease accompanying IH.

  7. Oral Health and Bone Disease

    Science.gov (United States)

    ... low bone mass. Research suggests a link between osteoporosis and bone loss in the jaw. The bone in the jaw supports and anchors the teeth. When the jawbone becomes less dense, tooth loss can occur, a common occurrence in older adults. Skeletal Bone Density and Dental Concerns Periodontal Disease ...

  8. Gaucher disease and bone manifestations.

    Science.gov (United States)

    Marcucci, Gemma; Zimran, Ari; Bembi, Bruno; Kanis, John; Reginster, Jean-Yves; Rizzoli, Renè; Cooper, Cyrus; Brandi, Maria Luisa

    2014-12-01

    Gaucher disease is a relatively rare metabolic disease caused by the inherited deficiency of the lysosomal enzyme glucocerebrosidase. Gaucher disease affects multiple organs, among which is the skeleton. Bone involvement occurs frequently in Gaucher disease, and is one of its most debilitating features, reducing the quality of life of patients. Bone status is an important consideration for treatment to ameliorate symptoms and reduce the risk of irreversible complications. We have conducted a systematic review of all the various aspects of Gaucher disease, focusing on different skeletal manifestations, pathophysiology of bone alterations, clinical symptoms, and current diagnostic and therapeutic approaches.

  9. Bone disease in primary hypercalciuria

    OpenAIRE

    Sella, Stefania; Cattelan, Catia; Realdi, Giuseppe; Giannini, Sandro

    2008-01-01

    Primary Hypercalciuria (PH) is very often accompanied with some degrees of bone demineralization. The most frequent clinical condition in which this association has been observed is calcium nephrolithiasis. In patients affected by this disorder bone density is very frequently low and increased susceptibility to fragility fractures is reported. The very poor definition of this bone disease from a histomorphometric point of view is a crucial aspect. At present, the most common finding seems to ...

  10. Bone disease and HIV infection.

    Science.gov (United States)

    Amorosa, Valerianna; Tebas, Pablo

    2006-01-01

    The high prevalence of bone demineralization among human immunodeficiency virus (HIV)-infected patients in the current therapeutic era has been described in multiple studies, sounding the alarm that we may expect an epidemic of fragility fractures in the future. However, despite noting high overall prevalences of osteopenia and osteoporosis, recent longitudinal studies that we review here have generally not observed accelerated bone loss during antiretroviral therapy beyond the initial period after treatment initiation. We discuss the continued progress toward understanding the mechanisms of HIV-associated bone loss, particularly the effects of HIV infection, antiretroviral therapy, and host immune factors on bone turnover. We summarize results of clinical trials published in the past year that studied the safety and efficacy of treatment of bone loss in HIV-infected patients and provide provisional opinions about who should be considered for bone disease screening and treatment.

  11. Investigations of Diabetic Bone Disease

    DEFF Research Database (Denmark)

    Linde, Jakob Starup

    Diabetes mellitus is associated with an increased risk of fracture with and current fracture predictors underestimate fracture risk in both type 1 and type 2 diabetes. Thus, further understanding of the underlying causes of diabetic bone disease may lead to better fracture predictors and preventive...... measures in patients with diabetes. This PhD thesis reports the results of two systematic reviews and a meta-analysis, a state-of-the-art intervention study, a clinical cross-sectional study and a registry-based study all examining the relationship between diabetes, glucose, and bone. Patients with type 2...... diabetes had lower bone turnover markers compared to patients with type 1 diabetes and bone mineral density and tissue stiffness were increased in patients with type 2 diabetes. The bone turnover markers were inversely associated with blood glucose in patients with diabetes and both an oral glucose...

  12. What Is Paget's Disease of Bone?

    Science.gov (United States)

    ... Size | S S M M L L Bone Basics Osteoporosis Osteogenesis Imperfecta Paget’s Disease of Bone Related Topics News Glossary ... focus(); */ } //--> Print-Friendly Page Home Bone Basics Osteoporosis Osteogenesis Imperfecta Paget’s Disease of Bone Related Topics About Us ...

  13. How Is Paget's Disease of Bone Diagnosed?

    Science.gov (United States)

    ... Size | S S M M L L Bone Basics Osteoporosis Osteogenesis Imperfecta Paget’s Disease of Bone Related Topics News Glossary ... focus(); */ } //--> Print-Friendly Page Home Bone Basics Osteoporosis Osteogenesis Imperfecta Paget’s Disease of Bone Related Topics About Us ...

  14. Bone Mineralization in Celiac Disease

    Directory of Open Access Journals (Sweden)

    Tiziana Larussa

    2012-01-01

    Full Text Available Evidence indicates a well-established relationship between low bone mineral density (BMD and celiac disease (CD, but data on the pathogenesis of bone derangement in this setting are still inconclusive. In patients with symptomatic CD, low BMD appears to be directly related to the intestinal malabsorption. Adherence to a strict gluten-free diet (GFD will reverse the histological changes in the intestine and also the biochemical evidence of calcium malabsorption, resulting in rapid increase of BMD. Nevertheless, GFD improves BMD but does not normalize it in all patients, even after the recovery of intestinal mucosa. Other mechanisms of bone injury than calcium and vitamin D malabsorption are thought to be involved, such as proinflammatory cytokines, parathyroid function abnormalities, and misbalanced bone remodeling factors, most of all represented by the receptor activator of nuclear factor B/receptor activator of nuclear factor B-ligand/osteoprotegerin system. By means of dual-energy X-ray absorptiometry (DXA, it is now rapid and easy to obtain semiquantitative values of BMD. However, the question is still open about who and when submit to DXA evaluation in CD, in order to estimate risk of fractures. Furthermore, additional information on the role of nutritional supplements and alternative therapies is needed.

  15. Bone disease in haemoglobin disorders

    Directory of Open Access Journals (Sweden)

    Ersi Voskaridou

    2013-03-01

    Full Text Available Bone disease represents a prominent cause of morbidity in patients with thalassaemia and other haemoglobin disorders. The delay in sexual maturation, the presence of diabetes and hypothyroidism, the parathyroid gland dysfunction, the haemolytic anaemia, the progressive marrow expansion, the iron toxicity on osteoblasts, the iron chelators, and the deficiency of growth hormone or insulin growth factors have been identified as major causes of osteoporosis in thalassaemia. Adequate hormonal replacement, effective iron chelation, improvement of hemoglobin levels, calcium and vitamin D administration, physical activity, and smoking cessation are the main to-date measures for the management of the disease. During the last decade, novel pathogenetic data suggest that the reduced osteoblastic activity, which is believed to be the basic mechanism of bone loss in thalassemia, is accompanied by a comparable or even greater increase in bone resorption. Therefore, potent inhibitors of osteoclast activation, such as the aminobisphosphonates, arise as key drugs for the management of osteoporosis in thalassaemia patients and other haemoglobin disorders.

  16. Photodynamic therapy of diseased bone

    Science.gov (United States)

    Bisland, Stuart K.; Yee, Albert; Siewerdsen, Jeffery; Wilson, Brian C.; Burch, Shane

    2005-08-01

    Objective: Photodynamic therapy (PDT) defines the oxygen-dependent reaction that occurs upon light-mediated activation of a photosensitizing compound, culminating in the generation of cytotoxic, reactive oxygen species, predominantly, singlet oxygen. We are investigating PDT treatment of diseased bone. Methods: Using a rat model of human breast cancer (MT-1)-derived bone metastasis we confirmed the efficacy of benzoporphyrin-derivative monoacid (BPD-MA)-PDT for treating metastatic lesions within vertebrae or long bones. Results: Light administration (150 J) 15 mins after BPDMA (2.5 mg/Kg, i.v.) into the lumbar (L3) vertebra of rats resulted in complete ablation of the tumour and surrounding bone marrow 48 hrs post-PDT without paralysis. Porcine vertebrae provided a model comparable to that of human for light propagation (at 150 J/cm) and PDT response (BPD-MA; 6 mg/m2, i.v.) in non-tumour vertebrae. Precise fibre placement was afforded by 3-D cone beam computed tomography. Average penetration depth of light was 0.16 +/- 0.04 cm, however, the necrotic/non-necrotic interface extended 0.6 cm out from the treatment fiber with an average incident fluence rate of 4.3 mW/cm2. Non-necrotic tissue damage was evident 2 cm out from the treatment fiber. Current studies involving BPD-MA-PDT treatment of primary osteosarcomas in the forelimbs of dogs are very promising. Magnetic resonance imaging 24 hr post treatment reveal well circumscribed margins of treatment that encompass the entire 3-4 cm lesion. Finally, we are also interested in using 5-aminolevulinic acid (ALA) mediated PDT to treat osteomyelitis. Response to therapy was monitored as changes in bioluminescence signal of staphylococcus aureus (SA)-derived biofilms grown onto 0.5 cm lengths of wire and subjected to ALA-PDT either in vitro or in vivo upon implant into the intramedullary space of rat tibia. Transcutaneous delivery of PDT (75 J/cm2) effectively eradicated SAbiofilms within bone. Conclusions: Results support

  17. Bone- and bone marrow scintigraphy in Gaucher disease type 1

    Energy Technology Data Exchange (ETDEWEB)

    Mikosch, P. [Dept. of Nuclear Medicine and Endocrinology, State Hospital Klagenfurt (Austria); Dept. of Internal Medicine II, State Hospital Klagenfurt (Austria); Zitter, F. [Dept. of Internal Medicine II, State Hospital Klagenfurt (Austria); Gallowitsch, H.J.; Lind, P. [Dept. of Nuclear Medicine and Endocrinology, State Hospital Klagenfurt (Austria); Wuertz, F. [Dept. of Pathology, State Hospital Klagenfurt (Austria); Mehta, A.B.; Hughes, D.A. [Lysosomal Storage Disorder Unit, Dept. of Academic Haematology, Royal Free and Univ. Coll. Medical School, London (United Kingdom)

    2008-07-01

    Scintigraphy is a method for imaging metabolism and should be viewed as complimentary to morphological imaging. Bone and bone marrow scintigraphy can particularly contribute to the detection of focal disease in Gaucher disease. In bone crises it can discriminate within three days after pain onset between local infection and aseptic necrosis. A further advantage of bone- and bone marrow scintigraphy is the visualization of the whole skeleton within one setting. Whole body imaging for focal lesions might thus be an objective in GD, in particular in patients complaining of several painful sites. Direct imaging of bone marrow deposits in GD by MIBI scintigraphy might be of special interest in children in whom bone marrow undergoes a developmental conversion from red to yellow marrow in the ap-pendicular skeleton. MRI interpretation in young GD patients is thus difficult in order to estimate the exact amount and extent of bone marrow infiltration by Gaucher cells. 99mTc-MIBI scintigraphy with its direct visualization of lipid storage could thus add interesting additional information not shown with other methods including MRI. Although MRI is the most accepted imaging modality in assessing the skeletal status in GD, a selective use of scintigraphy for imaging bone and bone marrow may add information in the evaluation of patients with Gaucher disease.

  18. Bone disease of primary hyperoxaluria in infancy

    Energy Technology Data Exchange (ETDEWEB)

    Ring, E.; Wendler, H.; Zobel, G. (Graz Univ. (Austria). Abt. fuer Kinderheilkunde); Ratschek, M. (Graz Univ. (Austria). Abt. fuer Pathologie)

    1989-11-01

    A patient with primary hyperoxaluria type I in infancy is reported. He had renal insufficiency, but urolithiasis was absent. Demonstration of diffuse nephrocalcinosis by renal ultrasound contributed to early diagnosis. Prolonged survival leads to extensive extrarenal oxalate deposition. Repeated skeletal surveys showed the development and the progression of severe hyperoxaluria-related bone disease. Translucent metaphyseal bands with sclerotic margins, wide areas of rarefaction at the ends of the long bones, and translucent rims around the epiphyses and the tarsal bones were signs of disordered bone growth. Bone density generally increased with time indicating progressive sclerosis due to oxalate deposition in the previously normal bone structure. (orig.).

  19. Rheumatological presentation of developmental bone diseases

    Energy Technology Data Exchange (ETDEWEB)

    Kalifa, Gabriel; Cohen, Pierre alain; Hamidou, Amine

    2000-02-01

    Developmental bone disease may be present, with rheumatological disorders as the major symptoms, even in children. The major lesions encountered are early osteo arthritis, osteo chondromatosis and vertebral involvement with two leading types, pseudo Scheuermann's disease or pseudo ankylosing spondylitis. This paper presents the different features and lists the rheumatological problems in bone dysplasia.

  20. Mechanisms of multiple myeloma bone disease

    Science.gov (United States)

    Galson, Deborah L; Silbermann, Rebecca; Roodman, G David

    2012-01-01

    Multiple myeloma is the second most common hematological malignancy and the most frequent cancer to involve the skeleton. Multiple myeloma bone disease (MMBD) is characterized by abnormal bone remodeling with dysfunction of both bone resorption and bone formation, and thus can be used as a paradigm for other inflammatory bone diseases, and the regulation of osteoclasts and osteoblasts in malignancy. Studies of MMBD have identified novel regulators that increase osteoclastogenesis and osteoclast function, repress osteoblast differentiation, increase angiogenesis, or permanently alter stromal cells. This review will discuss the current understanding of mechanisms of osteoclast and osteoblast regulation in MMBD, and therapeutic approaches currently in use and under development that target mediators of bone destruction and blockade of bone formation for myeloma patients, including new anabolic therapies. PMID:23951515

  1. Chronic kidney disease and bone metabolism.

    Science.gov (United States)

    Kazama, Junichiro James; Matsuo, Koji; Iwasaki, Yoshiko; Fukagawa, Masafumi

    2015-05-01

    Chronic kidney disease-related mineral and bone disease (CKD-MBD) is a syndrome defined as a systemic mineral metabolic disorder associated with CKD, and the term renal osteodystrophy indicates a pathomorphological concept of bone lesions associated with CKD-MBD. Cortical bone thinning, abnormalities in bone turnover and primary/secondary mineralization, elevated levels of circulating sclerostin, increased apoptosis in osteoblasts and osteocytes, disturbance of the coupling phenomenon, iatrogenic factors, accumulated micro-crackles, crystal/collagen disorientation, and chemical modification of collagen crosslinks are all possible candidates found in CKD that could promote osteopenia and/or bone fragility. Some of above factors are the consequences of abnormal systemic mineral metabolism but for others it seem unlikely. We have used the term uremic osteoporosis to describe the uremia-induced bone fragility which is not derived from abnormal systemic mineral metabolism. Interestingly, the disease aspect of uremic osteoporosis appears to be similar to that of senile osteoporosis.

  2. Histologic diagnosis of metabolic bone diseases: bone histomorphometry

    Directory of Open Access Journals (Sweden)

    L. Dalle Carbonare

    2011-09-01

    Full Text Available Histomorphometry or quantitative histology is the analysis on histologic sections of bone resorption parameters, formation and structure. It is the only technique that allows a dynamic evaluation of the activity of bone modelling after labelling with tetracycline. Moreover, the new measurement procedures through the use of the computer allow an assessment of bone microarchitecture too. Histomorphometric bone biopsy is a reliable and well-tolerated procedure. Complications are reported only in 1% of the subjects (hematoma, pain, transient neuralgia. Histomorphometry is used to exclude or confirm the diagnosis of osteomalacia. It is employed in the evaluation of bone damage associated with particular treatments (for example, anticonvulsants or in case of rare bone diseases (osteogenesis imperfecta, systemic mastocytosis. It is also an essential approach when clinical, biochemical and other diagnostic data are not consistent. Finally, it is a useful method to understand the pathophysiologic mechanisms of drugs. The bone sample is taken at the level of iliac crest under local anesthesia. It is then put into methyl-metacrilate resin where the sections are prepared for the microscopic analysis of the various histomorphometric parameters.

  3. Myeloma bone disease: Pathophysiology and management

    Science.gov (United States)

    Silbermann, Rebecca; Roodman, G. David

    2013-01-01

    Multiple myeloma bone disease is marked by severe dysfunction of both bone formation and resorption and serves as a model for understanding the regulation of osteoblasts (OBL) and osteoclasts (OCL) in cancer. Myeloma bone lesions are purely osteolytic and are associated with severe and debilitating bone pain, pathologic fractures, hypercalcemia, and spinal cord compression, as well as increased mortality. Interactions within the bone marrow microenvironment in myeloma are responsible for the abnormal bone remodeling in myeloma bone disease. Myeloma cells drive bone destruction that increases tumor growth, directly stimulates the OCL formation, and induces cells in the marrow microenvironment to produce factors that drive OCL formation and suppress OBL formation. Factors produced by marrow stromal cells and OCL promote tumor growth through direct action on myeloma cells and by increasing angiogenesis. Current therapies targeting MMBD focus on preventing osteoclastic bone destruction; however regulators of OBL inhibition in MMBD have also been identified, and targeted agents with a potential anabolic effect in MMBD are under investigation. This review will discuss the mechanisms responsible for MMBD and therapeutic approaches currently in use and in development for the management of MMBD. PMID:26909272

  4. Bone changes in alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Alcoholism has been associated with growth impairment,osteomalacia, delayed fracture healing, and asepticnecrosis (primarily necrosis of the femoral head), butthe main alterations observed in the bones of alcoholicpatients are osteoporosis and an increased risk offractures. Decreased bone mass is a hallmark of osteoporosis,and it may be due either to decreased bone synthesis and/or to increased bone breakdown. Ethanolmay affect both mechanisms. It is generally acceptedthat ethanol decreases bone synthesis, and most authorshave reported decreased osteocalcin levels (a "marker" ofbone synthesis), but some controversy exists regardingthe effect of alcohol on bone breakdown, and, indeed,disparate results have been reported for telopeptideand other biochemical markers of bone resorption.In addition to the direct effect of ethanol, systemicalterations such as malnutrition, malabsorption, liverdisease, increased levels of proinflammatory cytokines,alcoholic myopathy and neuropathy, low testosteronelevels, and an increased risk of trauma, play contributoryroles. The treatment of alcoholic bone disease should beaimed towards increasing bone formation and decreasingbone degradation. In this sense, vitamin D and calciumsupplementation, together with biphosphonates areessential, but alcohol abstinence and nutritional improvementare equally important. In this review we study thepathogenesis of bone changes in alcoholic liver diseaseand discuss potential therapies.

  5. Role of bone scan in rheumatic disease

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yun Young [Hanyang University College of Medicine, Seoul (Korea, Republic of)

    2003-06-01

    Rheumatic diseases can be categorized by pathology into several specific types of musculoskeletal problems, including synovitis (e.g. rheumatoid arthritis), enthesopathy (e.g. ankylosing spondylitis) and cartilage degeneration (e.g. osteoarthritis). Skeletal radiographs have contributed to the diagnosis of these articular diseases, and some disease entities need typical radiographic changes as a factor of the diagnostic criteria. However, they sometimes show normal radiographic findings in the early stage of disease, when there is demineralization of less than 30-50%. Bone scans have also been used in arthritis, but not widely because the findings are nonspecific and it is thought that bone scans do not add significant information to routine radiography. Bone scans do however play a different role than simple radiography, and it is a complementary imaging method in the course of management of arthritis. The image quality of bone scans can be improved by obtaining regional views and images under al pin-hole collimator, and through a variety of scintigraphic techniques including the three phase bone scan and bone SPECT. Therefore, bone scans could improve the diagnostic value, and answer multiple clinical questions, based on the pathophysiology of various forms of arthritis.

  6. Vitamin D and Bone Disease

    Directory of Open Access Journals (Sweden)

    S. Christodoulou

    2013-01-01

    Full Text Available Vitamin D is important for normal development and maintenance of the skeleton. Hypovitaminosis D adversely affects calcium metabolism, osteoblastic activity, matrix ossification, bone remodeling and bone density. It is well known that Vit. D deficiency in the developing skeleton is related to rickets, while in adults is related to osteomalacia. The causes of rickets include conditions that lead to hypocalcemia and/or hypophosphatemia, either isolated or secondary to vitamin D deficiency. In osteomalacia, Vit. D deficiency leads to impairment of the mineralisation phase of bone remodeling and thus an increasing amount of the skeleton being replaced by unmineralized osteoid. The relationship between Vit. D and bone mineral density and osteoporosis are still controversial while new evidence suggests that Vit. D may play a role in other bone conditions such as osteoarthritis and stress fractures. In order to maintain a “good bone health” guidelines concerning the recommended dietary intakes should be followed and screening for Vit. D deficiency in individuals at risk for deficiency is required, followed by the appropriate action.

  7. Osteoporotic fractures: a brain or bone disease?

    Science.gov (United States)

    Birge, Stanley J

    2008-06-01

    Osteoporosis is a skeletal disorder that predisposes individuals to increased risk of fracture. However, most osteoporotic fractures occur in women who do not meet criteria for osteoporosis. Hence, bone density, by itself, is a relatively poor predictor of fracture. Age and age-related factors are now recognized as increasingly important in determining fracture risk. Osteoporotic fractures are associated with increased disability and mortality, suggesting that osteoporosis may be a clinical manifestation of an underlying disease process affecting multiple systems. The systems affected, the musculo-skeletal system and the central nervous system, are shared in many respects with the frailty syndrome. Vitamin D deficiency is a major contributor to the frailty syndrome, osteoporosis, and osteoporotic fractures. Its effects are mediated by the development of cerebrovascular disease, postural instability, muscle weakness, and bone fragility. Thus, osteoporotic fractures result from both a bone and brain disease.

  8. Paget's disease of bone (osteitis deformans).

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    Ankrom, M A; Shapiro, J R

    1998-08-01

    Paget's disease of bone is important in geriatric populations because it is the second most common bone disorder after osteoporosis. In older people, it may be responsible for chronic back pain and joint pain, skeletal deformities, hearing loss, and cranial nerve compression. Paget's disease can reduce both function and mobility in the older people. In addition to newer tests for assessing the activity of Paget's disease, effective therapy is available in the form of salmon calcitonin for nasal administration and new third generation bisphosphonates. Frequently, treatment can reverse the course of the disease. For these reasons, it is feasible for the physician to adopt an aggressive approach to diagnosis and treatment. The objective should be to relieve pain, improve mobility, and forestall debilitating complications. This review will focus on the manifestations and clinical management of Paget's disease. Two cases are presented that illustrate common management problems in older patients.

  9. Diabetes mellitus related bone metabolism and periodontal disease

    Institute of Scientific and Technical Information of China (English)

    Ying-Ying Wu; E Xiao; Dana T Graves

    2015-01-01

    Diabetes mellitus and periodontal disease are chronic diseases affecting a large number of populations worldwide. Changed bone metabolism is one of the important long-term complications associated with diabetes mellitus. Alveolar bone loss is one of the main outcomes of periodontitis, and diabetes is among the primary risk factors for periodontal disease. In this review, we summarise the adverse effects of diabetes on the periodontium in periodontitis subjects, focusing on alveolar bone loss. Bone remodelling begins with osteoclasts resorbing bone, followed by new bone formation by osteoblasts in the resorption lacunae. Therefore, we discuss the potential mechanism of diabetes-enhanced bone loss in relation to osteoblasts and osteoclasts.

  10. EVALUATION OF RADIONUCLIDE BONE IMAGING FOR SKELETAL DISEASE

    Institute of Scientific and Technical Information of China (English)

    林奋; 袁济民

    1993-01-01

    Whole body bone scan imaging of 99mTc-MDP was performed in 80 casesfrom Sept 1991 to Feb 1992. Among them 20 patients showed negtive bone imaging and56 patients showed positive bone imaging. There were false-positive bone imaging in 4 pa-tients. Bone scan imaging has been regarded as a useful method in the early diagnosis ofshelatal disease, especially in old patients with bone metastasis. But the final confirmationof malignancy should be still cautious.

  11. Bone histology in chronic kidney disease-related mineral and bone disorder.

    Science.gov (United States)

    Kazama, Junichiro James

    2011-06-01

    A quantitative histological analysis of biopsied bone samples is currently regarded as the gold standard for a diagnosing procedure for bone diseases associated with chronic kidney disease-related mineral and bone disorder. Conventionally, "bone cell activities" and "bone mineralization" are applied as two independent assessment axes, and the histology results are classified into five categories according to these axes. Recently, a new bone histology classification system called the Turnover-Mineralization-Volume system, which applied "cancellous bone volume" as another major assessing axis, was advocated; however, both classification systems have many unsolved problems. Clinicians must realize the limitations in evaluating bone metabolism by bone histology. We will need to establish a new classification method for renal bone diseases independent of histological findings.

  12. Pathophysiology of chronic kidney disease-mineral and bone disorder.

    Science.gov (United States)

    Mac Way, Fabrice; Lessard, Myriam; Lafage-Proust, Marie-Hélène

    2012-12-01

    Chronic kidney disease (CKD) alters the metabolism of several minerals, thereby inducing bone lesions and vessel-wall calcifications that can cause functional impairments and excess mortality. The histological bone abnormalities seen in CKD, known as renal osteodystrophy, consist of alterations in the bone turnover rate, which may be increased (osteitis fibrosa [OF]) or severely decreased (adynamic bone disease [AD]); abnormal mineralization (osteomalacia [OM]), and bone loss. Secondary hyperparathyroidism is related to early phosphate accumulation (responsible for FGF23 overproduction by bone tissue), decreased calcitriol production by the kidneys, and hypocalcemia. Secondary hyperparathyroidism is associated with OF. Other factors that affect bone include acidosis, chronic inflammation, nutritional deficiencies, and iatrogenic complications.

  13. Fracture, aging and disease in bone

    Energy Technology Data Exchange (ETDEWEB)

    Ager, J.W.; Balooch, G.; Ritchie, R.O.

    2006-02-01

    fracture resistance, whereas regulating the level of the cytokine TGF-beta can offer significant improvements in the stiffness, strength and toughness of bone, and as such may be considered as a therapeutic target to treat increased bone fragility induced by aging, drugs, and disease.

  14. Bone turnover markers in patients with type 1 Gaucher disease

    Directory of Open Access Journals (Sweden)

    Gaetano Giuffrida

    2012-11-01

    Full Text Available Bone complications occur frequently in Gaucher disease (GD and reduce the quality of life of these patients. Skeletal involvement is an important indication for treatment to ameliorate symptoms and reduce the risk of irreversible and debilitating disease. Bone biomarkers have been used to assess disease status and the response to therapy in a number of bone disorders. Here, we examine the literature for evidence of abnormalities in bone turnover markers in patients with type 1 GD to assess whether they might be useful for the assessment of bone involvement in GD. We have found that bone biomarkers in GD show highly variable results which do not currently support their routine use for clinical assessment of bone status, as an indication for therapy initiation, or for monitoring the response to therapy. A greater understanding of bone markers and their relation to the bone manifestations of GD is required.

  15. Correlation of different bone markers with bone density in patients with rheumatic diseases on glucocorticoid therapy.

    Science.gov (United States)

    Loddenkemper, Konstanze; Bohl, Nicole; Perka, Carsten; Burmester, Gerd-Rüdiger; Buttgereit, Frank

    2006-02-01

    Osteoporosis is a common concomitant disease in patients with rheumatic diseases on glucocorticoid (GC) therapy. Bone status is usually evaluated by determination of bone density in combination with clinical examinations and laboratory tests. However, the strength of individual biochemical bone makers in GC-induced osteoporosis has yet to be fully clarified. For this reason, different bone markers were investigated in correlation with bone density in patients with rheumatic diseases. Approximately 238 patients (212 women, 26 men) with a rheumatic disease and under GC therapy were examined consecutively for the first time with regard to bone density (BMD) and bone markers [osteocalcin, bone-specific alkaline phosphatase (precipitation method/tandem-MP ostase), crosslinks [pyridinoline (PYD), deoxypyridinoline (DPX), N-terminal telopeptide (NTX)

  16. [Bone and Calcium Metabolisms Associated with Dental and Oral-Maxillofacial Diseases. Bone remodeling and alveolar bone homeostasis].

    Science.gov (United States)

    Nakashima, Tomoki

    2015-08-01

    Bone, which support motile organ and periodontal tissue, is renewing throughout our life. This restructuring process is called "bone remodeling" , and osteoclasts and osteoblasts play a crucial role in this process. Bone remodeling is important not only for normal bone mass and strength, but also for mineral homeostasis. Bone remodeling is stringently regulated by communication between bone component cells such as osteoclasts, osteoblasts and osteocytes. An imbalance of this process is often linked to various bone diseases. Alveolar bone remodeling is directly influenced by occlusal force from the teeth. Thus, the elucidation of the regulatory mechanisms involved in alveolar bone remodeling is critical for a deeper understanding of the maintenance of healthy tooth and dental disease.

  17. Celiac disease: A missed cause of metabolic bone disease

    Directory of Open Access Journals (Sweden)

    Ashu Rastogi

    2012-01-01

    Full Text Available Introduction: Celiac disease (CD is a highly prevalent autoimmune disease. The symptoms of CD are varied and atypical, with many patients having no gastrointestinal symptoms. Metabolic bone disease (MBD is a less recognized manifestation of CD associated with spectrum of musculoskeletal signs and symptoms, viz. bone pains, proximal muscle weakness, osteopenia, osteoporosis, and fracture. We here report five patients who presented with severe MBD as the only manifestation of CD. Materials and Methods: Records of 825 patients of CD diagnosed during 2002-2010 were retrospectively analyzed for clinical features, risk factors, signs, biochemical, and radiological parameters. Results: We were able to identify five patients (0.6% of CD who had monosymptomatic presentation with musculoskeletal symptoms and signs in the form of bone pains, proximal myopathy, and fragility fractures without any gastrointestinal manifestation. All the five patients had severe MBD in the form of osteopenia, osteoporosis, and fragility fractures. Four of the five patients had additional risk factors such as antiepileptic drugs, chronic alcohol consumption, malnutrition, and associated vitamin D deficiency which might have contributed to the severity of MBD. Conclusion: Severe metabolic disease as the only presentation of CD is rare. Patients show significant improvement in clinical, biochemical, and radiological parameters with gluten-free diet, calcium, and vitamin D supplementation. CD should be looked for routinely in patients presenting with unexplained MBD.

  18. Management of adynamic bone disease in chronic kidney disease: A brief review

    Directory of Open Access Journals (Sweden)

    Swathi K. Sista

    2016-09-01

    Full Text Available The Kidney Disease: Improving Global Outcomes (KDIGO work group released recommendations in 2006 to define the bone-related pathology associated with chronic kidney disease as renal osteodystrophy. In 2009, KDIGO released revised clinical practice guidelines which redefined systemic disorders of bone and mineral metabolism due to chronic kidney disease as chronic kidney disease-mineral and bone disorders. Conditions under this overarching term include osteitis fibrosa cystica, osteomalacia, and adynamic bone disease. We aim to provide a brief review of the histopathology, pathophysiology, epidemiology, and diagnostic features of adynamic bone disease, focusing on current trends in the management of this complex bone disorder.

  19. Re-evaluation of bone pain in patients with type 1 Gaucher disease suggests that bone crises occur in small bones as well as long bones.

    Science.gov (United States)

    Baris, Hagit N; Weisz Hubshman, Monika; Bar-Sever, Zvi; Kornreich, Liora; Shkalim Zemer, Vered; Cohen, Ian J

    2016-09-01

    Bone crises in type 1 Gaucher disease are reported in long bones and occasionally in weight bearing bones and other bones, but rarely in small bones of the hands and feet. We retrospectively examined the incidence of bone pain in patients followed at the Rabin Medical Center, Israel, before and following the initiation of enzyme replacement therapy (ERT) and evaluated them for bone crises. Of 100 type I Gaucher disease patients, 30 (30%) experienced one or more bone crises. Small bone crises represented 31.5% of all bone crises and were always preceded by crises in other bones. While the incidence of long bone crises reduced after the initiation of ERT, small bone crises increased. Almost 60% of patients with bone crises were of the N370S/84GG genotype suggesting a greater susceptibility of N370S/84GG patients to severe bone complications. These patients also underwent the greatest number of splenectomies (70.6% of splenectomised patients). Splenectomised patients showed a trend towards increased long and small bone crises after surgery. Active investigation of acute pain in the hands and feet in patients in our cohort has revealed a high incidence of small bone crises. Physicians should consider imaging studies to investigate unexplained pain in these areas.

  20. Orthopantomographic study of the alveolar bone level on periodontal disease

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ki Sik; You, Dong Soo [College of Dentistry, Seoul National University, Seoul (Korea, Republic of)

    1972-11-15

    The author had measured the alveolar bone level of periodontal disease on 50 cases of orthopantomogram to detect the degree of alveolar bone resorption of both sexes of Korean. The results were obtained as follows; 1. Alveolar bone resorption of mesial and distal portion was similar in same patient. 2. The order of alveolar bone resorption was mandibular anterior region, posterior region, canine and premolar region of both jaws. 3. The degree of alveolar bone destruction was severe in shorter root length than longer one. 4. The degree of alveolar bone resorption was severe in fourth decades.

  1. Combined scintigraphic and radiographic diagnosis of bone and joint diseases

    Energy Technology Data Exchange (ETDEWEB)

    Bahk, Yong Whee (Catholic Medical Coll., Seoul (Korea, Republic of). Dept. of Radiology and Nuclear Medicine)

    1994-01-01

    This book is intended to emphasize the tremendous value of pinhole scintigraphy in diagnosing nearly the whole spectrum of bone and joint diseases. Pinhole scintigraphy discloses anatomic and pathologic as well as chemical alterations in greater detail, permitting analytical interpretation and raising the sensitivity as well. Infections, nonspecific bone inflammation, rheumatic disorders, metabolic and endocrine bone diseases, trauma, and both primary tumors and metastasis can be effectively and specifically examined. By improving sensitivity, many false negative readings can be avoided in early bone metastasis, synovitis, enthesopathies, bone contusion, etc. (orig.)

  2. Lessons from rare diseases of cartilage and bone.

    Science.gov (United States)

    Gallagher, James A; Ranganath, Lakshminarayan R; Boyde, Alan

    2015-06-01

    Studying severe phenotypes of rare syndromes can elucidate disease mechanisms of more common disorders and identify potential therapeutic targets. Lessons from rare bone diseases contributed to the development of the most successful class of bone active agents, the bisphosphonates. More recent research on rare bone diseases has helped elucidate key pathways and identify new targets in bone resorption and bone formation including cathepsin K and sclerostin, for which drugs are now in clinical trials. By contrast, there has been much less focus on rare cartilage diseases and osteoarthritis (OA) remains a common disease with no effective therapy. Investigation of rare cartilage syndromes is identifying new potential targets in OA including GDF5 and lubricin. Research on the arthropathy of the ultra-rare disease alkaptonuria has identified several new features of the OA phenotype, including high density mineralized protrusions (HDMPs) which constitute a newly identified mechanism of joint destruction.

  3. Magnetic resonance in hematological diseases. Imaging of bone marrow

    DEFF Research Database (Denmark)

    Jensen, K.E.

    1995-01-01

    Magnetic resonance imaging (MRI) is a highly sensitive alternative to plain radiography, CT, and radionuclide studies for the imaging of normal and abnormal bone marrow. The cellularity and the corresponding fat/water ratio within the bone marrow show clear changes in haematological diseases....... This enables MRI to detect differences between fatty, fibrotic, aplastic and hypercellular marrow in patients with haematological disease. MRI can evaluate the distribution of bone marrow disease because it has the potential for visualization of almost the entire bone marrow compartment. However, MRI is unable...... to establish the primary diagnosis in haematological bone marrow disease with diffuse hypercellular marrow. In case of insufficient biopsy, MRI can provide important differential diagnostic information as well as guidance for further biopsy attempts. MRI is a useful complement to morphological bone marrow...

  4. MPS I: Early diagnosis, and treatment of bone disease

    NARCIS (Netherlands)

    Kingma, S.D.K.

    2015-01-01

    Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease (LSD) characterized by deficient degradation and subsequent accumulation of glycosaminoglycans (GAGs). Patients present with a spectrum of symptoms, including progressive mental retardation and bone disease. To optimize outcome, ear

  5. Paget's Disease of Bone and Osteoarthritis: Different Yet Related

    Science.gov (United States)

    ... and Other Conditions Paget’s Disease of Bone and Osteoarthritis: Different Yet Related Publication available in: PDF (59 ... for sure what causes Paget’s disease. What Is Osteoarthritis? Osteoarthritis is a condition that causes changes in ...

  6. Impact of lanthanum carbonate on cortical bone in dialysis patients with adynamic bone disease.

    Science.gov (United States)

    Yajima, Aiji; Inaba, Masaaki; Tominaga, Yoshihiro; Tanaka, Motoko; Otsubo, Shigeru; Nitta, Kosaku; Ito, Akemi; Satoh, Shigeru

    2013-04-01

    Among the most serious problems in patients with chronic kidney disease (CKD) is fragility of cortical bone caused by cortical thinning and increased cortical porosity; the cortical fragility is sometimes irreversible, with fractures generally initiating from cortical bone. Therefore, development of treatments for problems of cortical bone is urgently desired. Cortical bone has the three surfaces, including the periosteal surface, intracortical spaces and endocortical surface. Bone turnover at the endocortical surface and intracortical resorption spaces are increased as compared with that at cancellous surface. Bone growth sometimes depends on apposition at the periosteal surface. We treated hyperphosphatemia in two hemodialysis patients with adynamic bone disease with 750-1500 mg/day of lanthanum carbonate, which is a non-calcium containing phosphate binder; the treatment resulted in a decrease of the serum phosphorus levels (P levels), without significant change of the serum intact parathyroid hormone levels. We now report that treatment of these patients with lanthanum carbonate increased mineralization of the periosteal surface, increased bone mass within the intracortical resorption spaces and increased mineralization of the minimodeling surface at the endocortical surface. In addition, woven bone volume in cortical bone was decreased and mineralization of bone units, namely, osteons, was increased. Although these findings were not observed across all surfaces of the cortical bone in the patients, it is expected that lanthanum carbonate would increase the cortical stability in CKD patients, with consequent reduction in the fracture rate in these patients.

  7. Imaging of inflammatory and infectious diseases in the temporal bone.

    NARCIS (Netherlands)

    Lemmerling, M.M.; Foer, B. De; Verbist, B.M.; Vyver, V. van de

    2009-01-01

    Inflammatory and infectious diseases of the temporal bone are a major indication to perform high-resolution CT and MR imaging studies. Such studies allow one to evaluate the extent of the disease in the soft tissues and in the bony structures of the temporal bone. On these same imaging studies the p

  8. Asymptomatic Paget's disease of bone presenting with complete atrioventricular block

    Institute of Scientific and Technical Information of China (English)

    A.Rauoof Malik; Nazir A.Lone; Hilal A.Rather; Vicar M Jan; Javid A.Malik; Khursheed A.Khan; S.Jalal

    2008-01-01

    @@ Paget's disease of bone is a deforming bone disease (osteitis deformans) characterized by increased bone remodeling,bone hypertrophy,and abnormal bone structure,leading to bone expansion,deformities,easy fractures,and occasionally,neoplastic transformation.It is the second most common bone disorder after osteoporosis.1 The disease is relatively rare in Asia but is common in Europe and North America,affecting approximately 2% of the population over 50 years,although lately,a decline in the prevalence has been reported.2 Paget's disease commonly affects people in or past their middle age and is slightly more common in men than in women.1 The exact cause of Paget's disease is not known.Environmental agents,particularly paramyxoviral infections (measles and canine distemper viruses) have been postulated as potential etiological factors.3 Recently,a strong genetic component has been described,with candidate loci suggested at 18q,5q35-QTER,and particularly,the squestosome 1/p62.2,3 The pathological process in Paget's disease consists of one or more areas of aggressive and relentless osteoclastic activity,coupled with deposition of structurally abnormal excessive bone and matrix tissues.1,4 Most of the cases involve only one (monostotic) or few bones,particularly skull,vertebrae,pelvis,femur,and tibia.

  9. Bone marrow invasion in multiple myeloma and metastatic disease.

    Science.gov (United States)

    Vilanova, J C; Luna, A

    2016-04-01

    Magnetic resonance imaging (MRI) of the spine is the imaging study of choice for the management of bone marrow disease. MRI sequences enable us to integrate structural and functional information for detecting, staging, and monitoring the response the treatment of multiple myeloma and bone metastases in the spine. Whole-body MRI has been incorporated into different guidelines as the technique of choice for managing multiple myeloma and metastatic bone disease. Normal physiological changes in the yellow and red bone marrow represent a challenge in analyses to differentiate clinically significant findings from those that are not clinically significant. This article describes the findings for normal bone marrow, variants, and invasive processes in multiple myeloma and bone metastases.

  10. Role of osteocytes in multiple myeloma bone disease

    Science.gov (United States)

    Delgado-Calle, Jesus; Bellido, Teresita; Roodman, G. David

    2014-01-01

    Purpose of review Despite the increased knowledge of osteocyte biology, the contribution of this most abundant bone cell to the development and progression of multiple myeloma in bone is practically unexplored. Recent findings Multiple myeloma bone disease is characterized by exacerbated bone resorption and the presence of osteolytic lesions that do not heal because of a concomitant reduction in bone formation. Osteocytes produce molecules that regulate both bone formation and resorption. Recent findings suggest that the life span of osteocytes is compromised in multiple myeloma patients with bone lesions. In addition, multiple myeloma cells affect the transcriptional profile of osteocytes by upregulating the production of pro-osteoclastogenic cytokines, stimulating osteoclast formation and activity. Further, patients with active multiple myeloma have elevated circulating levels of sclerostin, a potent inhibitor of bone formation which is specifically expressed by osteocytes in bone. Summary Understanding the contribution of osteocytes to the mechanisms underlying the skeletal consequences of multiple myeloma bone disease has the potential to provide important new therapeutic strategies that specifically target multiple myeloma–osteocyte interactions. PMID:25289928

  11. Bone Allografts: What Is the Risk of Disease Transmission with Bone Allografts?

    Science.gov (United States)

    ... HIV antibody by ELISA. Autopsy of donor reveals occult disease. Donor bone tests positive for bacterial contamination. Donor and bone test positive for hepatitis B surface antigen (HbsAG) or hepatitis C virus (HCV). Donor tests positive for syphilis. Using ...

  12. The Role of Hedgehog Signaling in Tumor Induced Bone Disease

    Directory of Open Access Journals (Sweden)

    Shellese A. Cannonier

    2015-08-01

    Full Text Available Despite significant progress in cancer treatments, tumor induced bone disease continues to cause significant morbidities. While tumors show distinct mutations and clinical characteristics, they behave similarly once they establish in bone. Tumors can metastasize to bone from distant sites (breast, prostate, lung, directly invade into bone (head and neck or originate from the bone (melanoma, chondrosarcoma where they cause pain, fractures, hypercalcemia, and ultimately, poor prognoses and outcomes. Tumors in bone secrete factors (interleukins and parathyroid hormone-related protein that induce RANKL expression from osteoblasts, causing an increase in osteoclast mediated bone resorption. While the mechanisms involved varies slightly between tumor types, many tumors display an increase in Hedgehog signaling components that lead to increased tumor growth, therapy failure, and metastasis. The work of multiple laboratories has detailed Hh signaling in several tumor types and revealed that tumor establishment in bone can be controlled by both canonical and non-canonical Hh signaling in a cell type specific manner. This review will explore the role of Hh signaling in the modulation of tumor induced bone disease, and will shed insight into possible therapeutic interventions for blocking Hh signaling in these tumors.

  13. The Role of Hedgehog Signaling in Tumor Induced Bone Disease

    Energy Technology Data Exchange (ETDEWEB)

    Cannonier, Shellese A.; Sterling, Julie A., E-mail: Julie.sterling@vanderbilt.edu [Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN 37235 (United States); Vanderbilt Center for Bone Biology, Department of Medicine, Division of Clinical Pharmacology Vanderbilt University, Nashville, TN 372335 (United States); Department of Cancer Biology, Vanderbilt University, Nashville, TN 37235 (United States)

    2015-08-26

    Despite significant progress in cancer treatments, tumor induced bone disease continues to cause significant morbidities. While tumors show distinct mutations and clinical characteristics, they behave similarly once they establish in bone. Tumors can metastasize to bone from distant sites (breast, prostate, lung), directly invade into bone (head and neck) or originate from the bone (melanoma, chondrosarcoma) where they cause pain, fractures, hypercalcemia, and ultimately, poor prognoses and outcomes. Tumors in bone secrete factors (interleukins and parathyroid hormone-related protein) that induce RANKL expression from osteoblasts, causing an increase in osteoclast mediated bone resorption. While the mechanisms involved varies slightly between tumor types, many tumors display an increase in Hedgehog signaling components that lead to increased tumor growth, therapy failure, and metastasis. The work of multiple laboratories has detailed Hh signaling in several tumor types and revealed that tumor establishment in bone can be controlled by both canonical and non-canonical Hh signaling in a cell type specific manner. This review will explore the role of Hh signaling in the modulation of tumor induced bone disease, and will shed insight into possible therapeutic interventions for blocking Hh signaling in these tumors.

  14. Anemia and bone disease of chronic kidney disease: pathogenesis, diagnosis, and management.

    Science.gov (United States)

    Shemin, Douglas

    2014-12-02

    Anemia and metabolic bone disease accompany chronic kidney disease (CKD), and worsen as CKD progresses. It is likely that both processes contribute to the increased morbidity and mortality seen in CKD. This paper briefly reviews the pathogenesis and diagnosis of anemia and bone disease in CKD, and summarizes recent consensus guidelines for treatment.

  15. A probable new type of osteopenic bone disease

    Energy Technology Data Exchange (ETDEWEB)

    Widhe, Torulf L. [Department of Orthopaedics, Huddinge University Hospital (Sweden)

    2002-06-01

    A probable new type of osteopenic bone disease in two sisters and one female cousin is described. In infancy, the radiological findings were osteopenia, coxa vara, periosteal cloaking, bowing of the long bones, and flaring of the metaphyses. During growth, spinal pathology developed with compression of the vertebral bodies and scoliosis in one girl and kyphosis in another. All three children had genu valgum and two developed severe S-shaped bowing of the tibiae. Growth was stunted. Inheritance of this disorder is probably recessive. Type I and III collagen biosynthesis was normal. This condition is probably a hitherto undescribed form of osteogenesis imperfecta type III or a new bone disease. (orig.)

  16. Imaging Paget's disease of bone--from head to toe.

    Science.gov (United States)

    Cortis, K; Micallef, K; Mizzi, A

    2011-07-01

    Paget's disease of the bone is a common, non-inflammatory, metabolic, skeletal disorder of unknown aetiology characterized by an increase in osteoclast-mediated bone resorption and compensatory excessive osteoblast activation. Prevalence increases with age, and a pronounced geographical variation is well documented. The disease is often an incidental finding on a radiological examination requested for an unrelated indication. The osteolytic, mixed osteolytic/osteoblastic, and osteosclerotic phases may occur in the same patient and same bone in a synchronous or metachronous fashion. Radiological features in each phase mirror the histopathological appearances, and are distinctive enough to establish a diagnosis with confidence. Using multi-technique imaging, this review illustrates the most common and the not so common radiological patterns of involvement in Paget's disease of bone observed at our centre during the past 20 years.

  17. Zoledronic acid in the management of metastatic bone disease.

    Science.gov (United States)

    Santini, Daniele; Fratto, Maria Elisabetta; Vincenzi, Bruno; Galluzzo, Sara; Tonini, Giuseppe

    2006-12-01

    Bisphosphonate therapy has become a standard of therapy for patients with malignant bone disease. Moreover, in vivo preclinical and preliminary clinical data suggest that bisphosphonates may prevent cancer treatment-induced bone loss and the onset of malignant bone disease in patients with early-stage cancer. This comprehensive review critically reports the several preclinical evidences of action of bisphosphonates on osteoclasts, lymphocytes and tumour cells. In addition, all the clinical trials evaluating the effects of principal bisphosphonates on skeletal disease progression in patients with breast cancer, prostate cancer, non-small cell lung cancer and other cancers have been reported. Of the available bisphosphonates, intravenous zoledronic acid has demonstrated the broadest clinical activity and is actually approved for the treatment of bone metastases from any solid tumour in many countries. Renal safety is an important consideration for oncologists who are treating patients with bisphosphonates. This issue and the other topics relating to the safety of bisphosphonates are discussed in this review.

  18. Giant cell tumor complicating Paget disease of long bone

    Energy Technology Data Exchange (ETDEWEB)

    Hoch, Benjamin [Mount Sinai Medical Center, Department of Pathology, New York, NY (United States); Hermann, George [Mount Sinai Medical Center, Department of Radiology, New York, NY (United States); Klein, Michael J. [University of Alabama School of Medicine, Department of Pathology, Birmingham, AL (United States); Abdelwahab, Ibrahim F. [Coney Island Hospital affiliated with CUNY Downstate School of Medicine, Department of Radiology, New York, NY (United States); Springfield, Dempsey [Massachusetts General Hospital, Department of Orthopaedic Surgery, Boston, MA (United States)

    2007-10-15

    Giant cell tumor (GCT) is a rare complication of Paget disease of bone. It usually occurs in the skull or pelvic bones of patients with long-standing polyostotic disease. This report describes a 62-year-old patient who presented with monostotic Paget disease of the distal femur complicated by GCT. He had a 2-year history of discomfort and pain in his left knee. Conventional plain films and MRI demonstrated the characteristic bone changes of Paget disease and an associated lytic lesion involving the epiphyseal and metaphyseal regions of the distal femur. A diagnostic curettage showed the characteristic histopathologic features of Paget disease and GCT. There was no evidence of malignancy. The clinicopathologic features of this rare lesion are described and correlated with a review of the literature. (orig.)

  19. Bone Markers Status in Graves’ disease before and after Treatment

    Directory of Open Access Journals (Sweden)

    P Tofighi

    2008-11-01

    Full Text Available "nBackground:  Bone turnover is reported to increase in favor of resorption in overt hyperthyroidism and the rate of resorp­tion is associated with the levels of thyroid hormones. As persistent increase in bone turn over is responsible for accelerated bone loss, patients with Graves' disease may have increased risk for osteoporosis. The aim of this study was to determine relationship between Graves' disease and bone markers."nMethods: The subjects of our study were 31 consecutive untreated GD patients and 37 normal volunteers who were matched on sex proportion and age ranging was diagnosed by suppressed levels of TSH and elevated level of free T3 and free T4 and positive thyroid receptor antibody. Through a clinical trial study executed in endocrinology and metabolism research center, we investigated the relationship between serum osteocalcin & cross-laps with Graves' disease and then kinds of treatment with PTU and methimazole after 8 weeks follow up."nResults: No significant differences in age and sex between patients and controls were found. Significant differences in se­rum bone markers and thyroid hormones were detected between patients and controls before therapy (p< 0.001. After treatment we found a significant improvement and returning to normal range in all serum lab tests. There were not any dif­ferences in the effect of treatment on thyroid hormones and bone markers between two groups."nConclusion: We found close relationship between Graves' disease and bone markers. So that treatment of Graves' disease can improve bone turn over. These findings indicated that early diagnosis and management of Graves' disease can be effec­tive for osteoporosis prevention in these patients.

  20. Heterogeneous pattern of bone disease in adult type 1 Gaucher disease: clinical and pathological correlates.

    Science.gov (United States)

    van Dussen, L; Lips, P; van Essen, H W; Hollak, C E M; Bravenboer, N

    2014-09-01

    Gaucher disease (GD) is a lysosomal storage disorder characterized by accumulation of glucosylceramide in macrophages, so-called Gaucher cells, as a result of a deficiency of the lysosomal enzyme glucocerebrosidase. Bone complications are an important cause of morbidity of GD and are thought to result from imbalance in bone remodeling. Bone manifestations among GD patients demonstrate a large variation including increased osteoclastic bone resorption, low bone formation and osteonecrosis. The purpose of the current case series is to describe the histological features observed in undecalcified bone samples, obtained from three GD patients, and evaluate the relationship with clinical features in these patients. Bone fragments were obtained from three adult type 1 GD patients with variable degrees of bone disease during orthopedic surgery. Specimens were embedded without prior decalcification in methylmethacrylate and prepared for histology according to standardized laboratory procedures. Histology revealed a heterogeneous pattern of bone involvement. High cellularity of bone marrow, abundant presence of Gaucher cells (GCs) and high turnover were observed in a patient with a history of multiple bone complications, while minimal bone turnover and few GCs were detected in the mildest affected patient in this series. An intermediate picture with relatively low bone turnover and a substantial amount of Gaucher cells was demonstrated in the third, moderately affected patient. No gross abnormalities in three biochemical markers of bone turnover (osteocalcin, N-terminal propeptide of type 1 procollagen and type 1 collagen C-terminal telopeptide) were noted. Plastic embedding and subsequent Goldner and TRAP staining offered a unique possibility to study bone histological findings in GD. Our data show that bone manifestations in GD may vary both clinically as well as histologically and bone disease in GD will likely require a personalized approach.

  1. Paget disease of bone: A classic case report

    Directory of Open Access Journals (Sweden)

    Y Uday Shankar

    2013-01-01

    Full Text Available Paget disease of bone (PDB is a chronic progressive disease of the bone of uncertain etiology, characterized initially by an increase in bone resorption, followed by a disorganized and excessive formation of bone, leading to pain, fractures, and deformities. It can manifest as a monostotic or polyostotic disease. The prevalence of PDB is common in the Anglo-Saxon population, but relatively rare in India. The disease is often asymptomatic and commonly seen in an aging population. The diagnosis of the disease is mostly based on radiological examination and on biochemical markers of bone turnover. Markedly elevated serum alkaline phosphatase (SAP is a constant feature while calcium and phosphate levels are typically within normal limits. It is being successfully treated by biphosphonates, a group of anti-resorptive drugs, thereby decreasing the morbidity and mortality associated with the disease. We report a classic case of PDB with craniofacial involvement resulting in Leontiasis Ossea (lion like face, cotton wool appearance of the skull and elevated SAP.

  2. Chronic Kidney Disease Impairs Bone Defect Healing in Rats.

    Science.gov (United States)

    Liu, Weiqing; Kang, Ning; Seriwatanachai, Dutmanee; Dong, Yuliang; Zhou, Liyan; Lin, Yunfeng; Ye, Ling; Liang, Xing; Yuan, Quan

    2016-03-09

    Chronic kidney disease (CKD) has been regarded as a risk for bone health. The aim of this study was to evaluate the effect of CKD on bone defect repair in rats. Uremia was induced by subtotal renal ablation, and serum levels of BUN and PTH were significantly elevated four weeks after the second renal surgery. Calvarial defects of 5-mm diameter were created and implanted with or without deproteinized bovine bone mineral (DBBM). Micro-CT and histological analyses consistently revealed a decreased newly regenerated bone volume for CKD rats after 4 and 8 weeks. In addition, 1.4-mm-diameter cortical bone defects were established in the distal end of femora and filled with gelatin sponge. CKD rats exhibited significantly lower values of regenerated bone and bone mineral density (BMD) within the cortical gap after 2 and 4 weeks. Moreover, histomorphometric analysis showed an increase in both osteoblast number (N.Ob/B.Pm) and osteoclast number (N.Oc/B.Pm) in CKD groups due to hyperparathyroidism. Notably, collagen maturation was delayed in CKD rats as verified by Masson's Trichrome staining. These data indicate that declined renal function negatively affects bone regeneration in both calvarial and femoral defects.

  3. Proceedings of the 2015 Santa Fe Bone Symposium: Clinical Applications of Scientific Advances in Osteoporosis and Metabolic Bone Disease.

    Science.gov (United States)

    Lewiecki, E Michael; Baron, Roland; Bilezikian, John P; Gagel, Robert E; Leonard, Mary B; Leslie, William D; McClung, Michael R; Miller, Paul D

    2016-01-01

    The 2015 Santa Fe Bone Symposium was a venue for healthcare professionals and clinical researchers to present and discuss the clinical relevance of recent advances in the science of skeletal disorders, with a focus on osteoporosis and metabolic bone disease. Symposium topics included new developments in the translation of basic bone science to improved patient care, osteoporosis treatment duration, pediatric bone disease, update of fracture risk assessment, cancer treatment-related bone loss, fracture liaison services, a review of the most significant studies of the past year, and the use of telementoring with Bone Health Extension for Community Healthcare Outcomes, a force multiplier to improve the care of osteoporosis in underserved communities.

  4. Metabolic Bone Disease in the Bariatric Surgery Patient

    Directory of Open Access Journals (Sweden)

    Susan E. Williams

    2011-01-01

    Full Text Available Bariatric surgery has proven to be a life-saving measure for some, but for others it has precipitated a plethora of metabolic complications ranging from mild to life-threatening, sometimes to the point of requiring surgical revision. Obesity was previously thought to be bone protective, but this is indeed not the case. Morbidly obese individuals are at risk for metabolic bone disease (MBD due to chronic vitamin D deficiency, inadequate calcium intake, sedentary lifestyle, chronic dieting, underlying chronic diseases, and the use of certain medications used to treat those diseases. After bariatric surgery, the risk for bone-related problems is even greater, owing to severely restricted intake, malabsorption, poor compliance with prescribed supplements, and dramatic weight loss. Patients presenting for bariatric surgery should be evaluated for MBD and receive appropriate presurgical interventions. Furthermore, every patient who has undergone bariatric surgery should receive meticulous lifetime monitoring, as the risk for developing MBD remains ever present.

  5. Three-phase bone scintigraphy in Pellegrini-Stieda disease.

    Science.gov (United States)

    Liu, R S; Chou, C S; Yeh, S H

    1987-01-01

    In a patient with Pellegrini-Stieda disease, radiographs of the knees were unremarkable at the time the three-phase bone scintigraphy was abnormal. The results of follow-up radiographs three months later remained normal in the left knee, where local steroid injection was given, but revealed typical positive results in the right knee with no treatment. The three-phase bone scintigraphic pattern is rather typical and antedates the radiographic changes. Thus, the radionuclide technique would provide a useful procedure for the early diagnosis and treatment of Pellegrini-Stieda disease.

  6. Alcoholic liver disease and changes in bone mineral density

    Directory of Open Access Journals (Sweden)

    Germán López-Larramona

    2013-12-01

    Full Text Available Osteoporosis and osteopenia are alterations in bone mineral density (BMD that frequently occur in the context of chronic liver disease (CLD. These alterations have been studied predominantly in chronic cholestatic disease and cirrhosis of the liver. Alcohol consumption is an independent risk factor for the onset of osteoporosis, whose estimated prevalence in patients with alcoholic liver disease (ALD ranges between 5 % and 40 %. The loss of BMD in ALD is the result of an imbalance between bone formation and resorption. Its pathogenesis is multifactorial and includes the toxic effects of alcohol on bone and endocrine and nutritional disorders secondary to alcoholism and a deficiency of osteocalcin, vitamin D and insulin growth factor-1. The diagnosis of BMD alterations in ALD is based on its measurement using bone densitometry. Treatment includes smoking and alcohol cessation and general measures such as changes in nutrition and exercise. Calcium and vitamin D supplements are recommended in all patients with ALD and osteoporosis. Bisphosphonates are the most commonly prescribed drugs for the specific treatment of this condition. Alternatives include raloxifene, hormone replacement therapy and calcitonin. This review will address the most important aspects involved in the clinical management of abnormal BMD in the context of ALD, including its prevalence, pathogenesis and diagnosis. We will also review the treatment of osteoporosis in CLD in general, focusing on specific aspects related to bone loss in ALD.

  7. Bone scintigraphy in Erdheim-chester disease: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Siqueira, V.L.; Soares, L.M.M.; Ribeiro, V.P.B.; Coura Filho, G.B.; Sapienza, M.T.; Ono, C.R.; Watanabe, T.; Costa, P.L.A.; Hironaka, F.; Buchpiguel, C.A. [Universidade de Sao Paulo (FM/USP), SP (Brazil). Fac. de Medicina. Hospital das Clinicas

    2008-07-01

    Full text: Introduction: Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis, of unknown etiology, characterized by infiltration of foamy histiocytes. Clinically, patients usually present with bone pain, and various extraskeletal manifestations. ECD differs from Langerhans cell histiocytosis (LCH) by radiologic and immunohistochemistry features. Case report: A 57-year-old woman presented with a history of intense pain on her left hand, besides eyelid xanthelasmas and xanthoms on frontal area ten years ago. Four years late she presented with pain on hips, legs and feet. Xanthoms spread to perioral area, mento and neck. Radiographs of the hands showed osteolysis of carpal bones bilaterally, osteolysis of fifth left metacarpal bone, osteosclerosis of all metacarpal bones bilaterally, except the fifth, and osteosclerosis of the second and third proximal falanges bilaterally. The legs showed bilateral diaphyseal and metaphyseal osteosclerosis. Bone scintigraphy demonstrated increased uptake on face bone (maxilla), and symmetric intense uptake on elbows, distal radii and ulnae, hands, distal area of femurs, tibias particularly on proximal and distal area, and feet. A tibia biopsy and a biopsy of neck lesion were made. The analysis of histology and immunohistochemistry were consistent with ECD. She has been treated with a-interferon for 1,5 year, and she reports delay in xanthoms progression and bone pain remission. Discussion: ECD is an adult multisystemic xanthogranulomatous infiltrative disease of unknown etiology. It may be confused with LCH, however ECD have distinctive immunohistochemistry and radiologic findings. LCH shows typically lytic bone lesions on axial skeleton, whereas symmetrical long-bone osteosclerosis is the radiologic sign for ECD. LCH stain positive for CD1a and S-100 protein, and the electron microscopy of cytoplasm discloses Biberck granules. ECD stain positive for CD68, negative for CD1a and S-100 protein, shows absent of

  8. [Metabolic bone disease in premature infants and genetic polymorphisms

    NARCIS (Netherlands)

    Funke, S.; Morava, E.; Czako, M.; Vida, G.; Ertl, T.; Kosztolanyi, G.Y.

    2007-01-01

    Metabolic bone disease is an important complication among infants very-low-birth-weight (< 1500 g). In adults, osteoporosis has been shown to be associated with polymorphisms of vitamin D receptor, estrogen receptor, and collagen Ialpha1 receptor genes. AIM: The primary goal of the study was to i

  9. Influence of genetic polymorphisms on bone disease of preterm infants.

    NARCIS (Netherlands)

    Funke, S.; Morava, E.; Czako, M.; Vida, G.; Ertl, T.; Kosztolanyi, G.Y.

    2006-01-01

    Bone disease is an important complication among very low birth weight (VLBW, <1500 g) infants. In adults, osteoporosis is associated with polymorphisms of vitamin D receptor (VDR), estrogen receptor (ER), and collagen Ialpha1 (COLIA1) genes. However, limited information is available regarding the

  10. In vivo bone aluminum measurements in patients with renal disease

    Energy Technology Data Exchange (ETDEWEB)

    Ellis, K.J.; Kelleher, S.P.

    1986-01-01

    Contamination of the dialysis solution with trace amounts of aluminum and long-term use of aluminum-based phosphate binders have led to increased body burden of aluminum in patients with end-stage renal disease. A significant clinical problem associated with aluminum-overload is the early diagnosis of aluminum-induced dialysis dementia and osteomalacic osteodystrophy. There are few, if any, blood or urine indices that provide an early monitor of this bone disease, especially in the asymptomatic patient. Although a bone biopsy is usually the basis for the final clinical diagnosis, this procedure is not recommended for routine monitoring of patients. The present technique demonstrates the direct in vivo measurement of bone aluminum levels in patients with renal failure. The interference normally present from activation of bone phosphorus is eliminated by using a thermal/epithermal neutron beam. For the clinical management of the patients, the Al/Ca ratio for the hand may be more useful than an absolute measurement of the total body or skeletal aluminum burden. The relationship between the increased serum Al levels following disferrioxamine infusion and the direct in vivo measurement of bone aluminum using the Al/Ca ratio are currently under investigation. The neutron activation procedure presented in this pilot study is a promising new technique with an immediate clinical application. 5 refs., 3 figs., 1 tab.

  11. Role of Bone Biopsy in Stages 3 to 4 Chronic Kidney Disease

    Science.gov (United States)

    Gal-Moscovici, Anca; Sprague, Stuart M.

    2008-01-01

    Secondary hyperparathyroidism develops relatively early in chronic kidney disease as a consequence of impaired phosphate, calcium, and vitamin D homeostasis. The disease state in chronic kidney disease, which includes the histologic features of bone disease, defined as renal osteodystrophy, and the hormonal and biochemical disturbances, have recently been redefined as a disease syndrome and is referred to as “chronic kidney disease–mineral and bone disorder.” As chronic kidney disease progresses, specific histologic disturbances in the bone develop, which may or may not be predictable from the biochemical and hormonal changes that are associated with chronic kidney disease. In addition, patients may have had underlying bone disease before developing kidney failure or may have been treated with agents that will alter the classical pathologic findings of the bones in chronic kidney disease and their relation to parathyroid hormone. Thus, in stage 5 chronic kidney disease, bone biopsy with quantitative histomorphometric analysis is considered the gold standard in the diagnosis of renal osteodystrophy. In contrast to stage 5 chronic kidney disease, there are very few data on the histologic changes in bone in earlier stages of chronic kidney disease. There also is no adequate information on the etiopathogenesis of bone disease in stages 3 and 4 chronic kidney disease. Thus, because biochemical data cannot predict bone pathology in stages 3 and 4 chronic kidney disease, bone biopsy should be used to define these bone changes and to allow appropriate therapeutic approaches. PMID:18988703

  12. Bone disease in multiple myeloma: pathophysiology and management.

    Science.gov (United States)

    Hameed, Abdul; Brady, Jennifer J; Dowling, Paul; Clynes, Martin; O'Gorman, Peter

    2014-01-01

    Myeloma bone disease (MBD) is a devastating complication of multiple myeloma (MM). More than 80% of MM patients suffer from destructive bony lesions, leading to pain, fractures, mobility issues, and neurological deficits. MBD is not only a main cause of disability and morbidity in MM patients but also increases the cost of management. Bone destruction and lack of bone formation are main factors in the development of MBD. Some novel factors are found to be involved in the pathogenesis of MBD, eg, receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG) system (RANKL/OPG), Wingless (Wnt), dickkopf-1 (Wnt/DKK1) pathway. The addition of novel agents in the treatment of MM, use of bisphosphonates and other supportive modalities such as radiotherapy, vertebroplasty/kyphoplasty, and surgical interventions, all have significant roles in the treatment of MBD. This review provides an overview on the pathophysiology and management of MBD.

  13. Bone mineral density in adult coeliac disease: An updated review

    Directory of Open Access Journals (Sweden)

    Alfredo J. Lucendo

    2013-03-01

    Full Text Available Introduction and objectives: coeliac disease (CD affects around 1-2 % of the world population. Most patients are now diagnosed when adults, suffering the consequences of an impaired bone mineralization. This review aims to provide an updated discussion on the relationship between low bone mineral density (BMD, osteopenia and osteoporosis, and CD. Methods: a PubMed search restricted to the last 15 years was conducted. Sources cited in the results were also reviewed to identify potential sources of information. Results: low BMD affects up to 75 % of celiac patients, and can be found at any age, independently of positive serological markers and presence of digestive symptoms. The prevalence of CD among osteoporotic patients is also significantly increased. Two theories try to explain this origin of low BMD: Micronutrients malabsorption (including calcium and vitamin D determined by villous atrophy has been related to secondary hyperparathyroidism and incapacity to achieve the potential bone mass peak; chronic inflammation was also related with RANKL secretion, osteoclasts activation and increased bone resorption. As a consequence, celiac patients have a risk for bone fractures that exceed 40 % that of matched non-affected population. Treatment of low BMD in CD comprises gluten-free diet, calcium and vitamin D supplementation, and biphosphonates, although its effects on CD have not been specifically assessed. Conclusions: up to 75 % of celiac patients and 40 % of that diagnosed in adulthood present a low BMD and a variable increase in the risk of bone fractures. Epidemiological changes in CD make bone density scans more relevant for adult coeliacs.

  14. Bones of contention: bone mineral density recovery in celiac disease--a systematic review.

    Science.gov (United States)

    Grace-Farfaglia, Patricia

    2015-05-07

    Metabolic bone disease is a frequent co-morbidity in newly diagnosed adults with celiac disease (CD), an autoimmune disorder triggered by the ingestion of dietary gluten. This systematic review of studies looked at the efficacy of the gluten-free diet, physical activity, nutrient supplementation, and bisphosphonates for low bone density treatment. Case control and cohort designs were identified from PubMed and other academic databases (from 1996 to 2015) that observed newly diagnosed adults with CD for at least one year after diet treatment using the dual-energy x-ray absorptiometry (DXA) scan. Only 20 out of 207 studies met the inclusion criteria. Methodological quality was assessed using the Strengthening of the Reporting of Observational Studies in Epidemiology (STROBE) statement checklist. Gluten-free diet adherence resulted in partial recovery of bone density by one year in all studies, and full recovery by the fifth year. No treatment differences were observed between the gluten-free diet alone and diet plus bisphosphonates in one study. For malnourished patients, supplementation with vitamin D and calcium resulted in significant improvement. Evidence for the impact of physical activity on bone density was limited. Therapeutic strategies aimed at modifying lifestyle factors throughout the lifespan should be studied.

  15. RECENT ADVANCES IN PATHO-BIOLOGY OF MYELOMA BONE DISEASE: CLINICOPATHOLOGY AND LITERATURE OF REVIEW

    Directory of Open Access Journals (Sweden)

    Lohit Kumar

    2016-03-01

    Full Text Available Bone disease is a hallmark of multiple myeloma, presenting as lytic lesions associated with bone pain, pathological fractures requiring surgery and/or radiation to bone, spinal cord compression and hypercalcaemia. Increased osteoclastic activity unaccompanied by a compensatory increase in osteoblast function, leading to enhanced bone resorption results in bone disease. The interaction of plasma cells with the bone marrow microenvironment has been shown to play a vital role. Also, interactions of myeloma cells with osteoclasts enhance myeloma growth and survival, and thereby create a vicious cycle leading to extensive bone destruction and myeloma cell expansion.

  16. SERUM YKL-40 IS ASSOCIATED WITH BONE DISEASE IN MULTIPLE MYELOMA

    DEFF Research Database (Denmark)

    Mylin, Anne Kjærsgaard; Abildgaard, Niels; Johansen, Julia S.

    2007-01-01

    , in angiogenesis, and in cancer cell survival and invasion. The aim of this study was to investigate the association between serum YKL-40 (S-YKL-40) and the degree of bone disease in MM. Materials and Methods. S-YKL-40 was measured using an ELISA in 54 MM patients at diagnosis. Bone morbidity was assessed...... to progression of myeloma-related bone disease. A potential role for YKL-40 in the bone disease of MM must be considered....

  17. Assessment of bone density in children with Scheuermann's disease.

    Science.gov (United States)

    Popko, J; Konstantynowicz, J; Kossakowski, D; Kaczmarski, M; Piotrowska-Jastrzebska, J

    1997-01-01

    Twenty four children with Scheuermann's disease (11 girls and 13 boys) aged 9-18 years measured for bone mineral density. The total skeleton (TB BMD) and lumbar spine (L2-L4 BMD) mineral density were investigated by dual energy X-ray absorptiometry (DEXA). In nine patients with Scheuermann's disease and backache we found lower levels of TB BMD and L2-L4 BMD in comparison with reference population of Lunar database. Osteopenia in these children may be caused by decreased physical activity due to vertebral pain.

  18. Denosumab: the era of targeted therapies in bone metastatic diseases.

    Science.gov (United States)

    Santini, D; Fratto, M E; Vincenzi, B; Napoli, N; Galluzzo, S; Tantardini, M; Abbruzzese, A; Caraglia, M; Tonini, G

    2009-11-01

    This system constituted of the Receptor Activator of nuclear Factor-kB Ligand (RANKL), the Receptor Activator of Nuclear Factor-kB (RANK) and by the decoy Receptor Osteoprotegerin (OPG) plays a central role in bone resorption. Denosumab (AMG 162) is an investigational fully human monoclonal antibody with a high affinity and specificity for RANKL.This review will critically describe and discuss the recent results of clinical trial investigating denosumab in different settings of medical oncology. In particular, we will report the recently published data of clinical trials investigating denosumab in prevention of cancer treatment induced bone loss (CTIBL), in prevention of skeletal related events (SREs) in bone metastatic patients and the ongoing studies in prevention of disease recurrence in the adjuvant setting of solid tumours. The clinical data that will be reported in this review represent the first step in a path that will conduct us to explore new horizons in the field of bone health care in cancer patients.

  19. The Kidney-Vascular-Bone Axis in the Chronic Kidney Disease-Mineral Bone Disorder.

    Science.gov (United States)

    Seifert, Michael E; Hruska, Keith A

    2016-03-01

    The last 25 years have been characterized by dramatic improvements in short-term patient and allograft survival after kidney transplantation. Long-term patient and allograft survival remains limited by cardiovascular disease and chronic allograft injury, among other factors. Cardiovascular disease remains a significant contributor to mortality in native chronic kidney disease as well as cardiovascular mortality in chronic kidney disease more than doubles that of the general population. The chronic kidney disease (CKD)-mineral bone disorder (MBD) is a syndrome recently coined to embody the biochemical, skeletal, and cardiovascular pathophysiology that results from disrupting the complex systems biology between the kidney, skeleton, and cardiovascular system in native and transplant kidney disease. The CKD-MBD is a unique kidney disease-specific syndrome containing novel cardiovascular risk factors, with an impact reaching far beyond traditional notions of renal osteodystrophy and hyperparathyroidism. This overview reviews current knowledge of the pathophysiology of the CKD-MBD, including emerging concepts surrounding the importance of circulating pathogenic factors released from the injured kidney that directly cause cardiovascular disease in native and transplant chronic kidney disease, with potential application to mechanisms of chronic allograft injury and vasculopathy.

  20. Expression of Factors in the Hepatocyte Growth Factor (HGF) Pathway in Whole Bone Marrow Biopsies in Association to the Osteolytic Bone Disease of Multiple Myeloma

    DEFF Research Database (Denmark)

    Kristensen, Ida Bruun; Christensen, Jacob Haaber; Lyng, Maria Bibi;

    Expression of Factors in the Hepatocyte Growth Factor (HGF) Pathway in Whole Bone Marrow Biopsies in Association to the Osteolytic Bone Disease of Multiple Myeloma......Expression of Factors in the Hepatocyte Growth Factor (HGF) Pathway in Whole Bone Marrow Biopsies in Association to the Osteolytic Bone Disease of Multiple Myeloma...

  1. Expression of Wnt-Inhibitors and SDF-1 in Whole Bone Marrow Biopsies in Association to the Osteolytic Bone Disease of Multiple Myeloma

    DEFF Research Database (Denmark)

    Kristensen, Ida Bruun; Christensen, Jacob Haaber; Lyng, Maria Bibi

    Expression of Wnt-Inhibitors and SDF-1 in Whole Bone Marrow Biopsies in Association to the Osteolytic Bone Disease of Multiple Myeloma......Expression of Wnt-Inhibitors and SDF-1 in Whole Bone Marrow Biopsies in Association to the Osteolytic Bone Disease of Multiple Myeloma...

  2. Differential diagnosis of metastatic bone disease and benign bone disease on spine SPECT in patients with low back pain

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung Hun; Choi, Yun Young; Cho, Suk Shin [College of Medicine, Hanyang Univ., Seoul (Korea, Republic of)

    2001-12-01

    One or more abnormal vertebrae detected on bone scintigraphy is a common finding in clinical practice, and it could pose a diagnostic dilemma especially in cancer patients, as either metastasis or benign disease may cause scintigraphic abnormality. The purpose of this study was to determine whether additional spine SPECT has a role in differentiating malignant from benign lesions in patients with back pain. We reviewed spine SPECT studies obtained over a three-year period in 108 patients. Among them, forty-five patients with abnormal SPECT and clinically followed records were evaluated (20 cancer patients were included). Uptake patterns were classified as follows: 1. Body: diffusely increased uptake, linear increased uptake of end plate, segmental increased uptake, and cold defect, 2 Posterior element; posterior to body (pedicle), posterior to intervertebral disc space (facet joint), and spinous process. Lesions were correlated with radiological findings and with final diagnosis. Sixty-nine bone lesions were detected on SPECT images, including 18 metastases, 28 degenerative diseases and 21 compression fractures. Cold defect (6) and segmental increased uptake (5) were dominant findings in metastasis: linear increased uptake (12), and facet joint uptake (15) were in degenerative change; and diffuse increased uptake (9), and linear increased uptake (9) were in compression fracture. Cold defect and segmental increased uptake of body were characteristic findings of metastasis, but care should be taken because compression fracture also shows segmental increased uptake in some cases. Degenerative disease was easily diagnosed because of the typical finding of linear increased uptake of end plate and facet joint. Therefore, additional bone SPECT after planar bone scan would be helpful for differentiating metastasis from benign condition in cancer patients.

  3. Allogenic bone narrow transplantation in sickle-cell diseases.

    Directory of Open Access Journals (Sweden)

    Belinda Pinto Simões

    Full Text Available SUMMARY Sickle-cell diseases are the most common inherited hemoglobinopathies worldwide. Improvement in survival has been seen in the last decades with the introduction of careful screening and prevention of complications and the introduction of hydroxyurea. Stem-cell transplantation is currently the only curative option for these patients and has been indicated for patients with neurological events, repeated vaso-occlusive crisis, any organ damage or presence of red blood cell antibodies. Related bone-marrow or cord-blood transplant has shown an overall survival of more than 90% with a disease-free survival of 90% in 1,000 patients transplanted in the last decades. The use of unrelated donors unfortunately has not shown the same good results, but better typing methods and improved support may improve the outcome with this source of stem cells in the future. In Brazil, only recently stem cell transplant from related donors has been included in the procedures performed in the public health system. The use of related bone marrow or cord blood and a myeloablative conditioning regimen are considered standard of care for patients with sickle-cell diseases. Transplants with non-myeloablative regimens, unrelated donors or haploidentical donors should be performed only in controlled clinical trials.

  4. Natural History of Malignant Bone Disease in Renal Cancer: Final Results of an Italian Bone Metastasis Survey

    Science.gov (United States)

    Santini, Daniele; Procopio, Giuseppe; Porta, Camillo; Ibrahim, Toni; Barni, Sandro; Mazzara, Calogero; Fontana, Andrea; Berruti, Alfredo; Berardi, Rossana; Vincenzi, Bruno; Ortega, Cinzia; Ottaviani, Davide; Carteni, Giacomo; Lanzetta, Gaetano; Virzì, Vladimir; Santoni, Matteo; Silvestris, Nicola; Satolli, Maria Antonietta; Collovà, Elena; Russo, Antonio; Badalamenti, Giuseppe; Fedeli, Stefano Luzi; Tanca, Francesca Maria; Adamo, Vincenzo; Maiello, Evaristo; Sabbatini, Roberto; Felici, Alessandra; Cinieri, Saverio; Tonini, Giuseppe; Bracarda, Sergio

    2013-01-01

    Background Bone metastasis represents an increasing clinical problem in advanced renal cell carcinoma (RCC) as disease-related survival improves. There are few data on the natural history of bone disease in RCC. Patients and methods Data on clinicopathology, survival, skeletal-related events (SREs), and bone-directed therapies for 398 deceased RCC patients (286 male, 112 female) with evidence of bone metastasis were statistically analyzed. Results Median time to bone metastasis was 25 months for patients without bone metastasis at diagnosis. Median time to diagnosis of bone metastasis by MSKCC risk was 24 months for good, 5 months for intermediate, and 0 months for poor risk. Median number of SREs/patient was one, and 71% of patients experienced at least one SRE. Median times to first, second, and third SRE were 2, 5, and 12 months, respectively. Median survival was 12 months after bone metastasis diagnosis and 10 months after first SRE. Among 181 patients who received zoledronic acid (ZOL), median time to first SRE was significantly prolonged versus control (n = 186) (3 months vs 1 month for control; P<0.05). Conclusions RCC patients with bone metastasis are at continuous risk of SREs, and in this survey ZOL effectively reduced this risk. PMID:24386138

  5. Natural history of malignant bone disease in renal cancer: final results of an Italian bone metastasis survey.

    Directory of Open Access Journals (Sweden)

    Daniele Santini

    Full Text Available BACKGROUND: Bone metastasis represents an increasing clinical problem in advanced renal cell carcinoma (RCC as disease-related survival improves. There are few data on the natural history of bone disease in RCC. PATIENTS AND METHODS: Data on clinicopathology, survival, skeletal-related events (SREs, and bone-directed therapies for 398 deceased RCC patients (286 male, 112 female with evidence of bone metastasis were statistically analyzed. RESULTS: Median time to bone metastasis was 25 months for patients without bone metastasis at diagnosis. Median time to diagnosis of bone metastasis by MSKCC risk was 24 months for good, 5 months for intermediate, and 0 months for poor risk. Median number of SREs/patient was one, and 71% of patients experienced at least one SRE. Median times to first, second, and third SRE were 2, 5, and 12 months, respectively. Median survival was 12 months after bone metastasis diagnosis and 10 months after first SRE. Among 181 patients who received zoledronic acid (ZOL, median time to first SRE was significantly prolonged versus control (n = 186 (3 months vs 1 month for control; P<0.05. CONCLUSIONS: RCC patients with bone metastasis are at continuous risk of SREs, and in this survey ZOL effectively reduced this risk.

  6. Natural History of Malignant Bone Disease in Hepatocellular Carcinoma: Final Results of a Multicenter Bone Metastasis Survey

    Science.gov (United States)

    Santini, Daniele; Pantano, Francesco; Riccardi, Ferdinando; Di Costanzo, Giovan Giuseppe; Addeo, Raffaele; Guida, Francesco Maria; Ceruso, Mariella Spalato; Barni, Sandro; Bertocchi, Paola; Marinelli, Sara; Marchetti, Paolo; Russo, Antonio; Scartozzi, Mario; Faloppi, Luca; Santoni, Matteo; Cascinu, Stefano; Maiello, Evaristo; Silvestris, Franco; Tucci, Marco; Ibrahim, Toni; Masi, Gianluca; Gnoni, Antonio; Comandone, Alessandro; Fazio, Nicola; Conti, Alessandro; Imarisio, Ilaria; Pisconti, Salvatore; Giommoni, Elisa; Cinieri, Saverio; Catalano, Vincenzo; Palmieri, Vincenzo Ostilio; Infante, Giovanni; Aieta, Michele; Trogu, Antonio; Gadaleta, Cosmo Damiano; Brunetti, Anna Elisabetta; Lorusso, Vito; Silvestris, Nicola

    2014-01-01

    Background Bone is an uncommon site of metastasis in patients with advanced hepatocellular carcinoma (HCC). Therefore, there are few studies concerning the natural history of bone metastasis in patients with HCC. Patients and Methods Data on clinicopathology, survival, skeletal-related events (SREs), and bone-directed therapies for 211 deceased HCC patients with evidence of bone metastasis were statistically analyzed. Results The median age was 70 years; 172 patients were male (81.5%). The median overall survival was 19 months. The median time to the onset of bone metastasis was 13 months (22.2% at HCC diagnosis); 64.9% patients had multiple bone metastases. Spine was the most common site of bone metastasis (59.7%). Most of these lesions were osteolytic (82.4%); 88.5% of them were treated with zoledronic acid. At multivariate analysis, only the Child Score was significantly correlated with a shorter time to diagnosis of bone metastases (p = 0.001, HR = 1.819). The median survival from bone metastasis was 7 months. At multivariate analysis, HCC etiology (p = 0.005), ECOG performance status (p = 0.002) and treatment with bisphosphonate (p = 0.024) were associated with shorter survival after bone disease occurrence. The site of bone metastasis but not the number of bone lesions was associated with the survival from first skeletal related event (SRE) (p = 0.021) and OS (p = 0.001). Conclusions This study provides a significant improvement in the understanding the natural history of skeletal disease in HCC patients. An early and appropriate management of these patients is dramatically needed in order to avoid subsequent worsening of their quality of life. PMID:25170882

  7. Natural history of malignant bone disease in hepatocellular carcinoma: final results of a multicenter bone metastasis survey.

    Directory of Open Access Journals (Sweden)

    Daniele Santini

    Full Text Available BACKGROUND: Bone is an uncommon site of metastasis in patients with advanced hepatocellular carcinoma (HCC. Therefore, there are few studies concerning the natural history of bone metastasis in patients with HCC. PATIENTS AND METHODS: Data on clinicopathology, survival, skeletal-related events (SREs, and bone-directed therapies for 211 deceased HCC patients with evidence of bone metastasis were statistically analyzed. RESULTS: The median age was 70 years; 172 patients were male (81.5%. The median overall survival was 19 months. The median time to the onset of bone metastasis was 13 months (22.2% at HCC diagnosis; 64.9% patients had multiple bone metastases. Spine was the most common site of bone metastasis (59.7%. Most of these lesions were osteolytic (82.4%; 88.5% of them were treated with zoledronic acid. At multivariate analysis, only the Child Score was significantly correlated with a shorter time to diagnosis of bone metastases (p = 0.001, HR = 1.819. The median survival from bone metastasis was 7 months. At multivariate analysis, HCC etiology (p = 0.005, ECOG performance status (p = 0.002 and treatment with bisphosphonate (p = 0.024 were associated with shorter survival after bone disease occurrence. The site of bone metastasis but not the number of bone lesions was associated with the survival from first skeletal related event (SRE (p = 0.021 and OS (p = 0.001. CONCLUSIONS: This study provides a significant improvement in the understanding the natural history of skeletal disease in HCC patients. An early and appropriate management of these patients is dramatically needed in order to avoid subsequent worsening of their quality of life.

  8. Risk factors for developing mineral bone disease in phenylketonuric patients.

    Science.gov (United States)

    Mirás, Alicia; Bóveda, M Dolores; Leis, María R; Mera, Antonio; Aldámiz-Echevarría, Luís; Fernández-Lorenzo, José R; Fraga, José M; Couce, María L

    2013-03-01

    There is a compromised bone mass in phenylketonuria patients compared with normal population, but the mechanisms responsible are still a matter of investigation. In addition, tetrahydrobiopterin therapy is a new option for a significant proportion of these patients and the prevalence of mineral bone disease (MBD) in these patients is unknown. We conducted a cross-sectional observational study including 43 phenylketonuric patients. Bone densitometry, nutritional assessment, physical activity questionnaire, biochemical parameters, and molecular study were performed in all patients. Patients were stratified by phenotype, age and type of treatment. The MBD prevalence in phenylketonuria was 14%. Osteopenic and osteoporotic (n=6 patients) had an average daily natural protein intake significantly lower than the remaining (n=37) patients with PKU (14.33 ± 8.95 g vs 21.25 ± 20.85 g). Besides, a lower body mass index was found. There were no statistical differences in physical activity level, calcium, phosphorus and fat intake, and in phenylalanine, vitamin D, paratohormone, docosahexaenoic and eicosapentaenoic acid blood levels. Mutational spectrum was found in up to 30 different PAH genotypes and no relationship was established among genotype and development of MBD. None of the twelve phenylketonuric patients treated with tetrahydrobiopterin (27.9%), for an average of 7.1 years, developed MBD. Natural protein intake and blood levels of eicosapentaenoic acid were significantly higher while calcium intake was lower in these patients. This study shows that the decrease in natural protein intake can play an important role in MBD development in phenylketonuric patients. Therapy with tetrahydrobiopterin allows a more relaxed protein diet, which is associated with better bone mass.

  9. The Application of Bone Marrow Transplantation to the Treatment of Genetic Diseases

    Science.gov (United States)

    Parkman, Robertson

    1986-06-01

    Genetic diseases can be treated by transplantation of either normal allogeneic bone marrow or, potentially, autologous bone marrow into which the normal gene has been inserted in vitro (gene therapy). Histocompatible allogeneic bone marrow transplantation is used for the treatment of genetic diseases whose clinical expression is restricted to lymphoid or hematopoietic cells. The therapeutic role of bone marrow transplantation in the treatment of generalized genetic diseases, especially those affecting the central nervous system, is under investigation. The response of a generalized genetic disease to allogeneic bone marrow transplantation may be predicted by experiments in vitro. Gene therapy can be used only when the gene responsible for the disease has been characterized. Success of gene therapy for a specific genetic disease may be predicted by its clinical response to allogeneic bone marrow transplantation.

  10. Founders lecture 2007. Metabolic bone disease: what has changed in 30 years?

    Energy Technology Data Exchange (ETDEWEB)

    Sundaram, Murali [Cleveland Clinic, Diagnostic Radiology, MSK, Cleveland, OH (United States)

    2009-09-15

    To provide an update on imaging of metabolic bone disease based on new developments, findings, and changing practices over the past 30 years. Literature review of osteoporosis, osteomalacia, renal osteodystrophy, Paget's disease, bisphosphonates, with an emphasis on imaging. Cited references and pertinent findings. Significant developments have occurred in the imaging of metabolic bone disease over the past 30 years. (orig.)

  11. Bone: a new endocrine organ at the heart of chronic kidney disease and mineral and bone disorders.

    Science.gov (United States)

    Vervloet, Marc G; Massy, Ziad A; Brandenburg, Vincent M; Mazzaferro, Sandro; Cozzolino, Mario; Ureña-Torres, Pablo; Bover, Jordi; Goldsmith, David

    2014-05-01

    Recent reports of several bone-derived substances, some of which have hormonal properties, have shed new light on the bone-cardiovascular axis. Deranged concentrations of humoral factors are not only epidemiologically connected to cardiovascular morbidity and mortality, but can also be causally implicated, especially in chronic kidney disease. FGF23 rises exponentially with advancing chronic kidney disease, seems to reach maladaptive concentrations, and then induces left ventricular hypertrophy, and is possibly implicated in the process of vessel calcification. Sclerostin and DKK1, both secreted mainly by osteocytes, are important Wnt inhibitors and as such can interfere with systems for biological signalling that operate in the vessel wall. Osteocalcin, produced by osteoblasts or released from mineralised bone, interferes with insulin concentrations and sensitivity, and its metabolism is disturbed in kidney disease. These bone-derived humoral factors might place the bone at the centre of cardiovascular disease associated with chronic kidney disease. Most importantly, factors that dictate the regulation of these substances in bone and subsequent secretion into the circulation have not been researched, and could provide entirely new avenues for therapeutic intervention.

  12. Role of staging bone marrow examination in children with Hodgkin disease

    NARCIS (Netherlands)

    Mahoney, DH; Schreuders, LC; Gresik, MV; McClain, KL

    1998-01-01

    Purpose. To determine the value of bone marrow trephine biopsy as part of the clinical staging for children presenting with Hodgkin disease. Patients and Methods, A retrospective study of pre-treatment bone marrow examinations was undertaken to examine the value of bone marrow staging in children wi

  13. Patients with Van Buchem disease, an osteosclerotic genetic disease, have elevated bone formation markers, higher bone density, and greater derived polar moment of inertia than normal.

    Science.gov (United States)

    Wergedal, Jon E; Veskovic, Katarina; Hellan, Minea; Nyght, Christine; Balemans, Wendy; Libanati, Cesar; Vanhoenacker, Filip M; Tan, Johan; Baylink, David J; Van Hul, Wim

    2003-12-01

    Van Buchem disease is an autosomal recessive disease characterized by overgrowth of the skeleton. In a group of Dutch patients the disease is thought to be due to a 52-kb deletion that results in decreased expression of the SOST gene. To further characterize the disease, the morphology of the metacarpals of six adult subjects and two juveniles with Van Buchem disease were measured on hand x-rays along with nine normal adults and nine adult carriers of the disease. Serum bone formation markers, alkaline phosphatase, type I procollagen peptide, and osteocalcin, and the urinary bone resorption marker, cross-linked N-telopeptide, were determined. Van Buchem patients had increased metacarpal outer diameter, inner diameter, cortical thickness, and bone mineral density. Calculated bone volume and derived polar moment of inertia were markedly elevated (elevations of 158 +/- 33% and 497 +/- 95%, respectively) consistent with increased bone strength. Serum procollagen peptide and osteocalcin were significantly higher in Van Buchem patients. Urinary cross-linked N-telopeptide was significantly elevated in Van Buchem patients. None of these changes was found in Van Buchem carriers. These observations indicate that decreased expression of the SOST gene can lead to increased bone formation and to stronger bones.

  14. Pathological fracture of the femur in a patient with Paget's disease of bone: a case report.

    Science.gov (United States)

    Petrescu, Pompiliu HoraŢiu; Izvernariu, Dragoş Andrei; Iancu, Cătălina; Dinu, Gabriel Ovidiu; Berceanu-Văduva, Marcel Mihai; Crişan, Dan; Iacob, Mihaela; Bucur, Venera Margareta; RăuŢia, Ion Călin; Prejbeanu, Ion Radu; Dema, Sorin; DuŢă, Ciprian Constantin

    2016-01-01

    Paget's disease of bone is a benign disease characterized by exaggerated remodeling of the bone matrix after osteoclast-mediated bone destruction. Its etiology is still unknown, despite the fact that it was discovered and described in 1877, but genetic factors and environmental triggers were shown to play their part in the pathogenesis of the disease. The main clinical presentations of the disease are related to bone pain and deformities. Radiological diagnosis is the main detection tool, though many monostotic Paget's disease cases may remain undiagnosed. We present the case of an 81-year-old male patient admitted to the Clinic of Orthopedics, Emergency County Hospital, Timisoara, Romania, with intense pain and deformity of the upper left thigh. Radiological examination performed shows a complete fracture of the upper third diaphysis of the left femur with suggestive signs for Paget's disease of the bone therefore a biopsy was taken and the patient was treated by surgical realignment with favorable evolution. He was discharged 13 days after surgery. The biopsy of the bone revealed extensive bone remodeling with numerous osteoclasts and extensive bone matrix deposition, unevenly stained and unevenly mineralized and reverse cement lines, which are consistent with the diagnosis of Paget's disease of the bone. Histomorphometric analysis show intense matrix deposition with a highly active remodeling process. Computed tomography (CT) scans were performed three years later and show the extension of the disease into the lower half of the left femur.

  15. Camurati-Engelmann's Disease on {sup 99m}Tc-MDP Bone Scan

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Hai Jeon; Oh, So Won; Paeng, Jin Chul; Lee, You Kyung; Choi, In Ho; Lee, Dong Soo [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2009-12-15

    A 24 year-old female presented for a {sup 99m}Tc-methylene diphosphonate (MDP) whole body bone scan due to chronic pain in the bilateral lower extremities that has aggravated since 2002. She was diagnosed with Camurati-Engelmann disease (CED) based on the clinical and radiological findings in 2002, and she re-visited our institute to evaluate disease status at this time. CED is a rare autosomal dominant type of bone dysplasia characterized by progressive cortical thickening of long bones, and narrowing of medullary cavity, and thus presents with typical clinical symptoms and signs such as chronic pain in the extremities, muscle weakness, and waddling gait. On the {sup 99m}Tc-MDP bone scan performed to evaluate disease status, intense increased uptake was seen in the skull, facial bones, bilateral scapulae, bilateral long bones, and bilateral pelvic bones, which clearly demonstrated the extent of CED involvement.

  16. Clinical relevance of changes in bone metabolism in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Pal; Miheller; Katalin; Lrinczy; Peter; Laszlo; Lakatos

    2010-01-01

    Low bone mineral density is an established, frequent, but often neglected complication in patients with inflammatory bowel disease (IBD). Data regarding the diagnosis, therapy and follow-up of low bone mass in IBD has been partially extrapolated from postmenopausal osteoporosis; however, the pathophysiology of bone loss is altered in young patients with IBD. Fracture, a disabling complication, is the most important clinical outcome of low bone mass. Estimation of fracture risk in IBD is difficult. Numerous ...

  17. Correlation of serum parathyroid hormone with mineral bone disease in chronic kidney disease patients

    Directory of Open Access Journals (Sweden)

    Rajeshwari S Vhora

    2015-01-01

    Full Text Available Background: Mineral bone disease (MBD is a systemic disorder of mineral and bone metabolism due to chronic kidney disease (CKD. Bone disease in CKD is due to secondary hyperparathyroidism. Serum intact parathyroid hormone (iPTH level estimation is a potential noninvasive method for the diagnosis of MBD at early stage. Aim: Treating renal bone disease should be one of the primary aims of therapy for CKD. Evaluation of the biochemical parameters of CKD-MBD (primarily phosphorus, calcium, parathyroid hormone, and Vitamin D levels as early as CKD stage 3, and an assessment of bone status (by the best means available, should be used to guide treatment decisions. The adverse effects of high phosphorus intake relative to renal clearance (including stimulation of hyperparathyroidism precede hyperphosphatemia, which presents late in CKD. Early reduction of phosphorus load may ameliorate these adverse effects. Evidence that calcium load may influence progression of vascular calcification with effects on mortality, should also be considered when choosing the type and dose of phosphate binder to be used. MBD in CKD has high morbidity and mortality and hence it is important to detect it at an early stage. iPTH levels can be highly sensitive and it is one of the useful noninvasive biochemical parameters to detect MBD in CKD. Materials and Methods: This was an observational study carried out in a tertiary care teaching hospital. The study involved 60 patients of CKD. Detailed history, physical examination, and biochemical parameters were assessed in all of them. Results: There was a significant association between hypertension, diabetes with nephropathy, and highly significant association between serum iPTH and raised blood urea levels in MBD group, however there was no significant association between duration of CKD, hemoglobin, creatinine, uric acid, phosphorous, calcium, and alkaline phosphatase with MBD. Conclusions: MBD in CKD can be detected at early

  18. Current options for the treatment of Paget’s disease of the bone

    Directory of Open Access Journals (Sweden)

    Daniela Merlotti

    2009-07-01

    Full Text Available Daniela Merlotti, Luigi Gennari, Giuseppe Martini, Ranuccio NutiDepartment of Internal Medicine, Endocrine-Metabolic Sciences and Biochemistry, University of Siena, Siena, ItalyAbstract: Paget’s disease of bone (PDB is a chronic bone remodeling disorder characterized by increased osteoclast-mediated bone resorption, with subsequent compensatory increases in new bone formation, resulting in a disorganized mosaic of woven and lamellar bone at affected skeletal sites. This disease is most often asymptomatic but can be associated with bone pain or deformity, fractures, secondary arthritis, neurological complications, deafness, contributing to substantial morbidity and reduced quality of life. Neoplastic degeneration of pagetic bone is a relatively rare event, occurring with an incidence of less than 1%, but has a grave prognosis. Specific therapy for PDB is aimed at decreasing the abnormal bone turnover and bisphosphonates are currently considered the treatment of choice. These treatments are associated with a reduction in plasma alkaline phosphatase (ALP activity and an improvement in radiological and scintigraphic appearance and with a reduction in bone pain and bone deformity, Recently, the availability of newer, more potent nitrogen-containing bisphosphonates has improved treatment outcomes, allowing a more effective and convenient management of this debilitating disorder.Keywords: Paget’s disease of bone, bisphosphonates, aminobisphosphonates, bone remodeling

  19. Natural products for treatment of bone erosive diseases: The effects and mechanisms on inhibiting osteoclastogenesis and bone resorption.

    Science.gov (United States)

    An, Jing; Hao, Dingjun; Zhang, Qian; Chen, Bo; Zhang, Rui; Wang, Yi; Yang, Hao

    2016-07-01

    Excessive bone resorption plays a central role on the development of bone erosive diseases, including osteoporosis, rheumatoid arthritis, and periodontitis. Osteoclasts, bone-resorbing multinucleated cells, are differentiated from hemopoietic progenitors of the monocyte/macrophage lineage. Regulation of osteoclast differentiation is considered an effective therapeutic target to the treatment of pathological bone loss. Natural plant-derived products, with potential therapeutic and preventive activities against bone-lytic diseases, have received increasing attention in recent years because of their whole regulative effects and specific pharmacological activities, which are more suitable for long-term use than chemically synthesized medicines. In this review, we summarized the detailed research progress on the active compounds derived from medical plants with potential anti-resorptive effects and their molecular mechanisms on inhibiting osteoclast formation and function. The active ingredients derived from natural plants that are efficacious in suppressing osteoclastogenesis and bone resorption include flavonoids, terpenoids (sesquiterpenoids, diterpenoids, triterpenoids), glycosides, lignans, coumarins, alkaloids, polyphenols, limonoids, quinones and others (steroid, oxoxishhone, fatty acid). Studies have shown that above natural products exert the inhibitory effects via regulating many factors involved in the process of osteoclast differentiation and bone resorption, including the essential cytokines (RANKL, M-CSF), transcription factors (NFATc1, c-Fos), signaling pathways (NF-κB, MAPKs, Src/PI3K/Akt, the calcium ion signaling), osteoclast-specific genes (TRAP, CTSK, MMP-9, integrin β3, OSCAR, DC-STAMP, Atp6v0d2) and local factors (ROS, LPS, NO). The development of osteoclast-targeting natural products is of great value for the prevention or treatment of bone diseases and for bone regenerative medicine.

  20. The utility of magnetic resonance imaging for bone involvement in Gaucher disease. Assessing more than bone crises.

    Science.gov (United States)

    Andrade-Campos, Marcio; Valero, Esther; Roca, Mercedes; Giraldo, Pilar

    2016-10-21

    Bone effects are the most frequent cause of disability in Gaucher disease (GD). Magnetic resonance imaging (MRI) has improved the study of bone involvement making it possible to measure the extent of infiltration and to identify localized complications and other lesions. Here we describe the results of our analysis of all bone lesions registered in MRI studies performed in our GD Clinic. A retrospective study was undertaken for all patients with types 1 and 3 GD who underwent MRI evaluation and correlated with clinical, molecular, and other follow-up information obtained from the Spanish GD Registry. 350 MRI studies of 131 GD patients were reviewed (males 53.4%). Mean age: 37.5years (range 13-74yr), 94.6% (124) were GD1 patients. 113/131 (86.3%) of patients presented with at least one bone effect (bone infiltration, bone crisis, avascular necrosis) were 79.4%, while 28.8% showed another bone lesion such as neuronopathic-like arthropathy, hemangioma, other ischemic phenomena, infection-related lesions, secondary neoplasia and tissue infiltration. MRI is a routinely-used tool for the evaluation of GD lesions which improves the assessment of patients before and during therapy, identifies GD complications and finds other concomitant lesions. This work provides a new evaluation of MRI assessment in this complex rare disease.

  1. The Nature of Expansion of Paget’s Disease of Bone

    Science.gov (United States)

    2013-04-01

    cell line or normal marrow from uninvolved bones from PDB (5). We obtained the PSV10 cell line from Dr. G. David Roodman (Indiana University...H, Boykin CS, Zhang H, Ishizuka S, Dempster DW, Roodman GD, Windle JJ. A SQSTM1/p62 mutation linked to Paget’s disease increases the...Singer FR, Bruder JM, Roodman GD. Enhanced RANK ligand expression and responsivity of bone marrow cells in Paget’s disease of bone. J Clin Invest

  2. Proceedings of the 2016 Santa Fe Bone Symposium: New Concepts in the Management of Osteoporosis and Metabolic Bone Diseases.

    Science.gov (United States)

    Lewiecki, E Michael; Bilezikian, John P; Bukata, Susan V; Camacho, Pauline; Clarke, Bart L; McClung, Michael R; Miller, Paul D; Shepherd, John

    2017-02-06

    The Santa Fe Bone Symposium is an annual meeting of healthcare professionals and clinical researchers that details the clinical relevance of advances in knowledge of skeletal diseases. The 17th Santa Fe Bone Symposium was held in Santa Fe, New Mexico, USA, on August 5-6, 2016. The program included plenary lectures, oral presentations by endocrinology fellows, meet-the-professor sessions, and panel discussions, all aimed to provide ample opportunity for interactive discussions among all participants. Symposium topics included recent developments in the translation of basic bone science to patient care, new clinical practice guidelines for postmenopausal osteoporosis, management of patients with disorders of phosphate metabolism, new and emerging treatments for rare bone diseases, strategies to enhance fracture healing, and an update on Bone Health Extension for Community Healthcare Outcomes, using a teleconferencing platform to elevate the level of knowledge of healthcare professionals in underserved communities to deliver best practice care for skeletal diseases. The highlights and important clinical messages of the 2016 Santa Fe Bone Symposium are provided herein by each of the faculty presenters.

  3. Bone metabolism in advanced cholestatic liver disease : Analysis by bone histomorphometry

    NARCIS (Netherlands)

    Guichelaar, MMJ; Malinchoc, M; Sibonga, J; Clarke, BL; Hay, JE

    2002-01-01

    Despite the clinical importance of cholestatic osteopenia, little is known about its pathophysiologic mechanism. By tetracycline-labeled histomorphometric analysis of bone biopsies taken at the time of liver transplantation, we prospectively evaluated bone resorption and formation in 50 consecutive

  4. [Cytokines in bone diseases. Cytokine and postmenopausal osteoporosis].

    Science.gov (United States)

    Inada, Masaki; Miyaura, Chisato

    2010-10-01

    Bone resorption is regulated by various cytokines. In postmenopausal osteoporosis, bone loss due to estrogen deficiency is closely related to the production of bone-resorbing cytokine. Especially, the increased production of IL-1, IL-6 and TNF-α could induce the expression of RANKL in bone tissues to enhance osteoclastogenesis. Relationship between estrogen deficiency and various cytokines is important to clarify the pathogenesis of postmenopausal osteoporosis.

  5. Natural History of Malignant Bone Disease in Gastric Cancer: Final Results of a Multicenter Bone Metastasis Survey

    Science.gov (United States)

    Silvestris, Nicola; Pantano, Francesco; Ibrahim, Toni; Gamucci, Teresa; De Vita, Fernando; Di Palma, Teresa; Pedrazzoli, Paolo; Barni, Sandro; Bernardo, Antonio; Febbraro, Antonio; Satolli, Maria Antonietta; Bertocchi, Paola; Catalano, Vincenzo; Giommoni, Elisa; Comandone, Alessandro; Maiello, Evaristo; Riccardi, Ferdinando; Ferrara, Raimondo; Trogu, Antonio; Berardi, Rossana; Leo, Silvana; Bertolini, Alessandro; Angelini, Francesco; Cinieri, Saverio; Russo, Antonio; Pisconti, Salvatore; Brunetti, Anna Elisabetta; Azzariti, Amalia; Santini, Daniele

    2013-01-01

    Background Bone metastasis represents an increasing clinical problem in advanced gastric cancer (GC) as disease-related survival improves. In literature, few data on the natural history of bone disease in GC are available. Patients and Methods Data on clinicopathology, skeletal outcomes, skeletal-related events (SREs), and bone-directed therapies for 208 deceased GC patients with evidence of bone metastasis were statistically analyzed. Results Median time to bone metastasis was 8 months (CI 95%, 6.125–9.875 months) considering all included patients. Median number of SREs/patient was one. Less than half of the patients (31%) experienced at least one and only 4 and 2% experienced at least two and three events, respectively. Median times to first and second SRE were 2 and 4 months, respectively. Median survival was 6 months after bone metastasis diagnosis and 3 months after first SRE. Median survival in patients who did not experience SREs was 5 months. Among patients who received zoledronic acid before the first SRE, the median time to appearance of first SRE was significantly prolonged compared to control (7 months vs 4 months for control; P: 0.0005). Conclusions To our knowledge, this retrospective analysis is the largest multicenter study to demonstrate that bone metastases from GC are not so rare, are commonly aggressive and result in relatively early onset of SREs in the majority of patients. Indeed, our large study, which included 90 patients treated with ZOL, showed, for the first time in literature, a significant extension of time to first SRE and increase in the median survival time after diagnosis of bone metastasis. Taken together, these data may support the beneficial effects of ZOL in GC patients. PMID:24204569

  6. Questions from the clinician to the radiologist regarding the diagnosis of metabolic bone diseases

    Energy Technology Data Exchange (ETDEWEB)

    Schulz, W.; Schmidt, M.

    1986-12-01

    Macromorphological X-ray findings in metabolic bone diseases can be established only in advanced stages. Micromorphological X-ray diagnostic procedures will support the diagnosis even in early stages. Mineralometric examinations are adjuvant methods for early diagnosis and survey of therapy in metabolic bone diseases. The synopsis of parameters of calcium phosphate metabolism, bone histology (histomorphometry) and radiological morphology enables the type and stage of osteopathy to be diagnosed. The supplementary diagnostic methods are helpful in distinguishing bone diseases with increased turnover, inpaired bone modelling and absorption, disturbed mineralization and ectopic calcification. Within the metabolic osteopathies, osteoporosis is gaining more and more importance as a socioeconomic problem; therefore, early diagnosis and treatment are of significant relevance. Hyper-, hypoparathyroidism and osteoidosis are diseases at can be cured if diagnosed early.

  7. Bone loss in rheumatoid arthritis. Influence of disease activity, duration of the disease, functional capacity, and corticosteroid treatment

    DEFF Research Database (Denmark)

    Hansen, M; Florescu, A; Stoltenberg, M;

    1996-01-01

    Axial and appendicular bone mass were studied in 95 patients with rheumatoid arthritis. The aims were to quantify bone mineral density (BMD) and to evaluate the importance of disease activity, duration of disease, functional capacity, and corticosteroid treatment for bone loss in patients...... BMDARM. The decreased BMD in patients with rheumatoid arthritis seems primarily to be caused by an impaired physical activity which may be related to disease activity. Corticosteroids did not decrease BMD in neither the axial nor the appendicular skeleton. The antiinflammatory effect of steroids lead...

  8. Lumbar gibbus in storage diseases and bone dysplasias

    Energy Technology Data Exchange (ETDEWEB)

    Levin, T.L. [Department of Radiology, Division of Pediatric Radiology, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital of New York, NY (United States); Berdon, W.E. [Department of Radiology, Division of Pediatric Radiology, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital of New York, NY (United States); Lachman, R.S. [International Skeletal Dysplasia Registry, Los Angeles, CA (United States); Anyane-Yeboa, K. [Department of Pediatrics, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital of New York, NY (United States); Ruzal-Shapiro, C. [Department of Radiology, Division of Pediatric Radiology, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital of New York, NY (United States); Roye, D.P. Jr. [Department of Orthopedic Surgery, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital of New York, NY (United States)

    1997-04-01

    Objective. The objective of this study was to review the problem of lumbar gibbus in children with storage diseases and bone dysplasias utilizing plain films and MR imaging. Materials and methods. Clinical histories and radiographic images in five patients with storage diseases [four mucopolysaccharidosis (MPS) and one mucolipidosis] and two with achondroplasia were reviewed. The International Skeletal Dysplasia Registry (Los Angeles, Calif.), surveyed for all patients with lumbar gibbus and skeletal dysplasias, provided 12 additional cases. Results. All patients had localized gibbus of the upper lumbar spine, characterized by anterior wedging and posterior displacement of the vertebrae at the apex of the curve, producing a beaked appearance. The curve, exaggerated in the sitting or standing position, was most severe in the two patients with MPS-IV (one of whom died). Both developed severe neurologic signs and symptoms requiring surgical intervention. In four patients, MR images demonstrated the apex of the curve to be at or below the conus. Two patients demonstrated anterior herniation of the intervertebral discs at the apex of the curve, though the signal intensity of the intervertebral discs was normal. Conclusion. Lumbar gibbus has important neurologic and orthopedic implications, and is most severe in patients with MPS. The etiology of the gibbus with vertebral beaking is multifactorial and includes poor truncal muscle tone, weight-bearing forces, growth disturbance and anterior disc herniation. The curve is generally at or below the conus. Neurologic complications are unusual, although orthopedic problems can arise. Due to their longer survival, patients with achondroplasia or Morquio`s disease are more vulnerable to eventual gibbus-related musculoskeletal complications. (orig.). With 6 figs., 2 tabs.

  9. When, how, and why a bone biopsy should be performed in patients with chronic kidney disease.

    Science.gov (United States)

    Torres, Pablo Ureña; Bover, Jordi; Mazzaferro, Sandro; de Vernejoul, Marie Christine; Cohen-Solal, Martine

    2014-11-01

    In chronic kidney disease the excessive production of parathyroid hormone increases the bone resorption rate and leads to histologic bone signs of secondary hyperparathyroidism. However, in other situations, the initial increase in parathyroid hormone and bone remodeling may be slowed down excessively by a multitude of factors including age, ethnic origin, sex, and treatments such as vitamin D, calcium salts, calcimimetics, steroids, and so forth, leading to low bone turnover or adynamic bone disease. Both high and low bone turnover diseases actually are observed equally in chronic kidney disease patients treated by dialysis, and all types of renal osteodystrophy are associated with an increased risk of skeletal fractures, reduced quality of life, and poor clinical outcomes. Unfortunately, the diagnosis of these bone abnormalities cannot be obtained correctly by current clinical, biochemical, and imaging methods. Therefore, bone biopsy has been, and still remains, the gold standard analysis for assessing the exact type of renal osteodystrophy. It is also the unique way to assess the mechanisms of action, safety, and efficacy of new bone-targeting therapies.

  10. DIAGNOSTICS OF BONE METABOLISM DISORDERS IN ONCOLOGICAL DISEASES

    Directory of Open Access Journals (Sweden)

    O. I. Apolikhin

    2015-01-01

    Full Text Available Osteoporosis is one of the most significant bone complications of cancer. About 1.5 million cancer patients worldwide have bone metastases. Patients with myeloma, breast cancer, prostate, thyroid, bladder and lung have very high risk of development of bone lesions and related complications. Currently, osteodensitometry is the gold standard for the diagnosis of osteoporosis. In recent years we frequently use the innovative imaging techniques for bone metastases, such as CT, MRI, PET/CT. Unfortunately, the diagnostic value of these methods is that it is not always possible to identify abnormalities of bone metabolism in cancer, especially in the early stages. This review shows the world experience of usage of biochemical markers of bone resorption (calcium, hydroxyproline, NTX, CTX, PYD, DPD, TRAP-5b, bone sialoprotein - BSP and markers of bone synthesis (osteocalcin, CSF, ACF, Karlovy vary IFF, their advantages and disadvantages. The level of these markers is increased in most patients with osteoporosis and bone metastases, it is suggesting a potential role in early diagnosis of bone metastases.

  11. Rheumatic manifestations of primary and metastatic bone tumors and paraneoplastic bone disease.

    Science.gov (United States)

    Waimann, Christian A; Lu, Huifang; Suarez Almazor, Maria E

    2011-11-01

    Bone tumors can show a wide range of nonspecific rheumatic manifestations. The presence of unexplained or atypical chronic bone pain, an enlarging bone mass, neurovascular compression syndromes, or pathologic fractures should alert us to the possibility of a bone tumor causing these symptoms. These patients must undergo a complete physical examination; adequate imaging; and, if needed, a biopsy to confirm their diagnosis and offer them an opportune treatment. In addition, bone tumors and other malignancies can present remote clinical manifestations and unusual laboratory findings (eg, HOA, hypophosphatemia, hyperphosphaturia, and hypercalcemia) that may be the first and early manifestation of an occult cancer. These findings should motivate a cancer screening according to age, sex, and personal history. Cancer therapies also have a big impact on bone health, increasing the risk of osteoporosis, osteomalacia, and/or osteonecrosis. Rheumatologists should be aware of possible long-term adverse events of cancer treatment to avoid future complications.

  12. Bone mineral disorder in chronic kidney disease: Klotho and FGF23; cardiovascular implications.

    Science.gov (United States)

    Salanova Villanueva, Laura; Sánchez González, Carmen; Sánchez Tomero, José Antonio; Aguilera, Abelardo; Ortega Junco, Esther

    2016-01-01

    Cardiovascular factors are one of the main causes of morbidity and mortality in patients with chronic kidney disease. Bone mineral metabolism disorders and inflammation are pathological conditions that involve increased cardiovascular risk in chronic kidney disease. The cardiovascular risk involvement of bone mineral metabolism classical biochemical parameters such as phosphorus, calcium, vitamin D and PTH is well known. The newest markers, FGF23 and klotho, could also be implicated in cardiovascular disease.

  13. Bone

    Science.gov (United States)

    Helmberger, Thomas K.; Hoffmann, Ralf-Thorsten

    The typical clinical signs in bone tumours are pain, destruction and destabilization, immobilization, neurologic deficits, and finally functional impairment. Primary malignant bone tumours are a rare entity, accounting for about 0.2% of all malignancies. Also benign primary bone tumours are in total rare and mostly asymptomatic. The most common symptomatic benign bone tumour is osteoid osteoma with an incidence of 1:2000.

  14. Burden of metastatic bone disease from genitourinary malignancies.

    Science.gov (United States)

    Mulders, Peter F; Abrahamsson, Per-Anders; Bukowski, Ronald M

    2010-11-01

    Bone metastases are common among patients with stage IV genitourinary cancers. Most patients with bone metastases develop at least one debilitating and potentially life-limiting skeletal-related event. These events are associated with increased medical expenses and decreased quality of life. Current guidelines recommend screening for bone metastases in men with high-risk prostate cancer, but guidance for screening and treatment of bone metastases from genitourinary cancers varies by country and setting. Several bisphosphonates have been evaluated in the advanced genitourinary cancer setting. Zoledronic acid has demonstrated efficacy in significantly reducing the risk of skeletal-related events in patients with bone metastases from a broad range of solid tumors including prostate, renal and bladder cancers, and is recommended for preserving bone health.

  15. Bone disease in cystic fibrosis: new pathogenic insights opening novel therapies.

    Science.gov (United States)

    Jacquot, J; Delion, M; Gangloff, S; Braux, J; Velard, F

    2016-04-01

    Mutations within the gene encoding for the chloride ion channel cystic fibrosis transmembrane conductance regulator (CFTR) results in cystic fibrosis (CF), the most common lethal autosomal recessive genetic disease that causes a number of long-term health problems, as the bone disease. Osteoporosis and increased vertebral fracture risk associated with CF disease are becoming more important as the life expectancy of patients continues to improve. The etiology of low bone density is multifactorial, most probably a combination of inadequate peak bone mass during puberty and increased bone losses in adults. Body mass index, male sex, advanced pulmonary disease, malnutrition and chronic therapies are established additional risk factors for CF-related bone disease (CFBD). Consistently, recent evidence has confirmed that CFTR plays a major role in the osteoprotegerin (OPG) and COX-2 metabolite prostaglandin E2 (PGE2) production, two key regulators in the bone formation and regeneration. Several others mechanisms were also recognized from animal and cell models contributing to malfunctions of osteoblast (cell that form bone) and indirectly of bone-resorpting osteoclasts. Understanding such mechanisms is crucial for the development of therapies in CFBD. Innovative therapeutic approaches using CFTR modulators such as C18 have recently shown in vitro capacity to enhance PGE2 production and normalized the RANKL-to-OPG ratio in human osteoblasts bearing the mutation F508del-CFTR and therefore potential clinical utility in CFBD. This review focuses on the recently identified pathogenic mechanisms leading to CFBD and potential future therapies for treating CFBD.

  16. Combined bone scintigraphy and indium-111 leukocyte scans in neuropathic foot disease

    Energy Technology Data Exchange (ETDEWEB)

    Schauwecker, D.S.; Park, H.M.; Burt, R.W.; Mock, B.H.; Wellman, H.N.

    1988-10-01

    It is difficult to diagnose osteomyelitis in the presence of neurotrophic osteoarthropathy. We performed combined (99mTc)MDP bone scans and indium-111 (111In) leukocyte studies on 35 patients who had radiographic evidence of neuropathic foot disease and clinically suspected osteomyelitis. The (111In)leukocyte study determined if there was an infection and the bone scan provided the anatomic landmarks so that the infection could be localized to the bone or the adjacent soft tissue. Seventeen patients had osteomyelitis and all showed increased (111In)leukocyte activity localized to the bone, giving a sensitivity of 100%. Among the 18 patients without osteomyelitis, eight had no accumulation of (111In)leukocytes, seven had the (111In)leukocyte activity correctly localized to the soft tissue, two had (111In)leukocyte activity mistakenly attributed to the bone, and one had (111In)leukocyte accumulation in a proven neuroma which was mistakenly attributed to bone. These three false-positive results for osteomyelitis reduced the specificity to 83%. Considering only the 27 patients with a positive (111In)leukocyte study, the combined bone scan and (111In)leukocyte study correctly localized the infection to the soft tissues or bone in 89%. Uninfected neurotrophic osteoarthropathy does not accumulate (111In)leukocytes. We found the combined bone scan and (111In) leukocyte study useful for the detection and localization of infection to soft tissue or bone in patients with neuropathic foot disease.

  17. Role of TAF12 in the Increased VDR Activity in Paget’s Disease of Bone

    Science.gov (United States)

    2014-10-01

    November 25, 2013. Accepted manuscript online December 11, 2013. Address correspondence to: G David Roodman , MD, PhD, Department of Medicine, Hematology...Yukiko Kitagawa,1 Deborah L Galson,4 David W Dempster,2 Jolene J Windle,3 Noriyoshi Kurihara,1 and G David Roodman1,5 1Department of Medicine, Hematology...turnover in Paget’s disease of bone. Clin Orthop. 1987;217:26–36. 3. Siris ES, Roodman GD. Paget’s Disease of Bone, Primer on the Metabolic Bone Diseases

  18. Postnatal Changes in Humerus Cortical Bone Thickness Reflect the Development of Metabolic Bone Disease in Preterm Infants

    Directory of Open Access Journals (Sweden)

    Shuko Tokuriki

    2016-01-01

    Full Text Available Objective. To use cortical bone thickness (CBT of the humerus to identify risk factors for the development of metabolic bone disease in preterm infants. Methods. Twenty-seven infants born at <32 weeks of gestational age, with a birth weight of <1,500 g, were enrolled. Humeral CBT was measured from chest radiographs at birth and at 27-28, 31-32, and 36–44 weeks of postmenstrual age (PMA. The risk factors for the development of osteomalacia were statistically analyzed. Results. The humeral CBT at 36–44 weeks of PMA was positively correlated with gestational age and birth weight and negatively correlated with the duration of mechanical ventilation. CBT increased with PMA, except in six very early preterm infants in whom it decreased. Based on logistic regression analysis, gestational age and duration of mechanical ventilation were identified as risk factors for cortical bone thinning. Conclusions. Humeral CBT may serve as a radiologic marker of metabolic bone disease at 36–44 weeks of PMA in preterm infants. Cortical bones of extremely preterm infants are fragile, even when age is corrected for term, and require extreme care to lower the risk of fractures.

  19. Bone Markers

    Science.gov (United States)

    ... markers may be seen in conditions such as: Osteoporosis Paget disease Cancer that has spread to the bone (metastatic bone disease) Hyperparathyroidism Hyperthyroidism Osteomalacia in adults and rickets in children—lack of bone mineralization, ...

  20. Radionuclide conjugates of calcitonin for imaging bone disease and cancer

    Energy Technology Data Exchange (ETDEWEB)

    Greenland, William Edward Peverell

    2002-07-01

    Salmon calcitonin (sCt) is a peptide with a higher affinity for human calcitonin receptors (hCtR) than human calcitonin. It has been used for treating osteoporosis, Paget's disease and bone pain. High levels of hCtRs are expressed on osteoclasts, bone metastases and primary breast and prostate cancers. The peptide was chosen for radiolabelling as a possible imaging agent. Direct labelling with {sup 99m}Tc via simultaneous reduction of the indigenous disulfide bond and {sup 99m}TcO{sub 4}{sup -} (VII) with the water soluble phenyl phosphine (TPPDS) was performed. The radiolabelled peptide was not suitable for use as a radiopharmaceutical due to the heterogeneity of the product as observed by reverse phase HPLC and due to poor binding to the human breast cancer cell line MCF7. The electospray MS suggested a {sup 99}Tc-TPPDS (III) core instead of the expected {sup 99}Tc=O (V) core. Normal sCt has 3 conjugatible primary amines leading to a mixture of 8 possible products. A sCt analogue (sCtA) with a single primary amine was produced and conjugated to the chelator TETA to produce a single conjugated species. The sCtA-TETA was labelled with cold Cu and characterised by electospray MS. The monodentate ligand Hynic was synthesised directly into the peptide using N-{alpha}-Fmoc-N-{epsilon}-(Hynic-Boc)-Lys a novel orthogonally protected amino acid. The peptide was labelled with {sup 99m}Tc with tricine coligands. The radiolabelled peptide produced a single peak as observed by reverse phase HPLC and bound to MCF7 cell in a specific manner. The electospray MS suggested that one of the tricine coligands is lost due to the heating effect and possibly replaced by an adjacent histidine acting as a ternary ligand. The sCtLys{sup 18}-Hynic{sup 99m}Tc(tricine){sub 2} labelled peptide is the lead radiolabelled peptide and could be used for a normal biodistribution animal study, followed by clinical evaluation in humans. (author)

  1. Bone marrow stroma in idiopathic myelofibrosis and other haematological diseases. An immunohistochemical study

    DEFF Research Database (Denmark)

    Lisse, I; Hasselbalch, H; Junker, P

    1991-01-01

    Bone marrow stroma was investigated immunohistochemically in 31 patients with haematological diseases, mainly idiopathic myelofibrosis (n = 8) and related chronic myeloproliferative disorders (n = 14). The bone marrow from patients with idiopathic myelofibrosis and some CML patients showed marked...... and capillarization, with the development of continuous sheets of basement membrane material beneath endothelial cells....

  2. Bone mineral density and vitamin D status in Parkinson's disease patients

    NARCIS (Netherlands)

    Bos, F. van den; Speelman, A.D.; Nimwegen-Arrachart, M.L. van; Schouw, Y.T. van der; Backx, F.J.; Bloem, B.R.; Munneke, M.; Verhaar, H.J.

    2013-01-01

    Bone loss is more common in Parkinson's disease (PD) than in the general population. Several factors may be involved in the development of bone loss, including malnutrition, immobilization, low body mass index, decreased muscle strength, vitamin D deficiency and medication use. This study investigat

  3. Improvement of Lumbar Bone Mass after Infliximab Therapy in Crohn’s Disease Patients

    Directory of Open Access Journals (Sweden)

    Marina Mauro

    2007-01-01

    Full Text Available BACKGROUND: Patients with Crohn’s disease (CD have a high risk of developing osteoporosis, but the mechanisms underlying bone mass loss are unclear. Elevated proinflammatory cytokines, such as tumour necrosis factor-alpha (TNFα, have been implicated in the pathogenesis of bone resorption.

  4. Recurrent infarction of sphenoid bone with subperiosteal collection in a child with sickle cell disease.

    Science.gov (United States)

    Alsuhaibani, Adel H; Marzouk, Mohammed Abu

    2011-01-01

    Infarction of the orbital bone in patients with sickle cell disease is very rare. The authors report a young boy who presented twice with marked acute proptosis and eyelid swelling of the right eye resulting from infarction in the greater wing of the sphenoid bone accompanied by an orbital subperiosteal collection. The time interval between the 2 attacks was 3 years.

  5. Burden of metastatic bone disease from genitourinary malignancies.

    NARCIS (Netherlands)

    Mulders, P.F.A.; Abrahamsson, P.A.; Bukowski, R.M.

    2010-01-01

    Bone metastases are common among patients with stage IV genitourinary cancers. Most patients with bone metastases develop at least one debilitating and potentially life-limiting skeletal-related event. These events are associated with increased medical expenses and decreased quality of life. Current

  6. Emerging strategies and therapies for treatment of Paget’s disease of bone

    Directory of Open Access Journals (Sweden)

    Brown JP

    2011-04-01

    Full Text Available Laëtitia Michou, Jacques P BrownLaval University, Department of Medicine, CHUQ (CHUL Research Centre and Division of Rheumatology, Quebec City, QC, CanadaAbstract: Paget’s disease of bone (PDB is a progressive monostotic or polyostotic metabolic bone disease characterized by focal abnormal bone remodeling, with increased bone resorption and excessive, disorganized, new bone formation. PDB rarely occurs before middle age, and it is the second most frequent metabolic bone disorder after osteoporosis, affecting up to 3% of adults over 55 years of age. One of the most striking and intriguing clinical features is the focal nature of the disorder, in that once the disease is established within a bone, there is only local spread within that bone and no systemic dissemination. Despite many years of intense research, the etiology of PDB has still to be conclusively determined. Based on a detailed review of genetic and viral factors incriminated in PDB, we propose a unifying hypothesis from which we can suggest emerging strategies and therapies. PDB results in weakened bone strength and abnormal bone architecture, leading to pain, deformity or, depending on the bone involved, fracture in the affected bone. The diagnostic assessment includes serum total alkaline phosphatase, total body bone scintigraphy, skull and enlarged view pelvis x-rays, and if needed, additional x-rays. The ideal therapeutic option would eliminate bone pain, normalize serum total alkaline phosphatase with prolonged remission, heal radiographic osteolytic lesions, restore normal lamellar bone, and prevent recurrence and complications. With the development of increasingly potent bisphosphonates, culminating in the introduction of a single intravenous infusion of zoledronic acid 5 mg, these goals of treatment are close to being achieved, together with long-term remission in almost all patients. Based on the recent pathophysiological findings, emerging strategies and therapies are

  7. Surgery or radiotherapy for the treatment of bone hydatid disease: a retrospective case series

    Directory of Open Access Journals (Sweden)

    Zengru Xie

    2015-04-01

    Conclusion: This retrospective case series describes, for the first time, the clinical outcomes in a series of patients treated with radiotherapy for bone hydatid disease. Although no direct comparison between the treatment groups could be made due to methodological limitations of the study design, this study indicates that well-designed prospective randomized controlled clinical trials assessing radiotherapy may be warranted in patients with inoperable hydatid disease of the bones.

  8. Lessons from Microglia Aging for the Link between Inflammatory Bone Disorders and Alzheimer's Disease

    OpenAIRE

    Zhou Wu; Hiroshi Nakanishi

    2015-01-01

    Bone is sensitive to overactive immune responses, which initiate the onset of inflammatory bone disorders, such as rheumatoid arthritis and periodontitis, resulting in a significant systemic inflammatory response. On the other hand, neuroinflammation is strongly implicated in Alzheimer’s disease (AD), which can be enhanced by systemic inflammation, such as that due to cardiovascular disease and diabetes. There is growing clinical evidence supporting the concept that rheumatoid arthritis and p...

  9. Bone metabolism and RANKL/RANK/OPG trail in periodontal disease

    Directory of Open Access Journals (Sweden)

    Czupkallo Lukasz

    2016-12-01

    Full Text Available Periodontal disease is an inflammatory disease of multifactorial etiology. In order for it to appear there must come to an imbalance between the effects of pathogens and host defense mechanisms. As a result of its course the destruction of structures supporting the teeth appears (periodontium, cement, bone, and consequently leads to teeth loosening and loss. In recent years, the participation of RANKL/RANK/OPG in bone remodeling process was highligted.

  10. Bone x-ray

    Science.gov (United States)

    ... or broken bone Bone tumors Degenerative bone conditions Osteomyelitis (inflammation of the bone caused by an infection) ... Multiple myeloma Osgood-Schlatter disease Osteogenesis imperfecta Osteomalacia Osteomyelitis Paget disease of the bone Rickets X-ray ...

  11. Bone Disease in Myeloma: The Claws of CRAB.

    Science.gov (United States)

    Fonseca, Rafael; Jain, Tania

    2016-03-15

    A dynamic approach to use bisphosphonates according to biomarkers of bone metabolism is presented in the Z-MARK study by Raje and colleagues. This is a major step forward toward a rational approach to bisphosphonate usage.

  12. Bone and mineral metabolism in adult celiac disease

    Energy Technology Data Exchange (ETDEWEB)

    Caraceni, M.P.; Molteni, N.; Bardella, M.T.; Ortolani, S.; Nogara, A.; Bianchi, P.A.

    1988-03-01

    Bone mineral density (/sup 125/I photon absorptiometry) was lower in 20 untreated adult celiac patients than in sex- and age-matched controls (p less than 0.001), and plasma alkaline phosphatase, parathyroid hormone, urinary hydroxyproline/creatinine levels were higher than normal (p less than 0.05, less than 0.001, less than 0.05, respectively). Gluten-free diet was started, and the patients were divided randomly into two treatment groups, one which received oral 25-hydroxyvitamin D 50 micrograms/day and one which did not. After 12 months' treatment, bone turnover markers showed a decrease, which did not reach statistical significance, and bone mineral density did not show significant modifications compared with base line in either group. It was found that a gluten-free diet followed for 1 yr can prevent further bone loss, but no significant differences were detected between the two groups.

  13. Paget’s Disease of Bone Presented as Normal Pressure Hydrocephalus: A Case Report and Review of Literature

    Directory of Open Access Journals (Sweden)

    Abbas Tafakhori

    2012-07-01

    Full Text Available Background: Paget’s disease is a focal bone disorder manifested as bone overgrowth and disrupted bone integrity as a result of accelerated bone remodelling rate. Rarely, Paget’s disease of the base of the skull results in hydrocephalic dementia, and the triad of normal pressure hydrocephalus syndrome is a much more scarce entity.Case Report: Herein, we report an elderly woman who presented in Imam Khomeini Hospital, Tehran, Iran, with normal pressure hydrocephalus syndrome due to Paget’s bone disease. Furthermore, we have reviewed relevant previous studiesConclusion: Paget’s disease can be presented as normal pressure hydrocephalus syndrome

  14. Imaging Paget's disease of bone-from head to toe

    Energy Technology Data Exchange (ETDEWEB)

    Cortis, K.; Micallef, K. [Medical Imaging Department, Mater Dei Hospital, Msida (Malta); Mizzi, A., E-mail: adrian.mizzi@gov.mt [Medical Imaging Department, Mater Dei Hospital, Msida (Malta)

    2011-07-15

    Paget's disease of the bone is a common, non-inflammatory, metabolic, skeletal disorder of unknown aetiology characterized by an increase in osteoclast-mediated bone resorption and compensatory excessive osteoblast activation. Prevalence increases with age, and a pronounced geographical variation is well documented. The disease is often an incidental finding on a radiological examination requested for an unrelated indication. The osteolytic, mixed osteolytic/osteoblastic, and osteosclerotic phases may occur in the same patient and same bone in a synchronous or metachronous fashion. Radiological features in each phase mirror the histopathological appearances, and are distinctive enough to establish a diagnosis with confidence. Using multi-technique imaging, this review illustrates the most common and the not so common radiological patterns of involvement in Paget's disease of bone observed at our centre during the past 20 years.

  15. Pathogenesis of Bone Alterations in Gaucher Disease: The Role of Immune System

    Directory of Open Access Journals (Sweden)

    Juan Marcos Mucci

    2015-01-01

    Full Text Available Gaucher, the most prevalent lysosomal disorder, is an autosomal recessive inherited disorder due to a deficiency of glucocerebrosidase. Glucocerebrosidase deficiency leads to the accumulation of glucosylceramide primarily in cells of mononuclear-macrophage lineage. Clinical alterations are visceral, hematological, and skeletal. Bone disorder in Gaucher disease produces defects on bone metabolism and structure and patients suffer from bone pain and crisis. Skeletal problems include osteopenia, osteoporosis, osteolytic lesions, and osteonecrosis. On the other hand a chronic stimulation of the immune system is a well-accepted hallmark in this disease. In this review we summarize the latest findings in the mechanisms leading to the bone pathology in Gaucher disease in relationship with the proinflammatory state.

  16. Preliminary results of automated removal of degenerative joint disease in bone scan lesion segmentation

    Science.gov (United States)

    Chu, Gregory H.; Lo, Pechin; Kim, Hyun J.; Auerbach, Martin; Goldin, Jonathan; Henkel, Keith; Banola, Ashley; Morris, Darren; Coy, Heidi; Brown, Matthew S.

    2013-03-01

    Whole-body bone scintigraphy (or bone scan) is a highly sensitive method for visualizing bone metastases and is the accepted standard imaging modality for detection of metastases and assessment of treatment outcomes. The development of a quantitative biomarker using computer-aided detection on bone scans for treatment response assessment may have a significant impact on the evaluation of novel oncologic drugs directed at bone metastases. One of the challenges to lesion segmentation on bone scans is the non-specificity of the radiotracer, manifesting as high activity related to non-malignant processes like degenerative joint disease, sinuses, kidneys, thyroid and bladder. In this paper, we developed an automated bone scan lesion segmentation method that implements intensity normalization, a two-threshold model, and automated detection and removal of areas consistent with non-malignant processes from the segmentation. The two-threshold model serves to account for outlier bone scans with elevated and diffuse intensity distributions. Parameters to remove degenerative joint disease were trained using a multi-start Nelder-Mead simplex optimization scheme. The segmentation reference standard was constructed manually by a panel of physicians. We compared the performance of the proposed method against a previously published method. The results of a two-fold cross validation show that the overlap ratio improved in 67.0% of scans, with an average improvement of 5.1% points.

  17. S-MRI score: A simple method for assessing bone marrow involvement in Gaucher disease

    Energy Technology Data Exchange (ETDEWEB)

    Roca, M. [Radiology (Magnetic Resonance) Instituto Aragones de Ciencias de la Salud (I-CS), Zaragoza (Spain); Mota, J. [Diagnostic Imaging Department, Medimagen, Barcelona (Spain); Alfonso, P. [Radiology (Magnetic Resonance) Instituto Aragones de Ciencias de la Salud (I-CS), Zaragoza (Spain); Pocovi, M. [Biochemistry and Cellular and Molecular Biology Department, Zaragoza University (Spain); Giraldo, P. [Haematology Department, Miguel Servet University Hospital, 50009 Zaragoza (Spain)]. E-mail: pgiraldo@salud.aragon.es

    2007-04-15

    Semi quantitative MRI is a very useful procedure for evaluating the bone marrow burden (BMB) in Gaucher disease (GD). Score systems have been applied to obtain a parameter for evaluating the severity of bone disease. Our purpose was to test a simple, reproducible and accurate score to evaluate bone marrow involvement in GD patients. MRI was performed in spine, pelvis and femora at diagnosis in 54 adult GD1 patients, 61.1% of whom were female. Three MRI patterns and punctuation in each location were defined: normal, 0; non-homogeneous infiltration subtypes reticular, 1; mottled, 2; diffuse, 3; and homogeneous infiltration, 4. This score was called Spanish-MRI (S-MRI). Two independent observers applied the S-MRI and bone marrow burden score and compared the differences using the non-parametric Mann-Whitney test. Correlation rank test was calculated. In 46 patients (85.2%), bone involvement was observed. Thirty-nine (72.3%) had their spine affected, 35 (64.8%) pelvis and 33 (61.2%) femora. Fourteen patients had bone infarcts, 14 avascular necrosis, 2 vertebral fractures and 2 bone crises. Correlation analysis between S-MRI and BMB was (r {sup 2} = .675; p = .0001). No evidence of correlation was observed between CT activity and S-MRI nor between CT activity and BMB. We have found a relationship between genotype and bone infiltration according to S-MRI site and complications. S-MRI is a simple method that provides useful information to evaluate bone infiltration and detect silent complications. Our results correlated with the BMB score but offer higher sensitivity, specificity and accuracy for classifying the extent of bone disease.

  18. The influence of genetic variability and proinflammatory status on the development of bone disease in patients with Gaucher disease.

    Science.gov (United States)

    Gervas-Arruga, Javier; Cebolla, Jorge Javier; de Blas, Ignacio; Roca, Mercedes; Pocovi, Miguel; Giraldo, Pilar

    2015-01-01

    Gaucher disease, the most common lysosomal storage disorder, is caused by β-glucocerebrosidase deficiency. Bone complications are the major cause of morbidity in patients with type 1 Gaucher disease (GD1). Genetic components strongly influence bone remodelling. In addition, chronic inflammation produced by Gaucher cells induces the production of several cytokines, which leads to direct changes in the bone remodelling process and can also affect the process indirectly through other immune cells. In this study, we analysed the association between bone mineral density (BMD), bone marrow burden score, and relevant genetic polymorphisms related to bone metabolism, as well as profiles of proinflammatory cytokines in a GD1 cohort. This study included 83 patients distributed according to bone status. BMD was measured with DXA and broadband ultrasound attenuation; bone marrow involvement was evaluated using MRI. We also analysed 26 SNPs located in 14 genes related to bone metabolism. To assess proinflammatory status, we analysed IL-4, IL-6, IL-7, IL-10, IL-13, MIP-1α, MIP-1β, and TNFα in plasma samples from 71 control participants and GD1 patients. SNP genotype proportions and BMD differed significantly between ESRI c.453-397T>C and VDR c.1024+283G>A variants. We also observed significant associations between GD1 genotypes and bone affectation. When patients were stratified by spleen status, we observed significant correlations between non-/splenectomized groups and Spanish MRI (S-MRI) score. Across genotype proportions of non-/splenectomized patients and S-MRI, we observed significant differences in ESRI c.453-397T>C, VDR c.-83-25988G>A, and TNFRSF11B c.9C>G polymorphisms. We observed different significant proinflammatory profiles between control participants, treatment-naïve patients, and patients on enzyme replacement therapy (ERT); between non-/splenectomized patients (between untreated and ERT-treated patients) and among those with differing GBA genotypes. The

  19. The influence of genetic variability and proinflammatory status on the development of bone disease in patients with Gaucher disease.

    Directory of Open Access Journals (Sweden)

    Javier Gervas-Arruga

    Full Text Available Gaucher disease, the most common lysosomal storage disorder, is caused by β-glucocerebrosidase deficiency. Bone complications are the major cause of morbidity in patients with type 1 Gaucher disease (GD1. Genetic components strongly influence bone remodelling. In addition, chronic inflammation produced by Gaucher cells induces the production of several cytokines, which leads to direct changes in the bone remodelling process and can also affect the process indirectly through other immune cells. In this study, we analysed the association between bone mineral density (BMD, bone marrow burden score, and relevant genetic polymorphisms related to bone metabolism, as well as profiles of proinflammatory cytokines in a GD1 cohort. This study included 83 patients distributed according to bone status. BMD was measured with DXA and broadband ultrasound attenuation; bone marrow involvement was evaluated using MRI. We also analysed 26 SNPs located in 14 genes related to bone metabolism. To assess proinflammatory status, we analysed IL-4, IL-6, IL-7, IL-10, IL-13, MIP-1α, MIP-1β, and TNFα in plasma samples from 71 control participants and GD1 patients. SNP genotype proportions and BMD differed significantly between ESRI c.453-397T>C and VDR c.1024+283G>A variants. We also observed significant associations between GD1 genotypes and bone affectation. When patients were stratified by spleen status, we observed significant correlations between non-/splenectomized groups and Spanish MRI (S-MRI score. Across genotype proportions of non-/splenectomized patients and S-MRI, we observed significant differences in ESRI c.453-397T>C, VDR c.-83-25988G>A, and TNFRSF11B c.9C>G polymorphisms. We observed different significant proinflammatory profiles between control participants, treatment-naïve patients, and patients on enzyme replacement therapy (ERT; between non-/splenectomized patients (between untreated and ERT-treated patients and among those with differing GBA

  20. Contemporary Approaches for Identifying Rare Bone Disease Causing Genes

    Institute of Scientific and Technical Information of China (English)

    Charles R.Farber; Thomas L.Clemens

    2013-01-01

    Recent improvements in the speed and accuracy of DNA sequencing, together with increasingly sophisti-cated mathematical approaches for annotating gene networks, have revolutionized the field of human genetics and made these once time consuming approaches assessable to most investigators. In the field of bone research, a particularly active area of gene discovery has occurred in patients with rare bone disorders such as osteogenesis imperfecta (OI) that are caused by mutations in single genes. In this perspective, we highlight some of these technological advances and describe how they have been used to identify the genetic determinants underlying two previously unexplained cases of OI. The widespread availability of advanced methods for DNA sequencing and bioinformatics analysis can be expected to greatly facilitate identification of novel gene networks that normally function to control bone formation and maintenance.

  1. TGF-βand BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease

    Institute of Scientific and Technical Information of China (English)

    Mengrui Wu; Guiqian Chen; and Yi-Ping Li

    2016-01-01

    Transforming growth factor-beta (TGF-β) and bone morphogenic protein (BMP) signaling has fundamental roles in both embryonic skeletal development and postnatal bone homeostasis. TGF-βs and BMPs, acting on a tetrameric receptor complex, transduce signals to both the canonical Smad-dependent signaling pathway (that is, TGF-β/BMP ligands, receptors, and Smads) and the non-canonical-Smad-independent signaling pathway (that is, p38 mitogen-activated protein kinase/p38 MAPK) to regulate mesenchymal stem cell differentiation during skeletal development, bone formation and bone homeostasis. Both the Smad and p38 MAPK signaling pathways converge at transcription factors, for example, Runx2 to promote osteoblast differentiation and chondrocyte differentiation from mesenchymal precursor cells. TGF-βand BMP signaling is controlled by multiple factors, including the ubiquitin–proteasome system, epigenetic factors, and microRNA. Dysregulated TGF-βand BMP signaling result in a number of bone disorders in humans. Knockout or mutation of TGF-βand BMP signaling-related genes in mice leads to bone abnormalities of varying severity, which enable a better understanding of TGF-β/BMP signaling in bone and the signaling networks underlying osteoblast differentiation and bone formation. There is also crosstalk between TGF-β/BMP signaling and several critical cytokines’ signaling pathways (for example, Wnt, Hedgehog, Notch, PTHrP, and FGF) to coordinate osteogenesis, skeletal development, and bone homeostasis. This review summarizes the recent advances in our understanding of TGF-β/BMP signaling in osteoblast differentiation, chondrocyte differentiation, skeletal development, cartilage formation, bone formation, bone homeostasis, and related human bone diseases caused by the disruption of TGF-β/BMP signaling.

  2. Is there a role for scintigraphic imaging of bone manifestations in Gaucher disease? A review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Mikosch, P. [State Hospital Klagenfurt (Austria). Dept. of Nuclear Medicine and Endocrinology, PET Center]|[State Hospital Klagenfurt (Austria). Dept. of Internal Medicine II; Kohlfuerst, S.; Gallowitsch, H.J.; Kresnik, E.; Lind, P. [State Hospital Klagenfurt (Austria). Dept. of Nuclear Medicine and Endocrinology, PET Center; Mehta, A.B.; Hughes, D.A. [Royal Free and University College Medical School, London (United Kingdom). Dept. of Academic Haematology

    2008-07-01

    Gaucher disease is the most prevalent inherited, lysosomal storage disease and is caused by deficient activity of the enzyme {beta}-glucocerebrosidase. Bone and bone marrow alterations are frequent in the most prevalent non-neuronopathic form of Gaucher disease. Imaging of bone manifestations in Gaucher disease is performed by a variety of imaging methods, conventional X-ray and MRI as the most frequently and most important ones. However, different modalities of scintigraphic imaging have also been used. This article gives an overview on scintigraphic imaging with respect to bone manifestations in Gaucher disease discussing the advantages and limitations of scintigraphic imaging in comparison to other imaging methods. (orig.)

  3. Pain and bone disease: a patient’s view

    Directory of Open Access Journals (Sweden)

    L. Brunetta

    2011-12-01

    Full Text Available Pain in thalassemia proves to be an emergent issue even if it is not possible to correlate it definitely to bone disease, but we strongly believe that a multidisciplinary approach, may be as decisive in this case as it was in the struggle against thalassemia. In fact, we strongly believe that the involvement of various specialists such as endocrinologists, orthopedist, anesthesiologist, in a close team coordinated by a specialist in thalassemia is absolutely necessary for achieving our aims. First of all, we need to implement clinical trials to identify the mechanisms of disease, to find the optimal management of the problem in order to provide new therapeutic methods for preventing the thalassemia-induced osteoporosis and to reduce the presence of very disabling pain for patients. Patients’ expectations for the future are to continuously improve the quality of life. To do that it is needed to identify pathways to prevent all the complications of thalassemia that cause widespread pain, above all osteoporosis. Although we have seen that osteoporosis is not the sole cause of pain for thalassemia patients, it is true that this seems to have a great incidence in thalassemia patients and it gives a significant contribute to an increased pain. 地中海贫血疼痛亟待解决,即使它可能与和骨病毫不相关,但我们坚信可以找到一种战胜地中海贫血症的多学科结合疗法。 事实上,如果要完成我们的目标,绝对有必要邀请一名地中海贫血专家,在内分泌学家、矫形外科医师和麻醉学家组成的队伍的配合下紧密展开工作。 首先,我们需要开展临床试验,确认发病机制,找出疾病最佳的控制方法,以找到预防地中海贫血诱发骨质疏松症的新疗法和减少疼痛的频率。 病患者对未来的期望是能够不断地提高自己的生活质量。要做到,病患者需要找到预防地中海贫血所有并发症引起的疼痛的方

  4. Dynamic contrast-enhanced MR imaging of the water fraction of normal bone marrow and diffuse bone marrow disease

    Energy Technology Data Exchange (ETDEWEB)

    Katsuya, Tomoo; Inoue, Tomio; Ishizaka, Hiroshi; Aoki, Jun; Endo, Keigo [Gunma Univ., Maebashi (Japan). School of Medicine

    2000-10-01

    To clarify the contrast-enhancement pattern of the normal hematopoietic element by isolating the signal of the water fraction in vertebral bone marrow and to investigate whether this approach can be used to characterize bone marrow pathology in several diffuse bone marrow diseases. Two groups were examined: 30 normal healthy volunteers and 19 patients with primary diffuse bone marrow disease (aplastic anemia [n=8], myelodysplastic syndrome (MDS) [n=5], chronic myelogenic leukemia (CML) [n=4], polycythemia vera [n=2]). Isolation of the signal of hematopoietic tissue was done by the chemical-shift misregistration effect. Twenty consecutive T1-weighted midsagittal lumber vertebral images were obtained immediately after the intravenous administration of Gd-DTPA of 0.1 mmol/kg body weight, and the pattern of the time-intensity curve, the peak contrast-enhancement (CE) ratio, and the washout rate (%/min) of bone marrow in normal volunteers were compared with those in patients suffering from primary diffuse bone marrow disease. The pattern of the time-intensity curve of patients with aplastic anemia showed a low peak value followed by a slow washout. However, the pattern of time-intensity curves in patients with MDS, CML, and polycythemia vera was similar to that of normal volunteers. The peak CE ratio of the water fraction in normal marrow ranged from 0.45 to 1.26 (mean {+-}S.D.: 0.87{+-}0.18). Patients with aplastic anemia showed an abnormally lower peak CE ratio of the water fraction (mean {+-}S.D.: 0.34{+-}0.19, p<0.0001). On the other hand, the peak CE ratio of the water fraction in patients with MDS was significantly higher than that of normal volunteers (mean {+-}S.D. 1.35{+-}0.39, p<0.05). In contrast, the peak CE ratio of patients with CML or polycythemia vera did not differ significantly from that of normal volunteers. The mean washout rate of patients with aplastic anemia was significantly lower than that of normal volunteers (mean {+-}S.D.: 3.50{+-}2.51 %/min

  5. A Case Report of Hydatid Disease in Long Bone

    Directory of Open Access Journals (Sweden)

    H Fanian

    2005-03-01

    Full Text Available Hydatid cyst, caused by echinococcus granulosa, can produce tissue cyst everywhere in body. Skeletal cystic lesion is rare especially in long bones like tibia and because of its unusual presentation, its diagnosis may easily be missed, unless be kept in mind.

  6. Does dermatitis herpetiformis result in bone loss as coeliac disease does?: a cross sectional study

    Directory of Open Access Journals (Sweden)

    Katalin Lorinczy

    Full Text Available Introduction and objectives: coeliac disease (CD and its cutaneous manifestation, dermatitis herpetiformis are both (DH gluten-sensitive diseases. Metabolic bone disease is common among patients with CD, even in asymptomatic forms. Data are scarce about bone density in patients with dermatitis herpetiformis. The aim of our study was to compare bone mineral density (BMD of celiac and dermatitis herpetiformis patients. Methods: 34 coeliac patients, 53 with dermatitis herpetiformis and 42 healthy controls were studied. The mean age was 38.0 ± 12.1, 32.18 ± 14.95, 35.33 ± 10.41 years in CD, dermatitis herpetiformis, and healthy controls, respectively. Bone mineral density of the lumbar spine, the left femoral neck and radius were measured by dual-energy X-ray absorptiometry. Low bone density, osteopenia and osteoporosis were defined as a body mass density (BMD T-score between 0 and -1, between -1 and -2.5, and under -2.5, respectively. Results: at lumbar region, consisting of dominantly trabecular compartment, a decreased BMD was detected in 49 % (n = 26 patients with dermatitis herpetiformis, 62 % (n = 21 of CD patients, and 29 % (n = 12 of healthy controls, respectively. Lower BMD were measured at the lumbar region in dermatitis herpetiformis and CD compared to healthy subjects (0.993 ± 0.136 g/cm² and 0.880 ± 0.155 g/cm² vs. 1.056 ± 0.126 g/cm²; p < 0.01. Density of bones consisting of dominantly cortical compartment (femoral neck did not differ in dermatitis herpetiformis and healthy subjects. Conclusions: our results show that a low bone mass is also frequent among patients with dermatitis herpetiformis. Bone mineral content in these patients is significantly lower in those parts of the skeleton which contain more trabecular than cortical bone.

  7. Positive Celiac Disease Serology and Reduced Bone Mineral Density in Adult Women

    Directory of Open Access Journals (Sweden)

    Donald R Duerksen

    2010-01-01

    Full Text Available BACKGROUND: Low bone density and osteoporosis have been demonstrated in celiac disease populations in Europe, South America and the United States. Serological testing with tissue transglutaminase (TTG and immunoglobulin A endomysial (EMA antibodies is highly specific for celiac disease, while antigliadin antibody (AGA testing is less specific.

  8. Calcium Regulation and Bone Mineral Metabolism in Elderly Patients with Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Vickram Tejwani

    2013-05-01

    Full Text Available The elderly chronic kidney disease (CKD population is growing. Both aging and CKD can disrupt calcium (Ca2+ homeostasis and cause alterations of multiple Ca2+-regulatory mechanisms, including parathyroid hormone, vitamin D, fibroblast growth factor-23/Klotho, calcium-sensing receptor and Ca2+-phosphate product. These alterations can be deleterious to bone mineral metabolism and soft tissue health, leading to metabolic bone disease and vascular calcification and aging, termed CKD-mineral and bone disorder (MBD. CKD-MBD is associated with morbid clinical outcomes, including fracture, cardiovascular events and all-cause mortality. In this paper, we comprehensively review Ca2+ regulation and bone mineral metabolism, with a special emphasis on elderly CKD patients. We also present the current treatment-guidelines and management options for CKD-MBD.

  9. Gfi1 expressed in bone marrow stromal cells is a novel osteoblast suppressor in patients with multiple myeloma bone disease

    Science.gov (United States)

    D'Souza, Sonia; del Prete, Davide; Jin, Shunqian; Sun, Quanhong; Huston, Alissa J.; Kostov, Flavia Esteve; Sammut, Benedicte; Hong, Chang-Sook; Anderson, Judith L.; Patrene, Kenneth D.; Yu, Shibing; Velu, Chinavenmeni S.; Xiao, Guozhi; Grimes, H. Leighton; Roodman, G. David

    2011-01-01

    Protracted inhibition of osteoblast (OB) differentiation characterizes multiple myeloma (MM) bone disease and persists even when patients are in long-term remission. However, the underlying pathophysiology for this prolonged OB suppression is unknown. Therefore, we developed a mouse MM model in which the bone marrow stromal cells (BMSCs) remained unresponsive to OB differentiation signals after removal of MM cells. We found that BMSCs from both MM-bearing mice and MM patients had increased levels of the transcriptional repressor Gfi1 compared with controls and that Gfi1 was a novel transcriptional repressor of the critical OB transcription factor Runx2. Trichostatin-A blocked the effects of Gfi1, suggesting that it induces epigenetic changes in the Runx2 promoter. MM-BMSC cell-cell contact was not required for MM cells to increase Gfi1 and repress Runx2 levels in MC-4 before OBs or naive primary BMSCs, and Gfi1 induction was blocked by anti–TNF-α and anti–IL-7 antibodies. Importantly, BMSCs isolated from Gfi1−/− mice were significantly resistant to MM-induced OB suppression. Strikingly, siRNA knockdown of Gfi1 in BMSCs from MM patients significantly restored expression of Runx2 and OB differentiation markers. Thus, Gfi1 may have an important role in prolonged MM-induced OB suppression and provide a new therapeutic target for MM bone disease. PMID:22042697

  10. Diagnosis and Treatment of Bone Disease in Multiple Myeloma: Spotlight on Spinal Involvement

    Directory of Open Access Journals (Sweden)

    Patrizia Tosi

    2013-01-01

    Full Text Available Bone disease is observed in almost 80% of newly diagnosed symptomatic multiple myeloma patients, and spine is the bone site that is more frequently affected by myeloma-induced osteoporosis, osteolyses, or compression fractures. In almost 20% of the cases, spinal cord compression may occur; diagnosis and treatment must be carried out rapidly in order to avoid a permanent sensitive or motor defect. Although whole body skeletal X-ray is considered mandatory for multiple myeloma staging, magnetic resonance imaging is presently considered the most appropriate diagnostic technique for the evaluation of vertebral alterations, as it allows to detect not only the exact morphology of the lesions, but also the pattern of bone marrow infiltration by the disease. Multiple treatment modalities can be used to manage multiple myeloma-related vertebral lesions. Surgery or radiotherapy is mainly employed in case of spinal cord compression, impending fractures, or intractable pain. Percutaneous vertebroplasty or balloon kyphoplasty can reduce local pain in a significant fraction of treated patients, without interfering with subsequent therapeutic programs. Systemic antimyeloma therapy with conventional chemotherapy or, more appropriately, with combinations of conventional chemotherapy and compounds acting on both neoplastic plasma cells and bone marrow microenvironment must be soon initiated in order to reduce bone resorption and, possibly, promote bone formation. Bisphosphonates should also be used in combination with antimyeloma therapy as they reduce bone resorption and prolong patients survival. A multidisciplinary approach is thus needed in order to properly manage spinal involvement in multiple myeloma.

  11. Echinococcal disease of the bone: An unusual cause of a pathological fracture

    Directory of Open Access Journals (Sweden)

    Matthew Goodier

    2010-12-01

    Full Text Available Echinococcosis is caused by the larva of the tapeworm, Echinococcus granulosus or Echinococcus multiloccularis and is endemic in many rural areas of Southern Africa. Echinococcosis of the bone is an unusual manifestation of echinococcal disease and a rare cause of a lytic lesion of bone. This report describes a 30-yr old female who presented with an Echinococcal cyst of the right radius complicated by a pathological fracture.

  12. The role of bone in CKD-mediated mineral and vascular disease.

    Science.gov (United States)

    Khouzam, Nadine M; Wesseling-Perry, Katherine; Salusky, Isidro B

    2015-09-01

    Cardiovascular disease is the leading cause of death in pediatric patients with chronic kidney disease (CKD), and vascular calcifications start early in the course of CKD. Based on the growing body of evidence that alterations of bone and mineral metabolism and the therapies designed to treat the skeletal consequences of CKD are linked to cardiovascular calcifications, the Kidney Disease, Improving Global Outcomes (KDIGO) working group redefined renal osteodystrophy as a systemic disorder of mineral and bone metabolism due to CKD, and this newly defined disorder is now known as "chronic kidney disease-mineral bone disorder (CKD-MBD)". Elevated fibroblast growth factor 23 (FGF23), a bone-derived protein, is the first biochemical abnormality to be associated with CKD-MBD, and high FGF23 levels correlate with increased cardiovascular morbidity and mortality, suggesting that bone is central to both initiating and perpetuating the abnormal mineral metabolism and vascular disease in CKD. The current standard therapies for CKD-MBD affect FGF23 levels differently; non-calcium-based binders with or without concurrent use of dietary phosphate restriction reduce FGF23 levels, while calcium-based binders seem to either increase or have no effect on FGF23 levels. Active vitamin D sterols increase FGF23 levels, whereas therapy with calcimimetics decreases FGF23 levels. Thus, the appropriate therapy that will minimize the rise in FGF23 and prevent cardiovascular morbidity remains to be defined.

  13. The impact of methods for estimating bone health and the global burden of bone disease.

    Science.gov (United States)

    Cole, Zoë A; Dennison, Elaine M; Cooper, Cyrus

    2009-01-01

    Osteoporosis constitutes a major public health problem through its association with age related fractures. Fracture rates are generally higher in caucasian women than in other populations. Important determinants include estrogen deficiency in women, low body mass index, cigarette smoking, alcohol consumption, poor dietary calcium intake, physical inactivity, certain drugs and illnesses. Thus, modification of physical activity and dietary calcium/vitamin D nutrition should complement high risk approaches. In addition, the recently developed WHO algorithm for evaluation of 10-year absolute risk of fracture provides a means whereby various therapies can be targeted cost-effectively to those at risk. Risk factors, together with bone mineral density (BMD) and biochemical indices of bone turnover, can be utilised to derive absolute risks of fracture and cost-utility thresholds at which treatment is justified. These data will provide the basis for translation into coherent public health strategies aiming to prevent osteoporosis both in individuals and in the general population.

  14. Molecular aspects of osteopathy in type 1 Gaucher disease: correlation between genetics and bone density.

    Science.gov (United States)

    Arnheim, Efrat; Chicco, Gaya; Phillips, Mici; Lebel, Ehud; Foldes, A Joseph; Itzchaki, Menachem; Elstein, Deborah; Zimran, Ari; Altarescu, Gheona

    2008-07-01

    Bone-related complications in Gaucher disease are considered to be poorly responsive to specific enzyme replacement therapy. Polymorphisms of candidate genes associated with low bone density were investigated to see whether they are correlated with bone mineral density (BMD) and bone involvement in Gaucher disease. Genotyping for polymorphisms in candidate genes (interleukins 1alpha and 1beta, interleukin-1 receptor antagonist; cytochrome P450; collagen 1A1; low-density Lipoprotein Receptor; bone morphogenic protein 4; vitamin D receptor; and estrogen receptor 2beta) were performed using standard methodologies. BMD was measured by dual energy X-ray absorptiometry (DXA). One hundred and ninety-four patients and 100 controls were genotyped for the above polymorphisms. Thirteen haplotypes were obtained, with several correlations with BMD in patients; also, a haplotype (T889-T3954-C511-240VNTR of IL1) was significantly correlated with T-scores and Z-score for femur neck and lumbar spine (p = 0.01) in patients. Haplotypes of bone-specific candidate genes associated with BMD may predict severity of these features in Gaucher disease.

  15. Bone mass and vitamin D levels in Parkinson's disease: is there any difference between genders?

    Science.gov (United States)

    Ozturk, Erhan Arif; Gundogdu, Ibrahim; Tonuk, Burak; Kocer, Bilge Gonenli; Tombak, Yasemin; Comoglu, Selcuk; Cakci, Aytul

    2016-08-01

    [Purpose] The aim of this study was to determine the bone mineral density, vitamin D level, and frequencies of osteopenia and osteoporosis in patients with Parkinson's disease and to compare male and female patients with the controls separately. [Subjects and Methods] One hundred fifteen Parkinson's disease patients (47 males, 68 females; age range: 55-85 years) and 117 age- and gender-matched controls (47 males, 70 females) were enrolled in the study. Bone mineral density measured by dual-energy X-ray absorptiometry and serum D vitamin levels of each participant were recorded. [Results] The mean lumbar spine, femur neck, and total femur bone mineral density levels, T-scores, and vitamin D levels were found to be significantly lower in Parkinson's disease patients in both genders. Furthermore, osteoporosis rates were found be significantly higher only in female Parkinson's disease patients compared with female controls. [Conclusion] Data from the present study revealed that while osteoporosis was significantly higher only in female Parkinson's disease patients, all Parkinson's disease patients had lower bone mineral density scores and vitamin D levels compared with the controls regardless of gender, suggesting that clinicians should pay attention to the osteoporosis risk in Parkinson's disease and that adequate preventive measures should be taken in order to limit the future risk due to osteoporotic fractures.

  16. Bone diseases in rabbits with hyperparathyroidism:computed tomography, magnetic resonance imaging and histopathology

    Institute of Scientific and Technical Information of China (English)

    BAI Rong-jie; CONG De-gang; SHEN Bao-zhong; HAN Ming-jun; WU Zhen-hua

    2006-01-01

    Background Hyperparathyroidism (HPT) occurs at an early age and has a high disability rate. Unfortunately,confirmed diagnosis in most patients is done at a very late stage, when the patients have shown typical symptomsand signs, and when treatment does not produce any desirable effect. It has become urgent to find a method thatwould detect early bone diseases in HPT to obtain time for the ideal treatment. This study evaluated the accuracyof high field magnetic resonance imaging (MRI) combined with spiral computed tomography (SCT) scan indetecting early bone diseases in HPT, through imaging techniques and histopathological examinations on ananimal model of HPT.Methods Eighty adult rabbits were randomly divided into two groups with forty in each. The control group wasfed normal diet (Ca:P = 1:0.7); the experimental group was fed high phosphate diet (Ca:P = 1:7) for 3, 4, 5, or6-month intervals to establish the animal model of HPT. The staging and imaging findings of the early bonediseases in HPT were determined by high field MRI and SCT scan at the 3rd, 4th, 5th and 6th month. Each rabbitwas sacrificed after high field MRI and SCT scan, and the parathyroid and bones were removed for pathologicalexamination to evaluate the accuracy of imaging diagnosis.Results Parathyroid histopathological studies revealed hyperplasia, osteoporosis and early cortical boneresorption. The bone diseases in HPT displayed different levels of low signal intensity on T1WI and low tointermediate signal intensity on T2WI in bone of stage 0, Ⅰ, Ⅱ or Ⅲ, but showed correspondingly absent, probable,osteoporotic and subperiosteal cortical resorption on SCT scan.Conclusion High field MRI combined with SCT scan not only detects early bone diseases in HPT, but alsoindicates staging, and might be a reliable method of studying early bone diseases in HPT.

  17. Bone disorders in experimentally induced liver disease in growing rats

    Institute of Scientific and Technical Information of China (English)

    Viktória Ferencz; Ferenc Szalay; Csaba Horváth; Béla Kári; János Gaál; Szilvia Mészáros; Zsuzsanna Wolf; Dalma Hegedüs; Andrea Horváth; Anikó Folhoffer

    2005-01-01

    AIM: To investigate the change of bone parameters in a new model of experimentally induced liver cirrhosis and hepatocellular carcinoma (HCC) in growing rats.METHODS: Fischer-344 rats (n = 55) were used. Carbon tetrachloride (CCl4), phenobarbital (PB), and a single diethylnitrosamine (DEN) injection were used. Animals were killed at wk 8 and 16. Bone mineral content, femoral length, cortical index (quotient of cortical thickness and whole diameter) and ultimate bending load (Fmax)of the femora were determined. The results in animals treated with DEN+PB+CCl4 (DPC, n = 21) were compared to those in untreated animals (UNT,n = 14) and in control group treated only with DEN+PB (DP, n = 20).RESULTS: Fatty liver and cirrhosis developed in each DPC-treated rat at wk 8 and HCC was presented at wk 16. No skeletal changes were found in this group at wk 8,but each parameter was lower (P<0.05 for each) at wk 16 in comparison to the control group. Neither fatty liver nor cirrhosis was observed in DP-treated animals at any time point. Femoral length and Fmax values were higher (P<0.05 for both) in DP-treated animals at wk 8 compared to the UNT controls. However, no difference was found at wk 16.CONCLUSION: Experimental liver cirrhosis and HCC are accompanied with inhibited skeletal growth, reduced bone mass, and decreased mechanical resistance in growing rats. Our results are in concordance with the data of other studies using different animal models. A novel finding is the transiently accelerated skeletal growth and bone strength after a 8-wk long phenobarbital treatment following diethylnitrosamine injection.

  18. Radiologic aspects of metastatic bone disease; Imagerie des metastases osseuses

    Energy Technology Data Exchange (ETDEWEB)

    Proust, C.; Maubon, A. [Hopital Universitaire Dupuytren, Dept. de Radiologie et d' Imagerie Medicale, 87 - Limoges (France); Proust, J. [Hopital Universitaire Dupuytren, Dept. d' Orthopedie Traumatologie, 87 - Limoges (France)

    2006-03-15

    In the human body, metastases are the most frequently found bone tumors. We can distinguish between lytic, blastic and mixed forms. The authors recall the radiologic aspects of these last ones, and describe even so the imagery with magnetic resonance. they also recall that major differences between a compressive benign osteoporotic tumor and a malignant one remains an every day diagnostic problem. Finally, magnetic resonance is proven to be a better diagnostic tool in comparison with the radiologic standard examination. (author)

  19. The CT flare response of metastatic bone disease in prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Messiou, Christina; deSouza, Nandita M. (Cancer Research UK Clinical Magnetic Resonance Research Group, Inst. of Cancer Research and Royal Marsden NHS Foundation Trust, Surrey (United Kingdom)), email: Christina.Messiou@icr.ac.uk; Cook, Gary (Dept. of Nuclear Medicine, Royal Marsden NHS Foundation Trust, Surrey (United Kingdom)); Reid, Alison H.M.; Attard, Gerhardt; Dearnaley, David; deBono, Johann S. (Inst. of Cancer Research and Royal Marsden NHS Foundation Trust, Surrey (United Kingdom))

    2011-06-15

    Background New or worsening bone lesions in patients responding to treatment, known as the flare phenomenon is well described on 99mTc-MDP bone scintigraphy, but to our knowledge has not previously been described on CT. The appearance of new or worsening bone sclerosis on CT in patients with prostate cancer may therefore be erroneously classified as disease progression. Purpose To assess the incidence of osteoblastic healing flare response at 3-month CT assessment in patients with castrate-resistant prostate cancer and to identify associated features that enable differentiation from progressive metastatic bone disease at 3 months. Material and Methods CT scans of 67 patients with castrate-resistant prostate cancer undergoing treatment were reviewed by a radiologist blinded to clinical outcome. Changes in number, size, and density of metastatic bone lesions were documented and Response Evaluation Criteria in Solid Tumours (RECIST) in soft tissue lesions, alkaline phosphatase, prostate specific antigen, and 99mTc-MDP bone scans were used for correlation. Results Of the 39 patients who had 3- and 6-month follow-up, eight patients (21%) demonstrated an increase in number, size, or density of sclerotic lesions on the 3-month CT scan despite improvement in PSA and soft tissue lesions. Three out of eight patients (8%) maintained partial response/remained stable at follow-up and were defined as showing a flare response: in this group bone metastases evident on CT showed a qualitative and quantitative increase in density and no lesions faded at 3 months. In contrast, in all patients who progressed at 3 months by PSA/RECIST criteria (n = 8) bone lesions showed a mixed pattern with some lesions increasing and others decreasing in density. Conclusion The incidence of flare response of metastatic bone disease evident at 3-month post-treatment CT in patients with prostate cancer undergoing systemic treatment is 8%. In patients with falling PSA and stable/responding soft tissue

  20. Nutritional and metabolic correlates of cardiovascular and bone disease in HIV-infected patients.

    Science.gov (United States)

    Fitch, Kathleen; Grinspoon, Steven

    2011-12-01

    The treatment of HIV infection has dramatically reduced the incidence of AIDS-related illnesses. At the same time, non-AIDS-related illnesses such as cardiovascular and bone disease are becoming more prevalent in this population. The mechanisms of these illnesses are complex and are related in part to the HIV virus, antiretroviral medications prescribed for HIV infection, traditional risk factors exacerbated by HIV, and lifestyle and nutritional factors. Further prospective research is needed to clarify the mechanisms by which HIV, antiretroviral medications, and nutritional abnormalities contribute to bone and cardiovascular disease in the HIV population. Increasingly, it is being recognized that optimizing the treatment of HIV infection to improve immune function and reduce viral load may also benefit the development of non-AIDS-related illnesses such as cardiovascular and bone disease.

  1. MicroRNAs: Potential Biomarkers and Therapeutic Targets for Alveolar Bone Loss in Periodontal Disease

    Directory of Open Access Journals (Sweden)

    Tadayoshi Kagiya

    2016-08-01

    Full Text Available Periodontal disease is an inflammatory disease caused by bacterial infection of tooth-supporting structures, which results in the destruction of alveolar bone. Osteoclasts play a central role in bone destruction. Osteoclasts are tartrate-resistant acid phosphatase (TRAP-positive multinucleated giant cells derived from hematopoietic stem cells. Recently, we and other researchers revealed that microRNAs are involved in osteoclast differentiation. MicroRNAs are novel, single-stranded, non-coding, small (20–22 nucleotides RNAs that act in a sequence-specific manner to regulate gene expression at the post-transcriptional level through cleavage or translational repression of their target mRNAs. They regulate various biological activities such as cellular differentiation, apoptosis, cancer development, and inflammatory responses. In this review, the roles of microRNAs in osteoclast differentiation and function during alveolar bone destruction in periodontal disease are described.

  2. Long-term follow-up of children thought to have temporary brittle bone disease

    Directory of Open Access Journals (Sweden)

    Paterson CR

    2011-06-01

    Full Text Available Colin R Paterson1, Elizabeth A Monk21Department of Medicine (retired, 2School of Accounting and Finance, University of Dundee, Dundee, ScotlandBackground: In addition to nonaccidental injury, a variety of bone disorders may underlie the finding of unexplained fractures in young children. One controversial postulated cause is temporary brittle bone disease, first described in 1990.Methods: Eighty-five patients with fractures showing clinical and radiological features of temporary brittle bone disease were the subject of judicial hearings to determine whether it was appropriate for them to return home. Sixty-three patients did, and follow-up information was available for 61 of these. The mean follow-up period was 6.9 years (range 1–17, median 6.Results: We found that none of the children had sustained any further injuries that were thought to represent nonaccidental injury; no child was re-removed from home. Three children had fractures. In each case there was general agreement that the fractures were accidental. Had the original fractures in these children been the result of nonaccidental injury, it would have been severe and repeated; the average number of fractures was 9.1.Conclusion: The fact that no subsequent suspicious injuries took place after return home is consistent with the view that the fractures were unlikely to have been caused by nonaccidental injury, and that temporary brittle bone disease is a distinctive and identifiable disorder.Keywords: fractures, osteogenesis imperfecta, temporary brittle bone disease, nonaccidental injury

  3. Bone marrow accumulation in gallium scintigraphy in patients with adult still's disease

    Energy Technology Data Exchange (ETDEWEB)

    Kanegae, Futoshi; Tada, Yoshifumi; Ohta, Akihide; Ushiyama, Osamu; Suzuki; Noriaki; Koarada, Syuichi; Haruta, Yoshio; Yoshikai, Tomonori; Nagasawa, Kohei [Saga Medical School (Japan)

    2002-12-01

    We investigated the features and the usefulness of gallium scintigraphy in the diagnosis and the assessment of Adult Still's disease (ASD) by retrospective case review. Gallium scintigraphy have been done for 11 cases of ASD (3 males and 8 females) and 4 females were positive. Among these, 67 Ga-citrate was accumulated to the bone marrow in all 4 cases and to the major joints in 2 cases. Positive cases were rather serious and administered more immunosuppressants than negative cases. In order to characterize gallium scintigraphy findings of ASD, i.e. bone marrow accumulation, we analyzed 130 cases of collagen vascular disease. Although 101 cases (77.7%) were positive, only 7 cases (5.4%) showed the accumulation of {sup 67}Ga-citrate to the bone marrow. These include 3 cases with ASD, and 1 case with systemic lupus erythematosus, polyarteritis nodosa, Wegener's granulomatosis and Sjogren's syndrome. We also accumulated 18 patients who exhibited bone marrow accumulation of {sup 69}Ga-citrate, and found that 7 patients had collagen vascular and their related diseases. In conclusion, bone marrow accumulation in gallium scintigraphy is a specific feature of collagen vascular diseases, especially ASD, and it is suggested that cases with positive gallium scintigraphy in ASD can be serious and resistant to treatment. (author)

  4. Combined scintigraphic and radiographic diagnosis of bone and joint diseases. 3. rev. and enl. ed.

    Energy Technology Data Exchange (ETDEWEB)

    Bahk, Yong-Whee [Sung Ae General Hospital, Seoul (Korea). Dept. of Nuclear Medicine and Radiology

    2007-07-01

    The third edition of Combined Scintigraphic and Radiographic Diagnosis of Bone and Joint Diseases has been comprehensively rewritten and rearranged. It now encompasses, in addition to the bone and joint diseases described in the two earlier editions, hitherto unpublished novel applications of pinhole scanning to the diagnosis of a broader spectrum of skeletal disorders than ever before, including those of the soft tissues. A large number of state-of-the-art scans and corroboratory images obtained using CT, MRI and/or sonography are presented side by side. The book has been considerably expanded to discuss five new themes: Normal Variants and Artifacts, Drug-Induced Osteoporosis, Soft-Tissue Tumors and Tumor-like Conditions, PET/CT in Bone and Joint Diseases and A Genetic Consideration of Skeletal Disorders. Topical chapters on rheumatic skeletal disorders, malignant tumors of bone, benign tumors of bone and traumatic diseases have also been thoroughly rewritten and are complemented by the addition of some 90 recently acquired cases. (orig.)

  5. A novel role of IL-17–producing lymphocytes in mediating lytic bone disease in multiple myeloma

    Science.gov (United States)

    Noonan, Kimberly; Marchionni, Luigi; Anderson, Judy; Pardoll, Drew; Roodman, G. David

    2010-01-01

    Osteoclast (OC)–mediated lytic bone disease remains a cause of major morbidity in multiple myeloma. Here we demonstrate the critical role of interleukin-17–producing marrow infiltrating lymphocytes (MILs) in OC activation and development of bone lesions in myeloma patients. Unlike MILs from normal bone marrow, myeloma MILs possess few regulatory T cells (Tregs) and demonstrate an interleukin-17 phenotype that enhances OC activation. In univariate analyses of factors mediating bone destruction, levels of cytokines that selectively induce and maintain the Th17 phenotype tightly correlated with the extent of bone disease in myeloma. In contrast, MILs activated under conditions that skew toward a Th1 phenotype significantly reduced formation of mature OC. These findings demonstrate that interleukin-17 T cells are critical to the genesis of myeloma bone disease and that immunologic manipulations shifting MILs from a Th17 to a Th1 phenotype may profoundly diminish lytic bone lesions in multiple myeloma. PMID:20664052

  6. Role of TAF12 in the Increased VDR Activity in Paget’s Disease of Bone

    Science.gov (United States)

    2013-10-01

    on the metabolic bone diseases and disorders of mineral metabolism . 2003; Chapter 82: 495-506. 4. Roodman GD, Kurihara N, Ohsaki Y et al. Interleukin... thyroid hormone receptors. J Biol Chem. 2000;275:10064–71. 6. Hoffmann A, Roeder RG. Cloning and characterization of human TAF20/15. Multiple interactions...of manuscript. 18 Reference 1. Hosking DJ. Paget’s disease of bone. Br Med J (Clin Res Ed). 1981; 283:686-8. 2. Kanis JA and Simon LS. Metabolic

  7. Upper airway obstruction and pulmonary abnormalities due to lymphoproliferative disease following bone marrow transplantation in children

    Energy Technology Data Exchange (ETDEWEB)

    Fletcher, B.D. [Department of Diagnostic Imaging, St. Jude Children`s Research Hospital, 332 N. Lauderdale St., Memphis, TN 38105 (United States)]|[Departments of Radiology and Pediatrics, University of Tennessee, Memphis, Tennessee (United States); Heslop, H.E. [Department of Hematology/Oncology, St. Jude Children`s Research Hospital, Department of Pediatrics, University of Tennessee, Memphis, Tennessee (United States); Kaste, S.C. [Department of Diagnostic Imaging, St. Jude Children`s Research Hospital, Department of Radiology, University of Tennessee, Memphis, Tennessee (United States); Bodner, S. [Department of Pathology, St. Jude Children`s Research Hospital, Department of Pathology, University of Tennessee, Memphis, Tennessee (United States)

    1998-07-01

    We report three patients who developed severe supraglottic airway obstruction due to Epstein-Barr virus lymphoproliferative disease following allogeneic bone marrow transplantation. In addition to enlarged pharyngeal lymphoid tissue seen in all three patients, two had supraglottic airway narrowing and two developed pulmonary lymphoproliferative disease. They were treated with unmanipulated T cells or EBV-specific cytotoxic T lymphocytes. Life-threatening upper airway obstruction is a radiologically detectable complication of allogeneic bone marrow transplantation in children. (orig.) With 3 figs., 1 tab., 12 refs.

  8. Autologous Bone Marrow Stem Cell Infusion (AMBI therapy for Chronic Liver Diseases

    Directory of Open Access Journals (Sweden)

    Rajkumar JS

    2007-01-01

    Full Text Available Liver Cirrhosis is the end stage of chronic liver disease which may happen due to alcoholism, viral infections due to Hepatitis B, Hepatitis C viruses and is difficult to treat. Liver transplantation is the only available definitive treatment which is marred by lack of donors, post operative complications such as rejection and high cost. Autologous bone marrow stem cells have shown a lot of promise in earlier reported animal studies and clinical trials. We have in this study administered in 22 patients with chronic liver disease, autologous bone marrow stem cell whose results are presented herewith.

  9. On the Nature of Expansion of Paget’s Disease of Bone

    Science.gov (United States)

    2012-10-01

    PDB patients (7). We obtained the PSV10 cell line from Dr. G. David Roodman (Indiana University School of Medicine) and tested the cells for a SQSTM1...Zhou H, Boykin CS, Zhang H, Ishizuka S, Dempster DW, Roodman GD, Windle JJ. A SQSTM1/p62 mutation linked to Paget’s disease increases the...JM, Roodman GD. Enhanced RANK ligand expression and responsivity of bone marrow cells in Paget’s disease of bone. J Clin Invest. 2000;105(12):1833

  10. Alveolar bone loss associated to periodontal disease in lead intoxicated rats under environmental hypoxia.

    Science.gov (United States)

    Terrizzi, Antonela R; Fernandez-Solari, Javier; Lee, Ching M; Bozzini, Clarisa; Mandalunis, Patricia M; Elverdin, Juan C; Conti, María Ines; Martínez, María Pilar

    2013-10-01

    Previously reported studies from this laboratory revealed that rats chronically intoxicated with lead (Pb) under hypoxic conditions (HX) impaired growth parameters and induced damages on femoral and mandibular bones predisposing to fractures. We also described periodontal inflammatory processes under such experimental conditions. Periodontitis is characterised by inflammation of supporting tissues of the teeth that result in alveolar bone loss. The existence of populations living at high altitudes and exposed to lead contamination aimed us to establish the macroscopic, biochemical and histological parameters consistent with a periodontal disease in the same rat model with or without experimental periodontitis (EP). Sixty female rats were divided into: Control; Pb (1000ppm of lead acetate in drinking water); HX (506mbar) and PbHX (both treatments simultaneously). EP was induced by placing ligatures around the molars of half of the rats during the 14 days previous to the autopsy. Hemi-mandibles were extracted to evaluate bone loss by histomorphometrical techniques. TNFα plasmatic concentration was greater (palveolar bone loss, while Pb showed spontaneous bone loss also. In conclusion, these results show that lead intoxication under hypoxic environment enhanced not only alveolar bone loss but also systemic and oral tissues inflammatory parameters, which could aggravate the physiopathological alterations produced by periodontal disease.

  11. Current perspectives on bisphosphonate treatment in Paget’s disease of bone

    Directory of Open Access Journals (Sweden)

    Wat WZM

    2014-11-01

    Full Text Available Winnie Zee Man Wat Department of Medicine, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong Abstract: Paget’s disease of bone is a chronic metabolic bone disease with focal increase in bone turnover. The exact etiology of the disease is uncertain, although genetic and environmental factors are believed to be important. Bisphosphonate is the main class of medication being used to control disease activity via its antiresorptive effect. This review discusses the controversies concerning the use of bisphosphonates in the treatment of Paget’s disease of bone, the efficacy of different bisphosphonates in controlling disease activity, and the possible rare side effects of bisphosphonates. Symptoms are the main indication for treatment in Paget’s disease of bone. As treatment benefits in asymptomatic individuals remain controversial and nonevidence based, the decision to treat these patients should be individualized to their risk and benefit profiles. There are several trials conducted to evaluate and compare the efficacy of different regimes of bisphosphonates for treating Paget’s disease of bone. Most trials used biochemical markers rather than clinical symptoms or outcomes as parameters for comparison. Zoledronate is an attractive option as it can achieve high rates of biochemical remission and sustain long duration of suppression by a single dose. Atypical femoral fracture and osteonecrosis of the jaw are two rare and severe side effects reported, possibly related to the use of bisphosphonates in patients with osteoporosis and malignancy-induced hypercalcemia. As the regimes of bisphosphonates used for treating Paget’s disease of bone are different from those two diseases, the risks of developing these two possible side effects are expected to be very low, although this remains unknown. Vitamin D and calcium supplement should be given to patients at risk of vitamin D insufficiency when given zoledronate, as symptomatic

  12. Serum albumin and body weight as biomarkers for the antemortem identification of bone and gastrointestinal disease in the common marmoset.

    Science.gov (United States)

    Baxter, Victoria K; Shaw, Gillian C; Sotuyo, Nathaniel P; Carlson, Cathy S; Olson, Erik J; Zink, M Christine; Mankowski, Joseph L; Adams, Robert J; Hutchinson, Eric K; Metcalf Pate, Kelly A

    2013-01-01

    The increasing use of the common marmoset (Callithrix jacchus) in research makes it important to diagnose spontaneous disease that may confound experimental studies. Bone disease and gastrointestinal disease are two major causes of morbidity and mortality in captive marmosets, but currently no effective antemortem tests are available to identify affected animals prior to the terminal stage of disease. In this study we propose that bone disease and gastrointestinal disease are associated disease entities in marmosets and aim to establish the efficacy of several economical antemortem tests in identifying and predicting disease. Tissues from marmosets were examined to define affected animals and unaffected controls. Complete blood count, serum chemistry values, body weight, quantitative radiographs, and tissue-specific biochemical markers were evaluated as candidate biomarkers for disease. Bone and gastrointestinal disease were associated, with marmosets being over seven times more likely to have either concurrent bone and gastrointestinal disease or neither disease as opposed to lesions in only one organ system. When used in tandem, serum albumin disease. Progressive body weight loss of 0.05% of peak body weight per day predicted which marmosets would develop disease prior to the terminal stage. Bone tissue-specific tests, such as quantitative analysis of radiographs and serum parathyroid hormone levels, were effective for distinguishing between marmosets with bone disease and those without. These results provide an avenue for making informed decisions regarding the removal of affected marmosets from studies in a timely manner, preserving the integrity of research results.

  13. Compromised cortical bone compartment in type 2 diabetes mellitus patients with microvascular disease

    DEFF Research Database (Denmark)

    Shanbhogue, Vikram Vinod; Hansen, Stinus; Nielsen, Morten Frost Munk;

    2016-01-01

    OBJECTIVE AND DESIGN: Patients with type 2 diabetes mellitus (T2D) have an increased fracture risk despite a normal or elevated bone mineral density (BMD). The aim of this cross-sectional in vivo study was to assess parameters of peripheral bone microarchitecture, estimated bone strength and bone...... remodeling in T2D patients with and without diabetic microvascular disease (MVD+ and MVD- respectively) and to compare them with healthy controls. METHODS: Fifty-one T2D patients (MVD+ group: n=25) were recruited from Funen Diabetic Database and matched for age, sex and height with 51 healthy subjects. High...... deficits are not a characteristic of all T2D patients but of a subgroup characterized by the presence of microvascular complications. Whether this influences fracture rates in these patients needs further investigation....

  14. Usefulness of bone marrow magnetic resonance imaging and indium-111-chloride bone marrow scintigraphy in patients with various hematological diseases

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Yutaka; Umekawa, Tsunekazu; Chikayama, Satoshi [Osaka General Hospital of West Japan Railway Compapy (Japan)] [and others

    1995-03-01

    This study investigated the ability of magnetic resonance (MR) imaging and indium-111 chloride (In-111) scintigraphy to assess bone marrow in various hematological lesions. The subjects were 7 with aplastic anemia (AA), 4 with myelodysplastic syndrome (MDS), 3 with polycythemia (PC), 3 with essential thrombocythemia (ET), 2 with multiple myeloma (MM), 2 with monoclonal gammopathy of undetermined significance (MGUS), 3 with idiopathic thrombocytopenic purpura (ITP), one with acute lymphocytic leukemia (ALL), and one with secondary anemia due to chronic inflammation (SA). Bone marrow cellularity was assessed on MR images and both uptake and tissue distribution were assessed on In-111 scintigraphy. Hypo-cellularity was seen in all AA patients, but not seen in any other patient in each group. On the other hand, hyper-cellularity was seen in 3 MDS, one PC, all 3 ET, one ALL, and one SA patients. In the group of MM, the vertebral body was seen as heterogenous signal intensity on MR images. Bone marrow was seen as iso-intensity in one MDS, 2 PC, all 2 MGUS, and all 3 ITP patients. In-111 scintigraphy showed decrease or disappearance of tracer uptake and decreased tissue distribution in all 7 AA, one MDS, one PC, and one ALL patients. Increased tracer uptake and enlarged tissue distribution were seen in one MDS, one PC, and one SA patients. One MDS, one ET, all 2 MM, all 2 MGUS, all 3 ITP patients had tracer uptake and tissue distribution that were equal to those in the normal tissues. Since MR imaging and In-111 scintigraphy provided qualitatively different information, the combination of both modalities would contribute to the understanding of bone marrow condition in hematopoietic diseases. (N.K.).

  15. Comparative diagnostic value of bone scintigraphy and roentgenography in children with Legg-Calve-Perthes disease

    Energy Technology Data Exchange (ETDEWEB)

    Cavailloles, F.; Brauner, M.; Dandine, M.; Lonchampt, M.F.; Esteban, C.; Bensahel, H.; Patois, E.; Alperovitch, A.; Bock, B.

    1985-01-01

    To compare the value of hip roentgenograms and bone scintigraphy in Legg-Calve-Perthes (LCP) disease, a double blind study was done in 153 children, of whom 51 had LCP. Each procedure was read separately by two investigators who had no knowledge of clinical data. Variations across investigators were less significant for roentgenograms than for bone scans. Agreement on diagnosis between the two investigators was 95% for roentgenograms, against only 89% for bone scans. As regards the detailed analysis of each separate finding upon bone scintigraphy and assessment of this procedure's prognostic value, major discrepancies occurred between the two investigators. Diagnostic accuracy was very similar for the two procedures. Both bone scintigraphy and roentgenography showed a 0.86 sensitivity. Specificities were 0.93 and 0.99 respectively. For the subgroup of patients with early-stage LCP disease (33 cases), scintigraphy identified a slightly greater number of cases than roentgenography (0.88 and 0.76 respectively). Some disagreements between our results and those previously published in the literature may stem from biases such as the criteria for entering patients into the study or for establishing the final diagnosis. Roentgenography is obviously the first procedure to perform in a child with a painful hip or a limp. However, the results may be inconclusive in early-stage disease. In such cases, scintigraphy is needed and often avoids unnecessary traction or diagnostic delay.

  16. The use of bone scintigraphy to detect active Hansen's disease in mutilated patients

    Energy Technology Data Exchange (ETDEWEB)

    Braga, F.J.H.N. [Seccao de Medicina Nuclear do Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto, USP (Brazil); Departamento de Fisica e Biofisica, Instituto de Biociencias, UNESP, Botucato (Brazil); Foss, N.T.; Ferriolli, E. [Departamento de Clinica Medica da Faculdade de Medicina de Ribeirao Preto, USP (Brazil); Pagnano, C. [Secretaria da Saude, Ribeirao Preto (Brazil); Miranda, J.R.A.; De Moraes, R. [Departamento de Fisica e Biofisica, Instituto de Biociencias, UNESP, Botucato (Brazil)

    1999-11-01

    Mutilation of extremities was very frequent in patients affected by leprosy in the past; although it is now much less common, it is still seen, mainly in patients with long-term disease. In general, mutilation of the nose and ears is caused by the bacillus and mutilation of the hands and feet a consequence of chronic trauma. Leprosy must be chronically treated and any decision to interrupt therapy is based on laboratory tests and biopsy. Scintigraphy is a non-invasive procedure which could be of great value in to determining disease activity. We studied eight patients (five males and three females, aged 64-73 years) who presented with mutilation of the nose (2), ear (1), feet (3) or foot and hand (2). Conventional three-phase bone scintigraphy (750 MBq) and X-ray examinations of the affected areas were performed in all patients. Bone scintigraphy was abnormal in four patients (the presence of bacilli was confirmed by biopsy in two of them), and normal in the other four. In all patients except for the one with ear mutilation, radiography only showed the absence of bone. We conclude that bone scintigraphy is very useful to determine disease activity in cases of mutilation caused by leprosy. It seems to be superior to conventional radiography and may enable bone biopsies to be avoided. (orig.)

  17. Known VDR polymorphisms are not associated with bone mineral density measures in pediatric Cushing disease.

    Science.gov (United States)

    Lodish, Maya B; Mastroyannis, Spyridon A; Sinaii, Ninet; Boikos, Sosipatros A; Stratakis, Constantine A

    2012-01-01

    Decreased bone mineral density (BMD) has been documented in adults with Cushing disease (CD), and allelic variants of the vitamin D receptor (VDR) gene have been associated with osteopenia. Genetic factors play an important role in bone accrual and its response to various diseases; among them, the most studied are the allelic variants of the VDR gene. There is debate as to whether described variants in the VDR gene have an effect on BMD. In the current study, we sought to analyze whether BMD differences in patients with CD were associated with the Taq1 and Apal VDR allelotypes. The data showed lack of association between BMD and these widely studied VDR polymorphisms, suggesting that the effect of endogenous hypercortisolism on bone in the context of CD does not depend on VDR genotypes.

  18. Cytopenia and Bone Marrow Dysplasia in a Case of Wilson's Disease.

    Science.gov (United States)

    Rau, Aarathi R; Usha, M; Mallya, Pooja; Rau, A T K

    2014-09-01

    We describe a sixteen year old with Wilson's disease on copper chelation and subsequent high dose oral zinc who developed severe anemia and neutropenia. Bone marrow aspirate done to evaluate the cause of bicytopenia revealed trilineage dysplasia. Correlating the clinical context with bone marrow and biochemical parameters, copper deficiency was suspected and he was given a trial of therapy, following which the hematological parameters improved. This case highlights hypocupremia as a reversible cause of bone marrow dysplasia in patients with Wilson's disease on chelation, where serum copper levels are not useful in the diagnosis. We also believe that monitoring of the blood counts in patients on copper chelation may provide a clue to impending copper deficiency.

  19. Cardiovascular risk and mineral bone disorder in patients with chronic kidney disease.

    Science.gov (United States)

    Staude, Hagen; Jeske, Susann; Schmitz, Karin; Warncke, Gert; Fischer, Dagmar-Christiane

    2013-01-01

    The term chronic kidney disease-mineral bone disorder has been coined recently to highlight that the disturbed mineral and bone metabolism is a major contributor to vascular calcification and finally cardiovascular disease. This syndrome is characterized by clinical, biochemical and/or histological findings, i.e. i) biochemical alterations in the homeostasis of calcium, phosphate and their key player parathyroid hormone (PTH), Fibroblast growth factor-23 (FGF-23), klotho and vitamin-D, ii) the occurrence of vascular and/or soft tissue calcification, and iii) an abnormal bone structure and/or turnover. Apart from the combined and synergistic action of "traditional" and uremia-related risk factors, promoters and inhibitors of calcification have to be considered as well. This review will focus on the disturbed mineral metabolism as the triggering force behind distortion of vascular integrity and cardiovascular malfunction in CKD patients.

  20. Cardiovascular Risk and Mineral Bone Disorder in Patients with Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Hagen Staude

    2013-03-01

    Full Text Available The term chronic kidney disease-mineral bone disorder has been coined recently to highlight that the disturbed mineral and bone metabolism is a major contributor to vascular calcification and finally cardiovascular disease. This syndrome is characterized by clinical, biochemical and/or histological findings, i.e. i biochemical alterations in the homeostasis of calcium, phosphate and their key player parathyroid hormone (PTH, Fibroblast growth factor-23 (FGF-23, klotho and vitamin-D, ii the occurrence of vascular and/or soft tissue calcification, and iii an abnormal bone structure and/or turnover. Apart from the combined and synergistic action of "traditional" and uremia-related risk factors, promoters and inhibitors of calcification have to be considered as well. This review will focus on the disturbed mineral metabolism as the triggering force behind distortion of vascular integrity and cardiovascular malfunction in CKD patients.

  1. Radiological diagnostic in cat stratch disease and bone lesions - a case report; Doenca da arranhadura do gato e lesoes osseas - relato de um caso

    Energy Technology Data Exchange (ETDEWEB)

    Abreu, Marcelo Rodrigues de [Rio Grande do Sul Univ., Porto Alegre, RS (Brazil). Faculdade de Medicina; Abreu, Armando de; Santos, Leandro Durval dos [Hospital Mae de Deus, Porto Alegre, RS (Brazil). Servico de Radiologia; Scharnovski, Alvaro [Hospital de Taquara, RS (Brazil)

    1999-02-01

    Cat scratch disease is not a common disease in immunocompetent patients. Its association with bone lesions is rare. A patient with bone complain and radiologic alterations of bone lesion must be investigated for this disease. A simple story can make the differential diagnosis with more complex disease like Ewing sarcoma or eosinophilic granuloma. (author)

  2. Suspected fetal skeletal malformations or bone diseases: how to explore

    Energy Technology Data Exchange (ETDEWEB)

    Cassart, Marie [Erasme Hospital, Medical Imaging, Brussels (Belgium)

    2010-06-15

    Skeletal dysplasias are a heterogeneous and complex group of conditions that affect bone growth and development and result in various anomalies in shape and size of the skeleton. Although US has proved reliable for the prenatal detection of skeletal abnormalities, the precise diagnosis of a dysplasia is often difficult to make before birth (especially in the absence of a familial history) due to their various phenotypic presentations, the variability in the time at which they manifest and often, the lack of precise molecular diagnosis. In addition to the accuracy of the antenatal diagnosis, it is very important to establish a prognosis. This is a clinically relevant issue as skeletal dysplasias may be associated with severe disability and may even be lethal. We will therefore describe the respective role of two-dimensional (2-D) US, three-dimensional (3-D) US and CT in the antenatal assessment of skeletal malformations. (orig.)

  3. Bone marrow fat is increased in chronic kidney disease by magnetic resonance spectroscopy

    Science.gov (United States)

    Fadel, W.; Eckert, G. J.; Ponsler-Sipes, K.; Moe, S. M.; Lin, C.

    2015-01-01

    Summary In aging, the bone marrow fills with fat and this may lead to higher fracture risk. We show that a bone marrow fat measurement by magnetic resonance spectroscopy (MRS), a newer technique not previously studied in chronic kidney disease (CKD), is useful and reproducible. CKD patients have significantly higher bone marrow fat than healthy adults. Introduction Renal osteodystrophy leads to increased morbidity and mortality in patients with CKD. Traditional bone biopsy histomorphometry is used to study abnormalities in CKD, but the bone marrow, the source of osteoblasts, has not been well characterized in patients with CKD. Methods To determine the repeatability of bone marrow fat fraction assessment by MRS and water-fat imaging (WFI) at four sites in patients with CKD, testing was performed to determine the coefficients of reproducibility and intraclass coefficients (ICCs). We further determined if this noninvasive technique could be used to determine if there are differences in the percent bone marrow fat in patients with CKD compared to matched controls using paired t tests. Results The mean age of subjects with CKD was 59.8±7.2 years, and the mean eGFR was 24±8 ml/min. MRS showed good reproducibility at all sites in subjects with CKD and controls, with a coefficient of reproducibilities ranging from 2.4 to 13 %. MRS and WFI assessment of bone marrow fat showed moderate to strong agreement (ICC 0.6–0.7) at the lumbar spine, with poorer agreement at the iliac crest and no agreement at the tibia. The mean percent bone marrow fat at L2–L4 was 13.8 % (95 % CI 8.3–19.7) higher in CKD versus controls (p<0.05). Conclusions MRS is a useful and reproducible technique to study bone marrow fat in CKD. Patients with CKD have significantly higher bone marrow fat than healthy adults; the relationship with bone changes requires further analyses. PMID:25701052

  4. Photon-deficient bone scan lesion as a precursor of active Paget's disease

    Energy Technology Data Exchange (ETDEWEB)

    Jaspers, M.M.J.R.; Pauwels, E.K.J.; Blom, J. (Department of Diagnostic Radiology, Division of Nuclear Medicine, University Hospital Leiden (Netherlands)); Harinck, H.I.J. (Clinical Investigation Unit, Department of Endocrinology, University Hospital Leiden, Netherands)

    1984-05-15

    A case is presented in which a Pagetoid lesion was demonstrated as a photon-deficient area (cold spot) on the bone scan. This area changed into a hot spot 3 years after its discovery. Clinical and radiological observations provide evidence that a scintigraphically photon-deficient area may represent a precursor of active Paget's disease.

  5. Patient and implant survival following joint replacement because of metastatic bone disease

    DEFF Research Database (Denmark)

    Sørensen, Michala S; Gregersen, Kristine G; Grum-Schwensen, Tomas

    2013-01-01

    Patients suffering from a pathological fracture or painful bony lesion because of metastatic bone disease often benefit from a total joint replacement. However, these are large operations in patients who are often weak. We examined the patient survival and complication rates after total joint...

  6. Genetic sharing with cardiovascular disease risk factors and diabetes reveals novel bone mineral density loci

    NARCIS (Netherlands)

    S. Reppe (Sjur); Y. Wang (Yunpeng); W.K. Thompson (Wesley K.); L.K. McEvoy (Linda K.); N.J. Schork (Nicholas); V. Zuber (Verena); M. Leblanc (Marissa); F. Bettella (Francesco); I.G. Mills (Ian G.); R.S. Desikan (Rahul S.); S. Djurovic (Srdjan); K.M. Gautvik (Kaare); A.M. Dale (Anders); O.A. Andreassen (Ole A.); K. Estrada Gil (Karol); U. Styrkarsdottir (Unnur); E. Evangelou (Evangelos); Y.-H. Hsu (Yi-Hsiang); E.L. Duncan (Emma); E.E. Ntzani (Evangelia); L. Oei (Ling); O.M.E. Albagha (Omar M.); N. Amin (Najaf); J.P. Kemp (John); D.L. Koller (Daniel); G. Li (Guo); C.-T. Liu (Ching-Ti); R.L. Minster (Ryan); A. Moayyeri (Alireza); L. Vandenput (Liesbeth); D. Willner (Dana); S.-M. Xiao (Su-Mei); L.M. Yerges-Armstrong (Laura); H.-F. Zheng (Hou-Feng); N. Alonso (Nerea); J. Eriksson (Joel); C.M. Kammerer (Candace); S. Kaptoge (Stephen); P.J. Leo (Paul); G. Thorleifsson (Gudmar); S.G. Wilson (Scott); J.F. Wilson (James F); V. Aalto (Ville); M. Alen (Markku); A.K. Aragaki (Aaron); T. Aspelund (Thor); J.R. Center (Jacqueline); Z. Dailiana (Zoe); C. Duggan; M. Garcia (Melissa); N. Garcia-Giralt (Natàlia); S. Giroux (Sylvie); G. Hallmans (Göran); L.J. Hocking (Lynne); L.B. Husted (Lise Bjerre); K. Jameson (Karen); R. Khusainova (Rita); G.S. Kim (Ghi Su); C. Kooperberg (Charles); T. Koromila (Theodora); M. Kruk (Marcin); M. Laaksonen (Marika); A.Z. Lacroix (Andrea Z.); S.H. Lee (Seung Hun); P.C. Leung (Ping C.); J.R. Lewis (Joshua); L. Masi (Laura); S. Mencej-Bedrac (Simona); T.V. Nguyen (Tuan); X. Nogues (Xavier); M.S. Patel (Millan); J. Prezelj (Janez); L.M. Rose (Lynda); S. Scollen (Serena); K. Siggeirsdottir (Kristin); G.D. Smith; O. Svensson (Olle); S. Trompet (Stella); O. Trummer (Olivia); N.M. van Schoor (Natasja); J. Woo (Jean); K. Zhu (Kun); S. Balcells (Susana); M.L. Brandi; B.M. Buckley (Brendan M.); S. Cheng (Sulin); C. Christiansen; C. Cooper (Charles); G.V. Dedoussis (George); I. Ford (Ian); M. Frost (Morten); D. Goltzman (David); J. González-Macías (Jesús); M. Kähönen (Mika); M. Karlsson (Magnus); E.K. Khusnutdinova (Elza); J.-M. Koh (Jung-Min); P. Kollia (Panagoula); B.L. Langdahl (Bente); W.D. Leslie (William D.); P. Lips (Paul); O. Ljunggren (Östen); R. Lorenc (Roman); J. Marc (Janja); D. Mellström (Dan); B. Obermayer-Pietsch (Barbara); D. Olmos (David); U. Pettersson-Kymmer (Ulrika); D.M. Reid (David); J.A. Riancho (José); P.M. Ridker (Paul); M.F. Rousseau (Francois); P.E. Slagboom (Eline); N.L.S. Tang (Nelson L.S.); R. Urreizti (Roser); W. Van Hul (Wim); J. Viikari (Jorma); M.T. Zarrabeitia (María); Y.S. Aulchenko (Yurii); M.C. Castaño Betancourt (Martha); E. Grundberg (Elin); L. Herrera (Lizbeth); T. Ingvarsson (Torvaldur); H. Johannsdottir (Hrefna); T. Kwan (Tony); R. Li (Rui); R.N. Luben (Robert); M.C. Medina-Gomez (Carolina); S.T. Palsson (Stefan Th); J.I. Rotter (Jerome I.); G. Sigurdsson (Gunnar); J.B.J. van Meurs (Joyce); D.J. Verlaan (Dominique); F.M. Williams (Frances); A.R. Wood (Andrew); Y. Zhou (Yanhua); T. Pastinen (Tomi); S. Raychaudhuri (Soumya); J.A. Cauley (Jane); D.I. Chasman (Daniel); G.R. Clark (Graeme); S.R. Cummings (Steven R.); P. Danoy (Patrick); E.M. Dennison (Elaine); R. Eastell (Richard); J.A. Eisman (John); V. Gudnason (Vilmundur); A. Hofman (Albert); R.D. Jackson (Rebecca); G. Jones (Graeme); J.W. Jukema (Jan Wouter); K.T. Khaw; T. Lehtimäki (Terho); Y. Liu (Yongmei); M. Lorentzon (Mattias); E. McCloskey (Eugene); B.D. Mitchell (Braxton); K. Nandakumar (Kannabiran); G.C. Nicholson (Geoffrey); B.A. Oostra (Ben); M. Peacock (Munro); H.A.P. Pols (Huibert A. P.); R.L. Prince (Richard); O. Raitakari (Olli); I.R. Reid (Ian); J. Robbins (John); P.N. Sambrook (Philip); P.C. Sham (Pak Chung); A.R. Shuldiner (Alan); F.A. Tylavsky (Frances); C.M. van Duijn (Cock); N.J. Wareham (Nicholas J.); L.A. Cupples (Adrienne); M.J. Econs (Michael); D.M. Evans (David); T.B. Harris (Tamara B.); A.W.C. Kung (Annie Wai Chee); B.M. Psaty (Bruce); J. Reeve (Jonathan); T.D. Spector (Timothy); E.A. Streeten (Elizabeth); M.C. Zillikens (Carola); U. Thorsteinsdottir (Unnur); C. Ohlsson (Claes); D. Karasik (David); J.B. Richards (J. Brent); M.A. Brown (Matthew); J-A. Zwart (John-Anker); A.G. Uitterlinden (André); S.H. Ralston (Stuart); J.P.A. Ioannidis (John P.A.); D.P. Kiel (Douglas P.); F. Rivadeneira Ramirez (Fernando)

    2015-01-01

    textabstractBone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. W

  7. D-dimer assay in Egyptian patients with Gaucher disease: correlation with bone and lung involvement.

    Science.gov (United States)

    Sherif, Eman M; Tantawy, Azza A G; Adly, Amira A M; Kader, Hossam A; Ismail, Eman A R

    2011-04-01

    Gaucher disease is the most frequent lysosomal storage disorder. Bone and lung involvement are two major causes of morbidity in this disease. D-dimer is a reliable indicator of active microvascular thrombosis, even in patients without overt hypercoagulation. This study aimed to assess D-dimer levels in Gaucher disease, correlating this marker to clinical characteristics and radiological parameters to investigate its role as a potential predictor for the occurrence and severity of skeletal and pulmonary manifestations. The study population consisted of 56 Egyptian patients with Gaucher disease, 36 had type 1 Gaucher disease (64.3%) and 20 had type 3 Gaucher disease (35.7%). Thirty healthy individuals were enrolled as a control group. D-dimer levels were significantly higher in all patients with Gaucher disease compared with controls (P < 0.001). Patients with type 3 showed significantly higher D-dimer concentrations compared with type 1 (P < 0.001). Pulmonary involvement was present in a significant proportion among type 3 Gaucher patients (P < 0.05), whereas bone changes were present in a higher percentage in type 1 compared with type 3 Gaucher patients. D-dimers were significantly higher in patients with abnormal MRI findings of the long bones and in those with ground glass appearance on high-resolution computerized tomography of the chest compared with patients with normal radiology (P < 0.001). Splenectomized patients displayed significantly higher D-dimer levels compared with nonsplenectomized patients (P < 0.001). Our results suggest that D-dimer is significantly elevated in Gaucher disease, particularly type 3, and may be considered as a potential marker of risk prediction of bone and lung involvement that could be used to monitor treatment response.

  8. Mutifactorial analysis of risk factors for reduced bone mineral density in patients with Crohn's disease

    Institute of Scientific and Technical Information of China (English)

    Sarah A Bartram; Robert T Peaston; David J Rawlings; David Walshaw; Roger M Francis; Nick P Thompson

    2006-01-01

    AIM: To determine the prevalence of osteoporosis in a cohort of patients with Crohn's disease (CD) and to identify the relative significance of risk factors for osteoporosis.METHODS: Two hundred and fifty-eight unselected patients (92 M, 166 F) with CD were studied. Bone mineral density (BMD) was measured at the lumbar spine and hip by dual X-ray absorptiometry. Bone formation was assessed by measuring bone specific alkaline phosphatase (BSAP) and bone resorption by measuring urinary excretion of deoxypyridinoline (DPD)and N-telopeptide (NTX).RESULTS: Between 11.6%-13.6% patients were osteoporotic (T score < -2.5) at the lumbar spine and/or hip. NTX levels were significantly higher in the patients with osteoporosis (P < 0.05) but BSAP and DPD levels were not significantly different. Independent risk factors for osteoporosis at either the lumbar spine or hip were a low body mass index (P < 0.001), increasing corticosteroid use (P < 0.005), and male sex (P < 0.01).These factors combined accounted for 23% and 37% of the reduction in BMD at the lumbar spine and hip respectively.CONCLUSION: Our results confirm that osteoporosis is common in patients with CD and suggest that increased bone resorption is the mechanism responsible for the bone loss. However, less than half of the reduction in BMD can be attributed to risk factors such as corticosteroid use and low BMI and therefore remains unexplained.

  9. Lessons from Microglia Aging for the Link between Inflammatory Bone Disorders and Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Zhou Wu

    2015-01-01

    Full Text Available Bone is sensitive to overactive immune responses, which initiate the onset of inflammatory bone disorders, such as rheumatoid arthritis and periodontitis, resulting in a significant systemic inflammatory response. On the other hand, neuroinflammation is strongly implicated in Alzheimer’s disease (AD, which can be enhanced by systemic inflammation, such as that due to cardiovascular disease and diabetes. There is growing clinical evidence supporting the concept that rheumatoid arthritis and periodontitis are positively linked to AD, suggesting that inflammatory bone disorders are risk factors for this condition. Recent studies have suggested that leptomeningeal cells play an important role in transducing systemic inflammatory signals to brain-resident microglia. More importantly, senescent-type, but not juvenile-type, microglia provoke neuroinflammation in response to systemic inflammation. Because the prevalence of rheumatoid arthritis and periodontitis increases with age, inflammatory bone disorders may be significant sources of covert systemic inflammation among elderly people. The present review article highlights our current understanding of the link between inflammatory bone disorders and AD with a special focus on microglia aging.

  10. International Myeloma Working Group Recommendations for the Treatment of Multiple Myeloma–Related Bone Disease

    Science.gov (United States)

    Terpos, Evangelos; Morgan, Gareth; Dimopoulos, Meletios A.; Drake, Matthew T.; Lentzsch, Suzanne; Raje, Noopur; Sezer, Orhan; García-Sanz, Ramón; Shimizu, Kazuyuki; Turesson, Ingemar; Reiman, Tony; Jurczyszyn, Artur; Merlini, Giampaolo; Spencer, Andrew; Leleu, Xavier; Cavo, Michele; Munshi, Nikhil; Rajkumar, S. Vincent; Durie, Brian G.M.; Roodman, G. David

    2013-01-01

    Purpose The aim of the International Myeloma Working Group was to develop practice recommendations for the management of multiple myeloma (MM) –related bone disease. Methodology An interdisciplinary panel of clinical experts on MM and myeloma bone disease developed recommendations based on published data through August 2012. Expert consensus was used to propose additional recommendations in situations where there were insufficient published data. Levels of evidence and grades of recommendations were assigned and approved by panel members. Recommendations Bisphosphonates (BPs) should be considered in all patients with MM receiving first-line antimyeloma therapy, regardless of presence of osteolytic bone lesions on conventional radiography. However, it is unknown if BPs offer any advantage in patients with no bone disease assessed by magnetic resonance imaging or positron emission tomography/computed tomography. Intravenous (IV) zoledronic acid (ZOL) or pamidronate (PAM) is recommended for preventing skeletal-related events in patients with MM. ZOL is preferred over oral clodronate in newly diagnosed patients with MM because of its potential antimyeloma effects and survival benefits. BPs should be administered every 3 to 4 weeks IV during initial therapy. ZOL or PAM should be continued in patients with active disease and should be resumed after disease relapse, if discontinued in patients achieving complete or very good partial response. BPs are well tolerated, but preventive strategies must be instituted to avoid renal toxicity or osteonecrosis of the jaw. Kyphoplasty should be considered for symptomatic vertebral compression fractures. Low-dose radiation therapy can be used for palliation of uncontrolled pain, impending pathologic fracture, or spinal cord compression. Orthopedic consultation should be sought for long-bone fractures, spinal cord compression, and vertebral column instability. PMID:23690408

  11. Acute bone crises in sickle cell disease: the T1 fat-saturated sequence in differentiation of acute bone infarcts from acute osteomyelitis

    Energy Technology Data Exchange (ETDEWEB)

    Jain, R. [Department of Radiology, College of Medicine, Sultan Qaboos University, Muscat (Oman)], E-mail: rajeevjn@yahoo.com; Sawhney, S. [Department of Radiology, College of Medicine, Sultan Qaboos University, Muscat (Oman); Rizvi, S.G. [Department of Community Medicine and Public Health, College of Medicine, Sultan Qaboos University, Muscat (Oman)

    2008-01-15

    Aim: To prove the hypothesis that acute bone infarcts in sickle cell disease are caused by sequestration of red blood cells (RBCs) in bone marrow, and to evaluate the unenhanced T1 fat-saturated (fs) sequence in the differentiation of acute bone infarction from acute osteomyelitis in patients with sickle-cell disease. Materials and methods: Two studies were undertaken: an experimental study using in-vitro packed red blood cells and normal volunteers, and a retrospective clinical study of 86 magnetic resonance imaging (MRI) studies. For the experimental study containers of packed RBCs were placed between the knees of four healthy volunteers with a saline bag under the containers as an additional control, and were scanned with the pre-contrast T1-fs sequence. Signal intensity (SI) ratios were obtained for packed RBCs:skeletal muscle and packed RBCs:saline. For the clinical study, the SIs of normal bone marrow, packed RBCs, bone and/or soft-tissue lesions, and normal skeletal muscle of 74 patients (86 MRI studies) were measured using unenhanced, T1 fat-saturated MRI. The ratios of the above SIs to normal skeletal muscle were calculated and subjected to statistical analysis. Results: Fifty-one of 86 MRI studies were included in the final analysis. The ratios of SIs for normal bone marrow, packed red cells, bone infarction, acute osteomyelitis, and soft-tissue lesions associated with bone infarct, compared with normal skeletal muscle were (mean {+-} SD) 0.9 {+-} 0.2, 2.1 {+-} 0.7, 1.7 {+-} 0.5, 1.0 {+-} 0.3, and 2.2 {+-} 0.7, respectively. The difference in the ratio of SIs of bone infarcts and osteomyelitis was significant (p = 0.003). The final diagnoses were bone infarction (n = 50), acute osteomyelitis (n = 1), and co-existent bone infarction and osteomyelitis (n = 2). Seven patients who had suspected osteomyelitis underwent image-guided aspiration. Conclusion: Acute bone infarcts in sickle cell disease are caused by sequestration of red blood cells in the bone

  12. Bone diseases associated with human immunodeficiency virus infection: pathogenesis, risk factors and clinical management.

    Science.gov (United States)

    Bongiovanni, Marco; Tincati, Camilla

    2006-06-01

    Bone disorders such as osteopenia and osteoporosis have been recently reported in patients infected with the human immunodeficiency virus (HIV), but their etiology remains still unknown. The prevalence estimates vary widely among the different studies and can be affected by concomitant factors such as the overlapping of other possible conditions inducing bone loss as lypodystrophy, advanced HIV-disease, advanced age, low body weight or concomitant use of other drugs. All the reports at the moment available in the literature showed a higher than expected prevalence of reduced bone mineral density (BMD) in HIV-infected subjects both naïve and receiving potent antiretroviral therapy compared to healthy controls. This controversial can suggest a double role played by both antiretroviral drugs and HIV itself due to immune activation and/or cytokines disregulation. An improved understanding of the pathogenesis of bone disorders can result in better preventative and therapeutic measures. However, the clinical relevance and the risk of fractures remains undefined in HIV-population. The clinical management of osteopenia and osteoporosis in HIV-infected subjects is still being evaluated. Addressing potential underlying bone disease risk factors (e.g., smoking and alcohol intake, use of corticosteroids, advanced age, low body weight), evaluating calcium and vitamin D intake, and performing dual x-ray absorptiometry in HIV-infected individuals who have risk factors for bone disease can be important strategies to prevent osteopenia and osteoporosis in this population. The administration of bisphosphonates (e.g., alendronate), with calcium and vitamin D supplementation, may be a reasonable and effective option to treat osteoporosis in these subjects.

  13. Chemical and biomechanical characterization of hyperhomocysteinemic bone disease in an animal model

    Directory of Open Access Journals (Sweden)

    Howell David S

    2003-02-01

    Full Text Available Abstract Background Classical homocystinuria is an autosomal recessive disorder caused by cystathionine β-synthase (CBS deficiency and characterized by distinctive alterations of bone growth and skeletal development. Skeletal changes include a reduction in bone density, making it a potentially attractive model for the study of idiopathic osteoporosis. Methods To investigate this aspect of hyperhomocysteinemia, we supplemented developing chicks (n = 8 with 0.6% dl-homocysteine (hCySH for the first 8 weeks of life in comparison to controls (n = 10, and studied biochemical, biomechanical and morphologic effects of this nutritional intervention. Results hCySH-fed animals grew faster and had longer tibiae at the end of the study. Plasma levels of hCySH, methionine, cystathionine, and inorganic sulfate were higher, but calcium, phosphate, and other indices of osteoblast metabolism were not different. Radiographs of the lower limbs showed generalized osteopenia and accelerated epiphyseal ossification with distinct metaphyseal and suprametaphyseal lucencies similar to those found in human homocystinurics. Although biomechanical testing of the tibiae, including maximal load to failure and bone stiffness, indicated stronger bone, strength was proportional to the increased length and cortical thickness in the hCySH-supplemented group. Bone ash weights and IR-spectroscopy of cortical bone showed no difference in mineral content, but there were higher Ca2+/PO43- and lower Ca2+/CO32- molar ratios than in controls. Mineral crystallization was unchanged. Conclusion In this chick model, hyperhomocysteinemia causes greater radial and longitudinal bone growth, despite normal indices of bone formation. Although there is also evidence for an abnormal matrix and altered bone composition, our finding of normal biomechanical bone strength, once corrected for altered morphometry, suggests that any increase in the risk of long bone fracture in human hyperhomocysteinemic

  14. Turner′s syndrome presenting as metabolic bone disease

    Directory of Open Access Journals (Sweden)

    Sadishkumar Kamalanathan

    2012-01-01

    Full Text Available Turner′s syndrome is a genetic disorder with a complete or partial absence of one X chromosome with characteristic phenotypic features. The prevalence of renal anomalies in turner syndrome is 30-40%. However, the renal function is usually normal. We report a case of Turner′s syndrome presenting with chronic kidney disease and renal osteodystrophy.

  15. Calcific tendinitis of the gluteus medius tendon with bone marrow edema mimicking metastatic disease

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Ik [Department of Radiology, University of Michigan Health Systems, Ann Arbor (United States); Hayes, Curtis W. [Department of Radiology, University of Michigan Health Systems, Ann Arbor (United States); Taubman Clinic, Ann Arbor, MI (United States); Biermann, Sybil J. [Department of Orthopaedic Surgery, University of Michigan Health Systems, Ann Arbor, MI (United States)

    2002-06-01

    A case of calcific tendinitis of the gluteus medius is presented. This report describes a patient with a history of breast cancer who had the combination of amorphous calcifications in the gluteus medius tendon and the MR finding of conspicuous bone marrow edema in the adjacent greater trochanter, prompting concern for metastatic disease. We present images from radiography, bone scanning, CT, and MR imaging. The unusual combination of findings in these studies should be considered conclusive for calcific tendinitis, and should not be confused with malignancy. (orig.)

  16. Hemorrhage associated with 'bone crisis' in Gaucher's disease identified by magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Horev, G.; Kornreich, L. (TA Univ., Petach-Tikva (Israel). Dept. of Pediatric Radiology); Hadar, H. (TA Univ., Petach-Tikva (Israel). Dept. of Radiology); Katz, K. (TA Univ., Petach-Tikva (Israel). Dept. of Pediatric Orthopedics)

    1991-10-01

    Children suffering from Gaucher's disease were examined by magnetic resonance imaging (MRI) during a characteristic episode of 'bone crisis'. An unexpectedly high intramedullary as well as subperiosteal signal was observed on both the T1- and T2-weighted sequences in 5 patients, suggesting a subacute hemorrhage or hematoma. It is conceivable that such a painful hemorrhage is an important component of the 'bone crisis' phenomenon. Furthermore, in these cases this is a specific sign which may enable differentiation of bone crises from other types of bone pain associated with Gaucher's disease. (orig.).

  17. Aplastic Anemia & MDS International Foundation (AA&MDSIF): Bone Marrow Failure Disease Scientific Symposium 2014.

    Science.gov (United States)

    Visconte, Valeria; Lindsley, R Coleman; Berlyne, Deborah

    2015-01-01

    Bone marrow failure syndromes (BMFS) are characterized by a failure of the hematopoietic stem cells to produce adequate blood cells, resulting in either cytopenia (defect in one or more blood cell lineages) or pancytopenia (defect in all blood cell lineages). BMFS can be inherited or acquired. The pathogenesis of these diseases is very heterogeneous. Research efforts have been made all over the world to improve the basic knowledge of these diseases. The Aplastic Anemia and MDS International Foundation (AA&MDSIF) is an independent nonprofit organization whose mission is to help patients and family members cope with BMFS. Here, we summarize novel scientific discoveries in several BMFS that were presented at the 4th International Bone Marrow Failure Disease Scientific Symposium 2014 that AA&MDSIF sponsored on March 27-28, 2014, in Rockville, MD.

  18. Detection of Unknown sites of multiple enchondroma (Ollier′s Disease mimicking like metastasis using bone scintigraphy

    Directory of Open Access Journals (Sweden)

    Koramadai Karuppusamy Kamaleshwaran

    2015-01-01

    Full Text Available Ollier′s disease characterized by multiple skeletal enchondroma is a rare noninherited disease of unknown etiology. Majority of the skeletal enchondroma are present in the metaphyses and diaphysis of tubular limb bones. Ollier′s disease has a predilection for unilateral distribution. Malignant changes in Ollier′s disease may occur in adult patients. Radionuclide bone scanning is one method used to assess lesions depicted on radiographs or magnetic resonance images that are presumed to be enchondromas. Furthermore, a bone scan may give a clue to the multifocality of the disease. We report a case of right first phalangeal enchondroma in a 23-year-old male, who underwent bone scintigraphy detected multifocal asymmetric right side involvement of radius, humerus, femur, and tibia which confirm a diagnosis of Ollier′s disease.

  19. Calcium and vitamin D nutrition and bone disease of the elderly.

    Science.gov (United States)

    Gennari, C

    2001-04-01

    Osteoporosis, a systemic skeletal disease characterized by a low bone mass, is a major public health problem in EC member states because of the high incidence of fragility fractures, especially hip and vertebral fracture. In EC member states the high incidence of osteoporotic fractures leads to considerable mortality, morbidity, reduced mobility and decreased quality of life. In 1995 the number of hip fractures in 15 countries of EC has been 382,000 and the estimated total care cost of about 9 billion of ECUs. Given the magnitude of the problem public health measures are important for preventive intervention. Skeletal bone mass is determined by a combination of endogenous (genetic, hormonal) and exogenous (nutritional, physical activity) factors. Nutrition plays an important role in bone health. The two nutrients essential for bone health are calcium and vitamin D. Reduced supplies of calcium are associated with a reduced bone mass and osteoporosis, whereas a chronic and severe vitamin D deficiency leads to osteomalacia, a metabolic bone disease characterized by a decreased mineralization of bone. Vitamin D insufficiency, the preclinical phase of vitamin D deficiency, is most commonly found in the elderly. The major causes of vitamin D deficiency and insufficiency are decreased renal hydroxylation of vitamin D, poor nutrition, scarce exposition to sunlight and a decline in the synthesis of vitamin D in the skin. The daily average calcium intake in Europe has been evaluated in the SENECA study concerning the diet of elderly people from 19 towns of 10 European countries. In about one third of subjects the dietary calcium intake results were very low, between 300 and 600 mg/day in women, and 350 and 700 mg/day in men. Calcium supplements reduce the rate of bone loss in osteoporotic patients. Some recent studies have reported a significant positive effect of calcium treatment not only on bone mass but also on fracture incidence. The SENECA study, has also shown that

  20. Extent of Surgery Does Not Influence 30-Day Mortality in Surgery for Metastatic Bone Disease

    DEFF Research Database (Denmark)

    Sørensen, Michala Skovlund; Hindsø, Klaus; Hovgaard, Thea Bechmann

    2016-01-01

    retrospectively identified 270 consecutive patients who underwent joint replacement surgery or intercalary spacing for skeletal metastases in the appendicular skeleton from January 1, 2003 to December 31, 2013. We collected intraoperative (duration of surgery, extent of bone resection, and blood loss......Estimating patient survival has hitherto been the main focus when treating metastatic bone disease (MBD) in the appendicular skeleton. This has been done in an attempt to allocate the patient to a surgical procedure that outlives them. No questions have been addressed as to whether the extent...... of the surgery and thus the surgical trauma reduces survival in this patient group. We wanted to evaluate if perioperative parameters such as blood loss, extent of bone resection, and duration of surgery were risk factors for 30-day mortality in patients having surgery due to MBD in the appendicular skeleton. We...

  1. Bone Mineral Densitometry Findings of Children with Newly Diagnosed Celiac Disease

    Directory of Open Access Journals (Sweden)

    Tansel Ansal Balcı

    2011-08-01

    Full Text Available Objective: The effect of Celiac Disease (CD on children’s bone is the decrease in bone mineral density (BMD. Osteoporosis is a consequence of this decrease and usually manifests in adult ages. Studies in CD patients generally show that bone density of these patients can be different at the same ages for the same duration of disease. The aim of this study is to investigate the relationship between age and bone mineral density of CD patients at first diagnosis. Material and Methods: Ninety one patients (M/F: 36/55; age range: 3-16; mean age: 9.6±3.5 with diagnosis of CD were included in the study. BMD survey from L1-L4 lumbar spine and total hip of the patients was evaluated at presentation. We evaluated the patients in 3 groups according to their ages: Group 1: pre-school (3-7 years old, Group 2: elementary school (8-11 years old and Group 3: adolescent (12-16 years old. Results were compared using Student’s t test and correlation analysis. Results: The mean disease duration of the patients was 16.4±16.3 months. Mean height and weight of the patients were 124.8±17.9 cm and 27±9.3 kg, respectively and height and weight of 37 patients were in ≤ 3. percentile according to age. The BMD values of both lumbar spine and total hip and Z-scores of lumbar region were in mild correlation with age (r>0.5. There was significant difference between mean ages of patients with low bone mass for chronological age and normal bone densitometry values (p<0.05. There were 27, 36 and 28 patients in Group 1, Group 2 and Group 3, respectively. The difference between mean BMD values of these groups were statistically significant (p<0.05. The mean values of lumbar Z- scores of patients were -1.08±1.27, -1.42±1, -1.86±1.14, respectively for these three groups. Conclusion: Bone mineral densities of CD patients in childhood were lower in elder children at the time of diagnosis. This confirms the opinion that the diagnosis at earlier age results better treatment

  2. [Animal models for bone and joint disease. CIA, CAIA model].

    Science.gov (United States)

    Hirose, Jun; Tanaka, Sakae

    2011-02-01

    The collagen-induced arthritis (collagen-induced arthritis, CIA) is an autoimmune arthritis that resembles rheumatoid arthritis (RA) in many ways, therefore it has been used most commonly as a model of RA. CIA is induced by immunization with an emulsion of complete Freund's adjuvant (CFA) and type II collagen (C II ) . Collagen antibody-induced arthritis (CAIA) is induced by the administration of a cocktail of monoclonal antibodies recognizing conserved epitopes located within the CB11 fragment. CAIA offers several advantages over CIA, including rapid disease onset, high uptake rate, and the capacity to use genetically modified mice, such as transgenics and knockouts.

  3. Bone marrow transplantation in patients with storage diseases: a developing country experience

    Directory of Open Access Journals (Sweden)

    Lange Marcos C.

    2006-01-01

    Full Text Available Bone marrow transplantation (BMT is a therapeutic option for patients with genetic storage diseases. Between 1979 and 2002, eight patients, four females and four males (1 to 13 years old were submitted to this procedure in our center. Six patients had mucopolysaccharidosis (MPS I in 3; MPS III in one and MPS VI in 2, one had adrenoleukodystrophy (ALD and one had Gaucher disease. Five patients had related and three unrelated BMT donor. Three patients developed graft versus host disease (two MPS I and one MPS VI and died between 37 and 151 days after transplantation. Five patients survived 4 to 16 years after transplantation. Three patients improved (one MPS I; one MPS VI and the Gaucher disease patient, one patient had no disease progression (ALD and in one patient this procedure did not change the natural course of the disease (MPS III.

  4. Effect of chronic hepatitis C virus infection on bone disease in postmenopausal women.

    LENUS (Irish Health Repository)

    Nanda, Kavinderjit S

    2012-02-01

    BACKGROUND & AIMS: Limited data are available on the contribution of chronic HCV infection to the development of bone disease in postmenopausal women. We studied whether women who acquired HCV infection through administration of HCV genotype 1b-contaminated anti-D immunoglobulin from a single source had decreased bone mineral density (BMD) or altered levels of bone turnover markers (BTMs), compared with women who spontaneously resolved infection or age-matched healthy controls. METHODS: From a cohort of postmenopausal Irish women, we compared BMD, determined by dual-energy x-ray absorptiometry, and a panel of BTMs in 20 women chronically infected with HCV (PCR(+)), 21 women who had spontaneously resolved infection (PCR(-)), and 23 age-matched healthy controls. RESULTS: Levels of BTMs and BMD were similar in PCR(+) and PCR(-) women and healthy age-matched controls. However, there was an increased frequency of fractures in PCR(+) (n = 6) compared with PCR(-) women (n = 0, P = .007). PCR(+) women with fractures were postmenopausal for a longer time (median, 15.5, range, 5-20 years vs 4.5, range, 1-20 years in PCR(+) women without fractures; P = .033), had lower BMD at the hip (0.79, range, 0.77-0.9 g\\/cm(2) vs 0.96, range, 0.81-1.10 g\\/cm(2); P = .007), and had a lower body mass index (23.7, range 21.2-28.5 kg\\/m(2) vs 25.6, range 22.1-36.6 kg\\/m(2); P = .035). There was no difference in liver disease severity or BTMs in PCR(+) women with or without fractures. CONCLUSIONS: Chronic HCV infection did not lead to discernable metabolic bone disease in postmenopausal women, but it might be a risk factor for bone fractures, so preventive measures should be introduced. To view this article\\'s video abstract, go to the AGA\\'s YouTube Channel.

  5. Bone Marrow-Derived Cells as a Therapeutic Approach to Optic Nerve Diseases

    Directory of Open Access Journals (Sweden)

    Louise A. Mesentier-Louro

    2016-01-01

    Full Text Available Following optic nerve injury associated with acute or progressive diseases, retinal ganglion cells (RGCs of adult mammals degenerate and undergo apoptosis. These diseases have limited therapeutic options, due to the low inherent capacity of RGCs to regenerate and due to the inhibitory milieu of the central nervous system. Among the numerous treatment approaches investigated to stimulate neuronal survival and axonal extension, cell transplantation emerges as a promising option. This review focuses on cell therapies with bone marrow mononuclear cells and bone marrow-derived mesenchymal stem cells, which have shown positive therapeutic effects in animal models of optic neuropathies. Different aspects of available preclinical studies are analyzed, including cell distribution, potential doses, routes of administration, and mechanisms of action. Finally, published and ongoing clinical trials are summarized.

  6. Bone Marrow-Derived Cells as a Therapeutic Approach to Optic Nerve Diseases

    Science.gov (United States)

    Mesentier-Louro, Louise A.; Zaverucha-do-Valle, Camila; Rosado-de-Castro, Paulo H.; Silva-Junior, Almir J.; Pimentel-Coelho, Pedro M.; Mendez-Otero, Rosalia; Santiago, Marcelo F.

    2016-01-01

    Following optic nerve injury associated with acute or progressive diseases, retinal ganglion cells (RGCs) of adult mammals degenerate and undergo apoptosis. These diseases have limited therapeutic options, due to the low inherent capacity of RGCs to regenerate and due to the inhibitory milieu of the central nervous system. Among the numerous treatment approaches investigated to stimulate neuronal survival and axonal extension, cell transplantation emerges as a promising option. This review focuses on cell therapies with bone marrow mononuclear cells and bone marrow-derived mesenchymal stem cells, which have shown positive therapeutic effects in animal models of optic neuropathies. Different aspects of available preclinical studies are analyzed, including cell distribution, potential doses, routes of administration, and mechanisms of action. Finally, published and ongoing clinical trials are summarized. PMID:26649049

  7. Chronic Kidney Disease-Mineral Bone Disorder in the Elderly Peritoneal Dialysis Patient

    DEFF Research Database (Denmark)

    Heaf, James Goya

    2015-01-01

    PURPOSE: The purpose of this paper was to review the literature concerning the treatment of chronic kidney disease-mineral bone disorder (CKD-MBD) in the elderly peritoneal dialysis (PD) patient. ♦ RESULTS: Chronic kidney disease-mineral bone disorder is a major problem in the elderly PD patient......, with its associated increased fracture risk, vascular calcification, and accelerated mortality fracture risk. Peritoneal dialysis, however, bears a lower risk than hemodialysis (HD). The approach to CKD-MBD prophylaxis and treatment in the elderly PD patient is similar to other CKD patients, with some...... important differences. Avoidance of hypercalcemia, hyperphosphatemia, and hyperparathyroidism is important, as in other CKD groups, and is generally easier to attain. Calcium-free phosphate binders are recommended for normocalcemic and hypercalcemic patients. Normalization of vitamin D levels to > 75 nmol...

  8. Novel, near-infrared spectroscopic, label-free, techniques to assess bone abnormalities such as Paget's disease, osteoporosis and bone fractures

    Science.gov (United States)

    Sordillo, Diana C.; Sordillo, Laura A.; Shi, Lingyan; Budansky, Yury; Sordillo, Peter P.; Alfano, Robert R.

    2015-02-01

    Near- infrared (NIR) light with wavelengths from 650 nm to 950 nm (known as the first NIR window) has conventionally been used as a non-invasive technique that can reach deeper penetration depths through media than light at shorter wavelengths. Recently, several novel, NIR, label-free, techniques have been developed to assess Paget's disease of bone, osteoporosis and bone microfractures. We designed a Bone Optical Analyzer (BOA) which utilizes the first window to measure changes of Hb and HbO2. Paget's disease is marked by an increase in vascularization in bones, and this device can enable easy diagnosis and more frequent monitoring of the patient's condition, without exposing him to a high cumulative dose of radiation. We have also used inverse imaging algorithms to reconstruct 2D and 3D maps of the bone's structure. This device could be used to assess diseases such as osteoporosis. Using 800 nm femtosecond excitation with two-photon (2P) microscopy, we acquired 2PM images of the periosteum and spatial frequency spectra (based on emission of collagen) from the periosteal regions. This technique can provide information on the structure of the periosteum and can detect abnormalities which may be an indication of disease. Most recently, we showed that longer NIR wavelengths in the second and third NIR windows (1100 nm-1350 nm, 1600 nm-1870 nm), could be used to image bone microfractures. Use of NIR light could allow for repeated studies in patients with diseases such as Paget's and osteoporosis quickly and non-invasively, and could impact the current management for these diseases.

  9. Markers of bone metabolism are affected by renal function and growth hormone therapy in children with chronic kidney disease

    DEFF Research Database (Denmark)

    Doyon, Anke; Fischer, Dagmar Christiane; Bayazit, Aysun Karabay;

    2015-01-01

    Objectives: The extent and relevance of altered bone metabolism for statural growth in children with chronic kidney disease is controversial. We analyzed the impact of renal dysfunction and recombinant growth hormone therapy on a panel of serum markers of bone metabolism in a large pediatric chro...

  10. Diagnosis of temporal bone diseases using three-dimensional images with multislice CT

    Energy Technology Data Exchange (ETDEWEB)

    Toyama, Yoshihiro; Togami, Taro; Murota, Makiko; Fukunaga, Kotaro; Hino, Ichiro; Sato, Katashi; Ohkawa, Motoomi [Kagawa Medical Univ., Miki (Japan)

    2001-08-01

    We evaluated the usefulness of three-dimensional images with multislice CT in the temporal bone diseases. Fifty-nine cases (26 with medial otitis, 8 choresteatoma, 10 congenital malformation, 3 high jugular bulb, 2 otosclerosis, and 10 others) were included in this study. In the ossicular and inner ear lesions, oblique multiplanar images of the long axis of each ossicle was useful the detection of abnormality. Structural deformity of ossicles and bony labyrinth were clearly delineated by surface rendering images. (author)

  11. Radiological features of Paget disease of bone associated with VCP myopathy

    Energy Technology Data Exchange (ETDEWEB)

    Farpour, Farzin [University of California, Department of Radiology, VA Long Beach Health Care, Irvine, CA (United States); Queens Hospital Center, Mount Sinai School of Medicine, New York, NY (United States); Tehranzadeh, Jamshid [University of California, Department of Radiology, VA Long Beach Health Care, Irvine, CA (United States); Donkervoort, Sandra; Vanjara, Pari [University of California, Division of Genetics and Metabolism, Department of Pediatrics, Irvine, CA (United States); Smith, Charles [University of Kentucky, Department of Neurology and Sanders-Brown Center on Aging, Lexington, KY (United States); Martin, Barbara [University of Kentucky, Lexington, KY (United States); Osann, Kathryn [University of California, Department of Medicine, Division of Hematology/Oncology, Irvine, CA (United States); Kimonis, Virginia E. [University of California, Division of Genetics and Metabolism, Department of Pediatrics, Irvine, CA (United States); UC Irvine Medical Center, Division of Genetics and Metabolism, Orange, CA (United States)

    2012-03-15

    Mutations in the Valosin-containing protein (VCP) gene cause a unique disorder characterized by classic Paget disease of bone (PDB), inclusion body myopathy, and frontotemporal dementia (IBMPFD). Our objective was to analyze the radiographic features of PDB associated with VCP mutations since there is a dearth of literature on the PDB component of VCP disease. Radiographic bone surveys were examined in 23 individuals with VCP mutation and compared with their unaffected relatives. Laboratory testing relevant for VCP disease was performed in all individuals. Of the 17 affected individuals with clinical manifestations of VCP disease, 16 of whom had myopathy, radiographic analysis revealed classic PDB in 11 individuals (65%). The mean age of diagnosis for myopathy was 43.8 years and for PDB was 38.1 years of age. Radiological evidence of PDB was seen in one individual (16%) amongst six clinically asymptomatic VCP mutation carriers. Alkaline phosphatase was a useful marker for diagnosing PDB in VCP disease. Radiographic findings of classic PDB are seen in 52% of individuals carrying VCP mutations at a significantly younger age than conventional PDB. Screening for PDB is warranted in at-risk individuals because of the benefit of early treatment with the new powerful bisphosphonates that hold the potential for prevention of disease. (orig.)

  12. Deoxypyridinoline level in gingival crevicular fluid as alveolar bone loss biomarker in periodontal disease

    Directory of Open Access Journals (Sweden)

    Agustin Wulan Suci Dharmayanti

    2012-06-01

    Full Text Available Background: Periodontal diseases have high prevalence in Indonesia. They are caused by bacteria plaque that induced host response to release pro inflammatory mediator. Pro inflammatory mediators and bacteria product cause degradation of collagen fibers in periodontal tissue. Deoxypyridinoline is one of pyridinoline cross-link of collagen type I that can be used as biomarker in bone metabolic diseases, however, their contribution to detect alveolar bone loss in periodontal diseases remains unclear. Purpose: This study was to evaluate deoxypyridinoline level in gingival crevicular fluid as alveolar bone loss biomarker on periodontal disease. Methods: This study used 24 subjects with periodontal diseases and 6 healthy subjects. Dividing of periodontal disease was based on index periodontal. Gingival crevicular fluid was taken at mesial site of maxillary posterior tooth by paper point and deoxypyridinoline be measured by ELISA technique. Results: We found increasing of deoxypyridinoline level following of the severity of periodontal diseases. There was also significant difference between healthy subjects and periodontal diseases subjects (p<0.05. Conclusion: Deoxypyridinoline level in gingiva crevicular fluid can be used as alveolar bone loss biomarker in periodontal disease subjects.Latar belakang: Prevalensi penyakit periodontal di Indonesia cukup tinggi. Ini disebabkan oleh bakteri plak yang merangsang respon tubuh untuk mengeluarkan mediator keradangan. Mediator keradangan dan produk bakteri menyebabkan degradasi serat kolagen jaringan periodontal. Deoksipiridinolin merupakan salah satu ikatan piridinium dari kolagen tipe I yang dapat digunakan sebagai biomarker penyakit metabolisme tubuh. Akan tetapi, penggunaan deoksipiridinolin untuk mendeteksi kehilangan tulang alveolar pada penyakit periodontal masih belum jelas. Tujuan: Tujuan penelitian ini untuk mengetahui bahwa kadar deoksipiridinolin pada cairan krevikular gingival dapat digunakan

  13. MRI bone marrow findings in 63 patients with type I Gaucher's disease

    Energy Technology Data Exchange (ETDEWEB)

    Poll, L.W. [Berufsgenossenschaftliche Unfallklinik Duisburg GmbH (Germany). Abt. Radiologie; Willers, R. [Duesseldorf Univ. (Germany). Zentrum fuer Information, Kommunikation und Medientechnologie; Haeussinger, D. [Universitaetsklinikum Duesseldorf (Germany). Klinik fuer Gastroenterologie, Hepatologie und Infektiologie; Moedder, U. [Universitaetsklinikum Duesseldorf (Germany). Inst. fuer Radiologie; Dahl, S. vom [St.-Franziskus-Hospital Koeln, Akademisches Lehrkrankenhaus der Koeln Univ. (Germany). Klinik fuer Innere Medizin.

    2010-11-15

    Purpose: To determine whether MR bone marrow findings in Gaucher patients may help to identify patients at high risk of developing severe Gaucher bone complications exemplified by avascular necrosis (AVN) of the femoral head. Materials and Methods: MR images were obtained in 63 Type I Gaucher patients through a standard protocol using coronal T1 and T2-weighted sequences of the lower extremities. The location and extent of infiltrated marrow was established using a semi-quantitative MRI scoring method (Duesseldorf Gaucher score, DGS) and the morphological pattern of bone marrow involvement determined (whether homogeneous type A or non-homogeneous type B). The active marrow process with bone edema and AVN of the femoral head were also analyzed. Results: Bone marrow involvement was observed in femoral sites more than in tibial sites. A high DGS was significantly correlated with type B morphology and femoral AVN (both p < 0.0001). Splenectomized patients showed a significantly higher Duesseldorf Gaucher score and type B morphology than non-splenectomized patients (both p < 0.05). AVN was seen in 46 % of patients with type B morphology versus 3 % in type A morphology (p < 0.0001). DGS and morphology of bone marrow involvement were not significantly correlated with active marrow processes. Conclusion: Type B marrow morphology and extensive marrow packing were significantly associated with AVN of the femoral head (both p < 0.0001). These patterns are considered predictive and may be employed in a disease management context to alert physicians to the need for urgent therapeutic measures. (orig.)

  14. Bone mineral density and vitamin D status in Parkinson's disease patients.

    Science.gov (United States)

    van den Bos, F; Speelman, A D; van Nimwegen, M; van der Schouw, Y T; Backx, F J G; Bloem, B R; Munneke, M; Verhaar, H J J

    2013-03-01

    Bone loss is more common in Parkinson's disease (PD) than in the general population. Several factors may be involved in the development of bone loss, including malnutrition, immobilization, low body mass index, decreased muscle strength, vitamin D deficiency and medication use. This study investigates the prevalence of osteoporosis and possible risk factors associated with bone loss in early stage PD. In 186 PD patients (Hoehn and Yahr stage 1-2.5, mean age 64.1 years, 71 % men) bone mineral density (BMD) measurements were performed with DEXA. T- and Z-scores were calculated. Univariate linear regression analysis was performed to identify variables that contributed to BMD. 25-OH-vitamin D status of PD patients was compared with 802 controls (mean age 63.3 years, 50 % men) using linear regression analysis. Osteoporosis (11.8 %) and osteopenia (41.4 %) were common in PD patients. Mean Z-score for the hip was 0.24 (SD 0.93), and for the lumbar spine 0.72 (SD 1.91). Female gender, low weight, and low 25-OH-vitamin D were significantly correlated with BMD of the hip and lumbar spine. PD patients had lower 25(OH)D serum levels than controls (B = -10, p = 0.000). More than half of the patients with early stage PD had an abnormal BMD. Female gender, low weight, and low vitamin D concentration were associated with bone loss. Furthermore, vitamin D concentrations were reduced in PD patients. These results underscore the importance of proactive screening for bone loss and vitamin D deficiency, even in early stages of PD.

  15. Chronic obstructive pulmonary disease and low bone mass: A case-control study

    Directory of Open Access Journals (Sweden)

    Rakesh K Gupta

    2014-01-01

    Full Text Available Background and Objective: Low bone mass (osteopenia and osteoporosis is one of the effects associated with chronic obstructive pulmonary disease (COPD. There is very little data from Saudi Arabia on COPD and low bone mass. This retrospective study was done to assess the prevalence of osteoporosis and osteopenia in COPD patients attending King Fahd Hospital of the University (KFHU, Alkhobar. Patients and Methods: After obtaining the ethical approval from the research committee, all patients seen between at the King Fahd Hospital of the University between January 2010 and December 2012 were included. The inclusion criteria included a follow up of a minimum 2 years, and the Medical Records should have the details of forced expiratory volume in one second (FEV 1 , blood bone profile and bone biomarkers and dual-energy X-ray absorptiometry (DEXA scan. Patients were labeled as osteopenia if the T score was -<1 to <-2.5 and osteoporosis of <-2.5 as per the WHO definition of osteopenia and osteoporosis. Results: Seventy-three patients were being followed in the clinics and 49 patients satisfied the inclusion criteria. The average age was 60.6 ± 10.47 years; males were 43 and females 6. Three (6.1% were normal and the remaining 46 (93.9% were with low bone mass. Thirty-two (65.3% were osteoporotic and 14 (28.57% were osteopenic. The average duration of COPD was 4.5 ± 6.2 years. Majority (n = 36, 73.4% of patients were in the Global Initiative for COPD (GOLD class II and III. FEV 1 was significantly lower in the patients with low bone mass 1.66 ± 0.60 versus 3.61 ± 0.58 (P < 0.001. Conclusions: Our study shows that over 90% of Saudi Arabian patients with COPD suffer from osteopenia and osteoporosis and unfortunately they remain under-diagnosed and undertreated.

  16. Systemic mast cell disease (SMCD) and bone pain. A case treated with radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Hesselmann, S.; Micke, O.; Schaefer, U.; Willich, N. [University Hospital Muenster (Germany). Dept. of Radiotherapy and Radiooncology

    2002-05-01

    Background: Systemic mast cell disease (SMCD) is a rare disease characterized by a multitopic proliferation of cytologically and/or functionally abnormal tissue mast cells. SMCD preferentially involves the skin, spleen, liver, lymph nodes and the bone marrow. The cause of SMCD is unknown. Bony pain, caused by mast cell infiltration of the marrow cavity, is present in up to 28% of cases and is frequently chronic and difficult to palliate with medical therapy. Case Report: We report one case of refractory bone pain in a 54-year-old female Caucasian patient with advanced SMCD and associated bony involvement, which was treated with radiotherapy for pain palliation. Between 1995 and 1998, the patient was irradiated at four different locations: 1) right shoulder and proximal right humerus, 2) both hands, 3) both knees, 4) left humerus with a total dose of 40 Gy in 2.0 or 2.5 Gy daily fractions. Results: Different results of pain palliation were achieved. In one location the pain was reduced for 55 months until her death due to disease progression, whereas in two other locations a pain control was maintained for 3 and 6 months after radiotherapy. In one location, no pain reduction was achieved. Severe side effects were not observed. Conclusion: Palliative radiotherapy has a role in the control of severe intractable bone pain in patients with advanced SMCD, though in some cases the effect may be short or incomplete. The observed palliation of pain can even differ in the same patient. (orig.)

  17. Multiple myeloma mesenchymal stromal cells: Contribution to myeloma bone disease and therapeutics.

    Science.gov (United States)

    Garcia-Gomez, Antonio; Sanchez-Guijo, Fermin; Del Cañizo, M Consuelo; San Miguel, Jesus F; Garayoa, Mercedes

    2014-07-26

    Multiple myeloma is a hematological malignancy in which clonal plasma cells proliferate and accumulate within the bone marrow. The presence of osteolytic lesions due to increased osteoclast (OC) activity and suppressed osteoblast (OB) function is characteristic of the disease. The bone marrow mesenchymal stromal cells (MSCs) play a critical role in multiple myeloma pathophysiology, greatly promoting the growth, survival, drug resistance and migration of myeloma cells. Here, we specifically discuss on the relative contribution of MSCs to the pathophysiology of osteolytic lesions in light of the current knowledge of the biology of myeloma bone disease (MBD), together with the reported genomic, functional and gene expression differences between MSCs derived from myeloma patients (pMSCs) and their healthy counterparts (dMSCs). Being MSCs the progenitors of OBs, pMSCs primarily contribute to the pathogenesis of MBD because of their reduced osteogenic potential consequence of multiple OB inhibitory factors and direct interactions with myeloma cells in the bone marrow. Importantly, pMSCs also readily contribute to MBD by promoting OC formation and activity at various levels (i.e., increasing RANKL to OPG expression, augmenting secretion of activin A, uncoupling ephrinB2-EphB4 signaling, and through augmented production of Wnt5a), thus further contributing to OB/OC uncoupling in osteolytic lesions. In this review, we also look over main signaling pathways involved in the osteogenic differentiation of MSCs and/or OB activity, highlighting amenable therapeutic targets; in parallel, the reported activity of bone-anabolic agents (at preclinical or clinical stage) targeting those signaling pathways is commented.

  18. A pilot study on the impact of body composition on bone and mineral metabolism in Parkinson's disease.

    Science.gov (United States)

    Fernández, María C; Parisi, Muriel S; Díaz, Sergio P; Mastaglia, Silvina R; Deferrari, Juan M; Seijo, Mariana; Bagur, Alicia; Micheli, Federico; Oliveri, Beatriz

    2007-08-01

    The impact of body composition on bone and mineral metabolism in Parkinson's disease (PD) was evaluated. Body fat mass, lean mass, bone mineral content, and bone mineral density (BMD) were measured by DXA in 22 PD patients and 104 controls. Female patients exhibited reduced body mass index, fat mass, and BMD compared to controls (p<0.05). Significant positive correlation was found between 25 OHD levels and BMC. Diminished bone mass in women with PD was found to be associated with alterations in body composition and low 25 OHD levels.

  19. Dynamic contrast-enhanced MRI in Paget's disease of bone-correlation of regional microcirculation and bone turnover

    Energy Technology Data Exchange (ETDEWEB)

    Libicher, M. [University of Cologne, Department of Radiology, Cologne (Germany); Klinikum der Universitaet zu Koeln, Radiologische Klinik, Koeln (Germany); Kasperk, C. [University of Heidelberg, Department of Medicine, Division of Osteology, Heidelberg (Germany); Daniels, M.; Hosch, W. [University of Heidelberg, Department of Radiology, Heidelberg (Germany); Kauczor, H.U.; Delorme, S. [German Cancer Research Center, Department of Radiology, Heidelberg (Germany)

    2008-05-15

    The purpose of this study was to evaluate regional microcirculation in Paget's disease of bone (PD) with dynamic contrast-enhanced MR imaging (DCE-MRI). Additionally, we correlated regional bone perfusion with alkaline phosphatase as serum marker of bone turnover. We examined 71 patients with PD (27 men, 44 women, 67{+-}10 years) localized at the axial and appendicular skeleton. Contrast uptake was analyzed using a two-compartment model with the output variables amplitude A and exchange rate constant k{sub ep}. Color-coded parametric images were generated to visualize microcirculation. Serum levels of alkaline phosphatase (AP) were compared with DCE-MRI parameters. Amplitude A and exchange rate constant k{sub ep} were significantly increased in PD compared to unaffected bone (A{sub PD} 0.81{+-}0.24 vs. A{sub control} 0.34{+-}0.1 and k{sub ep} {sub PD} 4.0 {+-}2.86 vs. k{sub ep} {sub control} 1.73 {+-}0.88, p <0.001). There was a significant correlation (r{sub s}=0.5-0.7) of DCE-MRI parameters and AP at the axial (pelvis, spine) and appendicular skeleton (femur, tibia). The long bones showed increased circulation of the advancing peripheral zones and no vascularization of the central part, which had been replaced by fatty tissue. Regional microcirculation in PD is inhomogeneous with focal areas of excessive hypervascularity, especially in the advancing peripheral zone. There is a significant correlation of bone circulation and bone turnover in PD. DCE-MRI might therefore be a diagnostic tool for monitoring therapeutic effects of bisphoshonates in Paget's disease of bone. (orig.)

  20. Role of odanacatib in reducing bone loss due to endodontic disease: An overview

    Science.gov (United States)

    Bahuguna, Rachana; Jain, Atul; Khan, Suleman Abbas; Arvind, M. S.

    2016-01-01

    Aims and Objectives: Through a comprehensive literature review, this article provides an overview of the potential role of odanacatib (ODN) in reducing bone loss due to endodontic disease. Materials and Methods: A literature review was performed in PubMed Central, MEDLINE, Cochrane Library, and EBSCO databases. The articles identified included those published between 2002 and 2016. Based on the predetermined inclusion and exclusion criteria, out of 237 articles found, 50 were selected for this review. Results: Cathepsin K (CstK), which is indispensible to the immune system, also plays an important role in osteoclastic bone resorption. ODN, which is an orally active, selective, and effective inhibitor of CstK, decreases bone resorption by selectively inhibiting proteolysis of matrix proteins by CstK, without affecting other osteoclastic activity or osteoblast viability. Conclusion: The goal of endodontic treatment is to achieve a clinically asymptomatic state along with formation of reparative bone. This process could take 6 months or longer, hence, an earlier reversal of the resorption process could lead to faster healing and resolution of the periapical lesion. Use of ODN can be of help in achieving this goal. PMID:28217533

  1. MR analysis of sternal bone marrow using STIR in hematologic diseases

    Energy Technology Data Exchange (ETDEWEB)

    Kozawa, Eito [Saitama Medical School, Moroyama (Japan)

    1998-12-01

    The magnetic resonance (MR) signal intensity pattern of sternal bone marrow was examined in 21 normal volunteers and 10 patients with aplastic anemia (n=4), multiple myeloma (2), AML (2), gammaglobulinemia (1) and MDS (1) using a sagittal STIR sequence. Double Echo STIR images (TR/TI/TE/NEX=2000/180/20, 100/1) were obtained with a CP body array coil. Craniocaudal phase-encoding with a handmade positioning device effectively avoided overlapping artifacts due to cardiac pulsation. In the normal volunteers, age showed a significant inverse correlation with the calculated SIR (signal intensity ratio of bone marrow relative to subcutaneous fat) using STIR with short TE. The SIR in the sternal body was significantly higher than that in the manubrium (p<0.05). Knowledge of the sternal bone marrow distribution according to age is useful for evaluating hematologic diseases. The proposed method provided high spatial resolution and an excellent bone marrow signal, and may be useful for determining site for aspiration. (author)

  2. Low Bone Mineral Density in Chinese Adults with Nonalcoholic Fatty Liver Disease

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    Ran Cui

    2013-01-01

    Full Text Available Aim. To investigate bone metabolic characteristics in Chinese adults with nonalcoholic fatty liver disease (NAFLD. Methods. A total of 224 patients (99 males and 125 postmenopausal females were recruited and divided into 4 groups: males without NAFLD, males with NAFLD, females without NAFLD, and females with NAFLD. Bone mineral density (BMD was evaluated according to body mass index (BMI, waist circumference (WC, and serum biomarkers. β cell function was evaluated by HOMA2%B, HOMA2%S, and HOMA2IR. Results. Males in the NAFLD group had lower BMD of the right hip and the femoral neck (0.852±0.117 versus 0.930±0.123, P=0.002; 0.736±0.119 versus 0.812±0.132, P=0.004, and females had lower BMD of the right hip (0.725±0.141 versus 0.805±0.145, P=0.002 even after adjusted for weight, BMI, waist, HDL, and ALT. There was no significant difference in bone metabolic markers between patients with and without NAFLD. NAFLD was an important factor that affected the bone; moreover, the effect attenuated when HOMA2IR entered into the model (R2=0.160, β=−0.172, and P=0.008. Conclusions. NAFLD exerts a detrimental effect on BMD in both males and females. Insulin resistance may play an important role in this pathophysiological process.

  3. Leptin in chronic kidney disease: a link between hematopoiesis, bone metabolism, and nutrition.

    Science.gov (United States)

    Zhang, Jingjing; Wang, Ningning

    2014-06-01

    Anemia, dyslipidemia, malnutrition, together with mineral and bone disorders are common complications in patients with chronic kidney disease (CKD). All are associated with increased risk of mortality. Leptin is a small peptide hormone that is mainly but not exclusively produced in adipose tissue. It is also secreted by normal human osteoblasts, subchondral osteoblasts, placental syncytiotrophoblasts, and the gastric epithelium. Leptin binds to its receptors in the hypothalamus to regulate bone metabolism and food intake. Leptin also has several other important metabolic effects on peripheral tissues, including the liver, skeletal muscle, and bone marrow. Leptin is cleared principally by the kidney. Not surprisingly, serum leptin appears to increase concurrently with declines in the glomerular filtration rate in patients with CKD. A growing body of evidence suggests that leptin might be closely related to hematopoiesis, nutrition, and bone metabolism in CKD patients. Results are conflicting regarding leptin in patients with CKD, in whom both beneficial and detrimental effects on uremia outcome are found. This review elucidates the discovery of leptin and its receptors, changes in serum or plasma leptin levels, the functions of leptin, relationships between leptin and the complications mentioned above, and pharmaceutical interventions in serum leptin levels in patients with CKD.

  4. Is chronic kidney disease-mineral bone disorder (CKD-MBD) really a syndrome?

    Science.gov (United States)

    Cozzolino, Mario; Ureña-Torres, Pablo; Vervloet, Marc G; Brandenburg, Vincent; Bover, Jordi; Goldsmith, David; Larsson, Tobias E; Massy, Ziad A; Mazzaferro, Sandro

    2014-10-01

    The concept of chronic kidney disease-mineral bone disorder (CKD-MBD) does not appear to fulfil the requirements for a syndrome at first glance, but its definition has brought some clear-cut benefits for clinicians and patients, including wider and more complex diagnostic and therapeutic approaches to the management of this challenging set of issues. Admittedly, not all components of CKD-MBD are present in all patients at all times, but these are highly interrelated, involving mineral and bone laboratory abnormalities, clinical and histological bone disease and finally, cardiovascular disease. The presence of typical biological bone ossification processes in an ectopic anatomical location in CKD has helped to define the existence of an unprecedented bone-vascular relationship, extending its interest even to other medical specialities. For now, we believe that CKD-MBD does not reach full criteria to be defined as a syndrome. However, this novel concept has clearly influenced current clinical guidelines. The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF/KDOQI™) guidelines in 2003 for instance recommended that calcium-based phosphate binders should be avoided to treat hyperphosphataemia in the presence of cardiovascular calcifications. In 2009, the KDIGO and other guidelines reinforced and extended this recommendation by stating that it is reasonable to choose oral phosphate binder therapy by taking into consideration other components of CKD-MBD. Similarly, it is also considered reasonable to use information on vascular/valvular calcification to guide the management of CKD-MBD. Our current assumption as a working group 'CKD-MBD' is that CKD-MBD has the potential to be defined a true syndrome, such as a constellation of concurrent signs and symptoms that suggest a common underlying mechanism for these components as opposed to the term disease. The term 'syndrome' also implies that in any patient at risk due to the presence of one or a few

  5. Lumbar spine degenerative disease : effect on bone mineral density measurements in the lumbar spine and femoral neck

    Energy Technology Data Exchange (ETDEWEB)

    Juhng, Seon Kwan [Wonkwang Univ. School of Medicine, Iksan (Korea, Republic of); Koplyay, Peter; Jeffrey Carr, J.; Lenchik, Leon [Wake Forest Univ. School of Medicine, Winston-salem (United States)

    2001-04-01

    To determine the effect of degenerative disease of the lumbar spine on bone mineral density in the lumbar spine and femoral neck. We reviewed radiographs and dual energy x-ray absorptiometry scans of the lumbar spine and hip in 305 Caucasian women with suspected osteoporosis. One hundred and eight-six patient remained after excluding women less than 40 years of age (n=18) and those with hip osteoarthritis, scoliosis, lumbar spine fractures, lumbar spinal instrumentation, hip arthroplasty, metabolic bone disease other than osteoporosis, or medications known to influence bone metabolism (n=101). On the basis of lumbar spine radiographs, those with absent/mild degenerative disease were assigned to the control group and those with moderate/severe degenerative disease to the degenerative group. Spine radiographs were evaluated for degenerative disease by two radiologists working independently; discrepant evaluations were resolved by consensus. Lumbar spine and femoral neck bone mineral density was compared between the two groups. Forty-five (24%) of 186 women were assigned to the degenerative group and 141 (76%) to the control group. IN the degenerative group, mean bone mineral density measured 1.075g/cm? in the spine and 0.788g/cm{sup 2} in the femoral neck, while for controls the corresponding figures were 0.989g/cm{sup 2} and 0.765g/cm{sup 2}. Adjusted for age, weight and height by means of analysis of variance, degenerative disease of the lumbar spine was a significant predictor of increased bone mineral density in the spine (p=0.0001) and femoral neck (p=0.0287). Our results indicate a positive relationship between degenerative disease of the lumbar spine and bone mineral density in the lumbar spine and femoral neck, and suggest that degenerative disease in that region, which leads to an intrinsic increase in bone mineral density in the femoral neck, may be a good negative predictor of osteoporotic hip fractures.

  6. Modelling Gaucher disease progression: long-term enzyme replacement therapy reduces the incidence of splenectomy and bone complications.

    Science.gov (United States)

    van Dussen, Laura; Biegstraaten, Marieke; Dijkgraaf, Marcel Gw; Hollak, Carla Em

    2014-07-24

    Long-term complications and associated conditions of type 1 Gaucher Disease (GD) can include splenectomy, bone complications, pulmonary hypertension, Parkinson disease and malignancies. Enzyme replacement therapy (ERT) reverses cytopenia and reduces organomegaly. To study the effects of ERT on long-term complications and associated conditions, the course of Gaucher disease was modelled.

  7. High serum YKL-40 concentration is associated with severe bone disease in newly diagnosed multiple myeloma patients

    DEFF Research Database (Denmark)

    Mylin, Anne Kærsgaard; Abildgaard, N.; Johansen, J.S.

    2008-01-01

    Objectives: In multiple myeloma (MM) YKL-40 is present in the bone marrow microenvironment and is suggested to play a role in remodelling of the extracellular matrix. Here, the association between serum YKL-40 and severity of bone disease in MM is investigated. Methods: Serum YKL-40 was measured...... in 34 MM patients at diagnosis. Bone disease was assessed by radiography and biochemical markers of bone metabolism. Patients were treated with conventional chemotherapy and followed for up to 30 months. Results: Patients with a serum YKL-40 elevated above the age specific reference range (56%) had...... a higher total X-ray score (P = 0.003) and higher levels of the markers of bone resorption serum C-terminal telopeptide of collagen type I (P = 0.003), urine pyridinoline (P = 0.04) and urine deoxypyridinoline (P = 0.002), while the levels of urine N-terminal telopeptide of collagen type I (NTX-1...

  8. Can bone loss be reversed by antithyroid drug therapy in premenopausal women with Graves' disease?

    Directory of Open Access Journals (Sweden)

    Belsing Tina Z

    2010-09-01

    Full Text Available Abstract Context Hyperthyroidism can lead to reduced bone mineral density (BMD and increased fracture risk particularly in postmenopausal women, but the mechanism behind is still unclear. Objective Prospective examination of the influence of thyroid hormones and/or thyroid autoantibodies on BMD in premenopause. Design We have examined 32 premenopausal women with untreated active Graves' disease from time of diagnosis, during 18 months of antithyroid drug therapy (ATD and additionally 18 months after discontinuing ATD. Variables of thyroid metabolism, calcium homeostasis and body composition were measured every 3 months. BMD of lumbar spine and femoral neck were measured at baseline, 18 ± 3 and 36 ± 3 months. Data were compared to base line, a sex- and age matched control group and a group of patients with Hashimoto's thyroiditis treated with non-suppressive doses of levothyroxine. Results The study showed significantly (p Conclusion The results indicated a clinically relevant impact of thyroid function on bone modulation also in premenopausal women with Graves' disease, and further indicated the possibility for a direct action of TRAb on bones.

  9. Bilateral Knee Pain Associated with Bone Infarction in a Patient with Behcet's Disease

    Directory of Open Access Journals (Sweden)

    Pelin Oktayoglu

    2012-01-01

    Full Text Available We describe a 31-years-old female patient with severe pain in both knees who had been diagnosed as Behcet’s disease (BD for 12 years. She had had a history of complications due to BD including superior vena cava thrombosis, pulmonary thromboembolism, uveitis, and erythema nodosum and has reported the administration of corticosteroid therapy irregularly. After radiologic evaluation, she has been diagnosed with bone infarction of both left and right knee with the existance of lupus anticoagulants (LA positivity. Severe joint pain without the evidence of arthritis must alert the clinician to the possibility of bone necrosis of the extremity, although those may rarely occur bilateral in BD.

  10. The chronic kidney disease - Mineral bone disorder (CKD-MBD): Advances in pathophysiology.

    Science.gov (United States)

    Hruska, Keith A; Sugatani, Toshifumi; Agapova, Olga; Fang, Yifu

    2017-01-21

    The causes of excess cardiovascular mortality associated with chronic kidney disease (CKD) have been attributed in part to the CKD-mineral bone disorder syndrome (CKD-MBD), wherein, novel cardiovascular risk factors have been identified. New advances in the causes of the CKD-MBD are discussed in this review. They demonstrate that repair and disease processes in the kidneys release factors to the circulation that cause the systemic complications of CKD. The discovery of WNT inhibitors, especially Dickkopf 1 (Dkk1), produced during renal repair as participating in the pathogenesis of the vascular and skeletal components of the CKD-MBD implied that additional pathogenic factors are critical. This lead to the discovery that activin A is a second renal repair factor circulating in increased levels during CKD. Activin A derives from peritubular myofibroblasts of diseased kidneys, wherein it stimulates fibrosis, and decreases tubular klotho expression. Activin A binds to the type 2 activin A receptor, ActRIIA, which is variably affected by CKD in the vasculature. In diabetic/atherosclerotic aortas, specifically in vascular smooth muscle cells (VSMC), ActRIIA signaling is inhibited and contributes to CKD induced VSMC dedifferentiation, osteogenic transition and neointimal atherosclerotic calcification. In nondiabetic/nonatherosclerotic aortas, CKD increases VSMC ActRIIA signaling, and vascular fibroblast signaling causing the latter to undergo osteogenic transition and stimulate vascular calcification. In both vascular situations, a ligand trap for ActRIIA prevented vascular calcification. In the skeleton, activin A is responsible for CKD stimulation of osteoclastogenesis and bone remodeling increasing bone turnover. These studies demonstrate that circulating renal repair and injury factors are causal of the CKD-MBD and CKD associated cardiovascular disease.

  11. Extent of Surgery Does Not Influence 30-Day Mortality in Surgery for Metastatic Bone Disease

    Science.gov (United States)

    Sørensen, Michala Skovlund; Hindsø, Klaus; Hovgaard, Thea Bechmann; Petersen, Michael Mørk

    2016-01-01

    Abstract Estimating patient survival has hitherto been the main focus when treating metastatic bone disease (MBD) in the appendicular skeleton. This has been done in an attempt to allocate the patient to a surgical procedure that outlives them. No questions have been addressed as to whether the extent of the surgery and thus the surgical trauma reduces survival in this patient group. We wanted to evaluate if perioperative parameters such as blood loss, extent of bone resection, and duration of surgery were risk factors for 30-day mortality in patients having surgery due to MBD in the appendicular skeleton. We retrospectively identified 270 consecutive patients who underwent joint replacement surgery or intercalary spacing for skeletal metastases in the appendicular skeleton from January 1, 2003 to December 31, 2013. We collected intraoperative (duration of surgery, extent of bone resection, and blood loss), demographic (age, gender, American Society of Anesthesiologist score [ASA score], and Karnofsky score), and disease-specific (primary cancer) variables. An association with 30-day mortality was addressed using univariate and multivariable analyses and calculation of odds ratio (OR). All patients were included in the analysis. ASA score 3 + 4 (OR 4.16 [95% confidence interval, CI, 1.80–10.85], P = 0.002) and Karnofsky performance status below 70 (OR 7.34 [95% CI 3.16–19.20], P < 0.001) were associated with increased 30-day mortality in univariate analysis. This did not change in multivariable analysis. No parameters describing the extent of the surgical trauma were found to be associated with 30-day mortality. The 30-day mortality in patients undergoing surgery for MBD is highly dependent on the general health status of the patients as measured by the ASA score and the Karnofsky performance status. The extent of surgery, measured as duration of surgery, blood loss, and degree of bone resection were not associated with 30-day mortality. PMID:27082592

  12. Bone mineral density and disorders of mineral metabolism in chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    Joe George; Hosahithlu K Ganesh; Shrikrishna Acharya; Tushar R Bandgar; Vyankatesh Shivane; Anjana Karvat; Shobna J Bhatia; Samir Shah; Padmavathy S Menon; Nalini Shah

    2009-01-01

    AIM: To estimate the prevalence and identify the risk factors for metabolic bone disease in patients with cirrhosis. METHODS: The study was performed on 72 Indian patients with cirrhosis (63 male, 9 female; aged < 50 years). Etiology of cirrhosis was alcoholism ( n = 37), hepatitis B ( n = 25) and hepatitis C ( n = 10). Twenty-three patients belonged to Child class A, while 39 were in class B and 10 in class C. Secondary causes for metabolic bone disease and osteoporosis were ruled out. Sunlight exposure, physical activity and dietary constituents were calculated. Complete metabolic profiles were derived, and bone mineral density (BMD) was measured using dual energy X ray absorptiometry. Low BMD was defined as a Z score below -2. RESULTS: Low BMD was found in 68% of patients. Lumbar spine was the most frequently and severely affected site. Risk factors for low BMD included low physical activity, decreased sunlight exposure, and low lean body mass. Calcium intake was adequate, with unfavorable calcium: protein ratio and calcium: phosphorus ratio. Vitamin D deficiency was highly prevalent (92%). There was a high incidence of hypogonadism (41%). Serum estradiol level was elevated significantly in patients with normal BMD. Insulin-like growth factor (IGF) 1 and IGF binding protein 3 levels were below the age-related normal range in both groups. IGF-1 was significantly lower in patients with low BMD. Serum osteocalcin level was low (68%) and urinary deoxypyridinoline to creatinine ratio was high (79%), which demonstrated low bone formation with high resorption. CONCLUSION: Patients with cirrhosis have low BMD. Contributory factors are reduced physical activity, low lean body mass, vitamin D deficiency and hypogonadism and low IGF-1 level.

  13. Doença óssea em Mieloma Múltiplo Bone disease in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Vania T. M. Hungria

    2007-03-01

    Full Text Available As principais manifestações clínicas do mieloma múltiplo estão relacionadas à destruição óssea. Esta doença óssea pode levar a fraturas patológicas, compressão da medula espinhal, hipercalcemia e dor, sendo uma das principais causas de morbidade e mortalidade. Estas complicações resultam do desequilíbrio da reabsorção e formação óssea, decorrente do aumento da atividade osteoclástica. Este aumento é mediado pela liberação de fatores ativadores dos osteoclastos, que são produzidos no microambiente da medula óssea por células tumorais e não tumorais. Os bisfosfonatos são inibidores específicos da atividade osteoclástica e são eficazes no tratamento da hipercalcemia associada às neoplasias malignas e podem reduzir o aparecimento de complicações esqueléticas. Estudos recentes identificaram novas moléculas como o receptor de ativação nuclear kappa B (RANK, seu ligante (RANKL, osteoprotegerina (OPG, e a proteína inflamatória dos macrófagos-1alfa, que estão envolvidas na ativação e diferenciação dos osteoclastos, enquanto que a proteína dikkopf-1 inibe a formação óssea osteoblástica. Estas novas moléculas parecem não só interferir na biologia da destruição óssea do mieloma, mas também com a sobrevida e crescimento tumoral, sendo novos alvos para o desenvolvimento de drogas antimieloma. Estudos recentes com anticorpo monoclonal anti-RANKL são promissores. O tratamento da doença óssea do mieloma múltiplo inclui principalmente o uso de bisfosfonatos, radioterapia e procedimentos cirúrgicos.The major clinical manifestation of multiple myeloma is related to osteolytic bone destruction. Bone disease can lead to pathologic fractures, spinal cord compression, hypercalcemia, and pain, and is a major cause of morbidity and mortality. These complications result from asynchronous bone turnover wherein increased osteoclastic bone resorption is not accompanied by a comparable increase in bone formation

  14. The effect of naturally occurring chronic kidney disease on the micro-structural and mechanical properties of bone.

    Directory of Open Access Journals (Sweden)

    Anna Shipov

    Full Text Available Chronic kidney disease (CKD is a growing public health concern worldwide, and is associated with marked increase of bone fragility. Previous studies assessing the effect of CKD on bone quality were based on biopsies from human patients or on laboratory animal models. Such studies provide information of limited relevance due to the small size of the samples (biopsies or the non-physiologic CKD syndrome studied (rodent models with artificially induced CKD. Furthermore, the type, architecture, structure and biology of the bone of rodents are remarkably different from human bones; therefore similar clinicopathologic circumstances may affect their bones differently. We describe the effects of naturally occurring CKD with features resembling human CKD on the skeleton of cats, whose bone biology, structure and composition are remarkably similar to those of humans. We show that CKD causes significant increase of resorption cavity density compared with healthy controls, as well as significantly lower cortical mineral density, cortical cross-sectional area and cortical cross-sectional thickness. Young's modulus, yield stress, and ultimate stress of the cortical bone material were all significantly decreased in the skeleton of CKD cats. Cancellous bone was also affected, having significantly lower trabecular thickness and bone volume over total volume in CKD cats compared with controls. This study shows that naturally occurring CKD has deleterious effects on bone quality and strength. Since many similarities exist between human and feline CKD patients, including the clinicopathologic features of the syndrome and bone microarchitecture and biology, these results contribute to better understanding of bone abnormalities associated with CKD.

  15. Premature hair greying may predict reduced bone mineral density in Graves' disease.

    LENUS (Irish Health Repository)

    Leary, A C

    2012-02-03

    BACKGROUND: Premature hair greying has been associated with low bone mineral density (BMD), and it may be more frequent in Graves\\' disease. AIMS: To determine whether premature greying is associated with reduced BMD in women with Graves\\' disease and in control women, and to examine whether premature greying is more common in Graves\\' disease. METHODS: Premature greying (> 50% grey by 40 years) and BMD were determined in 44 women with a history of Graves\\' disease and 133 female controls referred for routine BMD measurement. Exclusion criteria included diseases or drugs known to affect BMD. RESULTS: Mean Z and T scores at the lumbar spine were significantly lower (P < 0.04) in subjects with premature greying than in those not prematurely grey among women with Graves\\' disease, but not among control women. Multiple regression confirmed this difference between Graves\\' and control women (P = 0.041). There were no differences at other measurement sites. Of Graves\\' patients, 36% were prematurely grey compared with 25% of control women (P = 0.14). CONCLUSION: Premature greying may be a weak marker for reduced BMD in women with a history of Graves\\' disease, but it is not a marker in normal women.

  16. Inhibition of autoimmune Chagas-like heart disease by bone marrow transplantation.

    Directory of Open Access Journals (Sweden)

    Maria C Guimaro

    2014-12-01

    Full Text Available Infection with the protozoan Trypanosoma cruzi manifests in mammals as Chagas heart disease. The treatment available for chagasic cardiomyopathy is unsatisfactory.To study the disease pathology and its inhibition, we employed a syngeneic chicken model refractory to T. cruzi in which chickens hatched from T. cruzi inoculated eggs retained parasite kDNA (1.4 kb minicircles. Southern blotting with EcoRI genomic DNA digests revealed main 18 and 20 kb bands by hybridization with a radiolabeled minicircle sequence. Breeding these chickens generated kDNA-mutated F1, F2, and F3 progeny. A targeted-primer TAIL-PCR (tpTAIL-PCR technique was employed to detect the kDNA integrations. Histocompatible reporter heart grafts were used to detect ongoing inflammatory cardiomyopathy in kDNA-mutated chickens. Fluorochromes were used to label bone marrow CD3+, CD28+, and CD45+ precursors of the thymus-dependent CD8α+ and CD8β+ effector cells that expressed TCRγδ, vβ1 and vβ2 receptors, which infiltrated the adult hearts and the reporter heart grafts.Genome modifications in kDNA-mutated chickens can be associated with disruption of immune tolerance to compatible heart grafts and with rejection of the adult host's heart and reporter graft, as well as tissue destruction by effector lymphocytes. Autoimmune heart rejection was largely observed in chickens with kDNA mutations in retrotransposons and in coding genes with roles in cell structure, metabolism, growth, and differentiation. Moreover, killing the sick kDNA-mutated bone marrow cells with cytostatic and anti-folate drugs and transplanting healthy marrow cells inhibited heart rejection. We report here for the first time that healthy bone marrow cells inhibited heart pathology in kDNA+ chickens and thus prevented the genetically driven clinical manifestations of the disease.

  17. Genomic deletion of a long-range bone enhancer misregulatessclerostin in Van Buchem disease

    Energy Technology Data Exchange (ETDEWEB)

    Loots, Gabriela G.; Kneissel, Michaela; Keller, Hansjoerg; Baptist, Myma; Chang, Jessie; Collette, Nicole M.; Ovcharenko, Dmitriy; Plajzer-Frick, Ingrid; Rubin, Edward M.

    2005-04-15

    Mutations in distant regulatory elements can negatively impact human development and health, yet due to the difficulty of detecting these critical sequences we predominantly focus on coding sequences for diagnostic purposes. We have undertaken a comparative sequence-based approach to characterize a large noncoding region deleted in patients affected by Van Buchem disease (VB), a severe sclerosing bone dysplasia. Using BAC recombination and transgenesis we characterized the expression of human sclerostin (sost) from normal (hSOSTwt) or Van Buchem(hSOSTvb D) alleles. Only the hSOSTwt allele faithfully expressed high levels of human sost in the adult bone and impacted bone metabolism, consistent with the model that the VB noncoding deletion removes a sost specific regulatory element. By exploiting cross-species sequence comparisons with in vitro and in vivo enhancer assays we were able to identify a candidate enhancer element that drives human sost expression in osteoblast-like cell lines in vitro and in the skeletal anlage of the E14.5 mouse embryo, and discovered a novel function for sclerostin during limb development. Our approach represents a framework for characterizing distant regulatory elements associated with abnormal human phenotypes.

  18. Higher bone turnover is related to spinal radiographic damage and low bone mineral density in ankylosing spondylitis patients with active disease: a cross-sectional analysis.

    Directory of Open Access Journals (Sweden)

    Suzanne Arends

    Full Text Available INTRODUCTION: Ankylosing spondylitis (AS is characterized by excessive bone formation and bone loss. Our aim was to investigate the association of bone turnover markers (BTM with spinal radiographic damage and bone mineral density (BMD in AS patients with active disease. METHODS: 201 consecutive AS outpatients of the Groningen Leeuwarden AS (GLAS cohort were included. Serum markers of bone resorption (C-telopeptides of type-I collagen, sCTX and bone formation (procollagen type-I N-terminal peptide, PINP; bone-specific alkaline phosphatase, BALP were measured. Z-scores were used to correct for the normal influence that age and gender have on bone turnover. Radiographs were scored by two independent readers according to modified Stoke AS Spinal Score (mSASSS. The presence of complete bridging (ankylosis of at least two vertebrae was considered as measure of more advanced radiographic damage. Low BMD was defined as lumbar spine and/or hip BMD Z-score ≤ -1. RESULTS: Of the 151 patients with complete data, 52 (34% had ≥ 1 complete bridge, 49 (33% had ≥ 1 syndesmophyte (non-bridging, and 50 (33% had no syndesmophytes. 66 (44% had low BMD. Patients with bridging had significantly higher sCTX and PINP Z-scores than patients without bridging (0.43 vs. -0.55 and 0.55 vs. 0.04, respectively. Patients with low BMD had significantly higher sCTX Z-score than patients with normal BMD (-0.08 vs. -0.61. After correcting for gender, symptom duration, and CRP, sCTX Z-score remained significantly related to the presence of low BMD alone (OR: 1.60, bridging alone (OR: 1.82, and bridging in combination with low BMD (OR: 2.26. CONCLUSIONS: This cross-sectional study in AS patients with active and relatively long-standing disease demonstrated that higher serum levels of sCTX, and to a lesser extent PINP, are associated with the presence of complete bridging. sCTX was also associated with low BMD. Longitudinal studies are needed to confirm that serum levels of s

  19. A "bone marrow score" for predicting hematological disease in immunocompetent patients with fevers of unknown origin.

    Science.gov (United States)

    Wang, Hao-Yuan; Yang, Ching-Fen; Chiou, Tzeon-Jye; Yang, Sheng-Hsiang; Gau, Jyh-Pyng; Yu, Yuan-Bin; Liu, Chun-Yu; Liu, Jin-Hwang; Chen, Po-Min; Hsu, Hui-Chi; Fung, Chang-Phone; Tzeng, Cheng-Hwai; Hsiao, Liang-Tsai

    2014-12-01

    Delayed diagnosis of hematological malignancies in immunocompetent patients with fever of unknown origin (FUO) remains an exhausting challenge for non-hematologist physicians. This retrospective cohort study aimed to establish a scoring system, "bone marrow (BM) score", to identify FUO patients who require early bone marrow biopsy (BMB) to diagnose hematological disease. Two cohorts, comprising 85 (training) and 20 (validation) eligible immunocompetent patients, with FUOs diagnosed between January 1, 2006 and July 31, 2013, underwent BMBs and were enrolled in the study. Demographic, laboratory, imaging, diagnostic, and outcome data were collected and retrospectively analyzed. Factors associated with hematological etiologies diagnosed using BMBs in the training cohort were identified and scored according to the relative hazards. These were further validated using the validation cohort. For the training cohort, 29 of 85 (34.1%) patients had hematological etiologies diagnosed using BMB. Seven factors significantly predicted the diagnostic yield of hematological diseases in the BM and were scored, with the 6 points for leucoerythroblastic changes in peripheral blood smears, 5.5 for elevated ferritin level (>1000 ng/mL), 4 for splenomegaly, 2 for thrombocytopenia, 1.5 for each of elevated lactate dehydrogenase levels and anemia, and 1 for neutropenia. When the cut-off value of the scoring system was set to 6, its sensitivity and specificity to diagnose hematological diseases in the BM of immunocompetent FUO patients were 93% and 58%, respectively. For the validation cohort, 7 of 20 (35%) patients had hematological disease, and all had BM scores higher than the cut-off, with the sensitivity and specificity at 100% and 77%, respectively. As immunocompetent FUO patients with hematological disease have poor prognoses, the "BM score" is valuable for non-hematologist physicians to identify immunocompetent FUO patients requiring early BMB.

  20. Gene expression profile in osteoclasts from patients with Paget's disease of bone.

    Science.gov (United States)

    Michou, Laetitia; Chamoux, Estelle; Couture, Julie; Morissette, Jean; Brown, Jacques P; Roux, Sophie

    2010-03-01

    Paget's disease of bone (PDB) is a common metabolic bone disorder with a significant genetic component. To date, only one gene associated with PDB has been identified, the p62-Sequestosome1 gene (SQSTM1), and more than 20 mutations of this gene have been reported in PDB, the most common being the P392L substitution. In order to search for differentially expressed genes in PDB, we investigated the relative gene expression profile of candidate genes in osteoclast (OCL) cultures from 12 PDB patients and six unmatched healthy controls with known genetic status regarding p62, including healthy carriers of the P392L mutation. We selected 48 OCL-expressed candidate genes that may be involved in relevant pathways of PDB pathogenesis, such as OCL signaling, survival, bone resorption activity, or adhesion. In OCL cultures derived from peripheral blood mononuclear cells, total RNA extraction was performed, followed by real-time PCR experiments. Relative quantification analysis utilized the qBase method where relative expression levels were normalized with respect to a set of reference primer pairs for three housekeeping genes. When compared to non-mutated healthy controls, OCL cultures from PDB patients displayed a significant down-regulation in genes involved in apoptosis (CASP3 and TNFRSF10A), in cell signaling (TNFRSF11A), in the OCL bone resorbing function (ACP5 and CTSK) and in the gene coding for Tau protein (MAPT) (all comparisons, pOCL, and highlight the role of altered apoptosis pathways in these cells. They also suggest that the SQSTM1 P392L mutation plays a role in PDB pathogenesis, even at early preclinical stages in healthy carriers of the P392L mutation.

  1. Mutant p62P392L stimulation of osteoclast differentiation in Paget's disease of bone.

    Science.gov (United States)

    Sundaram, Kumaran; Shanmugarajan, Srinivasan; Rao, D Sudhaker; Reddy, Sakamuri V

    2011-11-01

    Paget's disease of the bone (PDB) is an autosomal dominant trait with genetic heterogeneity, characterized by abnormal osteoclastogenesis. Sequestosome 1 (p62) is a scaffold protein that plays an important role in receptor activator of nuclear factor κB (RANK) signaling essential for osteoclast (OCL) differentiation. p62P392L mutation in the ubiquitin-associated (UBA) domain is widely associated with PDB; however, the mechanisms by which p62P392L stimulate OCL differentiation in PDB are not completely understood. Deubiquitinating enzyme cylindromatosis (CYLD) has been shown to negatively regulate RANK ligand-RANK signaling essential for OCL differentiation. Here, we report that CYLD binds with the p62 wild-type (p62WT), non-UBA mutant (p62A381V) but not with the UBA mutant (p62P392L) in OCL progenitor cells. Also, p62P392L induces expression of c-Fos (2.8-fold) and nuclear factor of activated T cells c1 (6.0-fold) transcription factors critical for OCL differentiation. Furthermore, p62P392L expression results in accumulation of polyubiquitinated TNF receptor-associated factor (TRAF)6 and elevated levels of phospho-IκB during OCL differentiation. Retroviral transduction of p62P392L/CYLD short hairpin RNA significantly increased TRAP positive multinucleated OCL formation/bone resorption activity in mouse bone marrow cultures. Thus, the p62P392L mutation abolished CYLD interaction and enhanced OCL development/bone resorption activity in PDB.

  2. Magnetic resonance imaging of bone marrow changes in Gaucher disease during enzyme replacement therapy: first German long-term results

    Energy Technology Data Exchange (ETDEWEB)

    Poll, L.W.; Koch, J.A.; Scherer, A.; Boerner, D.; Moedder, U. [Duesseldorf Univ. (Germany). Inst. fuer Diagnostische Radiologie; Dahl, S. vom; Niederau, C.; Haeussinger, D. [Duesseldorf Univ. (Germany). Medizinische Fakultaet; Willers, R. [Duesseldorf Univ. (Germany). Rechenzentrum

    2001-09-01

    Objective:. Since 1991, enzyme replacement therapy (ERT) has been available for patients with Gaucher disease in Germany. The aim of this study was to analyse the MR pattern of bone marrow involvement and response to ERT in Gaucher disease type I. Patients and design:. Thirty patients with Gaucher disease type I had MRI examinations prior to initiation of ERT with alglucerase/imiglucerase and during follow-up. Median MR follow-up and duration of ERT were 36 months. Coronal T1- and T2-weighted spin-echo images of the lower extremities were obtained to evaluate changes in the appearance of yellow marrow. MR images were categorized as having either a homogeneous (type A) or non-homogeneous patchy (type B) appearance of bone involvement and response to ERT was assessed by two radiologists. Results:. Overall, 19 of 30 patients (63%) showed an increased signal intensity on T1- and T2-weighted images after 36 months of ERT, consistent with partial reconversion of fatty marrow during treatment. Focal bone lesions surrounded by a low signal intensity (SI) rim did not respond to ERT, suggesting bone infarcts. Of the 11 patients with bone infarcts (low SI rim lesion), 82% had the non-homogeneous type B pattern (P=0.0021). In 86% of patients with splenectomy, bone infarcts were seen (P<0.05). Conclusions:. MRI using T1- and T2-weighted spin-echo sequences is a valuable, non-invasive method for monitoring bone marrow response in patients receiving ERT. A non- homogeneous patchy signal intensity of bone marrow involvement correlates with the presence of bone infarcts (P=0.0021). (orig.)

  3. The Impact of Conventional and Biological Disease Modifying Antirheumatic Drugs on Bone Biology. Rheumatoid Arthritis as a Case Study.

    Science.gov (United States)

    Barreira, Sofia Carvalho; Fonseca, João Eurico

    2016-08-01

    The bone and the immune system have a very tight interaction. Systemic immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA), induce bone loss, leading to a twofold increase in osteoporosis and an increase of fragility fracture risk of 1.35-2.13 times. This review focuses on the effects of conventional and biological disease modifying antirheumatic drugs (DMARDs) on bone biology, in the context of systemic inflammation, with a focus on RA. Published evidence supports a decrease in osteoclastic activity induced by DMARDs, which leads to positive effects on bone mineral density (BMD). It is unknown if this effect could be translated into fracture risk reduction. The combination with antiosteoclastic drugs can have an additional benefit.

  4. Factors that affect postnatal bone growth retardation in the twitcher murine model of Krabbe disease

    Science.gov (United States)

    Contreras, Miguel Agustin; Ries, William Louis; Shanmugarajan, Srinivasan; Arboleda, Gonzalo; Singh, Inderjit; Singh, Avtar Kaur

    2010-01-01

    Krabbe disease is an inherited lysosomal disorder in which galactosylsphingosine (psychosine) accumulates mainly in the central nervous system. To gain insight into the possible mechanism(s) that may be participating in the inhibition of the postnatal somatic growth described in the animal model of this disease (twitcher mouse, twi), we studied their femora. This study reports that twi femora are smaller than of those of wild type (wt), and present with abnormality of marrow cellularity, bone deposition (osteoblastic function), and osteoclastic activity. Furthermore, lipidomic analysis indicates altered sphingolipid homeostasis, but without significant changes in the levels of sphingolipid-derived intermediates of cell death (ceramide) or the levels of the osteoclast-osteoblast coupling factor (sphingosine-1-phosphate). However, there was significant accumulation of psychosine in the femora of adult twi animals as compared to wt, without induction of tumor necrosis factor-alpha or interleukin-6. Analysis of insulin-like growth factor-1 (IGF-1) plasma levels, a liver secreted hormone known to play a role in bone growth, indicated a drastic reduction in twi animals when compared to wt. To identify the cause of the decrease, we examined the IGF-1 mRNA expression and protein levels in the liver. The results indicated a significant reduction of IGF-1 mRNA as well as protein levels in the liver from twi as compared to wt littermates. Our data suggest that a combination of endogenous (psychosine) and endocrine (IGF-1) factors play a role in the inhibition of postnatal bone growth in twi mice; and further suggest that derangements of liver function may be contributing, at least in part, to this alteration. PMID:20441793

  5. Expression and significance of IL-18 in the bone marrow of patients with hema tological diseases

    Institute of Scientific and Technical Information of China (English)

    张斌; 饶青; 郑国光; 曹震宇; 马小彤; 李戈; 林永敏; 耿以琪; 吴克复

    2003-01-01

    Objective To investigate the levels of IL-18 in the bone marrow of both normal subjects a nd patients with hematological diseases and to determine the possible significan ce of IL-18 in pathogenesis of some hematological malignancies. Methods The IL-18 mRNA levels in the bone marrow of 140 patients with hematological dis eases and 15 normal donors were determined by the semi-quantitative reverse tra nscriptase polymerase chain reaction (RT-PCR). Immunohistochemical method was used to detect IL-18 protein in 12 patients with acute myeloid leukemia (AML). The possible regulation of IL-18 for proliferation of some leukemia cells was investigated using antisense techniques.Results IL-18 mRNA levels were obviously higher in the patients with leukemia or other malignant hematological diseases (OMHD) than in normal donors. However, no sign ificant difference was found in the level of transcription between patients with iron deficiency anemia (IDA) and normal controls. Immunohistochemical method c onfirmed the presence of IL-18 protein in 10 out of 12 AML cases with positive transcription. By 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium b romide (MTT) assay, IL-18 antisense oligodeoxynucleotides (ASON) clearly inhibi ted the growth of J6-1 and HL-60 cells (42% and 12% inhibited, respectively) i n a dose-dependant manner.Conclusions IL-18 was detected at elevated levels in the bone marrow of patients with some hematological malignancies, and might be involved in the proliferation of certai n leukemic cells in vivo through an autocrine mechanism.

  6. Interleukin-1 gene polymorphism disease activity and bone mineral metabolism in rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective To determine whether interleukin-1α and 1β gene polymorphism is associated with rheumatoid arthritis disease activity and bone mineral metabolism, and whether there is any relationship between IL-1β and rheumatoid arthritis (RA) motif gene. Methods IL-1 gene polymorphisms were analyzed in 65 RA patients who met American College of Radiology (ACR) criteria and 60 controls. From genomic DNA, 2 polymorphisms in each gene for IL1α-889 and IL-1β+3953 were typed by PCR-RFLP and HLA-DRB1 allele typing was also undertaken by PCR-SSOP. Some clinical and laboratory parameters were collected. The allelic frequencies and carriage rates were compared between RA patients and controls and between patients with active and quiescent disease. Comparison was also made between IL-1 polymorphism and parameters of bone mineral metabolism and between patients with the HLA-DRB1 RA motif plus IL-1β2 and patients without the two alleles. Fisher test and the analysis of variance was used to analyze the data.Results There was no significant difference in the frequency and carriage rate of IL-1α polymorphisms between RA patients and the controls. The β2/2 genotype of IL-1β was more common in female RA patients compared with controls (P=0.001). A lower carriage rate of IL-1β2 occurred in male RA patients (P=0.001). A higher carriage rate of IL-1α2 is associated with a higher ESR (P=0.008), HAQ score (P=0.03), and vit-D3 (P<0.001), but conversely a lower SJC (p=0.002), a lower RF (P=0.002) and a lower BMD at the lumbar spine (P=0.001). A higher frequency of IL-1α1 is associated with a lower CRP value (P=0.009). An increased IL-1β2 carriage is associated with active rheumatoid disease as indicated by a higher CRP (P<0.001), ESR (P<0.001) and pain score (P=0.001) and a higher BMD at the lumbar spine (P=0.007), lower vit-D3 and. Udpd/Crea level The presence of the HLA DRB1 RA motif and IL-1β allele 2 at same time did not contribute to disease activity

  7. Laronidase for cardiopulmonary disease in Hurler syndrome 12 years after bone marrow transplantation.

    Science.gov (United States)

    Valayannopoulos, Vassili; de Blic, Jacques; Mahlaoui, Nizar; Stos, Bertrand; Jaubert, Francis; Bonnet, Damien; Fischer, Alain; de Lonlay, Pascale

    2010-11-01

    A patient with severe mucopolysaccharidosis type I (Hurler syndrome) underwent bone marrow transplantation twice (at the ages of 2 and 2.5 years), both times with his HLA-identical heterozygous brother as the donor. Between the ages of 10 and 14 years, despite 92% donor engraftment and 50% normal α-L-iduronidase activity, he developed progressive respiratory failure with severe pulmonary arterial hypertension, upper airway obstruction, and interstitial lung disease. Noninvasive ventilation and weekly laronidase therapy were initiated. Within 24 months, his mean pulmonary artery pressure was within the upper limit of normal and interstitial lung disease and airway obstruction improved markedly. He went from using a wheelchair to having full ambulation, he no longer required daytime ventilation, and his quality-of-life scores (Child Health Assessment Questionnaire) significantly improved.

  8. THE DIFFERENCES OF BONE METABOLISM IN MALES WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND POSTMENOPAUSAL FEMALES

    Directory of Open Access Journals (Sweden)

    O. A. Mardanova

    2014-07-01

    Full Text Available Aim — to compare bone metabolism activity in males with chronic obstructive pulmonary disease (COPD and postmenopausal females.Materials and methods. The prospective cohort study was conducted. 33 male patients with COPD over 55 years old and 33 female patients without respiratory diseases over 55 were included. General examination, clinical and biochemical blood analyses, densitometry of lumbar spine and proximal part of left femoral bone, respiratory function, osteocalcin and C-telopeptids blood levels have been performed to the patients.Results. Male patients with COPD had lower T-score for the femoral neck than postmenopausal female patients without pulmonary disorders,(–1.05 ± 0.85 SD and –0.36 ± 1.24 SD respectively, р < 0.05. Osteocalcin level in males with COPD was significantly higher and C‑telopeptids level was significantly lower than in postmenopausal females (р < 0.05.Conclusion. Male patients with COPD have lower T‑score for the femoral neck than postmenopausal females without pulmonary disorders of the same age. Furthermore osteoclasts in COPD patients seem to be more activated than in postmenopausal females, on the contrary osteoblasts activity is significantly depressed. Therefore it is necessary to use another approach of prevention and treatment of osteoporosis in patients with COPD.

  9. β-Glucans (Saccharomyces cereviseae) Reduce Glucose Levels and Attenuate Alveolar Bone Loss in Diabetic Rats with Periodontal Disease.

    Science.gov (United States)

    Silva, Viviam de Oliveira; Lobato, Raquel Vieira; Andrade, Eric Francelino; de Macedo, Cristina Gomes; Napimoga, Juliana Trindade Clemente; Napimoga, Marcelo Henrique; Messora, Michel Reis; Murata, Ramiro Mendonça; Pereira, Luciano José

    2015-01-01

    The objective of this study was to assess the effects of oral ingestion of β-glucans isolated from Saccharomyces cereviseae on the metabolic profile, expression of gingival inflammatory markers and amount of alveolar bone loss in diabetic rats with periodontal disease. Diabetes mellitus was induced in 48 Wistar rats by intraperitoneal injection of streptozotocin (80 mg/kg). After confirming the diabetes diagnosis, the animals were treated with β-glucans (by gavage) for 28 days. On the 14th day of this period, periodontal disease was induced using a ligature protocol. β-glucans reduced the amount of alveolar bone loss in animals with periodontal disease in both the diabetic and non-diabetic groups (p periodontal disease (p periodontal disease (p periodontal effects in diabetic rats with periodontal disease.

  10. Hepatocyte growth factor pathway upregulation in the bone marrow microenvironment in multiple myeloma is associated with lytic bone disease

    DEFF Research Database (Denmark)

    Kristensen, Ida B; Christensen, Jacob H; Lyng, Maria Bibi;

    2013-01-01

    using bone marrow biopsies (BMBs) of patients with MM and monoclonal gammopathy of undetermined significance (MGUS), and healthy volunteers (HV). BMBs (N = 110) obtained at diagnosis were snap-frozen and used to evaluate gene expression by quantitative reverse transcription polymerase chain reaction....... LBD was evaluated using standard radiographs. Enzyme-linked immunosorbent assay (ELISA) was performed on matched bone marrow plasma and immunohistochemistry on matched formalin-fixed paraffin-embedded biopsies. Gene expression of HGF, SDC1, and MET in BMBs were significantly altered in MM versus HV...

  11. Novel Lesions of Bones and Joints Associated with Chikungunya Virus Infection in Two Mouse Models of Disease: New Insights into Disease Pathogenesis.

    Directory of Open Access Journals (Sweden)

    Brad A Goupil

    Full Text Available Chikungunya virus is an arbovirus spread predominantly by Aedes aegypti and Ae. albopictus mosquitoes, and causes debilitating arthralgia and arthritis. While these are common manifestations during acute infection and it has been suggested they can recur in patients chronically, gaps in knowledge regarding the pathogenesis still exist. Two established mouse models were utilized (adult IRF 3/7 -/- -/- and wild-type C57BL/6J mice to evaluate disease manifestations in bones and joints at various timepoints. Novel lesions in C57BL/6J mice consisted of periostitis (91% and foci of cartilage of necrosis (50% of mice at 21 DPI. Additionally, at 21 DPI, 50% and 75% of mice exhibited periosteal bone proliferation affecting the metatarsal bones, apparent via histology and μCT, respectively. μCT analysis did not reveal any alterations in trabecular bone volume measurements in C57BL/6J mice. Novel lesions demonstrated in IRF 3/7 -/- -/- mice at 5 DPI included focal regions of cartilage necrosis (20%, periosteal necrosis (66%, and multifocal ischemic bone marrow necrosis (100%. Contralateral feet in 100% of mice of both strains had similar, though milder lesions. Additionally, comparison of control IRF 3/7 -/- -/- and wild-type C57BL/6J mice demonstrated differences in cortical bone. These experiments demonstrate novel manifestations of disease similar to those occurring in humans, adding insight into disease pathogenesis, and representing new potential targets for therapeutic interventions. Additionally, results demonstrate the utility of μCT in studies of bone and joint pathology and illustrate differences in bone dynamics between mouse strains.

  12. Novel Lesions of Bones and Joints Associated with Chikungunya Virus Infection in Two Mouse Models of Disease: New Insights into Disease Pathogenesis

    Science.gov (United States)

    Goupil, Brad A.; McNulty, Margaret A.; Martin, Matthew J.; McCracken, Michael K.; Christofferson, Rebecca C.; Mores, Christopher N.

    2016-01-01

    Chikungunya virus is an arbovirus spread predominantly by Aedes aegypti and Ae. albopictus mosquitoes, and causes debilitating arthralgia and arthritis. While these are common manifestations during acute infection and it has been suggested they can recur in patients chronically, gaps in knowledge regarding the pathogenesis still exist. Two established mouse models were utilized (adult IRF 3/7 -/- -/- and wild-type C57BL/6J mice) to evaluate disease manifestations in bones and joints at various timepoints. Novel lesions in C57BL/6J mice consisted of periostitis (91%) and foci of cartilage of necrosis (50% of mice at 21 DPI). Additionally, at 21 DPI, 50% and 75% of mice exhibited periosteal bone proliferation affecting the metatarsal bones, apparent via histology and μCT, respectively. μCT analysis did not reveal any alterations in trabecular bone volume measurements in C57BL/6J mice. Novel lesions demonstrated in IRF 3/7 -/- -/- mice at 5 DPI included focal regions of cartilage necrosis (20%), periosteal necrosis (66%), and multifocal ischemic bone marrow necrosis (100%). Contralateral feet in 100% of mice of both strains had similar, though milder lesions. Additionally, comparison of control IRF 3/7 -/- -/- and wild-type C57BL/6J mice demonstrated differences in cortical bone. These experiments demonstrate novel manifestations of disease similar to those occurring in humans, adding insight into disease pathogenesis, and representing new potential targets for therapeutic interventions. Additionally, results demonstrate the utility of μCT in studies of bone and joint pathology and illustrate differences in bone dynamics between mouse strains. PMID:27182740

  13. A 3-D analysis of the protympanum in human temporal bones with chronic ear disease.

    Science.gov (United States)

    Pauna, Henrique F; Monsanto, Rafael C; Schachern, Patricia; Paparella, Michael M; Cureoglu, Sebahattin

    2017-03-01

    Eustachian tube dysfunction is believed to be an important factor to cholesteatoma development and recurrence of disease after surgical treatment. Although many studies have described prognostic factors, evaluation methods, or surgical techniques for Eustachian tube dysfunction, they relied on the soft tissues of its structure; little is known about its bony structure-the protympanum-which connects the Eustachian tube to the tympanic cavity, and can also be affected by several inflammatory conditions, both from the middle ear or from the nasopharynx. We studied temporal bones from patients with cholesteatoma, chronic otitis media (with and without retraction pockets), purulent otitis media, and non-diseased ears, looking for differences between the volume of the protympanum, the diameter of the Eustachian tube isthmus, and the distance between the anterior tympanic annulus and the promontory. Light microscopy and 3-D reconstruction software were used for the measurements. We observed a decrease of volume in the lumen of the four middle ear diseased ears compared to the control group. We observed a significant decrease in the volume of the protympanic space in the cholesteatoma group compared to the chronic otitis media group. We also observed a decrease in the bony space (protympanum space) in cholesteatoma, chronic otitis media with retraction pockets, and purulent otitis media compared to the control group. We found a correlation in middle ear diseases and a decrease in the middle ear space. Our findings may suggest that a smaller bony volume in the protympanic area may trigger middle ear dysventilation problems.

  14. Multiscale Modeling of Bone

    Science.gov (United States)

    2014-12-01

    DISEASE Both age and disease can affect the structure of bone, the effects of which are often similar. The most common bone disease is osteoporosis ... Osteoporosis is a disease that results in reduced bone mass and density. This reduction of bone mass and density has a greater impact on trabecular...Bone loss in females is linked to a decrease in estrogen ; the decrease of estrogen associated with menopause increases osteoclast activity [89]. This

  15. From "Kidneys Govern Bones" to Chronic Kidney Disease, Diabetes Mellitus, and Metabolic Bone Disorder: A Crosstalk between Traditional Chinese Medicine and Modern Science.

    Science.gov (United States)

    Wang, Xiao-Qin; Zou, Xin-Rong; Zhang, Yuan Clare

    2016-01-01

    Although traditional Chinese medicine (TCM) and Western medicine have evolved on distinct philosophical foundations and reasoning methods, an increasing body of scientific data has begun to reveal commonalities. Emerging scientific evidence has confirmed the validity and identified the molecular mechanisms of many ancient TCM theories. One example is the concept of "Kidneys Govern Bones." Here we discuss the molecular mechanisms supporting this theory and its potential significance in treating complications of chronic kidney disease (CKD) and diabetes mellitus. Two signaling pathways essential for calcium-phosphate metabolism can mediate the effect of kidneys in bone homeostasis, one requiring renal production of bioactive vitamin D and the other involving an endocrine axis based on kidney-expressed Klotho and bone-secreted fibroblast growth factor 23. Disruption of either pathway can lead to calcium-phosphate imbalance and vascular calcification, accelerating metabolic bone disorder. Chinese herbal medicine is an adjunct therapy widely used for treating CKD and diabetes. Our results demonstrate the therapeutic effects and underlying mechanisms of a Chinese herbal formulation, Shen-An extracts, in diabetic nephropathy and renal osteodystrophy. We believe that the smart combination of Eastern and Western concepts holds great promise for inspiring new ideas and therapies for preventing and treating complications of CKD and diabetes.

  16. Radiographic evaluation of the effect of obesity on alveolar bone in rats with ligature-induced periodontal disease.

    Science.gov (United States)

    do Nascimento, Cassiane Merigo; Cassol, Tiago; da Silva, Fernanda Soares; Bonfleur, Maria Lucia; Nassar, Carlos Augusto; Nassar, Patricia Oehlmeyer

    2013-01-01

    There is evidence that the lack of metabolic control of obese patients may accelerate periodontitis. The aim of this study was to evaluate radiographically the effect of cafeteria-diet-induced obesity on alveolar bone loss in rats subjected to periodontal disease. Twenty male Wistar rats were randomly divided into four groups: 1) control group, 2) control and ligature group; 3) cafeteria group; and 4) cafeteria and ligature group. The animals were evaluated for obesity and euthanized, and the mandible of each rat was removed to perform a radiographic evaluation of alveolar bone loss and its effect on diet-induced obesity. The results showed greater alveolar bone loss in the mice in Group 4 (P<0.01). Thus, we concluded that obese mice, on average, showed greater radiographic evidence of alveolar bone loss than mice undergoing induction of obesity.

  17. Eradication of bone marrow minimal residual disease may prompt early treatment discontinuation in CLL.

    Science.gov (United States)

    Strati, Paolo; Keating, Michael J; O'Brien, Susan M; Burger, Jan; Ferrajoli, Alessandra; Jain, Nitin; Tambaro, Francesco Paolo; Estrov, Zeev; Jorgensen, Jeffrey; Challagundla, Pramoda; Faderl, Stefan H; Wierda, William G

    2014-06-12

    The high complete remission rate with first-line combined fludarabine, cyclophosphamide, and rituximab (FCR) begs the question of the value of minimal residual disease (MRD)-negative status as a treatment end point. We report on 237 patients with chronic lymphocytic leukemia who received first-line FCR. MRD was prospectively assessed by 4-color flow cytometry in bone marrow after course 3 and at final response assessment. After course 3 and at final response assessment, 17% and 43% of patients were MRD negative in bone marrow, respectively. A mutated immunoglobulin heavy chain variable gene and trisomy 12 were independently associated with MRD-negative status both after 3 courses of FCR and at final response assessment in multivariable analyses (MVAs). MRD-negative status was independently associated with significantly longer progression-free survival (PFS) and overall survival (OS) in MVA (P = .03 and .02, respectively). This association was confirmed also on landmark MVA at the time of MRD assessment (P = .04 and .05, respectively). MRD-negative patients had comparable PFS and OS, independent of the number of courses received or interim staging. Early MRD eradication may be a desirable goal, prompting consideration of early discontinuation of treatment. This trial was registered at www.clinicaltrials.gov as #NCT00759798.

  18. Object analysis of bone marrow MR imaging using double echo STIR sequence in hematological diseases

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    Mizuno, Hitomi [Saitama Medical School, Moroyama (Japan)

    1995-07-01

    The bone marrow of 84 patients with hematological disorders was investigated using short inversion time inversion recovery sequence (STIR) on an 1.5 Tesla superconducting MRI system. Double echo times of 20 and 100 msec were applied to research the signal characteristics of the lesion and carry out quantitative analysis of the receiver operating characteristic curve (ROC). The hematological diseases included 19 cases of myelodysplastic syndrome (MDS), 18 of multiple myeloma (MM), 18 of chronic myelocytic leukemia (CML), 9 of aplastic anemia (AA), 8 of acute myelocytic leukemia (AML), 3 of chronic lymphocytic leukemia (CLL), 3 of myelofibrosis, and 3 others. Using STIR with double echo times, bone marrow showed high signal intensity (SI) on short TE and low SI on long TE in MDS and CML; high SI on short and long TE in myelofibrosis and CLL; high SI on short TE and high to moderately high SI on long TE in MM; and low SI on short and long TE in AA. Quantitative analysis of 33 patients showed high sensitivity and specificity in AA (81% and 94%, respectively) and moderate sensitivity and high specificity in MM (61%, 88%). CML and MDS were similar with low sensitivities (40%, 41%) and high specificities (80%, 78%). Differential diagnosis between CML and MDS was difficult using STIR with the double echo time method. (author).

  19. The Effect of Glucocorticoids on Bone Mass in Patients with Asthma and Chronic obstructive Pulmonary Disease

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    Evrim Karadağ Saygı

    2005-06-01

    Full Text Available Inhaled corticosteroids and bronchodilators have become a key element in the maintenance treatment of bronchial asthma and chronic obstructive pulmanory disease (COPD. It is well known that long-term systemic steroid use causes osteoporosis, whereas inhaled corticosteroids and bronchodilators have been discussed to be cause of such side-affect. The aim of this study was to detect the effect of long term inhaled/oral steroids and bronchodilators on bone mineral density (BMD with asthma and COPD. Fifty-three patients with bronchial asthma (n=44 and COPD (n=9 were enrolled in this study. BMD were measured and risk factors for osteoporosis were detected. BMD measurements of lumbar area of the spine (L2-4, neck of femur and femoral ward’s triangle zone were performed by the dual energy x-ray absorptiometer (LUNAR. 53 patients evaluated in three groups according to treatment type; 26 patients were using inhaled corticosteroids and bronchodilators (group 1, 18 patients were using only bronchodilators (group 2 and 9 patients were using (group 3 oral corticosteroids and bronchodilators. There were significant differences between group 3 and other two groups in terms of BMD, T and Z scores of the lumbar and femoral neck (p0.05. As a result, we suggest that systemic corticosteroids negatively affect bone mineral density more than inhaled corticosteroids in patients with COPD.

  20. Molecular Imaging of Bone Marrow Mononuclear Cell Survival and Homing in Murine Peripheral Artery Disease

    Science.gov (United States)

    van der Bogt, Koen E.A.; Hellingman, Alwine A.; Lijkwan, Maarten A.; Bos, Ernst-Jan; de Vries, Margreet R.; Fischbein, Michael P.; Quax, Paul H.; Robbins, Robert C.; Hamming, Jaap F.; Wu, Joseph C.

    2013-01-01

    Introduction Bone marrow mononuclear cell (MNC) therapy is a promising treatment for peripheral artery disease (PAD). This study aims to provide insight into cellular kinetics using molecular imaging following different transplantation methods. Methods and Results MNCs were isolated from F6 transgenic mice (FVB background) that express firefly luciferase (Fluc) and green fluorescence protein (GFP). Male FVB and C57Bl6 mice (n=50) underwent femoral artery ligation and were randomized into 4 groups receiving: (1) single intramuscular (i.m.) injection of 2×106 MNC; (2) four weekly i.m. injections of 5×105 MNC; (3) 2×106 MNCs intravenously (i.v.); and (4) PBS. Cellular kinetics, measured by in vivo bioluminescence imaging (BLI), revealed near-complete donor cell death 4 weeks after i.m. transplantation. Following i.v. transplantation, BLI monitored cells homed in on the injured area in the limb, as well as to the liver, spleen, and bone marrow. Ex vivo BLI showed presence of MNCs in the scar tissue and adductor muscle. However, no significant effects on neovascularisation were observed as monitored by Laser-Doppler-Perfusion-Imaging and histology. Conclusion This is one of the first studies to assess kinetics of transplanted MNCs in PAD using in vivo molecular imaging. MNC survival is short lived and MNCs do not significantly stimulate perfusion in this model. PMID:22239892

  1. Comparison of two methods for alveolar bone loss measurement in an experimental periodontal disease model in rats

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    Diego Nique Liberman

    2011-02-01

    Full Text Available There are many studies that evaluate possible risk factors for periodontal diseases in animals. Most of them have focused only on the biological aspects of disease occurrence; therefore, it has been difficult to compare studies of the different methodological approaches. The aim of the present study was to compare different methods - linear and area - of the evaluation of morphometrical alveolar bone loss. Sixty hemimaxillae, defleshed and stained with 1% methylene blue to delineate the cementoenamel junction and alveolar bone crest, were obtained from a previous study that induced periodontal disease by means of ligatures in two groups of fifteen Wistar rats during 9 weeks. Ligatures were placed around the right upper second molars, and the contra-lateral teeth remained as intra-group controls. Digital photographs were taken from the specimens and submitted to a single, calibrated, blind examiner who performed the morphometrical evaluation of alveolar bone loss using both linear and area methods. Mean values of linear and area measurements were obtained from each side - buccal and palatal - of the specimens. The degree of association between the two methods was determined by Pearson's Correlation Coefficient. An almost perfect association (0.98 was determined between the linear and area evaluations. A mathematical formula was subsequently created to estimate the total area of alveolar bone loss, from linear mean measurements. Both methods were suitable for detecting bone level alterations. The results of the present study allow for the transformation of data and better compilation of results from different studies.

  2. Combined scintigraphic and radiographic diagnosis of bone and joint diseases. Including gamma correction interpretation. 4. rev. and enl. ed.

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    Bahk, Yong-Whee [Sung Ae General Hospital, Seoul (Korea, Republic of). Dept. of Nuclear Medicine and Radiology

    2013-07-01

    In this fourth edition of Combined Scintigraphic and Radiographic Diagnosis of Bone and Joint Diseases, the text has been thoroughly amended, updated, and partially rearranged to reflect the latest advances. In addition to discussing the role of pinhole imaging in the range of disorders previously covered, the new edition pays detailed attention to the novel diagnostic use of gamma correction pinhole bone scan in a broad spectrum of skeletal disorders, including physical, traumatic, and sports injuries, infectious and non-infectious bone diseases, benign and malignant bone tumors, and soft tissue diseases. A large number of state of the art pinhole scans and corroborative CT, MRI, and/or ultrasound images are presented side by side. The book has been enlarged to encompass various new topics, including occult fractures; cervical sprain and whiplash trauma; bone marrow edema; microfractures of trabeculae; evident, gaping, and stress fractures; and differential diagnosis. This new edition will be essential reading for practitioners and researchers in not only nuclear medicine but also radiology, orthopedic surgery, and pathology.

  3. The negative bone effects of the disease and of chronic corticosteroid treatment in premenopausal women affected by rheumatoid arthritis

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    A. Fassio

    2016-09-01

    Full Text Available Osteoporosis is a well-known extra-articular complication in rheumatoid arthritis (RA. The chronic corticosteroid treatment, the functional impairment associated with RA and the disease itself appear to be the most relevant determinants. Most of the previous studies involved postmenopausal women, in whom the estrogenic deficiency might amplify the negative effect towards bone of both RA and corticosteroid therapy. We decided to evaluate bone health in a cohort of premenopausal RA patients. The study population includes 47 premenopausal women attending our outpatient clinic for RA and twice as many healthy age-matched control women selected from the hospital personnel. The bone density at the spine and femoral neck were significantly lower in patients with RA as compared with controls. When spine bone mineral density (BMD values were adjusted for the cumulative glucocorticoid (GC dose alone and for the cumulative GC dose plus body mass index (BMI the mean differences between two groups decreased but they remained statistically significant. We found no difference when the spine BMD was adjusted for cumulative GC dose, BMI and health assessment questionnaire. The difference in femoral neck BMD remained statistically significant also after all the same adjustments. In conclusion, our study shows that a BMD deficiency is frequent also in premenopausal women affected by RA, especially at femoral site and that the main determinants of this bone loss are not only the disease-related weight loss, corticosteroid therapy and functional impairment, but also the systemic effects of the disease itself.

  4. Subtle changes in bone mineralization density distribution in most severely affected patients with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Misof, B M; Roschger, P; Jorgetti, V; Klaushofer, K; Borba, V Z C; Boguszewski, C L; Cohen, A; Shane, E; Zhou, H; Dempster, D W; Moreira, C A

    2015-10-01

    Chronic obstructive pulmonary disease (COPD) is associated with low aBMD as measured by DXA and altered microstructure as assessed by bone histomorphometry and microcomputed tomography. Knowledge of bone matrix mineralization is lacking in COPD. Using quantitative backscatter electron imaging (qBEI), we assessed cancellous (Cn.) and cortical (Ct.) bone mineralization density distribution (BMDD) in 19 postmenopausal women (62.1 ± 7.3 years of age) with COPD. Eight had sustained fragility fractures, and 13 had received treatment with inhaled glucocorticoids. The BMDD outcomes from the patients were compared with healthy reference data and were correlated with previous clinical and histomorphometric findings. In general, the BMDD outcomes for the patients were not significantly different from the reference data. Neither the subgroups of with or without fragility fractures or of who did or did not receive inhaled glucocorticoid treatment, showed differences in BMDD. However, subgroup comparison according to severity revealed 10% decreased cancellous mineralization heterogeneity (Cn.CaWidth) for the most severely affected compared with less affected patients (p=0.042) and compared with healthy premenopausal controls (p=0.021). BMDD parameters were highly correlated with histomorphometric cancellous bone volume (BV/TV) and formation indices: mean degree of mineralization (Cn.CaMean) versus BV/TV (r=0.58, p=0.009), and Cn.CaMean and Ct.CaMean versus bone formation rate (BFR/BS) (r=-0.71, p50th percentile) BV/TV. The normality in most of the BMDD parameters and bone formation rates as well as the significant correlations between them suggests unaffected mineralization processes in COPD. Our findings also indicate no significant negative effect of treatment with inhaled glucocorticoids on the bone mineralization pattern. However, the observed concomitant occurrence of relatively lower bone volumes with lower bone matrix mineralization will both contribute to the reduced a

  5. Osteoblast CFTR inactivation reduces differentiation and osteoprotegerin expression in a mouse model of cystic fibrosis-related bone disease.

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    Michael S Stalvey

    Full Text Available Low bone mass and increased fracture risk are recognized complications of cystic fibrosis (CF. CF-related bone disease (CFBD is characterized by uncoupled bone turnover--impaired osteoblastic bone formation and enhanced osteoclastic bone resorption. Intestinal malabsorption, vitamin D deficiency and inflammatory cytokines contribute to CFBD. However, epidemiological investigations and animal models also support a direct causal link between inactivation of skeletal cystic fibrosis transmembrane regulator (CFTR, the gene that when mutated causes CF, and CFBD. The objective of this study was to examine the direct actions of CFTR on bone. Expression analyses revealed that CFTR mRNA and protein were expressed in murine osteoblasts, but not in osteoclasts. Functional studies were then performed to investigate the direct actions of CFTR on osteoblasts using a CFTR knockout (Cftr-/- mouse model. In the murine calvarial organ culture assay, Cftr-/- calvariae displayed significantly less bone formation and osteoblast numbers than calvariae harvested from wildtype (Cftr+/+ littermates. CFTR inactivation also reduced alkaline phosphatase expression in cultured murine calvarial osteoblasts. Although CFTR was not expressed in murine osteoclasts, significantly more osteoclasts formed in Cftr-/- compared to Cftr+/+ bone marrow cultures. Indirect regulation of osteoclastogenesis by the osteoblast through RANK/RANKL/OPG signaling was next examined. Although no difference in receptor activator of NF-κB ligand (Rankl mRNA was detected, significantly less osteoprotegerin (Opg was expressed in Cftr-/- compared to Cftr+/+ osteoblasts. Together, the Rankl:Opg ratio was significantly higher in Cftr-/- murine calvarial osteoblasts contributing to a higher osteoclastogenesis potential. The combined findings of reduced osteoblast differentiation and lower Opg expression suggested a possible defect in canonical Wnt signaling. In fact, Wnt3a and PTH-stimulated canonical Wnt

  6. Clinical benefits of biochemical markers of bone turnover in Egyptian children with chronic liver diseases

    Institute of Scientific and Technical Information of China (English)

    Karam A Mahdy; Hanaa H Ahmed; Fathia Mannaa; Azza Abdel-Shaheed

    2007-01-01

    AIM: To investigate the association between serum insulin-like growth factor 1 (IGF-1), osteocalcin, and parathyroid hormone (PTH) levels with the etiology and clinical condition of patients with chronic liver disease.METHODS: Eighty children with hepatocellular damage were divided into 3 groups according to the etiology of disease infection: bilharziasis (9 patients), hepatitis B virus (HBV, 12 patients) and hepatitis C virus (HCV, 29 patients). The Child score index was found as A in 24 patients, B in 22 patients, C in 4 patients. Thirty healthy children served as control group. HBsAg, HBcAbIgM,HBcAbIgG, and anti-HCV were detected using ELISA technique. HCV-RNA was measured by reverse transcription polymerase chain reaction (RT-PCR). Antibilharzial antibodies were detected by indirect haemagglutination test. Liver function tests were performed using autoanalyser. Serum IGF-1, osteocalcin and PTH levels were measured by ELISA technique. Abdominal ultrasonography was also conducted.RESULTS: Serum IGF-1 level was significantly lower in all patient groups with liver diseases, while serum osteocalcin and PTH levels were significantly elevated in patients with HBV and HCV infections compared with the control group. Serum osteocalcin and PTH concentrations were measured with the severity of liver disease from Child A to C. Child A patients unexpectedly showed significantly reduced IGF-1 levels in comparison to patients staged as Child B or C. Serum osteocalcin level was negatively correlated with albumin (14.7 ± 0.54 vs 3.6± 0.10, P < 0.05), while that for PTH was positively correlated with total protein (70.1 ± 2.17 vs 6.7 + 0.10,P < 0.05) in patients with HCV infection.CONCLUSION: Low serum IGF-1 level seems to play a critical role in the bone loss in patients with chronic liver disease. Elevated biochemical markers of bone remodeling suggest high-turnover in patients with viral infection and reflect severity of the clinical stage.

  7. Graft-versus-Host Disease-Associated Vulvovaginal Symptoms after Bone Marrow Transplantation.

    Science.gov (United States)

    Chung, Christopher P; Sargent, Rachel E; Chung, Nadia T; Lacey, James V; Wakabayashi, Mark T

    2016-02-01

    We conducted a retrospective review to assess the prevalence of graft-versus-host disease (GVHD)-associated gynecologic conditions among bone marrow transplantation (BMT) patients at City of Hope Medical Center. We calculated the associations among the estimated risks of various gynecologic complications, including vaginal stenosis, by performing chi-square tests and t-test statistics. Between 2010 and 2014, 180 patients were referred to the gynecologic clinic after their BMT. One hundred twenty-four patients (69%) had GVHD; among these patients, 51 (41%) experienced dyspareunia and 43 (35%) had vaginal stenosis. GVHD patients were significantly more likely to have vaginal stenosis (P vulvovaginal symptoms, such as dyspareunia and pelvic pain. Patients with GVHD are at high risk for vaginal stenosis requiring the use of a vaginal dilator. However, they are at low risk for developing UI and POP.

  8. Role of RANKL-RANK/Osteoprotegerin Pathway in Cardiovascular and Bone Disease Associated with HIV Infection

    Science.gov (United States)

    Kelesidis, Theodoros; Currier, Judith S.; Yang, Otto O.; Brown, Todd T

    2016-01-01

    Patients with HIV-1 infection often develop multiple complications and comorbidities, including osteoporosis and atherosclerosis. The receptor activator of nuclear factor kappa-B/receptor activator of nuclear factor kappa-B ligand/osteoprotegerin axis has been identified as a possible common link between osteoporosis and vascular diseases. Since the discovery of this axis, much has been learned about its role in controlling skeletal biology and less about its role in the context of vascular biology. However, the exact role of the receptor activator of nuclear factor kappa-B ligand/osteoprotegerin axis in HIV infection is not completely understood. In this review we examine the mechanisms by which inflammation and immune dysregulation in HIV-1 infection may impact bone turnover and atherogenesis through perturbations in the receptor activator of nuclear factor kappa-B/receptor activator of nuclear factor kappa-B ligand/osteoprotegerin axis. PMID:25102334

  9. XBONE: a hybrid expert system for supporting diagnosis of bone diseases.

    Science.gov (United States)

    Hatzilygeroudis, I; Vassilakos, P J; Tsakalidis, A

    1997-01-01

    In this paper, XBONE, a hybrid medical expert system that supports diagnosis of bone diseases is presented. Diagnosis is based on various patient data and is performed in two stages. In the early stage, diagnosis is based on demographic and clinical data of the patient, whereas in the late stage it is mainly based on nuclear medicine image data. Knowledge is represented via an integrated formalism that combines production rules and the Adaline artificial neural unit. Each condition of a rule is assigned a number, called its significance factor, representing its significance in drawing the conclusion of the rule. This results in better representation, reduction of the knowledge base size and gives the system learning capabilities.

  10. Potential Roles of Bone Morphogenetic Protein (BMP-9 in Human Liver Diseases

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    Blanca Herrera

    2014-03-01

    Full Text Available Bone morphogenetic proteins (BMP-2 to BMP-15 belong to the Transforming Growth Factor (TGF-β superfamily and, besides their well-documented roles during embryogenesis and bone formation, some of them have recently been described to be involved in the pathogenesis of different organs, including the liver. The role of BMPs in liver damage responses including hepatocellular carcinoma (HCC development has only begun to be addressed and strong evidence supports the concept of a pro-tumorigenic role of BMP signaling in HCC cells. BMP-9 (also termed Growth and Differentiation Factor (GDF-2 represents the most recently discovered member of the BMP family. We have previously demonstrated that in HCC patient samples BMP-9 expression was positively associated with the tumor seize (“T stage” and that it enhanced cell migration and induced epithelial to mesenchymal transition (EMT in HCC cells in vitro. In another study we recently found that BMP-9 promotes growth in HCC cells, but not in non-transformed hepatocytes. Published as well as unpublished results obtained with primary hepatocytes support the concept of a dual function of BMP-9 in the liver: while in primary, non-malignant cells BMP-9 stabilizes the epithelial phenotype and inhibits proliferation, in HCC cells it induces cell growth and the acquisition of a migratory phenotype. In this review article we summarize current knowledge about BMPs in liver diseases, with special focus on the role of BMP-9 in HCC development and progression, that may provide new clues for a better understanding of the contribution of BMP-signaling to chronic liver diseases.

  11. Potential Roles of Bone Morphogenetic Protein (BMP)-9 in Human Liver Diseases

    Science.gov (United States)

    Herrera, Blanca; Dooley, Steven; Breitkopf-Heinlein, Katja

    2014-01-01

    Bone morphogenetic proteins (BMP-2 to BMP-15) belong to the Transforming Growth Factor (TGF)-β superfamily and, besides their well-documented roles during embryogenesis and bone formation, some of them have recently been described to be involved in the pathogenesis of different organs, including the liver. The role of BMPs in liver damage responses including hepatocellular carcinoma (HCC) development has only begun to be addressed and strong evidence supports the concept of a pro-tumorigenic role of BMP signaling in HCC cells. BMP-9 (also termed Growth and Differentiation Factor (GDF)-2) represents the most recently discovered member of the BMP family. We have previously demonstrated that in HCC patient samples BMP-9 expression was positively associated with the tumor seize (“T stage”) and that it enhanced cell migration and induced epithelial to mesenchymal transition (EMT) in HCC cells in vitro. In another study we recently found that BMP-9 promotes growth in HCC cells, but not in non-transformed hepatocytes. Published as well as unpublished results obtained with primary hepatocytes support the concept of a dual function of BMP-9 in the liver: while in primary, non-malignant cells BMP-9 stabilizes the epithelial phenotype and inhibits proliferation, in HCC cells it induces cell growth and the acquisition of a migratory phenotype. In this review article we summarize current knowledge about BMPs in liver diseases, with special focus on the role of BMP-9 in HCC development and progression, that may provide new clues for a better understanding of the contribution of BMP-signaling to chronic liver diseases. PMID:24670474

  12. Autotransplantation of bone marrow-derived stem cells as a therapy for neurodegenerative diseases.

    Science.gov (United States)

    Kan, I; Melamed, E; Offen, D

    2007-01-01

    Neurodegenerative diseases are characterized by a progressive degeneration of selective neural populations. This selective hallmark pathology and the lack of effective treatment modalities make these diseases appropriate candidates for cell therapy. Bone marrow-derived mesenchymal stem cells (MSCs) are self-renewing precursors that reside in the bone marrow and may further be exploited for autologous transplantation. Autologous transplantation of MSCs entirely circumvents the problem of immune rejection, does not cause the formation of teratomas, and raises very few ethical or political concerns. More than a few studies showed that transplantation of MSCs resulted in clinical improvement. However, the exact mechanisms responsible for the beneficial outcome have yet to be defined. Possible rationalizations include cell replacement, trophic factors delivery, and immunomodulation. Cell replacement theory is based on the idea that replacement of degenerated neural cells with alternative functioning cells induces long-lasting clinical improvement. It is reasoned that the transplanted cells survive, integrate into the endogenous neural network, and lead to functional improvement. Trophic factor delivery presents a more practical short-term approach. According to this approach, MSC effectiveness may be credited to the production of neurotrophic factors that support neuronal cell survival, induce endogenous cell proliferation, and promote nerve fiber regeneration at sites of injury. The third potential mechanism of action is supported by the recent reports claiming that neuroinflammatory mechanisms play an important role in the pathogenesis of neurodegenerative disorders. Thus, inhibiting chronic inflammatory stress might explain the beneficial effects induced by MSC transplantation. Here, we assemble evidence that supports each theory and review the latest studies that have placed MSC transplantation into the spotlight of biomedical research.

  13. Graft versus host disease in the bone marrow, liver and thymus humanized mouse model.

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    Matthew B Greenblatt

    Full Text Available Mice bearing a "humanized" immune system are valuable tools to experimentally manipulate human cells in vivo and facilitate disease models not normally possible in laboratory animals. Here we describe a form of GVHD that develops in NOD/SCID mice reconstituted with human fetal bone marrow, liver and thymus (NS BLT mice. The skin, lungs, gastrointestinal tract and parotid glands are affected with progressive inflammation and sclerosis. Although all mice showed involvement of at least one organ site, the incidence of overt clinical disease was approximately 35% by 22 weeks after reconstitution. The use of hosts lacking the IL2 common gamma chain (NOD/SCID/γc(-/- delayed the onset of disease, but ultimately did not affect incidence. Genetic analysis revealed that particular donor HLA class I alleles influenced the risk for the development of GVHD. At a cellular level, GVHD is associated with the infiltration of human CD4+ T cells into the skin and a shift towards Th1 cytokine production. GVHD also induced a mixed M1/M2 polarization phenotype in a dermal murine CD11b+, MHC class II+ macrophage population. The presence of xenogenic GVHD in BLT mice both presents a major obstacle in the use of humanized mice and an opportunity to conduct preclinical studies on GVHD in a humanized model.

  14. Activator protein 1 (Fos/Jun) functions in inflammatory bone and skin disease.

    Science.gov (United States)

    Zenz, Rainer; Eferl, Robert; Scheinecker, Clemens; Redlich, Kurt; Smolen, Josef; Schonthaler, Helia B; Kenner, Lukas; Tschachler, Erwin; Wagner, Erwin F

    2008-01-01

    Activator protein 1 (AP-1) (Fos/Jun) is a transcriptional regulator composed of members of the Fos and Jun families of DNA binding proteins. The functions of AP-1 were initially studied in mouse development as well as in the whole organism through conventional transgenic approaches, but also by gene targeting using knockout strategies. The importance of AP-1 proteins in disease pathways including the inflammatory response became fully apparent through conditional mutagenesis in mice, in particular when employing gene inactivation in a tissue-specific and inducible fashion. Besides the well-documented roles of Fos and Jun proteins in oncogenesis, where these genes can function both as tumor promoters or tumor suppressors, AP-1 proteins are being recognized as regulators of bone and immune cells, a research area termed osteoimmunology. In the present article, we review recent data regarding the functions of AP-1 as a regulator of cytokine expression and an important modulator in inflammatory diseases such as rheumatoid arthritis, psoriasis and psoriatic arthritis. These new data provide a better molecular understanding of disease pathways and should pave the road for the discovery of new targets for therapeutic applications.

  15. Potential of bone marrow mesenchymal stem cells in management of Alzheimer's disease in female rats.

    Science.gov (United States)

    Salem, Ahmed M; Ahmed, Hanaa H; Atta, Hazem M; Ghazy, Mohamed A; Aglan, Hadeer A

    2014-12-01

    Alzheimer's disease (AD) has been called the disease of the century with significant clinical and socioeconomic impacts. Pharmacological treatment has limited efficacy and only provides symptomatic relief without long-term cure. Accordingly, there is an urgent need to develop novel and effective medications for AD. Stem cell-based therapy is a promising approach to handling neurodegenerative diseases. Therefore, the current study aimed to explore the possible therapeutic role of single intravenous injection of bone marrow derived mesenchymal stem cells (BM-MSCs) after 4 months in management of AD in the experimental model. The work also extended to compare the therapeutic potential of BM-MSCs with 2 conventional therapies of AD; rivastigmine and cerebrolysin administered daily. BM-MSCs were able to home at the injured brains and produced significant increases in the number of positive cells for choline acetyltransferase (ChAT) and survivin expression, as well as selective AD indicator-1 (seladin-1) and nestin gene expression. Histopathological examination indicated that BM-MSCs could remove beta-amyloid plaques from hippocampus. Significant improvement in these biomarkers was similar to or better sometimes than the reference drugs, clearly showing the potential therapeutic role of BM-MSCs against AD through their anti-apoptotic, neurogenic and immunomodulatory properties.

  16. UNREMITTING EARLY STAGE HODGKIN’S DISEASE: REPORT OF 7 CASES AND BONE MARROW TISSUE IMMUNOHISTOCHEMICAL MARKER STUDY

    Directory of Open Access Journals (Sweden)

    D. Tamiolakis

    2006-07-01

    Full Text Available Bone marrow is infrequently implicated in early stages of Hodgkin’s disease. We studied the immunohistochemical bone marrow tissue of 7 out of 20 cases with early stage Hodgkin’s disease of the mixed cellularity variant, diagnosed by lymph node biopsy at initial presentation, not responding to radiotherapy alone, in order to examine possible marrow attack. A statistically significant prevalence of CD45, CD45RO, and CD4 positive infiltrates, to the advantage of unremitting hosts, was found. The predominance of CD4-positive cells in the bone marrow space might be suggestive of involvement in the process and could explain the abnormal cytokine production leading to reduced T-cell immunity and inefficient antitumor response despite the existence of a vast majority of reactive infiltrating immune cells.

  17. [Bone and calcium update; diagnosis and therapy of metabolic bone disease update. Advances in clinical trials for osteoporosis in Japan].

    Science.gov (United States)

    Nakamura, Toshitaka

    2011-12-01

    Microdensitometry of the metacarpal bone on radiograph was first set up as the endpoint of the treatment in clinical trials in Japan in 1980s. Then, radial bone mineral content obtained by single photon absorptiometry was used. In 1990s, lumbar spine BMD measured by DXA became the major endpoint of the study which was designed as prospective, randomized, double-blind, controlled trial. In 2000s, assessments on the incidences of the vertebral fractures have become mandatory as the primary endpoint of the placebo-controlled trial. The numbers of the subjects required in the study are getting larger and the subtleties in the study including adverse events more important along the progress of evidence-based medicine.

  18. Machine learning based analytics of micro-MRI trabecular bone microarchitecture and texture in type 1 Gaucher disease.

    Science.gov (United States)

    Sharma, Gulshan B; Robertson, Douglas D; Laney, Dawn A; Gambello, Michael J; Terk, Michael

    2016-06-14

    Type 1 Gaucher disease (GD) is an autosomal recessive lysosomal storage disease, affecting bone metabolism, structure and strength. Current bone assessment methods are not ideal. Semi-quantitative MRI scoring is unreliable, not standardized, and only evaluates bone marrow. DXA BMD is also used but is a limited predictor of bone fragility/fracture risk. Our purpose was to measure trabecular bone microarchitecture, as a biomarker of bone disease severity, in type 1 GD individuals with different GD genotypes and to apply machine learning based analytics to discriminate between GD patients and healthy individuals. Micro-MR imaging of the distal radius was performed on 20 type 1 GD patients and 10 healthy controls (HC). Fifteen stereological and textural measures (STM) were calculated from the MR images. General linear models demonstrated significant differences between GD and HC, and GD genotypes. Stereological measures, main contributors to the first two principal components (PCs), explained ~50% of data variation and were significantly different between males and females. Subsequent PCs textural measures were significantly different between GD patients and HC individuals. Textural measures also significantly differed between GD genotypes, and distinguished between GD patients with normal and pathologic DXA scores. PCA and SVM predictive analyses discriminated between GD and HC with maximum accuracy of 73% and area under ROC curve of 0.79. Trabecular STM differences can be quantified between GD patients and HC, and GD sub-types using micro-MRI and machine learning based analytics. Work is underway to expand this approach to evaluate GD disease burden and treatment efficacy.

  19. Feeding flaxseed oil but not secoisolariciresinol diglucoside results in higher bone mass in healthy rats and rats with kidney disease.

    Science.gov (United States)

    Weiler, H A; Kovacs, H; Nitschmann, E; Bankovic-Calic, N; Aukema, H; Ogborn, M

    2007-05-01

    Flaxseed's oil and lignan, secoisolariciresinol diglucoside (SDG), are implicated in attainment of health and treatment of renal injury and osteoporosis. To test for these benefits, weanling Han:SPRD-cy rats (n=171) with or without kidney disease were randomized to diets made with either corn oil or flaxseed oil and with or without SDG for 12 weeks. In females, weight was lower with the SDG diet. In males fed flaxseed oil, lean mass was higher and fat % was lower. In both sexes, fat % was lower in diseased rats. Bone mineral content (BMC) and density were higher in rats fed flaxseed oil and lower in diseased rats, additionally; BMC was lower in SDG-supplemented females. The benefit of flaxseed oil on body composition is sex specific but the effect on bone mass is not. Lastly, reduced weight due to early rat kidney disease is not due to loss of lean body mass.

  20. A Fatal Case of Immune Hyperhemolysis with Bone Marrow Necrosis in a Patient with Sickle Cell Disease

    Science.gov (United States)

    Singavi, Arun; Johnson, Susan T.; Field, Joshua J.

    2017-01-01

    In patients with sickle cell disease, hyperhemolysis is a rare but life-threatening complication of transfusion. In this case report, we describe a 61 year-old woman with hemoglobin sickle cell (SC) disease and history of alloimmunization who developed hyperhemolysis associated with a transfusion. She was found to have a warm and a clinically-significant cold autoantibody. Severe anemia (Hb 2.7 g/dL) with reticulocytopenia and thrombocytopenia prompted a bone marrow biopsy, which demonstrated extensive bone marrow necrosis. Despite treatment, the bone marrow failure did not improve and the patient died on hospital day 38. This case illustrates the potential risks of transfusion in a patient with sickle cell disease, especially one with previous hemolytic reactions. While uncommon, hyperhemolysis can cause death, in this case by extensive bone marrow necrosis. In patients with sickle cell disease, judicious use of red cell transfusions with phenotypically-matched units can diminish, but never completely abrogate, the risks associated with transfusion. PMID:28286630

  1. INFLUENCE OF VITAMIN D RECEPTOR GENE POLYMORPHISM ON THE EFFECTIVENESS OF α-D3 FOR RENAL BONE DISEASE

    Institute of Scientific and Technical Information of China (English)

    赵宝春; 傅淑霞; 戴秀华

    2002-01-01

    Objective To discuss the effectiveness of Vitamin D receptor (VDR)gene polymorphism on renal bone disease with α-D3.Methods VDR genotype was tested in 150 patients suffering from chronic renal failure using RFLPS method meanwhile the patients’ thyroxin in wholephase blood was assessed using radioactive and immune methods, and the bone specific mass (BUA) of right heel was detected by quantitative ultrasound before and eight weeks after the medication began.Results The incidence of the disease for BB type was 80%, for Bb was 60.87%, and for bb was 50. 5%. The difference of cure rates(P<0.05) was significant, being 100% for BB, 75.03% for Bb and 81.64% for bb.Conclusion The VDR genotype has important impact upon the occurrence of renal bone disease for chronic renal filure patients. Patients with BB genotype and b-equal grade have a low incidence rate for renal bone disease and those with α-D3 have good effects.

  2. Markers of bone metabolism are affected by renal function and growth hormone therapy in children with chronic kidney disease

    DEFF Research Database (Denmark)

    Doyon, Anke; Fischer, Dagmar Christiane; Bayazit, Aysun Karabay

    2015-01-01

    chronic kidney disease cohort. Methods: Bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin and C-terminal FGF-23 (cFGF23) normalized for age and sex were analyzed in 556 children aged 6-18 years with an estimated glomerular filtration rate (eGFR) of 10-60 ml...

  3. [Results of a combined therapy of patients with metastatic bone diseases].

    Science.gov (United States)

    Protsenko, V V; Konovalenko, V F; Boĭchuk, S I; Volkov, I B

    2007-01-01

    In the department of bone and soft tissue tumors of Institute of oncology the authors performed a combined treatment (surgery + combined chemotherapy + bisphosphonates + radiation) in 20 patients with bone metastases. Results showed that postoperative complications were observed in 2 patients, new bone lesions in 4 patients. Those satisfactory results prove the efficacy of these treatment options.

  4. Bone metabolism in patients with systemic lupus erythematosus. Effect of disease activity and glucocorticoid treatment

    DEFF Research Database (Denmark)

    Hansen, M; Halberg, P; Kollerup, G

    1998-01-01

    The bone metabolism in patients with systemic lupus erythematosus (SLE) has previously been examined, but the results are conflicting. In the present study the bone mineral density (BMD) of the axial and the appendicular skeleton was examined by means of dual energy x-ray absorptiometry. The bone...

  5. Bone mineral density and body composition of children and adolescents in health and disease

    NARCIS (Netherlands)

    A.M. Boot (Annemieke)

    1997-01-01

    textabstractOsteoporosis is characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk. Osteoporosis is a major public health problem involving postmenopausal women and aging individuals. The life

  6. Ex vivo exposure of bone marrow from chronic kidney disease donor rats to pravastatin limits renal damage in recipient rats with chronic kidney disease

    NARCIS (Netherlands)

    Koppen, A. van; Papazova, D.A.; Oosterhuis, N.R.; Gremmels, H.; Giles, R.H.; Fledderus, J.O.; Joles, J.A.; Verhaar, M.C.

    2015-01-01

    Introduction: Healthy bone marrow cell (BMC) infusion improves renal function and limits renal injury in a model of chronic kidney disease (CKD) in rats. However, BMCs derived from rats with CKD fail to retain beneficial effects, demonstrating limited therapeutic efficacy. Statins have been reported

  7. Ex vivo exposure of bone marrow from chronic kidney disease donor rats to pravastatin limits renal damage in recipient rats with chronic kidney disease

    NARCIS (Netherlands)

    van Koppen, Arianne; Papazova, Diana A.; Oosterhuis, Nynke R.; Gremmels, Hendrik; Giles, Rachel H.; Fledderus, Joost O.; Joles, Jaap A.; Verhaar, Marianne C.

    2015-01-01

    INTRODUCTION: Healthy bone marrow cell (BMC) infusion improves renal function and limits renal injury in a model of chronic kidney disease (CKD) in rats. However, BMCs derived from rats with CKD fail to retain beneficial effects, demonstrating limited therapeutic efficacy. Statins have been reported

  8. Detection of active alveolar bone destruction in human periodontal disease by analysis of radiopharmaceutical uptake after a single injection of 99m-Tc-methylene diphosphonate

    Energy Technology Data Exchange (ETDEWEB)

    Jeffcoat, M.K.; Williams, R.C.; Holman, B.L.; English, R.; Goldhaber, P.

    1986-01-01

    Previous studies have shown that, following a single injection of 99m-Tc-MDP, measurement of bone-seeking radiopharmaceutical uptake can detect ''active'' alveolar bone loss due to periodontal disease in beagle dogs, as determined by radiographs taken at the time of, and several months after, the nuclear medicine procedure. The efficacy of this diagnostic test, however, had not been assessed in human periodontal disease. The ability of a single boneseeking radiopharmaceutical uptake examination to detect ''active'' alveolar bone loss due to periodontal disease in human patients was assessed by comparing a single uptake measurement to the rate of bone loss determined from serial radiographs taken over a 6-month period. Uptake was expressed as a ratio of the cpm from the alveolar bone divided by the cpm from the non-tooth supporting bone of the nuchal crest. High uptake ratios were associated with ''active'' loss and low uptake ratios were associated with little if any change in alveolar bone height (p<0.001). The nuclear medicine examination was an accurate detector of periodontal disease activity in nearly 80% of the individual teeth studied. These data indicate that high bone-seeking radiopharmaceutical uptake ratios may be pathognomonic of active bone loss in human periodontal disease.

  9. Low serum and bone vitamin K status in patients with longstanding Crohn's disease: another pathogenetic factor of osteoporosis in Crohn's disease?

    OpenAIRE

    Schoon, E; Muller, M; Vermeer, C.; Schurgers, L; Brummer, R; Stockbrugger, R.

    2001-01-01

    BACKGROUND—A high prevalence of osteoporosis is reported in Crohn's disease. The pathogenesis is not completely understood but is probably multifactorial. Longstanding Crohn's disease is associated with a deficiency of fat soluble vitamins, among them vitamin K. Vitamin K is a cofactor in the carboxylation of osteocalcin, a protein essential for calcium binding to bone. A high level of circulating uncarboxylated osteocalcin is a sensitive marker of vitamin K deficiency.
AIMS—To determine seru...

  10. Normal Parathyroid Function with Decreased Bone Mineral Density in Treated Celiac Disease

    Directory of Open Access Journals (Sweden)

    Bernard Lemieux

    2001-01-01

    Full Text Available Decreased bone mineral density (BMD has been reported in patients with celiac disease in association with secondary hyperparathyroidism. The present study investigated whether basal parathyroid hormone (PTH remained elevated and whether abnormalities of parathyroid function were still present in celiac disease patients treated with a gluten-free diet. Basal seric measurements of calcium and phosphate homeostasis and BMD were obtained in 17 biopsy-proven patients under treatment for a mean period of 5.7±3.7 years (range 1.1 to 15.9. In addition, parathyroid function was studied with calcium chloride and sodium citrate infusions in seven patients. Basal measurements of patients were compared with those of 26 normal individuals, while parathyroid function results were compared with those of seven sex- and age-matched controls. Basal results were similar in patients and controls except for intact PTH (I-PTH (3.77±0.88 pmol/L versus 2.28±0.63 pmol/L, P<0.001, which was higher in the former group but still within normal limits. Mean 25-hydroxy vitamin D and 1,25-dihydroxy vitamin D values were normal in patients. Parathyroid function results were also found to be similar in both groups. Compared with a reference population of the same age (Z score, patients had significantly lower BMDs of the hip (-0.60±0.96 SDs, P<0.05 and lumbar spine (-0.76±1.15 SDs, P<0.05. T scores were also decreased for the hip (-1.3±0.9 SDs, P<0.0001 and lumbar spine (-1.4±1.35 SDs, P<0.0001, with two to three patients being osteoporotic (T score less than -2.5 SDs and seven to eight osteopenic (T score less than -1 SDs but greater than or equal to -2.5 SDs in at least one site. Height and weight were the only important determinants of BMD values by multivariate or logistical regression analysis in these patients. The results show higher basal I-PTH values with normal parathyroid function in treated celiac disease. Height and weight values are, but I-PTH values are not

  11. Transplantation of mononuclear cells from bone marrow in a rat model of Huntington’s disease

    Directory of Open Access Journals (Sweden)

    Serrano T

    2016-12-01

    Full Text Available Teresa Serrano,1 Paula Pierozan,2 Esteban Alberti,1 Lisette Blanco,1 Karelys de la Cuétara Bernal,1 María E González,1 Nancy Pavón,1 Lourdes Lorigados,1 María A Robinson-Agramonte,1 Jorge A Bergado1 1International Center for Neurological Restoration (CIREN, La Habana, Cuba; 2Department of Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil Abstract: This article investigates the possible effects of transplantation of mononuclear bone marrow cells (mBMCs to ameliorate or prevent the behavioral impairments and the cellular damage observed in a quinolinic acid (QA model of Huntington’s disease. mBMCs were isolated using a standard procedure and implanted within the QA-lesioned striatum. Behavior was explored using motor (beam test and memory (object recognition and Morris water maze tests. Morphology was evaluated using conventional histology (cresyl violet, bisbenzimide (to evaluate cell vitality, and immunohystochemistry to identify neurons or glia. mBMC-transplanted animals showed improvements in motor coordination (beam test. Regarding memory, object recognition was significantly improved in transplanted animals, while spatial memory (Morris water maze test was not severely affected by QA and, therefore, the results after transplantation were significant only in the probe-trial retention test. In samples taken from the animals that participated in the behavioral tests, a preserved morphology of striatal neurons and a reduced glial reaction indicated a possible neuroprotective effect of the transplanted mBMCs. A parallel study confirmed that the transplanted mBMCs have a long survival period (1 year follow-up. The results presented confirm the possibility that mBMC transplantation may be a viable therapeutic option for Huntington’s disease. Keywords: mononuclear bone marrow cells, Huntington’s disease, quinolinic acid, transplant, Fluoro-Jade C

  12. VCP associated inclusion body myopathy and paget disease of bone knock-in mouse model exhibits tissue pathology typical of human disease.

    Directory of Open Access Journals (Sweden)

    Mallikarjun Badadani

    Full Text Available Dominant mutations in the valosin containing protein (VCP gene cause inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD. We have generated a knock-in mouse model with the common R155H mutation. Mice demonstrate progressive muscle weakness starting approximately at the age of 6 months. Histology of mutant muscle showed progressive vacuolization of myofibrils and centrally located nuclei, and immunostaining shows progressive cytoplasmic accumulation of TDP-43 and ubiquitin-positive inclusion bodies in quadriceps myofibrils and brain. Increased LC3-II staining of muscle sections representing increased number of autophagosomes suggested impaired autophagy. Increased apoptosis was demonstrated by elevated caspase-3 activity and increased TUNEL-positive nuclei. X-ray microtomography (uCT images show radiolucency of distal femurs and proximal tibiae in knock-in mice and uCT morphometrics shows decreased trabecular pattern and increased cortical wall thickness. Bone histology and bone marrow derived macrophage cultures in these mice revealed increased osteoclastogenesis observed by TRAP staining suggestive of Paget bone disease. The VCP(R155H/+ knock-in mice replicate the muscle, bone and brain pathology of inclusion body myopathy, thus representing a useful model for preclinical studies.

  13. Quality Indices Of Jaw Bone Tissue In Screening Diagnostics Of Parodontal Diseases

    Directory of Open Access Journals (Sweden)

    V.P. Konev

    2009-12-01

    Full Text Available The objective of the work is to develop and motivate screening methods of the estimation of paradontal tissues by digital X-ray study. The used methods are X-ray digital scene with estimation of bone tissue density in program Trophy 2000, clinically anatomical parallels of bone tissue density and their qualitative indices. Parallels between qualitative indices of bones of mandibular alveolar process and bone tissue density of these areas have been revealed. It is reasonable to carry out the estimation of bone tissue density indices for revealing early stages of parodontal pathology

  14. The risk of renal disease is increased in lambda myeloma with bone marrow amyloid deposits

    Science.gov (United States)

    Kozlowski, Piotr; Montgomery, Scott; Befekadu, Rahel; Hahn-Strömberg, Victoria

    2017-01-01

    Background Light chain amyloidosis (AL) is a rare deposition disease and is present in 10–15% of patients with myeloma (MM). In contrast to symptomatic AL in MM, presence of bone marrow (BM) amyloid deposits (AD) in MM is not connected to kidney damage. Renal AD but not BM-AD occur mostly in MM with lambda paraprotein (lambda MM). Methods We investigated amyloid presence in BM clots taken at diagnosis in 84 patients with symptomatic MM and compared disease characteristics in MM with kappa paraprotein (kappa MM)/lambda MM with and without BM-AD. Results Lambda MM with BM-AD was compared with kappa MM without BM-AD, kappa MM with BM-AD, and lambda MM without BM-AD: lambda MM with BM-AD patients had a significantly higher mean creatinine level (4.23 mg/dL vs 1.69, 1.14, and 1.28 mg/dL, respectively) and a higher proportion presented with severe kidney failure (6/11 [55%] vs 6/32 [19%], 1/22 [5%], and 3/19 [16%], respectively). Proteinuria was more common in lambda MM with BM-AD patients compared with kappa MM without BM-AD patients (8/11 [73%] vs 5/32 [16%], respectively). Conclusion Kidney damage was more common in lambda MM with BM-AD indicating presence of renal AD. PMID:28293126

  15. Intracerebroventricular transplanted bone marrow stem cells survive and migrate into the brain of rats with Parkinson’s disease

    Institute of Scientific and Technical Information of China (English)

    Ping Gu; Zhongxia Zhang; Dongsheng Cui; Yanyong Wang; Lin Ma; Yuan Geng; Mingwei Wang

    2012-01-01

    In this study, 6-hydroxydopamine was stereotaxically injected into the right substantia nigra compact and ventral tegmental area of rats to establish Parkinson’s disease models. The rats then received a transplantation of bone marrow stromal cells that were previously isolated, cultured and labeled with 5-bromo-2’-deoxyuridine in vitro. Transplantation of the bone marrow stromal cells significantly decreased apomorphine-induced rotation time and the escape latency in the Morris water maze test as compared with rats with untreated Parkinson’s disease. Immunohistochemical staining showed that, 5-bromo-2’-deoxyuridine-immunoreactive cells were present in the lateral ventricular wall and the choroid plexus 1 day after transplantation. These immunoreactive cells migrated to the surrounding areas of the lateral cerebral ventricle along the corpus callosum. The results indicated that bone marrow stromal cells could migrate to tissues surround the cerebral ventricle via the cerebrospinal fluid circulation and fuse with cells in the brain, thus altering the phenotype of cells or forming neuron-like cells or astrocytes capable of expressing neuron-specific proteins. Taken together, the present findings indicate that bone marrow stromal cells transplanted intracerebroventricularly could survive, migrate and significantly improve the rotational behavior and cognitive function of rats with experimentally induced Parkinson’s disease.

  16. A New Data Analysis System to Quantify Associations between Biochemical Parameters of Chronic Kidney Disease-Mineral Bone Disease.

    Directory of Open Access Journals (Sweden)

    Mariano Rodriguez

    Full Text Available In hemodialysis patients, deviations from KDIGO recommended values of individual parameters, phosphate, calcium or parathyroid hormone (PTH, are associated with increased mortality. However, it is widely accepted that these parameters are not regulated independently of each other and that therapy aimed to correct one parameter often modifies the others. The aim of the present study is to quantify the degree of association between parameters of chronic kidney disease and mineral bone disease (CKD-MBD.Data was extracted from a cohort of 1758 adult HD patients between January 2000 and June 2013 obtaining a total of 46.141 records (10 year follow-up. We used an advanced data analysis system called Random Forest (RF which is based on self-learning procedure with similar axioms to those utilized for the development of artificial intelligence. This new approach is particularly useful when the variables analyzed are closely dependent to each other.The analysis revealed a strong association between PTH and phosphate that was superior to that of PTH and Calcium. The classical linear regression analysis between PTH and phosphate shows a correlation coefficient is 0.27, p<0.001, the possibility to predict PTH changes from phosphate modification is marginal. Alternatively, RF assumes that changes in phosphate will cause modifications in other associated variables (calcium and others that may also affect PTH values. Using RF the correlation coefficient between changes in serum PTH and phosphate is 0.77, p<0.001; thus, the power of prediction is markedly increased. The effect of therapy on biochemical variables was also analyzed using this RF.Our results suggest that the analysis of the complex interactions between mineral metabolism parameters in CKD-MBD may demand a more advanced data analysis system such as RF.

  17. [CKD-MBD (Chronic Kidney Disease-Mineral and Bone Disorder). Lanthanum carbonate and new phosphate binders in patients with chronic kidney disease].

    Science.gov (United States)

    Negi, Shigeo; Shigematsu, Takashi

    2010-07-01

    Hyperphosphatemia is a serious complication which has been linked with an increased risk of cardiovascular mortality in patients with chronic kidney disease. Lanthanum carbonate is a novel non-calcium, non-aluminum phosphate-binding agent, and has approved for clinical use in patients on hemodialysis in Japan on March in 2009. Compared to calcium carbonate and sevelamer hydrochloride, lanthanum carbonate is a powerful phosphate binder. There is no evidence of bone toxicity and neurotoxicity of lanthanum carbonate previously reported for aluminium hydroxide. However, further studies are needed to address the longer term toxic effect on bone and other organs.

  18. Radiography, Bone Scan, and F-18 FDG PET/CT Imaging Findings in a Patient with Paget's Disease

    Energy Technology Data Exchange (ETDEWEB)

    Park, Eun Tae; Kim, Sung Eun [Korea University Guro Hospital, Seoul (Korea, Republic of)

    2010-04-15

    Background A 52-year-old female patient sought evaluation at our hospital for an incidental abnormal finding on an abdominal radiograph. The initial radiograph showed irregular sclerotic changes involving the right pelvic bone. At the same time, bone scintigraphy showed intense hot uptake in the right iliac and pubic bones. CT images showed characteristic thickening of the pelvic brim, suggesting the mixed phase of Paget's disease. The level of alkaline phosphatase (ALP) was 266 IU/I. {sup 18}F-FDG PET/CT images also showed diffusely increased {sup 18}F-FDG uptake in the right pelvic bone. However, the findings of {sup 18}F-FDG PET/CT were less notable than those of bone scintigraphy. We report the imaging findings of a patient with Paget's disease evaluated by radiography, bone scintigraphy, and {sup 18}F-FDG PET/CT.

  19. Transcriptomic profile induced in bone marrow mesenchymal stromal cells after interaction with multiple myeloma cells: implications in myeloma progression and myeloma bone disease

    Science.gov (United States)

    Garcia-Gomez, Antonio; Las Rivas, Javier De; Ocio, Enrique M.; Díaz-Rodríguez, Elena; Montero, Juan C.; Martín, Montserrat; Blanco, Juan F.; Sanchez-Guijo, Fermín M.; Pandiella, Atanasio; San Miguel, Jesús F.; Garayoa, Mercedes

    2014-01-01

    Despite evidence about the implication of the bone marrow (BM) stromal microenvironment in multiple myeloma (MM) cell growth and survival, little is known about the effects of myelomatous cells on BM stromal cells. Mesenchymal stromal cells (MSCs) from healthy donors (dMSCs) or myeloma patients (pMSCs) were co-cultured with the myeloma cell line MM.1S, and the transcriptomic profile of MSCs induced by this interaction was analyzed. Deregulated genes after co-culture common to both d/pMSCs revealed functional involvement in tumor microenvironment cross-talk, myeloma growth induction and drug resistance, angiogenesis and signals for osteoclast activation and osteoblast inhibition. Additional genes induced by co-culture were exclusively deregulated in pMSCs and predominantly associated to RNA processing, the ubiquitine-proteasome pathway, cell cycle regulation, cellular stress and non-canonical Wnt signaling. The upregulated expression of five genes after co-culture (CXCL1, CXCL5 and CXCL6 in d/pMSCs, and Neuregulin 3 and Norrie disease protein exclusively in pMSCs) was confirmed, and functional in vitro assays revealed putative roles in MM pathophysiology. The transcriptomic profile of pMSCs co-cultured with myeloma cells may better reflect that of MSCs in the BM of myeloma patients, and provides new molecular insights to the contribution of these cells to MM pathophysiology and to myeloma bone disease. PMID:25268740

  20. Partial resolution of bone lesions. A child with severe combined immunodeficiency disease and adenosine deaminase deficiency after enzyme-replacement therapy

    Energy Technology Data Exchange (ETDEWEB)

    Yulish, B.S.; Stern, R.C.; Polmar, S.H.

    1980-01-01

    A child with severe combined immunodeficiency disease and adenosine deaminase deficiency, with characteristic bone dysplasia, was treated with transfusions of frozen irradiated RBCs as a means of enzyme replacement. This therapy resulted in restoration of immunologic competence and partial resolution of the bone lesions. Although the natural history of these lesions without therapy is not known, enzyme-replacement therapy may have played a role in the resolution of this patient's bone lesions.

  1. Bone pain

    DEFF Research Database (Denmark)

    Frost, Charlotte Ørsted; Hansen, Rikke Rie; Heegaard, Anne-Marie

    2016-01-01

    Skeletal conditions are common causes of chronic pain and there is an unmet medical need for improved treatment options. Bone pain is currently managed with disease modifying agents and/or analgesics depending on the condition. Disease modifying agents affect the underlying pathophysiology...... of the disease and reduce as a secondary effect bone pain. Antiresorptive and anabolic agents, such as bisphosphonates and intermittent parathyroid hormone (1-34), respectively, have proven effective as pain relieving agents. Cathepsin K inhibitors and anti-sclerostin antibodies hold, due to their disease...... modifying effects, promise of a pain relieving effect. NSAIDs and opioids are widely employed in the treatment of bone pain. However, recent preclinical findings demonstrating a unique neuronal innervation of bone tissue and sprouting of sensory nerve fibers open for new treatment possibilities....

  2. Topical HPMC/S-Nitrosoglutathione Solution Decreases Inflammation and Bone Resorption in Experimental Periodontal Disease in Rats.

    Directory of Open Access Journals (Sweden)

    Conceição S Martins

    Full Text Available S-nitrosoglutathione (GSNO is a nitric oxide (NO donor, which exerts antioxidant, anti-inflammatory, and microbicidal actions. Intragingival application of GSNO was already shown to decrease alveolar bone loss, inflammation and oxidative stress in an experimental periodontal disease (EPD model. In the present study, we evaluated the potential therapeutic effect of topical applications of hydroxypropylmethylcellulose (HPMC/GSNO solutions on EPD in Wistar rats. EPD was induced by placing a sterilized nylon (3.0 thread ligature around the cervix of the second left upper molar of the animals, which received topical applications of a HPMC solutions containing GSNO 2 or 10 mM or vehicle (HPMC solution, 1 h prior to the placement of the ligature and then twice daily until sacrifice on day 11. Treatment with HPMC/GSNO 10 mM solution significantly reduced alveolar bone loss, oxidative stress and TNF-α e IL-1β levels in the surrounding gingival tissue, and led to a decreased transcription of RANK and TNF-α genes and elevated bone alkaline phosphatase, compared to the HPMC group. In conclusion, topical application of HPMC/GSNO solution is a potential treatment to reduce inflammation and bone loss in periodontal disease.

  3. Topical HPMC/S-Nitrosoglutathione Solution Decreases Inflammation and Bone Resorption in Experimental Periodontal Disease in Rats

    Science.gov (United States)

    Martins, Conceição S.; Leitão, Renata F. C.; Costa, Deiziane V. S.; Melo, Iracema M.; Santos, Glaylton S.; Lima, Vilma; Baldim, Victor; Wong, Deysi V. T.; Bonfim, Luana E.; Melo, Cíntia B.; Brito, Gerly A. C.

    2016-01-01

    S-nitrosoglutathione (GSNO) is a nitric oxide (NO) donor, which exerts antioxidant, anti-inflammatory, and microbicidal actions. Intragingival application of GSNO was already shown to decrease alveolar bone loss, inflammation and oxidative stress in an experimental periodontal disease (EPD) model. In the present study, we evaluated the potential therapeutic effect of topical applications of hydroxypropylmethylcellulose (HPMC)/GSNO solutions on EPD in Wistar rats. EPD was induced by placing a sterilized nylon (3.0) thread ligature around the cervix of the second left upper molar of the animals, which received topical applications of a HPMC solutions containing GSNO 2 or 10 mM or vehicle (HPMC solution), 1 h prior to the placement of the ligature and then twice daily until sacrifice on day 11. Treatment with HPMC/GSNO 10 mM solution significantly reduced alveolar bone loss, oxidative stress and TNF-α e IL-1β levels in the surrounding gingival tissue, and led to a decreased transcription of RANK and TNF-α genes and elevated bone alkaline phosphatase, compared to the HPMC group. In conclusion, topical application of HPMC/GSNO solution is a potential treatment to reduce inflammation and bone loss in periodontal disease. PMID:27116554

  4. Radiographic evaluation of the effect of obesity on alveolar bone in rats with ligature-induced periodontal disease

    Directory of Open Access Journals (Sweden)

    do Nascimento CM

    2013-10-01

    Full Text Available Cassiane Merigo do Nascimento,1 Tiago Cassol,2 Fernanda Soares da Silva,3 Maria Lucia Bonfleur,4 Carlos Augusto Nassar,5 Patricia Oehlmeyer Nassar5 1Biologica Science and Health Center, State University of West Paraná (UNIOESTE, Cascavel, Paraná, Brazil; 2State University of West Paraná (UNIOESTE, Cascavel, Paraná, Brazil; Department of 3Pharmacy, 4Fisiology, 5Periodontology, Dental School, State University of West Paraná (UNIOESTE, Cascavel, Paraná, Brazil Abstract: There is evidence that the lack of metabolic control of obese patients may accelerate periodontitis. The aim of this study was to evaluate radiographically the effect of cafeteria-diet-induced obesity on alveolar bone loss in rats subjected to periodontal disease. Twenty male Wistar rats were randomly divided into four groups: 1 control group, 2 control and ligature group; 3 cafeteria group; and 4 cafeteria and ligature group. The animals were evaluated for obesity and euthanized, and the mandible of each rat was removed to perform a radiographic evaluation of alveolar bone loss and its effect on diet-induced obesity. The results showed greater alveolar bone loss in the mice in Group 4 (P<0.01. Thus, we concluded that obese mice, on average, showed greater radiographic evidence of alveolar bone loss than mice undergoing induction of obesity. Keywords: periodontal disease, radiography, obesity

  5. CYR61/CCN1 overexpression in the myeloma microenvironment is associated with superior survival and reduced bone disease

    Science.gov (United States)

    Stewart, James P.; Bam, Rakesh; Qu, Pingping; Barlogie, Bart; van Rhee, Frits; Shaughnessy, John D.; Epstein, Joshua; Yaccoby, Shmuel

    2014-01-01

    Secreted protein CCN1, encoded by CYR61, is involved in wound healing, angiogenesis, and osteoblast differentiation. We identified CCN1 as a microenvironmental factor produced by mesenchymal cells and overexpressed in bones of a subset of patients with monoclonal gammopathy of undetermined significance (MGUS), asymptomatic myeloma (AMM), and multiple myeloma (MM). Our analysis showed that overexpression of CYR61 was independently associated with superior overall survival of MM patients enrolled in our Total Therapy 3 protocol. Moreover, elevated CCN1 was associated with a longer time for MGUS/AMM to progress to overt MM. During remission from MM, high levels of CCN1 were associated with superior progression-free and overall survival and stratified patients with molecularly defined high-risk MM. Recombinant CCN1 directly inhibited in vitro growth of MM cells, and overexpression of CYR61 in MM cells reduced tumor growth and prevented bone destruction in vivo in severe combined immunodeficiency-hu mice. Signaling through αvβ3 was required for CCN1 prevention of bone disease. CYR61 expression may signify early perturbation of the microenvironment before conversion to overt MM and may be a compensatory mechanism to control MM progression. Therapeutics that upregulate CYR61 should be investigated for treating MM bone disease. PMID:25061178

  6. Dietary phosphorus excess: a risk factor in chronic bone, kidney, and cardiovascular disease?

    Science.gov (United States)

    Uribarri, Jaime; Calvo, Mona S

    2013-09-01

    There is growing evidence in the nephrology literature supporting the deleterious health effect of excess dietary phosphorus intake. This issue has largely escaped the attention of nutrition experts until this symposium, which raised the question of whether the same health concerns should be extended to the general population. The potential hazard of a high phosphorus intake in the healthy population is illustrated by findings from acute and epidemiologic studies. Acute studies in healthy young adults demonstrate that phosphorus intakes in excess of nutrient needs may significantly disrupt the hormonal regulation of phosphorus contributing to disordered mineral metabolism, vascular calcification, bone loss, and impaired kidney function. One of the hormonal factors acutely affected by dietary phosphorus loading is fibroblast growth factor-23, which may be a key factor responsible for many of the cardiovascular disease (CVD) complications of high phosphorus intake. Increasingly, large epidemiological studies suggest that mild elevations of serum phosphorus within the normal range are associated with CVD risk in healthy populations. Few population studies link high dietary phosphorus intake to mild changes in serum phosphorus due to study design issues specific to phosphorus and inaccurate nutrient composition databases. The increasing phosphorus intake due to the use of phosphorus-containing ingredients in processed food and the growing consumption of processed convenience and fast foods is an important factor that needs to be emphasized.

  7. Temporary brittle bone disease: relationship between clinical findings and judicial outcome

    Directory of Open Access Journals (Sweden)

    Colin R. Paterson

    2011-10-01

    Full Text Available There is a wide differential diagnosis for the child with unexplained fractures including non-accidental injury, osteogenesis imperfecta and vitamin D deficiency rickets. Over the last 20 years we and others have described a self-limiting syndrome characterised by fractures in the first year of life. This has been given the provisional name temporary brittle bone disease. This work had proved controversial mostly because the fractures, including rib fractures and metaphyseal fractures, were those previously regarded as typical or even diagnostic of non-accidental injury. Some have asserted that the condition does not exist. Over the years 1985 to 2000 we investigated 87 such cases with fractures with a view to determining the future care of the children. In 85 of these the judiciary was involved. We examined the clinical and radiological findings in the 33 cases in which there was a judicial finding of abuse, the 24 cases in which the parents were exonerated and the 28 cases in which no formal judicial finding was made. The three groups of patients were similar in terms of demographics, age at fracturing and details of the fractures. The clinical similarities between the three groups of patients contrasts with the very different results of the judicial process.

  8. [Disorders of carbohydrate metabolism, dyslipidemia, and bone metabolic disease after hematopoietic stem cell transplantation].

    Science.gov (United States)

    Wędrychowicz, Anna; Starzykk, Jerzy

    2013-01-01

    Among long-term survivors after hematopoietic stem cell transplantation (HSCT) late endocrine complications are observed in 20-50%. Very often these complications influence significantly the patient´s life and have to be treated till the end of life. Their proper prevention and monitoring are extremely important in patients who underwent HSCT during childhood. Since the 90s of the last millennium/century, thyroid dysfunction, disorders of somatic and sexual development, and disturbances of fertility have been presented in several publications. In the paper, less known endocrine complications after HSCT published in the last years are discussed. Disorders of carbohydrate metabolism, post-transplant diabetes and insulin resistance are presented. Moreover, dyslipidemia, hypertension, and post-transplant bone metabolic disease are demonstrated/shown. The paper describes the etiopathogenesis, methods of prevention as well as treatment and the results of the treatment of these endocrine complications after HSCT. Moreover, actual recommendations for screening and prevention of endocrine complications in long-term HCT survivors are presented.

  9. Repeated Administration of Bone Marrow-Derived Cells Prevents Disease Progression in Experimental Silicosis

    Directory of Open Access Journals (Sweden)

    Miquéias Lopes-Pacheco

    2013-12-01

    Full Text Available Background/Aims: Bone marrow-derived cells (BMDCs reduced mechanical and histologic changes in the lung in a murine model of silicosis, but these beneficial effects did not persist in the course of lung injury. We hypothesized that repeated administration of BMDCs may decrease lung inflammation and remodeling thus preventing disease progression. Methods: One hundred and two C57BL/6 mice were randomly divided into SIL (silica, 20 mg intratracheally [IT] and control (C groups (saline, IT. C and SIL groups were further randomized to receive BMDCs (2×106 cells or saline IT 15 and 30 days after the start of the protocol. Results: By day 60, BMDCs had decreased the fractional area of granuloma and the number of polymorphonuclear cells, macrophages (total and M1 phenotype, apoptotic cells, the level of transforming growth factor (TGF-β‚ and types I and III collagen fiber content in the granuloma. In the alveolar septa, BMDCs reduced the amount of collagen and elastic fibers, TGF-β, and the number of M1 and apoptotic cells. Furthermore, interleukin (IL-1β, IL-1R1, caspase-3 mRNA levels decreased and the level of IL-1RN mRNA increased. Lung mechanics improved after BMDC therapy. The presence of male donor cells in lung tissue was not observed using detection of Y chromosome DNA. Conclusion: repeated administration of BMDCs reduced inflammation, fibrogenesis, and elastogenesis, thus improving lung mechanics through the release of paracrine factors.

  10. Co-existent Paget’s Disease of the Bone, Prostate Carcinoma Skeletal Metastases and Fracture on Skeletal Scintigraphy-Lessons to be Learned

    Directory of Open Access Journals (Sweden)

    Luke I Sonoda

    2013-08-01

    Full Text Available Bone scintigraphy, despite being non-specific, is a very sensitive and simple investigation for patients with active Paget’s disease of the bone. Skeletal metastases and Paget’s disease may co-exist in the elderly patients as both conditions are commonly seen in this age group. Clinical and radiological correlation may help to improve the diagnostic specificity of a bone scintigram. We report a patient in whom concurrent Paget’s disease and a rib fracture became evident only on repeat scintigraphy following successful treatment of prostate carcinoma skeletal metastases.

  11. Acute renal graft-versus-host disease in a murine model of allogeneic bone marrow transplantation.

    Science.gov (United States)

    Schmid, Peter M; Bouazzaoui, Abdellatif; Schmid, Karin; Birner, Christoph; Schach, Christian; Maier, Lars S; Holler, Ernst; Endemann, Dierk H

    2017-03-23

    Acute kidney injury (AKI) is a very common complication after allogeneic bone marrow transplantation (BMT) and associated with poor prognosis. Generally kidneys are assumed to be no direct target of Graft-versus-Host Disease (GvHD), and renal impairment is often attributed to several other factors occurring in the early phase after BMT. Our study aimed to prove the existence of renal GvHD in a fully MHC-mismatched model of BALB/c mice conditioned and transplanted according to two different intensity protocols. Syngeneically transplanted and untreated animals served as controls. 4 weeks after transplantation, allogeneic animals developed acute GvHD that was more pronounced in the high-intensity protocol (HIP) group than in the low-intensity protocol (LIP) group. Urea and creatinine as classic serum markers of renal function could not verify renal impairment 4 weeks after BMT. Creatinine levels were even reduced as a result of catabolic metabolism and loss of muscle mass due to acute GvHD. Proteinuria, albuminuria, and urinary N-acetyl-beta-Dglucosaminidase (NAG) levels were measured as additional renal markers before and after transplantation. Albuminuria and NAG were only significantly increased after allogeneic transplantation, correlating with disease severity between HIP and LIP animals. Histological investigations of the kidneys showed renal infiltration of T-cells and macrophages with endarteriitis, interstitial nephritis, tubulitis, and glomerulitis. T-cells consisted of CD4+, CD8+, and FoxP3+ cells. Renal expression analysis of allogeneic animals showed increases in indoleamine-2,3 dioxygenase (IDO), different cytokines (TNFα, IFN-γ, IL-1α, IL2, IL-6, and IL-10), and adhesion molecules (ICAM-1 and VCAM-1), resembling findings from other tissues in acute GvHD. In summary, our study supports the entity of renal GvHD with histological features suggestive of cell-mediated renal injury. Albuminuria and urinary NAG levels may serve as early markers of renal

  12. Efficacy and safety of medical therapy for low bone mineral density in patients with Crohn disease

    Science.gov (United States)

    Zhao, Xiaojing; Zhou, Changcheng; Chen, Han; Ma, Jingjing; Zhu, Yunjuan; Wang, Peixue; Zhang, Yi; Ma, Haiqin; Zhang, Hongjie

    2017-01-01

    Abstract Background: Low bone mineral density (BMD) is a frequent complication of inflammatory bowel disease (IBD), particularly in patients with Crohn disease (CD). The aim of our study is to determine the efficacy and safety of different drugs used to treat low BMD in patients with CD. Methods: PUBMED/MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were searched for eligible studies. A random-effects model within a Bayesian framework was applied to compare treatment effects as standardized mean difference (SMD) with their corresponding 95% credible interval (CrI), while odds ratio (OR) was applied to compare adverse events with 95% CrI. The surface under the cumulative ranking area (SUCRA) was calculated to make the ranking of the treatments for outcomes. Results: Twelve randomized controlled trials (RCTs) were eligible. Compared with placebo, zoledronate (SMDs 2.74, 95% CrI 1.36–4.11) and sodium-fluoride (SMDs 1.23, 95% CrI 0.19–2.26) revealed statistical significance in increasing lumbar spine BMD (LSBMD). According to SUCRA ranking, zoledronate (SUCRA = 2.5%) might have the highest probability to be the best treatment for increasing LSBMD in CD patients among all agents, followed by sodium-fluoride (27%). For safety assessment, the incidence of adverse events (AEs) demonstrated no statistical difference between agents and placebo. The corresponding SUCRA values indicated that risedronate (SUCRA = 77%) might be the most safe medicine for low BMD in CD patients and alendronate ranked the worst (SUCRA = 16%). Conclusions: Zoledronate might have the highest probability to be the best therapeutic strategy for increasing LSBMD. For the safety assessment, risedronate showed the greatest trend to decrease the risk of AEs. In the future, more RCTs with higher qualities are needed to make head-to-head comparison between 2 or more treatments. PMID:28296781

  13. The effects of untreated and treated HIV infection on bone disease.

    LENUS (Irish Health Repository)

    Cotter, Aoife G

    2013-11-20

    Low bone mineral density (BMD) is common in those with HIV, associated with higher bone turnover and a higher prevalence of fractures. This review explores low BMD in HIV, focusing on underlying mechanisms and relationships between low BMD and HIV infection, immune dysfunction, and antiretroviral therapy (ART).

  14. Inclusion body myopathy, Paget's disease of the bone and fronto-temporal dementia: a disorder of autophagy

    OpenAIRE

    Ju, Jeong-Sun; Weihl, Conrad C

    2010-01-01

    Inclusion body myopathy associated with Paget's disease of the bone and fronto-temporal dementia (IBMPFD) is a progressive autosomal dominant disorder caused by mutations in p97/VCP (valosin-containing protein). p97/VCP is a member of the AAA+ (ATPase associated with a variety of activities) protein family and participates in multiple cellular processes. One particularly important role for p97/VCP is facilitating intracellular protein degradation. p97/VCP has traditionally been thought to med...

  15. Gaucher's disease. Plain radiography, US, CT and MR diagnosis of lungs, bone and liver lesions

    Energy Technology Data Exchange (ETDEWEB)

    Hainaux, B.; Christophe, C.; Hanquinet, S.; Perlmutter, N. (Free Univ. of Brussels (Belgium). Dept. of Pediatric Radiology)

    1992-04-01

    We report our observations made by conventional radiography, ultrasound, computerized tomography (CT), and magnetic resonance imaging (MRI) on a 3 1/2-year-old girl with Gaucher's disease. The interest of the case consists in the exceptional lungs involvement, the demonstration by MRI of the bone marrow involvement and the necrosis and fibrosis of the liver, as shown by CT. This liver complication has been previously reported only once. (orig.).

  16. State of the Art Systematic Review of Bone Disease in Anorexia Nervosa

    Science.gov (United States)

    Misra, Madhusmita; Golden, Neville H.; Katzman, Debra K.

    2016-01-01

    Objective Low bone mineral density (BMD) is a known consequence of anorexia nervosa (AN) and is particularly concerning during adolescence, a critical time for bone accrual. A comprehensive synthesis of available data regarding impaired bone health, its determinants, and associated management strategies in AN is currently lacking. This systematic review aims to synthesize information from key physiologic and prospective studies and trials, and provide a thorough understanding of impaired bone health in AN and its management. Method Search terms included “anorexia nervosa” AND “bone density” for the period 1995–2015, limited to articles in English. Papers were screened manually based on journal impact factor, sample size, age of participants, and inclusion of a control group. When necessary, we included seminal papers published before 1995. Results AN leads to low BMD, impaired bone quality and increased fracture risk. Important determinants are low lean mass, hypogonadism, IGF-1 deficiency, and alterations in other hormones that impact bone health. Weight gain and menses restoration are critical for improving bone outcomes in AN. Physiologic estrogen replacement as the transdermal patch was shown to increase bone accrual in one study in adolescent females with AN; however, residual deficits persist. Bisphosphonates are potentially useful in adults with AN. Discussion To date, evidence suggests that the safest and most effective strategy to improve bone health in AN is normalization of weight with restoration of menses. Pharmacotherapies that show promise include physiologic estradiol replacement (as the transdermal estradiol patch), and in adults, bisphosphonates. Further studies are necessary to determine the best strategies to normalize BMD in AN. PMID:26311400

  17. Utility of unenhanced fat-suppressed T1-weighted MRI in children with sickle cell disease - can it differentiate bone infarcts from acute osteomyelitis?

    Energy Technology Data Exchange (ETDEWEB)

    Delgado, Jorge; Bedoya, Maria A. [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); Green, Abby M. [The Children' s Hospital of Philadelphia, Division of Oncology, Philadelphia, PA (United States); Jaramillo, Diego; Ho-Fung, Victor [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA (United States)

    2015-12-15

    Children with sickle cell disease (SCD) are at risk of bone infarcts and acute osteomyelitis. The clinical differentiation between a bone infarct and acute osteomyelitis is a diagnostic challenge. Unenhanced T1-W fat-saturated MR images have been proposed as a potential tool to differentiate bone infarcts from osteomyelitis. To evaluate the reliability of unenhanced T1-W fat-saturated MRI for differentiation between bone infarcts and acute osteomyelitis in children with SCD. We retrospectively reviewed the records of 31 children (20 boys, 11 girls; mean age 10.6 years, range 1.1-17.9 years) with SCD and acute bone pain who underwent MR imaging including unenhanced T1-W fat-saturated images from 2005 to 2010. Complete clinical charts were reviewed by a pediatric hematologist with training in infectious diseases to determine a clinical standard to define the presence or absence of osteomyelitis. A pediatric radiologist reviewed all MR imaging and was blinded to clinical information. Based on the signal intensity in T1-W fat-saturated images, the children were further classified as positive for osteomyelitis (low bone marrow signal intensity) or positive for bone infarct (high bone marrow signal intensity). Based on the clinical standard, 5 children were classified as positive for osteomyelitis and 26 children as positive for bone infarct (negative for osteomyelitis). The bone marrow signal intensity on T1-W fat-saturated imaging was not significant for the differentiation between bone infarct and osteomyelitis (P = 0.56). None of the additional evaluated imaging parameters on unenhanced MRI proved reliable in differentiating these diagnoses. The bone marrow signal intensity on unenhanced T1-W fat-saturated MR images is not a reliable criterion to differentiate bone infarcts from osteomyelitis in children. (orig.)

  18. The management of metastatic bone disease with the combination of bisphosphonates and radiotherapy: from theory to clinical practice.

    Science.gov (United States)

    Vassiliou, V; Kardamakis, D

    2009-03-01

    Bone metastases are common in the event of malignancy and are inevitably associated with serious complications that may deteriorate the quality of life (QOL) of patients and threaten life. Both radiotherapy (RT) and bisphosphonates (BPs) have an established role in the management of metastatic bone disease. Many clinical trials have demonstrated their effectiveness when used as sole treatment modalities, but only a few have evaluated their therapeutic value when applied concomitantly. We herein discuss the pathophysiology of bone metastases and the potential interactions between RT and BPs. Moreover, the results of both animal models and clinical studies are presented in detail. Apart from aspects of normal tissue tolerance, other interactions include spatial cooperation and additive or super-additive effects. The latter brings about a synergistic activity that results in an enhanced reossification, improved bone stability and microarchitecture, and increased mechanical strength, as documented through animal model studies. The results of published clinical studies investigating the effectiveness of concomitant application of RT and BPs are promising, reporting a significant clinical and radiologic response. More specifically, a significant reduction of pain scores and a worth noticing improvement in QOL and performance status (PS) were noted, accompanied by a considerable increase in bone density. Pain relief was accompanied by a marked reduction in analgesic opioid need. The enhanced reossification may be responsible for the improved therapeutic response, since it was shown that the correlation between pain and bone density is negative and strong. Although promising and encouraging, the results of such studies should be corroborated by larger, randomized trials.

  19. Treatment of Moyamoya disease by multipoint skull drilling for indirect revascularization combined with mobilization of autologous bone marrow stem cells.

    Science.gov (United States)

    Wu, R; Su, N; Zhang, Z; Jia, F

    2015-07-06

    This study discusses the clinical efficacy of multipoint skull drilling for indirect revascularization combined with mobilization of autologous bone marrow stem cells and use of simvastatin in the treatment of moyamoya disease. Seventy-eight patients [control group (group A), 39 patients; experimental group (group B), 39 patients] with moyamoya disease were selected. Group A underwent indirect revascularization, and group B, in addition to indirect revascularization, received alternate subcutaneous injections from day 7 post-surgery. The number and differentiation of the mobilized bone marrow stem cells were detected by the proportion of hematopoietic progenitor cell (HPCs) in mononuclear cells (MNCs) in the peripheral blood. There was no statistical difference in the BI (80.2 ± 13.7) and NIHSS (6.7 ± 2.3) scores between the groups before treatment (P > 0.05). The CSS score of group B was 13.5 ± 0.6 and there was a statistical significance compared to group A (18.2 ± 0.8) (P 0.05) and the proportions of CD34+ CDl33+ cells in MNCs in peripheral blood in groups A and B at 30 days after surgery were significantly higher than those before surgery (P moyamoya disease by multipoint skull drilling for indirect revascularization combined with mobilization of autologous bone marrow stem cells and simvastatin is a safe and effective method as it can promote recovery of neurological functions and improve patients' daily living abilities and quality of life.

  20. The benefits of estrogen or selective estrogen receptor modulator on kidney and its related disease-chronic kidney disease-mineral and bone disorder: osteoporosis.

    Science.gov (United States)

    Lee, Wen-Ling; Cheng, Ming-Huei; Tarng, Der-Cherng; Yang, Wu-Chang; Lee, Fa-Kung; Wang, Peng-Hui

    2013-07-01

    An umbrella concept addressing the relationship between chronic kidney disease (CKD) and mineral and bone disorders has been developed in recent years. Given the high prevalence of osteoporosis-related fractures in postmenopausal women with CKD, especially those undergoing chronic hemodialysis, the strategy used in the prevention and management of CKD and its associated osteoporosis in these postmenopausal women has become a topic of substantial debate. This controversy has ongoing relevance because osteoporosis results in a significant economic burden secondary to increased morbidity and mortality. The perfect goal of treatment and prevention includes both bone protection and renal protection, or at least protection of one disease without compromising the other disease. Both CKD and osteoporosis are frequently observed in the same patients, and often have parallel progression in postmenopausal women. Estrogen, the main female hormone during reproductive age, has been reported to have a protective effect on kidney fibrosis in several animal models, and is also considered one of the most effective drugs in the management of postmenopausal women with osteoporosis and prevention of osteoporosis. However, due to the many adverse events associated with the use of estrogen with and without progestin, some of which have contributed to significant morbidity and mortality, drug modification, which has had fewer reported incidences of adverse events without compromising the protective effect on both the kidney and bone, may have an easier road to acceptance. Therapeutic alternatives, such as the selective estrogen receptor modulators (SERMs), have shown the benefits of estrogen on bone, serum lipid levels, and renal protection, without any adverse effects on the breast and endometrium. The Multiple Outcomes of Raloxifene Evaluation trial (MORE) and its extension-Continuing Outcomes Relevant to Evista (CORE), a double-blind, randomized clinical trial encompassing

  1. A SQSTM1/p62 mutation linked to Paget’s disease increases the osteoclastogenic potential of the bone microenvironment

    Science.gov (United States)

    Hiruma, Yuko; Kurihara, Noriyoshi; Subler, Mark A.; Zhou, Hua; Boykin, Christina S.; Zhang, Heju; Ishizuka, Seiichi; Dempster, David W.; Roodman, G. David; Windle, Jolene J.

    2008-01-01

    Paget’s disease of bone (PDB) is the second most common bone disease and is characterized by focal bone lesions which contain large numbers of abnormal osteoclasts (OCLs) and very active normal osteoblasts in a highly osteoclastogenic marrow microenvironment. The etiology of PDB is not well understood and both environmental and genetic causes have been implicated in its pathogenesis. Mutations in the SQSTM1/p62 gene have been identified in up to 30% of Paget’s patients. To determine if p62 mutation is sufficient to induce PDB, we generated mice harboring a mutation causing a P-to-L (proline-to-leucine) substitution at residue 394 (the murine equivalent of human p62P392L, the most common PDB-associated mutation). Bone marrow cultures from p62P394L mice formed increased numbers of OCLs in response to receptor activator of NF-κB ligand (RANKL), tumor necrosis factor α (TNF-α) or 1α,25-(OH)2D3, similar to PDB patients. However, purified p62P394L OCL precursors depleted of stromal cells were no longer hyper-responsive to 1α,25-(OH)2D3, suggesting effects of the p62P394L mutation on the marrow microenvironment in addition to direct effects on OCLs. Co-cultures of purified p62P394L stromal cells with either wild-type (WT) or p62P394L OCL precursors formed more OCLs than co-cultures containing WT stromal cells due to increased RANKL production by the mutant stromal cells. However, despite the enhanced osteoclastogenic potential of both OCL precursors and marrow stromal cells, the p62P394L mice had histologically normal bones. These results indicate that this PDB-associated p62 mutation is not sufficient to induce PDB and suggest that additional factors acting together with p62 mutation are necessary for the development of PDB in vivo. PMID:18765443

  2. Role of (99m)Tc-MDP bone scan in the diagnosis of Erdheim-Chester disease.

    Science.gov (United States)

    Mukherjee, Anirban; Damle, Nishikant; Bal, Chandrasekhar; Arora, Arundeep; Singhal, Abhinav; Tripathi, Madhavi; Peepre, Karan

    2014-07-01

    Erdheim-Chester disease (ECD) is a rare systemic non-Langerhans cell histiocytosis. It is a progressive disease of unknown etiology. The (99m)technetium-methylene diphosphonate ((99m)Tc-MDP) bone scan is useful in finding the sites of involvement in the skeleton and is helpful in excluding other causes of bony pain. Also a scintigraphic pattern consistent with ECD should alert the physician to evaluate the patient for visceral sites of involvement using fludeoxyglucose positron emission tomography/computed tomography (FDG PET/CT), as this is known to be fatal at times.

  3. Orchestration of bone remodeling

    NARCIS (Netherlands)

    Moester, Martiene Johanna Catharina

    2014-01-01

    In healthy individuals, a balance exists between bone formation and resorption. Disruption of this balance can lead to higher or lower bone mass, and disease such as osteoporosis. Treatment for osteoporosis generally inhibits bone resorption, but does not rebuild bone to a healthy strength. More kno

  4. The role of 18F–NaF PET/CT in metastatic bone disease

    Directory of Open Access Journals (Sweden)

    Mine Araz

    2015-09-01

    Conclusion: Although further prospective clinical studies in specific cancer populations are indicated to set the place of 18F–NaF PET/CT in diagnostic scheme, the results of this pilot study from our country support the superiority of 18F–NaF PET/CT in investigation of bone metastasis over 99mTc-MDP bone scan and 18F-FDG PET/CT in various malignancies. 18F–NaF PET/CT is coming forward as a single step bone seeking study, considering all the advantages, but especially potential of detecting occult metastases and reliably directing patient management.

  5. Bone mineral density and cardiovascular risk factors in postmenopausal women with coronary artery disease.

    Science.gov (United States)

    Alissa, Eman M; Alnahdi, Wafa A; Alama, Nabil; Ferns, Gordon A

    2015-01-01

    It has been suggested that osteoporosis and coronary artery disease (CAD) have overlapping pathophysiological mechanisms and related risk factors. The aim of this study was to investigate the association between several traditional cardiovascular risk factors and measures of bone mineral density (BMD) in postmenopausal women with and without clinically significant CAD defined angiographically. A case-control study was undertaken of 180 postmenopausal women (aged between 48 and 88 years) who were recruited from King Abdulaziz University Hospital, Saudi Arabia. Study subjects underwent dual-energy x-ray absorptiometry and coronary angiography. The presence of hypertension, diabetes, dyslipidemia, obesity, smoking and physical activity was identified from clinical examination and history. Demographic, anthropometric and biochemical characteristics were measured. Univariate and multivariate analyses were employed to explore the relationships between cardiovascular risk factors, including BMD, and the presence of CAD. CAD patients were more likely to have a lower BMD and T-score at the femoral neck than those without CAD (P<0.05). Significant differences were found between the groups for fasting lipid profile, fasting blood glucose and anthropometric measures (P<0.05). Conditional logistic regression showed that 3 risk factors were significantly related with the presence of CAD: high-density lipoprotein-cholesterol (odds ratio, OR: 0.226, 95% confidence interval, CI: 0.062-0.826), fasting plasma glucose (OR: 1.154, 95% CI: 1.042-1.278) and femoral neck T-score (OR: 0.545, 95% CI: 0.374-0.794). This study suggests an association of low BMD and elevated CAD risk. Nevertheless, additional longitudinal studies are needed to determine the temporal sequence of this association.

  6. Pre-B cell colony enhancing factor/NAMPT/visfatin and its role in inflammation-related bone disease

    Energy Technology Data Exchange (ETDEWEB)

    Moschen, Alexander R.; Geiger, Sabine; Gerner, Romana [Christian Doppler Research Laboratory for Gut Inflammation and Department of Internal Medicine II (Gastroenterology and Hepatology), Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck (Austria); Tilg, Herbert, E-mail: herbert.tilg@i-med.ac.at [Christian Doppler Research Laboratory for Gut Inflammation and Department of Internal Medicine II (Gastroenterology and Hepatology), Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck (Austria)

    2010-08-07

    Chronic inflammation affects bone metabolism and is commonly associated with the presence of osteoporosis. Bone loss is directed by various immune mediators such as the pro-inflammatory cytokines tumour necrosis factor-alpha, interleukin 1-beta or interferon-gamma. Pre-B cell colony enhancing factor (PBEF)/nicotinamide phosphoribosyl transferase (NAMPT)/visfatin is a pleiotropic mediator acting as growth factor, cytokine and enzyme involved in energy and nicotinamide adenine dinucleotide (NAD) metabolism. PBEF/NAMPT/visfatin has been recently demonstrated to exert several pro-inflammatory functions. We studied serum levels of PBEF/NAMPT/visfatin in patients with inflammatory bowel diseases (IBD) and their relation with bone mineral density (BMD). Furthermore, we were interested whether PBEF/NAMPT/visfatin affects osteoclastogenesis and involved mediators. PBEF/NAMPT/visfatin serum levels were increased in patients with IBD, correlated positively with disease activity and negatively with BMD, especially in the lumbar spine. Osteoclast precursor cells were generated from peripheral blood mononuclear cells after stimulation with various growth factors such as macrophage colony-stimulating factor (M-CSF) and soluble ligand of receptor activator of nuclear factor kappa B (RANK). In these in vitro studies, PBEF/NAMPT/visfatin suppressed osteoclastogenesis and inhibited the differentiation of osteoclast precursors into tartrate-resistant acid phosphatase positive multinucleated cells. These effects were paralleled by the suppression of the osteoclast typical markers RANK, nuclear factor of activated T-cells c1 (NFATc1) and cathepsin-K. This is the first report demonstrating a potential role for this important cytokine/enzyme in inflammation-related bone disease.

  7. Founder Effect in Different European Countries for the Recurrent P392L SQSTM1 Mutation in Paget’s Disease of Bone

    NARCIS (Netherlands)

    Chung, P.Y.J.; Beyens, G.; Guanabens, N.; Boonen, S.; Papapoulos, S.; Karperien, H.B.J.; Eekhoff, M.; Wesenbeek, van L.; [et al.],

    2008-01-01

    Paget’s Disease of Bone (PDB) is one of the most frequent metabolic bone diseases, affecting 1–5% of Western populations older than 55 years. Mutations in the sequestosome1 (SQSTM1) gene cause PDB in about one-third of familial PDB cases and in 2.4–9.3% of nonfamilial PDB cases, with the 1215C→T (P3

  8. Treatment of bone loss in osteopenic patients with Crohn's disease : a double-blind, randomised trial of oral risedronate 35 mg once weekly or placebo, concomitant with calcium and vitamin D supplementation

    NARCIS (Netherlands)

    van Bodegraven, Ad A.; Bravenboer, Nathalie; Witte, Birgit I.; Dijkstra, Gerard; van der Woude, C. Janneke; Stokkers, Pieter C. M.; Russel, Maurice G.; Oldenburg, Bas; Pierik, Marieke; Roos, Jan C.; van Hogezand, Ruud A.; Dik, Vincent K.; Oostlander, Angela E.; Netelenbos, J. Coen; van de langerijt, Lex; Hommes, Daniel W.; Lips, Paul

    2014-01-01

    Objective Osteoporosis and fractures are frequently encountered in patients with Crohn's disease. In order to prevent fractures, treatment with bone protecting drugs appears warranted early in the course of bone disease when bone loss is not yet prominent. We therefore aimed to demonstrate a benefic

  9. Development of a preclinical orthotopic xenograft model of ewing sarcoma and other human malignant bone disease using advanced in vivo imaging.

    Directory of Open Access Journals (Sweden)

    Britta Vormoor

    Full Text Available Ewing sarcoma and osteosarcoma represent the two most common primary bone tumours in childhood and adolescence, with bone metastases being the most adverse prognostic factor. In prostate cancer, osseous metastasis poses a major clinical challenge. We developed a preclinical orthotopic model of Ewing sarcoma, reflecting the biology of the tumour-bone interactions in human disease and allowing in vivo monitoring of disease progression, and compared this with models of osteosarcoma and prostate carcinoma. Human tumour cell lines were transplanted into non-obese diabetic/severe combined immunodeficient (NSG and Rag2(-/-/γc(-/- mice by intrafemoral injection. For Ewing sarcoma, minimal cell numbers (1000-5000 injected in small volumes were able to induce orthotopic tumour growth. Tumour progression was studied using positron emission tomography, computed tomography, magnetic resonance imaging and bioluminescent imaging. Tumours and their interactions with bones were examined by histology. Each tumour induced bone destruction and outgrowth of extramedullary tumour masses, together with characteristic changes in bone that were well visualised by computed tomography, which correlated with post-mortem histology. Ewing sarcoma and, to a lesser extent, osteosarcoma cells induced prominent reactive new bone formation. Osteosarcoma cells produced osteoid and mineralised "malignant" bone within the tumour mass itself. Injection of prostate carcinoma cells led to osteoclast-driven osteolytic lesions. Bioluminescent imaging of Ewing sarcoma xenografts allowed easy and rapid monitoring of tumour growth and detection of tumour dissemination to lungs, liver and bone. Magnetic resonance imaging proved useful for monitoring soft tissue tumour growth and volume. Positron emission tomography proved to be of limited use in this model. Overall, we have developed an orthotopic in vivo model for Ewing sarcoma and other primary and secondary human bone malignancies, which

  10. Disease-modifying antirheumatic drugs and bone mass in rheumatoid arthritis.

    Science.gov (United States)

    Di Munno, O; Delle Sedie, A; Rossini, M; Adami, S

    2005-01-01

    This article reviews the effects of DMARDs (including biologic agents) on bone metabolism in rheumatoid arthritis (RA). At present there is no evidence that methotrexate, at least at dosages ranging from 5 to 20 mg/week, negatively affects bone mass as measured by DXA (BMD) as documented in both cross-sectional and longitudinal studies. Most studies of cyclosporine (CyA) use reporting a reduction in erosions and joint damage with no adverse effects on bone, did not measure BMD; CyA treatment is associated with a dose-dependent increase of bone turnover as well as a decrease in both animal and human studies; however, its use in RA setting at a dose < or =5 mg/Kg/ day has so far not been associated with clinical relevant adverse effects on bone metabolism. Anti-TNF-alpha agents, infliximab reduced markers of bone turnover in two longitudinal studies. Data on BMD are not available in RA; nevertheless, an increase in BMD has been documented in spondyloarthropathies with infliximab and etanercept. No clinical data concerning BMD are available on leflunomide as well as on the newer biologic agents (adalimumab, rituximab, anakinra).

  11. Effect of paricalcitol and cinacalcet on serum phosphate, FGF-23, and bone in rats with chronic kidney disease

    Science.gov (United States)

    Finch, Jane L.; Tokumoto, Masanori; Nakamura, Hironori; Yao, Wei; Shahnazari, Mohammad; Lane, Nancy

    2010-01-01

    Calcimimetics activate the calcium-sensing receptor (CaR) and reduce parathyroid hormone (PTH) by increasing the sensitivity of the parathyroid CaR to ambient calcium. The calcimimetic, cinacalcet, is effective in treating secondary hyperparathyroidism in dialysis patients [chronic kidney disease (CKD 5)], but little is known about its effects on stage 3–4 CKD patients. We compared cinacalcet and paricalcitol in uremic rats with creatinine clearances “equivalent” to patients with CKD 3–4. Uremia was induced in anesthetized rats using the 5/6th nephrectomy model. Groups were 1) uremic control, 2) uremic + cinacalcet (U+Cin; 15 mg·kg−1·day−1 po for 6 wk), 3) uremic + paricalcitol (U+Par; 0.16 μg/kg, 3 × wk, ip for 6 wk), and 4) normal. Unlike U+Par animals, cinacalcet promoted hypocalcemia and marked hyperphosphatemia. The Ca × P in U+Cin rats was twice that of U+Par rats. Both compounds suppressed PTH. Serum 1,25-(OH)2D3 was decreased in both U+Par and U+Cin rats. Serum FGF-23 was increased in U+Par but not in U+Cin, where it tended to decrease. Analysis of tibiae showed that U+Cin, but not U+Par, rats had reduced bone volume. U+Cin rats had similar bone formation and reduced osteoid surface, but higher bone resorption. Hypocalcemia, hyperphosphatemia, low 1,25-(OH)2D3, and cinacalcet itself may play a role in the detrimental effects on bone seen in U+Cin rats. This requires further investigation. In conclusion, due to its effects on bone and to the hypocalcemia and severe hyperphosphatemia it induces, we believe that cinacalcet should not be used in patients with CKD without further detailed studies. PMID:20200094

  12. Cardiovascular diseases in older patients with osteoporotic hip fracture: prevalence, disturbances in mineral and bone metabolism, and bidirectional links

    Directory of Open Access Journals (Sweden)

    Fisher A

    2013-02-01

    Full Text Available A Fisher,1,3 W Srikusalanukul,1 M Davis,1,3 P Smith2,31Departments of Geriatric Medicine, 2Orthopaedic Surgery, The Canberra Hospital, 3Australian National University Medical School, Canberra, ACT, AustraliaBackground: Considerable controversy exists regarding the contribution of mineral/bone metabolism abnormalities to the association between cardiovascular diseases (CVDs and osteoporotic fractures.Aims and methods: To determine the relationships between mineral/bone metabolism biomarkers and CVD in 746 older patients with hip fracture, clinical data were recorded and serum concentrations of parathyroid hormone (PTH, 25-hydroxyvitamin D, calcium, phosphate, magnesium, troponin I, parameters of bone turnover, and renal, liver, and thyroid functions were measured.Results: CVDs were diagnosed in 472 (63.3% patients. Vitamin D deficiency was similarly prevalent in patients with (78.0% and without (82.1% CVD. The CVD group had significantly higher mean PTH concentrations (7.6 vs 6.0 pmol/L, P < 0.001, a higher prevalence of secondary hyperparathyroidism (SPTH (PTH > 6.8 pmol/L, 43.0% vs 23.3%, P < 0.001, and excess bone resorption (urinary deoxypyridinoline corrected by creatinine [DPD/Cr] > 7.5 nmol/µmol, 87.9% vs 74.8%, P < 0.001. In multivariate regression analysis, SHPT (odds ratio [OR] 2.6, P = 0.007 and high DPD/Cr (OR 2.8, P = 0.016 were independent indictors of CVD. Compared to those with both PTH and DPD/Cr in the normal range, multivariate-adjusted ORs for the presence of CVD were 17.3 (P = 0.004 in subjects with SHPT and 9.7 (P < 0.001 in patients with high DPD/Cr. CVD was an independent predicator of SHPT (OR 2.8, P = 0.007 and excess DPD/Cr (OR 2.5, P = 0.031. CVD was predictive of postoperative myocardial injury, while SHPT was also an independent predictor of prolonged hospital stay and in-hospital death.Conclusion: SHPT and excess bone resorption are independent pathophysiological mediators underlying the bidirectional associations

  13. Relationship of Dickkopf1 (DKK1 with cardiovascular disease and bone metabolism in Caucasian type 2 diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Antonia Garcia-Martín

    Full Text Available OBJECTIVES: Dickkopf-1 (DKK1 is a potent inhibitor of Wnt signalling, which exerts anabolic effects on bone and also takes part in the regulation of vascular cells. Our aims were to evaluate serum DKK1 in type 2 diabetes (T2DM patients and to analyze its relationships with cardiovascular disease (CVD. We also evaluated the relationship between DKK1 and bone metabolism. DESIGN: We conducted a cross-sectional study in which we measured serum DKK1 (ELISA, Biomedica in 126 subjects: 72 patients with T2DM and 54 non-diabetic subjects. We analysed its relationship with clinical CVD, preclinical CVD expressed as carotid intima media thickness (IMT, and bone metabolism. RESULTS: T2DM patients with CVD (P = 0,026 and abnormal carotid IMT (P = 0,038 had higher DKK1 concentrations. DKK1 was related to the presence of CVD in T2DM, independently of the presence of risk factors for atherosclerosis. Therefore, for each increase of 28 pg/ml of serum DKK1 there was a 6,2% increase in the risk of CVD in T2DM patients. The ROC curve analysis to evaluate the usefulness of DKK1 as a marker for high risk of CVD showed an area under the curve of 0,667 (95% CI: 0,538-0,795; P = 0,016. In addition, there was a positive correlation between serum DKK1 and spine bone mineral density in the total sample (r =  0,183; P = 0,048. CONCLUSION: In summary, circulating DKK1 levels are higher in T2DM with CVD and are associated with an abnormal carotid IMT in this cross-sectional study. DKK1 may be involved in vascular disease of T2DM patients.

  14. BONE IN OSTEOPETROSIS

    Directory of Open Access Journals (Sweden)

    Ramkumar

    2014-04-01

    Full Text Available Osteopetrosis, a generalized developmental bone disease due to genetic disturbances, characterized by failure of bone re sorption and continuous bone formation making the bone hard, dense and brittle. Bones of intramembranous ossification and enchondrial ossification are affected genetically and symmetrically. During the process of disease the excess bone formation obliterates the cranial foramina and presses the optic, auditory and facial nerves resulting in defective vision, impaired hearing and facial paralysis. The bone formation in osteopetrosis affects bone marrow function leading to severe anemia and deficient of blood cells. The bone devoid of blood supply due to compression of blood vessels by excess formation of bone are prone to osteomyelitic changes with suppuration and pathological fracture if exposed to infection. Though the condition is chronic progressive, it produces changes leading to fatal condition, it should be studied thoroughly by everyone and hence this article presents a classical case of osteopetrosis with detailed description and discussion for the benefit of readers

  15. Diabetes, Biochemical Markers of Bone Turnover, Diabetes Control, and Bone

    OpenAIRE

    Starup-Linde, Jakob

    2013-01-01

    Diabetes mellitus is known to have late complications including micro vascular and macro vascular disease. This review focuses on another possible area of complication regarding diabetes; bone. Diabetes may affect bone via bone structure, bone density, and biochemical markers of bone turnover. The aim of the present review is to examine in vivo from humans on biochemical markers of bone turnover in diabetics compared to non-diabetics. Furthermore, the effect of glycemic control on bone marker...

  16. Bone tumor

    Science.gov (United States)

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor; Bone tumor - benign ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  17. Meat and bone meal and mineral feed additives may increase the risk of oral prion disease transmission

    Science.gov (United States)

    Johnson, Christopher J.; McKenzie, Debbie; Pedersen, Joel A.; Aiken, Judd M.

    2011-01-01

    Ingestion of prion-contaminated materials is postulated to be a primary route of prion disease transmission. Binding of prions to soil (micro)particles dramatically enhances peroral disease transmission relative to unbound prions, and it was hypothesized that micrometer-sized particles present in other consumed materials may affect prion disease transmission via the oral route of exposure. Small, insoluble particles are present in many substances, including soil, human foods, pharmaceuticals, and animal feeds. It is known that meat and bone meal (MBM), a feed additive believed responsible for the spread of bovine spongiform encephalopathy (BSE), contains particles smaller than 20 μm and that the pathogenic prion protein binds to MBM. The potentiation of disease transmission via the oral route by exposure to MBM or three micrometer-sized mineral feed additives was determined. Data showed that when the disease agent was bound to any of the tested materials, the penetrance of disease was increased compared to unbound prions. Our data suggest that in feed or other prion-contaminated substances consumed by animals or, potentially, humans, the addition of MBM or the presence of microparticles could heighten risks of prion disease acquisition.

  18. Meat and bone meal and mineral feed additives may increase the risk of oral prion disease transmission.

    Science.gov (United States)

    Johnson, Christopher J; McKenzie, Debbie; Pedersen, Joel A; Aiken, Judd M

    2011-01-01

    Ingestion of prion-contaminated materials is postulated to be a primary route of prion disease transmission. Binding of prions to soil (micro)particles dramatically enhances peroral disease transmission relative to unbound prions, and it was hypothesized that micrometer-sized particles present in other consumed materials may affect prion disease transmission via the oral route of exposure. Small, insoluble particles are present in many substances, including soil, human foods, pharmaceuticals, and animal feeds. It is known that meat and bone meal (MBM), a feed additive believed responsible for the spread of bovine spongiform encephalopathy (BSE), contains particles smaller than 20 μm and that the pathogenic prion protein binds to MBM. The potentiation of disease transmission via the oral route by exposure to MBM or three micrometer-sized mineral feed additives was determined. Data showed that when the disease agent was bound to any of the tested materials, the penetrance of disease was increased compared to unbound prions. Our data suggest that in feed or other prion-contaminated substances consumed by animals or, potentially, humans, the addition of MBM or the presence of microparticles could heighten risks of prion disease acquisition.

  19. Effect of age and disease on bone mass in Japanese patients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Sugawara Norio

    2012-02-01

    Full Text Available Abstract Background There have been a limited number of studies comparing bone mass between patients with schizophrenia and the general population. The aim of this study was to compare the bone mass of schizophrenia patients with that of healthy subjects in Japan. Methods We recruited patients (n = 362, aged 48.8 ± 15.4 (mean ± SD years who were diagnosed with schizophrenia or schizoaffective disorder based on the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV. Bone mass was measured using quantitative ultrasound densitometry of the calcaneus. The osteosono-assessment index (OSI was calculated as a function of the speed of sound and the transmission index. For comparative analysis, OSI data from 832 adults who participated in the Iwaki Health Promotion Project 2009 was used as representative of the general community. Results Mean OSI values among male schizophrenic patients were lower than those in the general population in the case of individuals aged 40 and older. In females, mean OSI values among schizophrenic patients were lower than those in the general community in those aged 60 and older. In an analysis using the general linear model, a significant interaction was observed between subject groups and age in males. Conclusions Older schizophrenic patients exhibit lower bone mass than that observed in the general population. Our data also demonstrate gender and group differences among schizophrenic patients and controls with regard to changes in bone mass associated with aging. These results indicate that intervention programs designed to delay or prevent decreased bone mass in schizophrenic patients might be tailored according to gender.

  20. Inflammatory diseases of the petrous portion of the temporal bone; Entzuendliche Erkrankungen des Felsenbeins

    Energy Technology Data Exchange (ETDEWEB)

    Koerner, H. [Universitaetsklinikum des Saarlandes, Klinik fuer Diagnostische und Interventionelle Neuroradiologie, Homburg/Saar (Germany)

    2014-04-15

    Inflammatory lesions of the petrous portion of the temporal bone are very common and can be followed by cerebral complications. Thin layer computed tomography (CT) is useful for detecting bony changes of the temporal bone and contrast-enhanced magnetic resonance imaging (CE MRI) is a sensitive method for detecting cerebral complications. (orig.) [German] Entzuendliche Erkrankungen des Felsenbeins sind sehr haeufig und koennen mit zerebralen Komplikationen einhergehen. Mit der Duennschicht-CT lassen sich sehr gut ossaere Veraenderungen im Felsenbein nachweisen. Die kontrastmittelgestuetzte MRT ist sensitiv fuer zerebrale Komplikationen. (orig.)

  1. Bone marrow depletion with haemorrhagic diathesis in calves in Germany: characterization of the disease and preliminary investigations on its aetiology.

    Science.gov (United States)

    Kappe, Eva C; Halami, Mohammad Yahya; Schade, Benjamin; Alex, Michaela; Hoffmann, Doris; Gangl, Armin; Meyer, Karsten; Dekant, Wolfgang; Schwarz, Bernd-Andreas; Johne, Reimar; Buitkamp, Johannes; Böttcher, Jens; Müller, Hermann

    2010-01-01

    Since 2007 a new fatal haemorrhagic diathesis in calves has been observed in all areas of Germany. Analysis of 56 cases submitted for necropsy allowed its characterization. Calves fell ill within the first month of life independent of breed and sex. Only single or a few animals per herd were affected. Petechial and ecchymotic haemorrhages in many organs and tissues, particularly in skin, subcutis and gastrointestinal tract, were major findings in all animals. Microscopically a severe depletion of bone marrow cells was always observed. Lymphocytic depletion (43%) and inflammatory lesions (46%) were less frequently observed. Blood analysis of five animals indicated an aplastic pancytopenia. The resulting thrombocytopenia is regarded as major pathomechanism of this Haemorrhagic Disease Syndrome (HDS). Pedigree analysis gave no indication of hereditary disease. Tests for specific toxins such as S-(1,2-Dichlorovinyl)-L-cysteine (DCVC), furazolidone, or mycotoxins resulting in bone marrow depletion were negative. Bacterial infections, Bovine Viral Diarrhoea Virus, and Bluetongue Virus were ruled out as cause of the disease. HDS shares similarities with a circoviral infection in chickens (chicken infectious anaemia). A broad-spectrum PCR allowed detection of circoviral DNA in 5 of 25 HDS cases and in 1 of 8 non-HDS cases submitted for necropsy. Sequencing of the whole viral genome revealed a high similarity (up to 99%) with Porcine Circovirus type 2b. Single bone marrow cells stained weakly positive for PCV2 antigen by immunohistochemistry in 1 of 8 tested HDS animals. This is the first report of circovirus detection in cattle in Germany. The exact cause of HDS still remains unknown. A multifactorial aetiology involving infection, poisoning, immunopathy, or a genetic predisposition is conceivable. Additional research is necessary to clarify the pathogenesis and the potential role of PCV2 in HDS.

  2. Feasibility and safety of autologous bone marrow mononuclear cell transplantation in patients with advanced chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    Andre Castro Lyra; Bernd Genser; Ricardo Ribeiro dos Santos; Luiz Guilherme Costa Lyra; Milena Botelho Pereira Soares; Luiz Flavio Maia da Silva; Marcos Fraga Fortes; André Goyanna Pinheiro Silva; Augusto César de Andrade Mota; Sheilla A Oliveira; Eduardo Lorens Braga; Wilson Andrade de Carvalho

    2007-01-01

    AIM:To evaluate the safety and feasibility of bone marrow cell(BMC)transplantation in patients with chronic liver disease on the waiting list for liver transplantation.METHODS:Ten patients(eight males)with chronic liver disease were enrolled to receive infusion of autologous bone marrow-derived cells.Seven patients were classified as Child-Pugh B and three as Child-Pugh C.Baseline assessment included complete clinical and laboratory evaluation and abdominal MRI.Approximately 50 mL of bone marrow aspirate was prepared by centrifugation in a ficoll-hypaque gradient.At least of 100 millions of mononuclear-enriched BMCs were infused into the hepatic artery using the routine technique for arterial chemoembolization for liver tumors.Patients were followed up for adverse events up to 4 mo.RESULTS:The median age of the patients was 52 years(range 24-70 years).All patients were discharged 48 h after BMC infusion.Two patients complained of mild pain at the bone marrow needle puncture site.No other complications or specific side effects related to the procedure were observed.Bilirubin levels were lower at 1(2.19 ± 0.9)and 4 mo(2.10 ± 1.0)after cell transplantation that baseline levels(2.78 ± 1.2).Albumin levels 4 mo after BMC infusion(3.73 ± 0.5)were higher than baseline levels(3.47 ± 0.5).International normalized ratio(INR)decreased from 1.48(SD = 0.23)to 1.43(SD = 0.23)one month after cell transplantation.CONCLUSION:BMC infusion into hepatic artery of patients with advanced chronic liver disease is safe and feasible.In addition,a decrease in mean serum bilirubin and INR levels and an increase in albumin levels are observed.Our data warrant further studies in order to evaluate the effect of BMC transplantation in patients with advanced chronic liver disease.

  3. Non-alcoholic fatty liver disease connections with fat-free tissues: A focus on bone and skeletal muscle

    Science.gov (United States)

    Poggiogalle, Eleonora; Donini, Lorenzo Maria; Lenzi, Andrea; Chiesa, Claudio; Pacifico, Lucia

    2017-01-01

    The estimates of global incidence and prevalence of non-alcoholic fatty liver disease (NAFLD) are worrisome, due to the parallel burden of obesity and its metabolic complications. Indeed, excess adiposity and insulin resistance represent two of the major risk factors for NAFLD; interestingly, in the last years a growing body of evidence tended to support a novel mechanistic perspective, in which the liver is at the center of a complex interplay involving organs and systems, other than adipose tissue and glucose homeostasis. Bone and the skeletal muscle are fat- free tissues which appeared to be independently associated with NAFLD in several cross-sectional studies. The deterioration of bone mineral density and lean body mass, leading to osteoporosis and sarcopenia, respectively, are age-related processes. The prevalence of NAFLD also increases with age. Beyond physiological aging, the three conditions share some common underlying mechanisms, and their elucidations could be of paramount importance to design more effective treatment strategies for the management of NAFLD. In this review, we provide an overview on epidemiological data as well as on potential contributors to the connections of NAFLD with bone and skeletal muscle.

  4. Dual photon absorptiometry in patients with Paget disease (bone mineral contents of lumbar spine and femoral neck)

    Energy Technology Data Exchange (ETDEWEB)

    Talbot, J.N.; Piketty, C.; Kiffel, T.; Coutris, G.; Milhaud, G.

    1988-01-01

    The bone mineral contents (BMC) of the lumbar spine (84 cases) and of one femoral neck (53 cases) were measured by dual photon absorptiometry (DPA) in patients suffering from Paget's disease of bone. The BMC of the patients and of 53 controls were compared, taking into account the occurrence of a scintigraphic hyperfixation, in each patient. A hyperfixation of the technetium labelled diphosphonate in the lumbar spine, more frequent in males, was associated with an elevated mean BMC value. The difference versus controls was significant in men but not in women. A hyperfixation of the femoral neck was associated with an elevated mean BMC value in both sexes. BMC values greater than the mean BMC of controls + 2 SD were observed in 83 per cent of these male patients and 50 per cent of the females. In contrast, BMC values lower than in controls were observed in non-pagetic areas. DPA allows the quantification of these abnormalities which cannot be evidenced by bone scintigraphy even if alkaline phosphatases levels are assayed.

  5. Metabolic bone disease in lion cubs at the London Zoo in 1889: the original animal model of rickets.

    Science.gov (United States)

    Chesney, Russell W; Hedberg, Gail

    2010-08-24

    In 1889 Dr. John Bland-Sutton, a prominent London surgeon, was consulted about fatal rickets in over 20 successive litters of lion cubs born at the London Zoo. He evaluated the diet and found the cause of rickets to be nutritional in origin. He recommended that goat meat with crushed bones and cod-liver oil be added to the lean horsemeat diet of the cubs and their mothers. Rickets were reversed, the cubs survived, and subsequent litters thrived. Thirty years later, in classic controlled studies conducted in puppies and young rats, the definitive role of calcium, phosphate and vitamin D in prevention and therapy of rickets was elucidated. Further studies led to identifying the structural features of vitamin D.Although the Bland-Sutton diet provided calcium and phosphate from bones and vitamins A and D from cod-liver oil, some other benefits of this diet were not recognized. Taurine-conjugated bile salts, necessary for intestinal absorption of fat-soluble vitamins, were provided in the oil cold-pressed from cod liver. Unlike canine and rodent species, felines are unable to synthesize taurine, yet conjugate bile acids exclusively with taurine; hence, it must be provided in the diet. The now famous Bland-Sutton "experiment of nature," fatal rickets in lion cubs, was cured by addition of minerals and vitamin D. Taurine-conjugated bile salts undoubtedly permitted absorption of vitamins A and D, thus preventing the occurrence of metabolic bone disease and rickets.

  6. Reconversion of bone marrow in Gaucher disease treated with enzyme therapy documented by MR

    Energy Technology Data Exchange (ETDEWEB)

    Allison, J.W.; James, C.A. [Department of Radiology, Arkansas Children`s Hospital, Little Rock, AR (United States); Arnold, G.L.; Stine, K.C.; Becton, D.L. [Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children`s Hospital, Little Rock, Arkansas (United States); Bell, J.M. [Department of Pathology, University of Arkansas for Medical Sciences, Arkansas Children`s Hospital, Little Rock, Arkansas (United States)

    1998-04-01

    Background. Skeletal complications are responsible for significant morbidity in Gaucher patients. Plain radiographs have been unreliable in assessing bone marrow infiltration and activity. A way to assess bone marrow improvement is needed during enzyme therapy. Objective. The purpose of this paper is to assess the usefulness of MR in following improvement of abnormal bone marrow in Gaucher patients on enzyme therapy. Materials and methods. Three patients aged 2, 7, and 24 years underwent serial MR scans of the lower extremities before and during treatment with Alglucerase (two patients) and Imiglucerase (one patient). T1-weighted, T2-weighted, STIR and FSE T2-weighted images were utilized. Two patients were imaged after 16 months of therapy, and one patient was imaged after 6 months of therapy. Results. All patients had improvement in marrow signal consistent with partial reconversion to fatty marrow during treatment. The findings were more marked after prolonged therapy. T1-weighted images demonstrated findings most clearly. Conclusion. MR consistently showed improvement in marrow signal in Gaucher patients on enzyme therapy. As smaller doses of enzyme therapy are the trend, MR can be utilized to determine if therapy is effecting a change in the bone marrow. (orig.) With 2 figs., 2 tabs., 7 refs.

  7. Reliability analysis of instrument design of noninvasive bone marrow disease detector

    Science.gov (United States)

    Su, Yu; Li, Ting; Sun, Yunlong

    2016-02-01

    Bone marrow is an important hematopoietic organ, and bone marrow lesions (BMLs) may cause a variety of complications with high death rate and short survival time. Early detection and follow up care are particularly important. But the current diagnosis methods rely on bone marrow biopsy/puncture, with significant limitations such as invasion, complex operation, high risk, and discontinuous. It is highly in need of a non-invasive, safe, easily operated, and continuous monitoring technology. So we proposed to design a device aimed for detecting bone marrow lesions, which was based on near infrared spectrum technology. Then we fully tested its reliabilities, including the sensitivity, specificity, signal-to-noise ratio (SNR), stability, and etc. Here, we reported this sequence of reliability test experiments, the experimental results, and the following data analysis. This instrument was shown to be very sensitive, with distinguishable concentration less than 0.002 and with good linearity, stability and high SNR. Finally, these reliability-test data supported the promising clinical diagnosis and surgery guidance of our novel instrument in detection of BMLs.

  8. Bariatric surgery and bone disease: from clinical perspective to molecular insights.

    Science.gov (United States)

    Folli, F; Sabowitz, B N; Schwesinger, W; Fanti, P; Guardado-Mendoza, R; Muscogiuri, G

    2012-11-01

    The use of bariatric surgery for the treatment of morbid obesity has increased annually for the last decade. Although many studies have demonstrated the efficacy and durability of bariatric surgery for weight loss, there are limited data regarding long-term side effects of these procedures. Recently, there has been an increased focus on the impact of bariatric surgery on bone metabolism. Bariatric surgery utilizes one or more of three mechanisms of action resulting in sustained weight loss. These include restriction (gastric banding, vertical banded gastroplasty and sleeve gastrectomy), malabsorption surgery with or without associated restriction (Roux en Y gastric bypass, duodenal switch, biliopancreatic diversion and jejunoileal bypass) and changes in gut-derived hormones that control energy metabolism also referred to as neuro-hormonal control of energy metabolism (Roux en Y gastric bypass, duodenal switch, biliopancreatic diversion, jejunoileal bypass, surgical procedures as above and gastric sleeve). Weight reduction has been associated with increased bone resorption but the mechanisms behind this have not yet been fully elucidated. Each of the mechanisms of action of bariatric surgery (restriction, malabsorption, neuro-hormonal control of energy metabolism) may uniquely affect bone resorption. In this paper we will review the current state of knowledge regarding the relationship between bariatric surgery and bone metabolism with emphasis on possible mechanisms of action such as malnutrition, hormonal interactions and mechanical unloading of the skeleton. Further, we suggest a future research agenda.

  9. Evaluation of /sup 99m/Tc diphosphonate kinetics and bone scans in patients with Paget's disease before and after calcitonin treatment

    Energy Technology Data Exchange (ETDEWEB)

    Waxman, A.D.; Ducker, S.; McKee, D.; Siemsen, J.K.; Singer, F.R.

    1977-12-01

    Eleven patients with Paget's disease of bone underwent serial total body bone scans before and after therapy with calcitonin. All patients studied showed improvement clinically as well as biochemically. Scan improvement was noted in patients with mild disease. Patients with severe disease showed either no change or only slight improvement on the serial bone scans. The scan was of greatest value in determining the extent of disease, especially in 3 patients in whom biochemical values were normal. A single pulse injection of 50 M.R.C. units of salmon calcitonin produced a significant increase in the blood clearance of /sup 99m/Tc diphosphonate. The mechanism of this effect is not clear from this study.

  10. Bone Marrow and Kidney Transplant for Patients With Chronic Kidney Disease and Blood Disorders

    Science.gov (United States)

    2017-03-21

    Chronic Kidney Disease; Acute Myeloid Leukemia (AML); Acute Lymphoblastic Leukemia (ALL); Chronic Myelogenous Leukemia (CML); Chronic Lymphocytic Leukemia (CLL); Non-Hodgkin's Lymphoma (NHL); Hodgkin Disease; Multiple Myeloma; Myelodysplastic Syndrome (MDS); Aplastic Anemia; AL Amyloidosis; Diamond Blackfan Anemia; Myelofibrosis; Myeloproliferative Disease; Sickle Cell Anemia; Autoimmune Diseases; Thalassemia

  11. NOD/SCID-GAMMA mice are an ideal strain to assess the efficacy of therapeutic agents used in the treatment of myeloma bone disease.

    Science.gov (United States)

    Lawson, Michelle A; Paton-Hough, Julia M; Evans, Holly R; Walker, Rebecca E; Harris, William; Ratnabalan, Dharshi; Snowden, John A; Chantry, Andrew D

    2015-01-01

    Animal models of multiple myeloma vary in terms of consistency of onset, degree of tumour burden and degree of myeloma bone disease. Here we describe five pre-clinical models of myeloma in NOD/SCID-GAMMA mice to specifically study the effects of therapeutic agents on myeloma bone disease. Groups of 7-8 week old female irradiated NOD/SCID-GAMMA mice were injected intravenously via the tail vein with either 1x106 JJN3, U266, XG-1 or OPM-2 human myeloma cell lines or patient-derived myeloma cells. At the first signs of morbidity in each tumour group all animals were sacrificed. Tumour load was measured by histological analysis, and bone disease was assessed by micro-CT and standard histomorphometric methods. Mice injected with JJN3, U266 or OPM-2 cells showed high tumour bone marrow infiltration of the long bones with low variability, resulting in osteolytic lesions. In contrast, mice injected with XG-1 or patient-derived myeloma cells showed lower tumour bone marrow infiltration and less bone disease with high variability. Injection of JJN3 cells into NOD/SCID-GAMMA mice resulted in an aggressive, short-term model of myeloma with mice exhibiting signs of morbidity 3 weeks later. Treating these mice with zoledronic acid at the time of tumour cell injection or once tumour was established prevented JJN3-induced bone disease but did not reduce tumour burden, whereas, carfilzomib treatment given once tumour was established significantly reduced tumour burden. Injection of U266, XG-1, OPM-2 and patient-derived myeloma cells resulted in less aggressive longer-term models of myeloma with mice exhibiting signs of morbidity 8 weeks later. Treating U266-induced disease with zoledronic acid prevented the formation of osteolytic lesions and trabecular bone loss as well as reducing tumour burden whereas, carfilzomib treatment only reduced tumour burden. In summary, JJN3, U266 or OPM-2 cells injected into NOD/SCID-GAMMA mice provide robust models to study anti-myeloma therapies

  12. NOD/SCID-GAMMA mice are an ideal strain to assess the efficacy of therapeutic agents used in the treatment of myeloma bone disease.

    Directory of Open Access Journals (Sweden)

    Michelle A Lawson

    Full Text Available Animal models of multiple myeloma vary in terms of consistency of onset, degree of tumour burden and degree of myeloma bone disease. Here we describe five pre-clinical models of myeloma in NOD/SCID-GAMMA mice to specifically study the effects of therapeutic agents on myeloma bone disease. Groups of 7-8 week old female irradiated NOD/SCID-GAMMA mice were injected intravenously via the tail vein with either 1x106 JJN3, U266, XG-1 or OPM-2 human myeloma cell lines or patient-derived myeloma cells. At the first signs of morbidity in each tumour group all animals were sacrificed. Tumour load was measured by histological analysis, and bone disease was assessed by micro-CT and standard histomorphometric methods. Mice injected with JJN3, U266 or OPM-2 cells showed high tumour bone marrow infiltration of the long bones with low variability, resulting in osteolytic lesions. In contrast, mice injected with XG-1 or patient-derived myeloma cells showed lower tumour bone marrow infiltration and less bone disease with high variability. Injection of JJN3 cells into NOD/SCID-GAMMA mice resulted in an aggressive, short-term model of myeloma with mice exhibiting signs of morbidity 3 weeks later. Treating these mice with zoledronic acid at the time of tumour cell injection or once tumour was established prevented JJN3-induced bone disease but did not reduce tumour burden, whereas, carfilzomib treatment given once tumour was established significantly reduced tumour burden. Injection of U266, XG-1, OPM-2 and patient-derived myeloma cells resulted in less aggressive longer-term models of myeloma with mice exhibiting signs of morbidity 8 weeks later. Treating U266-induced disease with zoledronic acid prevented the formation of osteolytic lesions and trabecular bone loss as well as reducing tumour burden whereas, carfilzomib treatment only reduced tumour burden. In summary, JJN3, U266 or OPM-2 cells injected into NOD/SCID-GAMMA mice provide robust models to study anti

  13. Bone Density Is Directly Associated With Glomerular Filtration and Metabolic Acidosis but Do Not Predict Fragility Fractures in Men With Moderate Chronic Kidney Disease.

    Science.gov (United States)

    Lima, Guilherme Alcantara Cunha; de Paula Paranhos-Neto, Francisco; Silva, Luciana Colonese; de Mendonça, Laura Maria Carvalho; Delgado, Alvimar Gonçalves; Leite, Maurilo; Gomes, Carlos Perez; Farias, Maria Lucia Fleiuss

    2016-01-01

    Hyperparathyroidism, vitamin D deficiency, increased fibroblast growth factor-23 (FGF-23), and metabolic acidosis promote bone fragility in chronic kidney disease (CKD). Although useful in predicting fracture risk in the general population, the role of dual-energy X-ray absorptiometry (DXA) in CKD remains uncertain. This cross-sectional study included 51 men aged 50-75 yr with moderate CKD. The stage 4 CKD patients had higher levels of parathyroid hormone (pmetabolic acidosis for bone impairment and to the inadequacy of DXA to evaluate bone fragility in CKD patients.

  14. Low Infection Rate after Tumor Hip Arthroplasty for Metastatic Bone Disease in a Cohort Treated with Extended Antibiotic Prophylaxis

    Directory of Open Access Journals (Sweden)

    Werner H. Hettwer

    2015-01-01

    Full Text Available Background. Compared to conventional hip arthroplasty, endoprosthetic reconstruction after tumor resection is associated with a substantially increased risk of periprosthetic joint infection (PJI, with reported rates of around 10% in a recent systematic review. The optimal duration of antibiotic prophylaxis for this patient population remains unknown. Material and Methods. To establish the infection rate associated with prolonged antibiotic prophylaxis in our department, we performed a retrospective review of all adult patients who underwent endoprosthetic reconstruction of the proximal femur after tumor resection for metastatic bone disease during a 4-year period from 2010 to 2013 (n=105 patients. Results. Intravenous antibiotic prophylaxis was administrated for an extended duration of a mean of 7.4 days. The overall infection rate was 3.6% (4/111 implants, infection free survival was 96% at 2 years, and the risk of amputation associated with infection was 25% (1/4 patients. Discussion. Preemptive eradication of bacterial contamination may be of value in certain clinical situations, where the risk level and consequences of implant-associated infection are unacceptable. Our findings suggest that extended postoperative antibiotic prophylaxis may reduce the risk of PJI in patients undergoing tumor resection and endoprosthetic replacement for metastatic bone disease associated impending or de facto pathologic fractures of the proximal femur.

  15. Low Infection Rate after Tumor Hip Arthroplasty for Metastatic Bone Disease in a Cohort Treated with Extended Antibiotic Prophylaxis

    Science.gov (United States)

    Hettwer, Werner H.; Horstmann, Peter Frederik; Hovgaard, Thea Bechmann; Grum-Scwensen, Tomas Andreas; Petersen, Michael M.

    2015-01-01

    Background. Compared to conventional hip arthroplasty, endoprosthetic reconstruction after tumor resection is associated with a substantially increased risk of periprosthetic joint infection (PJI), with reported rates of around 10% in a recent systematic review. The optimal duration of antibiotic prophylaxis for this patient population remains unknown. Material and Methods. To establish the infection rate associated with prolonged antibiotic prophylaxis in our department, we performed a retrospective review of all adult patients who underwent endoprosthetic reconstruction of the proximal femur after tumor resection for metastatic bone disease during a 4-year period from 2010 to 2013 (n = 105 patients). Results. Intravenous antibiotic prophylaxis was administrated for an extended duration of a mean of 7.4 days. The overall infection rate was 3.6% (4/111 implants), infection free survival was 96% at 2 years, and the risk of amputation associated with infection was 25% (1/4 patients). Discussion. Preemptive eradication of bacterial contamination may be of value in certain clinical situations, where the risk level and consequences of implant-associated infection are unacceptable. Our findings suggest that extended postoperative antibiotic prophylaxis may reduce the risk of PJI in patients undergoing tumor resection and endoprosthetic replacement for metastatic bone disease associated impending or de facto pathologic fractures of the proximal femur. PMID:25705521

  16. Low infection rate after tumor hip arthroplasty for metastatic bone disease in a cohort treated with extended antibiotic prophylaxis.

    Science.gov (United States)

    Hettwer, Werner H; Horstmann, Peter Frederik; Hovgaard, Thea Bechmann; Grum-Scwensen, Tomas Andreas; Petersen, Michael M

    2015-01-01

    Background. Compared to conventional hip arthroplasty, endoprosthetic reconstruction after tumor resection is associated with a substantially increased risk of periprosthetic joint infection (PJI), with reported rates of around 10% in a recent systematic review. The optimal duration of antibiotic prophylaxis for this patient population remains unknown. Material and Methods. To establish the infection rate associated with prolonged antibiotic prophylaxis in our department, we performed a retrospective review of all adult patients who underwent endoprosthetic reconstruction of the proximal femur after tumor resection for metastatic bone disease during a 4-year period from 2010 to 2013 (n = 105 patients). Results. Intravenous antibiotic prophylaxis was administrated for an extended duration of a mean of 7.4 days. The overall infection rate was 3.6% (4/111 implants), infection free survival was 96% at 2 years, and the risk of amputation associated with infection was 25% (1/4 patients). Discussion. Preemptive eradication of bacterial contamination may be of value in certain clinical situations, where the risk level and consequences of implant-associated infection are unacceptable. Our findings suggest that extended postoperative antibiotic prophylaxis may reduce the risk of PJI in patients undergoing tumor resection and endoprosthetic replacement for metastatic bone disease associated impending or de facto pathologic fractures of the proximal femur.

  17. Bone marrow oedema on MR imaging indicates ARCO stage 3 disease in patients with AVN of the femoral head

    Energy Technology Data Exchange (ETDEWEB)

    Meier, Reinhard; Schaeffeler, Christoph; Waldt, Simone; Rummeny, Ernst J.; Woertler, Klaus [Klinikum rechts der Isar, Technische Universitaet Muenchen, Department of Diagnostic and Interventional Radiology, Munich (Germany); Kraus, Tobias M. [Klinikum rechts der Isar, Technische Universitaet Muenchen, Department of Orthopaedics, Munich (Germany); Berufsgenossenschaftliche Unfallklinik Tuebingen, Department of Trauma and Orthopaedics, Tuebingen (Germany); Torka, Sebastian [Klinikum rechts der Isar, Technische Universitaet Muenchen, Department of Orthopaedics, Munich (Germany); Berufsgenossenschaftliche Unfallklinik Murnau, Department of Trauma and Orthopaedics, Murnau (Germany); Schlitter, Anna Melissa; Specht, Katja [Klinikum rechts der Isar, Technische Universitaet Muenchen, Institute of Pathology, Munich (Germany); Haller, Bernhard [Klinikum rechts der Isar, Technische Universitaet Muenchen, Institute of Medical Statistics and Epidemiology, Munich (Germany); Rechl, Hans [Klinikum rechts der Isar, Technische Universitaet Muenchen, Department of Orthopaedics, Munich (Germany)

    2014-09-15

    To test the hypothesis that bone marrow oedema (BME) observed on MRI in patients with avascular necrosis (AVN) of the femoral head represents an indicator of subchondral fracture. Thirty-seven symptomatic hips of 27 consecutive patients (53 % women, mean age 49.2) with AVN of the femoral head and associated BME on magnetic resonance (MR) imaging were included. MR findings were correlated with computed tomography (CT) of the hip and confirmed by histopathological examination of the resected femoral head. Imaging studies were analysed by two radiologists with use of the ARCO classification. On MR imaging a fracture line could be identified in 19/37 (51 %) cases, which were classified as ARCO stage 3 (n = 15) and stage 4 (n = 4). The remaining 18/37 (49 %) cases were classified as ARCO stage 2. However, in all 37/37 (100 %) cases a subchondral fracture was identified on CT, indicating ARCO stage 3/4 disease. The extent of subchondral fractures and the femoral head collapse was graded higher on CT as compared to MRI (P < 0.05). Histopathological analysis confirmed bone necrosis and subchondral fractures. In patients with AVN, BME of the femoral head represents a secondary sign of subchondral fracture and thus indicates ARCO stage 3 disease. circle BME on MRI in AVN of femoral head indicates a subchondral fracture. (orig.)

  18. Giant Cell Tumor Developing in Paget’s Disease of Bone: A Case Report with Review of Literature

    Science.gov (United States)

    Verma, Vivek; Puri, Ajay; Shah, Sanket; Rekhi, Bharat; Gulia, Ashish

    2016-01-01

    Introduction: Paget’s disease of bone (PDB) is a disease of elderly characterized by disorganized bone remodeling. Development of secondary neoplasm in PDB is a known but rare phenomenon. Development of giant cell tumor in PDB (GCT-PDB) is extremely rare, and little is known about its etiopathogenesis and management. We present a case report of such a development with a review of the literature and the role of various new modalities of treatment available in the management of this rare condition. Case Report: A 40-year-old gentleman presented with back pain and on evaluation was diagnosed as a case of polyostotic PDB. He was treated with intravenous bisphosphonates, calcium, and vitamin D supplements. After an asymptomatic period of 3-year, he presented with a gluteal mass involving ilium and sacrum which was confirmed as GCT on biopsy. Serial angioembolization was attempted but mass progressed, so surgery performed with excision and curettage of the lesion. He presented with a local recurrence 2 years later with a large soft tissue component. He was started on denosumab, RANKL inhibitor, with the aim to downstage the lesion. The patient showed a good response after 6 doses with reduction in soft tissue mass followed by which he underwent surgery with partial T-1 internal hemipelvectomy and curettage of sacrum. Currently, the patient is asymptomatic at a follow-up of 15 months. Conclusion: GCT-PDB is a rare phenomenon occurring mainly in polyostotic PDB and is associated with more severe manifestations of the disease. The management is challenging and requires multimodality management. Pharmacological agents include use of bisphosphonates and RANK ligand inhibitor - denosumab. Although surgery is the mainstay of treatment for GCT, other modalities of treatment such as RANK ligand inhibitors (denosumab), selective arterial embolization, or radiation therapy has to be used for inoperable cases or where surgery would be functionally too morbid, especially in cases

  19. The impact of bone marrow micrometastases on metastatic disease-free survival in patients with colorectal carcinoma.

    LENUS (Irish Health Repository)

    O'Connor, O J

    2012-02-03

    AIMS: The biological relevance of bone marrow micrometastases (BMM) in colorectal cancer remains unknown. Here, we investigate their nature by examining the impact of the presence of BMM on metastatic disease-free survival in a cohort of patients with this disease. METHODS: Sixty-three consecutive patients undergoing surgery for colorectal cancer of any stage were studied after approval of the study protocol by the local ethics committee and with full individual informed consent. All had bilateral iliac crest bone marrow aspirates prior to operation. Aspirates were then examined for the presence of aberrant cytokeratin-18-positive cells by a blinded observer using both flow cytometric and APAAP immunohistochemical techniques. RESULTS: Mean follow-up after surgery was 4.6 years (range 1.9-6.9) for those without hepatic metastases at diagnosis. Seven of 34 patients with Dukes\\' stage A or B developed metastatic disease after a mean interval of 4.7 years (range 3.8-6.8). However, only 2 of these patients demonstrated BMM at the time of surgery. Nine of 15 patients with Dukes\\' C carcinoma at the time of surgery subsequently developed metastases after a mean interval of 4.4 years (range 1.9-6.9). Again, only two of these patients had BMM detectable initially. In only three of the 14 patients known to have metastases at the time of operation (i.e. Dukes\\'\\'D\\' disease) were BMM found. CONCLUSION: The presence of BMM as detected by this methodology was not predictive of tumour recurrence or metastasis. This study does not support the consideration of adjuvant therapy based on the presence of BMM at a single pre-operative time point in patients with colorectal cancer.

  20. Pediatric and adult MRI atlas of bone marrow. Normal appearances, variants and diffuse disease states

    Energy Technology Data Exchange (ETDEWEB)

    Ilaslan, Hakan; Sundaram, Murali [Cleveland Clinic Lerner College of Medicine, OH (United States); Cleveland Clinic Department of Radiology, OH (United States)

    2016-08-01

    This comprehensive atlas is unique in being devoted to the MRI appearances of bone marrow in the axial and appendicular skeleton of adults and children. Normal MRI findings, including common variants and degenerative changes, are first documented. MRI appearances in the entire spectrum of neoplastic and non-neoplastic infiltrative marrow disorders are then presented, with accompanying explanatory text. Among the conditions considered are multiple myeloma, the acute and chronic leukemias, diffuse metastases, diffuse lymphomas, the anemias, polycythemia vera, myelofibrosis, storage disorders, and infections. Characteristic changes to bone marrow following various forms of treatment are also displayed and discussed. The selected images reflect the use of a variety of sequences and techniques, such as fat suppression, and contrast-enhanced imaging.

  1. Metabolic bone disease in the preterm infant: Current state and future directions

    Science.gov (United States)

    Rehman, Moghis Ur; Narchi, Hassib

    2015-01-01

    Neonatal osteopenia is an important area of interest for neonatologists due to continuing increased survival of preterm infants. It can occur in high-risk infants such as preterm infants, infants on long-term diuretics or corticosteroids, and those with neuromuscular disorders. Complications such as rickets, pathological fractures, impaired respiratory function and poor growth in childhood can develop and may be the first clinical evidence of the condition. It is important for neonatologists managing such high-risk patients to regularly monitor biochemical markers for evidence of abnormal bone turnover and inadequate mineral intake in order to detect the early phases of impaired bone mineralization. Dual-energy X-ray absorptiometry has become an increasingly used research tool for assessing bone mineral density in children and neonates, but more studies are still needed before it can be used as a useful clinical tool. Prevention and early detection of osteopenia are key to the successful management of this condition and oral phosphate supplements should be started as soon as is feasible. PMID:26413483

  2. The relation between bone mineral density, bone turnover markers, and vitamin D status in ankylosing spondylitis patients with active disease : a cross-sectional analysis

    NARCIS (Netherlands)

    Arends, S.; Spoorenberg, A.; Bruyn, G. A. W.; Houtman, P. M.; Leijsma, M. K.; Kallenberg, C. G. M.; Brouwer, E.; van der Veer, E.

    2011-01-01

    Osteoporosis is a well recognized complication of ankylosing spondylitis (AS). This study indicates that increased bone turnover, inflammation, and low vitamin D levels are important in the pathophysiology of AS-related osteoporosis, and that bone turnover markers (BTM) are valuable markers to detec

  3. Bone grafting: An overview

    Directory of Open Access Journals (Sweden)

    D. O. Joshi

    2010-08-01

    Full Text Available Bone grafting is the process by which bone is transferred from a source (donor to site (recipient. Due to trauma from accidents by speedy vehicles, falling down from height or gunshot injury particularly in human being, acquired or developmental diseases like rickets, congenital defects like abnormal bone development, wearing out because of age and overuse; lead to bone loss and to replace the loss we need the bone grafting. Osteogenesis, osteoinduction, osteoconduction, mechanical supports are the four basic mechanisms of bone graft. Bone graft can be harvested from the iliac crest, proximal tibia, proximal humerus, proximal femur, ribs and sternum. An ideal bone graft material is biologically inert, source of osteogenic, act as a mechanical support, readily available, easily adaptable in terms of size, shape, length and replaced by the host bone. Except blood, bone is grafted with greater frequency. Bone graft indicated for variety of orthopedic abnormalities, comminuted fractures, delayed unions, non-unions, arthrodesis and osteomyelitis. Bone graft can be harvested from the iliac crest, proximal tibia, proximal humerus, proximal femur, ribs and sternum. By adopting different procedure of graft preservation its antigenicity can be minimized. The concept of bone banking for obtaining bone grafts and implants is very useful for clinical application. Absolute stability require for successful incorporation. Ideal bone graft must possess osteogenic, osteoinductive and osteocon-ductive properties. Cancellous bone graft is superior to cortical bone graft. Usually autologous cancellous bone graft are used as fresh grafts where as allografts are employed as an alloimplant. None of the available type of bone grafts possesses all these properties therefore, a single type of graft cannot be recomm-ended for all types of orthopedic abnormalities. Bone grafts and implants can be selected as per clinical problems, the equipments available and preference of

  4. Features of the physical development, calcium-phosphorus metabolism and mineral density of the bones in children with chronic lung diseases

    Directory of Open Access Journals (Sweden)

    Olya Sharipova

    2011-03-01

    Full Text Available We have studied features of physical development, calcium-phosphorus metabolism and mineral density of the bones in children with chronic lung diseases. Comparison of received results with the standards of physical development in children and adolescents has shown the most significant differences in ages of 10, 11 and 15 years old who had the stature level lower than average. The data obtained suggest that children with this pathology undergoes substantial adverse changes in the main somatomertric indicators and bone mineral density, the degree of which depends on the nature of the primary lesion in the bronchopulmonary system, and duration and severity of disease.

  5. Bone marrow mesenchymal stem cells from patients with aplastic anemia maintain functional and immune properties and do not contribute to the pathogenesis of the disease.

    Science.gov (United States)

    Bueno, Clara; Roldan, Mar; Anguita, Eduardo; Romero-Moya, Damia; Martín-Antonio, Beatriz; Rosu-Myles, Michael; del Cañizo, Consuelo; Campos, Francisco; García, Regina; Gómez-Casares, Maite; Fuster, Jose Luis; Jurado, Manuel; Delgado, Mario; Menendez, Pablo

    2014-07-01

    Aplastic anemia is a life-threatening bone marrow failure disorder characterized by peripheral pancytopenia and marrow hypoplasia. The majority of cases of aplastic anemia remain idiopathic, although hematopoietic stem cell deficiency and impaired immune responses are hallmarks underlying the bone marrow failure in this condition. Mesenchymal stem/stromal cells constitute an essential component of the bone marrow hematopoietic microenvironment because of their immunomodulatory properties and their ability to support hematopoiesis, and they have been involved in the pathogenesis of several hematologic malignancies. We investigated whether bone marrow mesenchymal stem cells contribute, directly or indirectly, to the pathogenesis of aplastic anemia. We found that mesenchymal stem cell cultures can be established from the bone marrow of aplastic anemia patients and display the same phenotype and differentiation potential as their counterparts from normal bone marrow. Mesenchymal stem cells from aplastic anemia patients support the in vitro homeostasis and the in vivo repopulating function of CD34(+) cells, and maintain their immunosuppressive and anti-inflammatory properties. These data demonstrate that bone marrow mesenchymal stem cells from patients with aplastic anemia do not have impaired functional and immunological properties, suggesting that they do not contribute to the pathogenesis of the disease.

  6. 多学科协同治疗骨关节疾病%Multidisciplinary treatment of bone and joint diseases

    Institute of Scientific and Technical Information of China (English)

    张奉春

    2012-01-01

    The bone and joint diseases are very common, have chronic, recurrent characteristics and often lead to discomfort and disability in China. These diseases affect human health seriously. The etiology and pathogenesis are unknown. They may be related with genetic, environmental factors and autoimmune reaction. Rehabilitation exercise, health education, medical treatment and operation are the main methods in the treatment of the diseases. The expected benefits of the treatment are pain relief, improvement or prevention of further deterioration, and prevention of deformity. The types of treatments are different for various diseases. Short-term or long-term treatment with non-steroidal anti-inflammatory drugs (NSAIDs) can relive the pain of bone and joint. Disease-modifying antirheumatic drugs (DMARDs) are selected in the first-line treatment as soon as possible in rheumatoid arthritis, and seronegative spondylo-arthropathies can be treated with SASP and symptoms of some patients are relieved. Advances in the understanding of the pathogenesis of the disease have fostered the development of new therapeutics (biological drugs such as TNF-a inhibitors and rituximab), with improved outcomes. However, operation for advanced stage or medicine ineffective patients is also very important. Rheumatology is very young in China, which is still facing the lack of the rheumatology physician after more than 20 years' development. The cooperation of surgeons and rheumatology physicians is very important, but it has not been recognized and emphasized so far. We should pay more attention to the cooperation in the clinical work in the future.%@@ 一、概述 世界卫生组织将2000年至2010年定为"骨与关节的十年",这一项以"增进患有肌肉与骨骼疾病患者的健康,进一步改善他们的生活质量"作为目标的活动意义重大.骨关节病的范围广泛,除了骨关节炎、类风湿关节炎等各种关节疾病外,还包括脊柱疾病、骨质疏松症以

  7. [Cytokines in bone diseases. Genetic defects of PTH/PTHrP receptor in chondrodysplasia].

    Science.gov (United States)

    Ogata, Naoshi

    2010-10-01

    Parathyroid hormone-related protein (PTHrP) signaling plays important roles in regulating the differentiation of chondrocytes in endochondral bone development. PTHrP signaling functions as an inhibitory effect on chondrocyte hypertrophy which is a terminal stage of differentiation at a growth plate. Mutations of the PTH÷PTHrP receptor have been identified in Jansen metaphyseal chondrodysplasia, Blomstrand's lethal chondrodysplasia, and enchondromatosis. Furthermore, genetic manipulations of the PTHrP and its receptor genes in mice have demonstrated the critical roles of these proteins in regulating both the switch between proliferation and differentiation of chondrocytes.

  8. Favourable prognostic features in histiocytosis X: bone involvement and absence of skin disease.

    OpenAIRE

    Broadbent, V

    1986-01-01

    The records of 70 patients presenting to this hospital since 1961 with histiocytosis X confirmed by biopsy examination have been reviewed. The patients were subdivided into three groups: group A, those under 2 years of age at diagnosis; group B, those between 2 and 5 years; and group C, those over 5 years. All eight patients who died (11% overall mortality) were under 2 years of age at diagnosis. Involvement of lung, liver, and bone marrow were confirmed as poor prognostic features. The prese...

  9. Updates in the pathophysiological mechanisms of Parkinson’s disease: Emerging role of bone marrow mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    Hanaa; H; Ahmed; Ahmed; M; Salem; Hazem; M; Atta; Emad; F; Eskandar; Abdel; Razik; H; Farrag; Mohamed; A; Ghazy; Neveen; A; Salem; Hadeer; A; Aglan

    2016-01-01

    AIM: To explore the approaches exerted by mesenchymal stem cells(MSCs) to improve Parkinson’s disease(PD) pathophysiology.METHODS: MSCs were harvested from bone marrowof femoral bones of male rats, grown and propagated in culture. Twenty four ovariectomized animals were classified into 3 groups: Group(1) was control, Groups(2) and(3) were subcutaneously administered with rotenone for 14 d after one month of ovariectomy for induction of PD. Then, Group(2) was left untreated, while Group(3) was treated with single intravenous dose of bone marrow derived MSCs(BM-MSCs). SRY gene was assessed by PCR in brain tissue of the female rats. Serum transforming growth factor beta-1(TGF-β1), monocyte chemoattractant protein-1(MCP-1) and brain derived neurotrophic factor(BDNF) levels were assayed by ELISA. Brain dopamine DA level was assayed fluorometrically, while brain tyrosine hydroxylase(TH) and nestin gene expression were detected by semi-quantitative real time PCR. Brain survivin expression was determined by immunohistochemical procedure. Histopathological investigation of brain tissues was also done.RESULTS: BM-MSCs were able to home at the injured brains and elicited significant decrease in serum TGF-β1(489.7 ± 13.0 vs 691.2 ± 8.0, P 0.05) expression. Finally, the brain sections showed intact histological structure of the striatum as a result of treatment with BM-MSCs. CONCLUSION: The current study sheds light on the therapeutic potential of BM-MSCs against PD pathophysiology via multi-mechanistic actions.

  10. Lower bone mineral density in Patients with Parkinson’s disease: a cross-sectional study from Chinese Mainland

    Directory of Open Access Journals (Sweden)

    Huimin eGao

    2015-10-01

    Full Text Available Objectives Although several lines of evidence have suggested that patients with Parkinson’s disease (PD have a higher risk of osteoporosis and fracture, the association between bone mineral density and severity of PD patients is unknown. Methods We performed a cross-sectional study of 54 patients with PD and 59 healthy age-matched controls. Multiple clinical scales were used to evaluate the severity of PD, and serum levels of calcium, phosphorus, and homocysteine were measured to determine bone mineral density’s association with PD severity. Results BMD in PD patients was significantly lower than in healthy controls. The BMD scores of the spine, femoral neck, and hip were lower in females than in males in the healthy group. In the PD group, BMD in the hip was significantly lower in females compared to males. There was a negative correlation between daily L-dopa dosage and BMD in the spine and hip in the PD group, while BMD in the spine, neck, and hip was significantly correlated with severity of PD. Besides, we found that among the lumbar spine, femoral neck and hip, bone loss in the lumbar spine was the most severe in PD patients based on the T-scores. Conclusions Our findings support the hypothesis that patients with PD have a higher risk of osteoporosis, and that low BMD in the spine, femoral neck, and hip may indirectly reflect the severity of PD. Our findings have prompted us to pay more attention to osteoporosis in the lumbar spine in Chinese PD patients.

  11. Quantitative (31)P NMR spectroscopy and (1)H MRI measurements of bone mineral and matrix density differentiate metabolic bone diseases in rat models.

    Science.gov (United States)

    Cao, Haihui; Nazarian, Ara; Ackerman, Jerome L; Snyder, Brian D; Rosenberg, Andrew E; Nazarian, Rosalynn M; Hrovat, Mirko I; Dai, Guangping; Mintzopoulos, Dionyssios; Wu, Yaotang

    2010-06-01

    In this study, bone mineral density (BMD) of normal (CON), ovariectomized (OVX), and partially nephrectomized (NFR) rats was measured by (31)P NMR spectroscopy; bone matrix density was measured by (1)H water- and fat-suppressed projection imaging (WASPI); and the extent of bone mineralization (EBM) was obtained by the ratio of BMD/bone matrix density. The capability of these MR methods to distinguish the bone composition of the CON, OVX, and NFR groups was evaluated against chemical analysis (gravimetry). For cortical bone specimens, BMD of the CON and OVX groups was not significantly different; BMD of the NFR group was 22.1% (by (31)P NMR) and 17.5% (by gravimetry) lower than CON. For trabecular bone specimens, BMD of the OVX group was 40.5% (by (31)P NMR) and 24.6% (by gravimetry) lower than CON; BMD of the NFR group was 26.8% (by (31)P NMR) and 21.5% (by gravimetry) lower than CON. No significant change of cortical bone matrix density between CON and OVX was observed by WASPI or gravimetry; NFR cortical bone matrix density was 10.3% (by WASPI) and 13.9% (by gravimetry) lower than CON. OVX trabecular bone matrix density was 38.0% (by WASPI) and 30.8% (by gravimetry) lower than CON, while no significant change in NFR trabecular bone matrix density was observed by either method. The EBMs of OVX cortical and trabecular specimens were slightly higher than CON but not significantly different from CON. Importantly, EBMs of NFR cortical and trabecular specimens were 12.4% and 26.3% lower than CON by (31)P NMR/WASPI, respectively, and 4.0% and 11.9% lower by gravimetry. Histopathology showed evidence of osteoporosis in the OVX group and severe secondary hyperparathyroidism (renal osteodystrophy) in the NFR group. These results demonstrate that the combined (31)P NMR/WASPI method is capable of discerning the difference in EBM between animals with osteoporosis and those with impaired bone mineralization.

  12. Intra-bone marrow-bone marrow transplantation slows disease progression and prolongs survival in G93A mutant SOD1 transgenic mice, an animal model mouse for amyotrophic lateral sclerosis.

    Science.gov (United States)

    Ohnishi, Shizuo; Ito, Hidefumi; Suzuki, Yasuhiro; Adachi, Yasushi; Wate, Reika; Zhang, Jianhua; Nakano, Satoshi; Kusaka, Hirofumi; Ikehara, Susumu

    2009-11-03

    It has been reported that bone marrow transplantation (BMT) has clinical effects on not only hematopoietic diseases and autoimmune diseases but also solid malignant tumors and metabolic diseases. We have found that intra-bone marrow-bone marrow transplantation (IBM-BMT) is superior to conventional intravenous BMT, since IBM-BMT enables rapid recovery of donor hematopoiesis and reduces the extent of graft-versus-host disease (GVHD). In this experiment, we examined the effects of IBM-BMT on symptomatic G93A mutant SOD1 transgenic mice (mSOD1 Tg mice), a model mouse line for amyotrophic lateral sclerosis (ALS). Symptomatic mSOD1 Tg mice (12 weeks old) were irradiated with 6Gyx2 at a 4-hour interval, one day before IBM-BMT. The mice were transplanted with bone marrow cells (BMCs) from 12-wk-old eGFP-transgenic C57BL/6 mice (eGFP Tg mice) or BMCs from 12-wk-old mSOD1 Tg mice. The ALS model mice transplanted with BMCs from eGFP Tg mice showed longer survival and slower disease progression than those transplanted with BMCs from mSOD1 Tg mice or untreated mSOD1 Tg mice. There was a significantly high number of eGFP(+) cells in the anterior horn of the spinal cord of the mSOD1 Tg mice transplanted with BMCs of eGFP Tg mice, some of which expressed Iba-1, a marker of microglia, although they did not differentiate into neural cells. These results suggest that the replacement with normal hematopoietic cells improved the neural cell environment, thereby slowing the progression of the disease.

  13. Assessment of Bone Mineral Density in Male Patients with Chronic Obstructive Pulmonary Disease by DXA and Quantitative Computed Tomography

    Directory of Open Access Journals (Sweden)

    George Fountoulis

    2016-01-01

    Full Text Available The purpose of this study is to identify the prevalence of osteoporosis in male patients with chronic obstructive pulmonary disease (COPD by dual-energy X-ray absorptiometry (DXA and quantitative computed tomography (QCT and to compare the diagnostic abilities of the above methods. Thirty-seven male patients with established COPD were examined with DXA and standard QCT in lumbar spine, including L1, L2, and L3 vertebrae. T-scores and bone mineral density values were calculated by DXA and QCT method, respectively. Comparative assessment of the findings was performed and statistical analysis was applied. QCT measurements found more COPD patients with impaired bone mineral density compared to DXA, namely, 13 (35.1% versus 12 (32.4% patients with osteopenia and 16 (43.2% versus 9 (16.2% patients with osteoporosis (p=0.04. More vertebrae were found with osteoporosis by QCT compared to DXA (p=0.03. The prevalence of osteoporosis among male patients with COPD is increased and DXA may underestimate this risk. QCT measurements have an improved discriminating ability to identify low BMD compared to DXA measurements because QCT is able to overcome diagnostic pitfalls including aortic calcifications and degenerative spinal osteophytes.

  14. Transplanted bone marrow mesenchymal stem cells improve memory in rat models of Alzheimer's disease.

    Science.gov (United States)

    Babaei, Parvin; Soltani Tehrani, Bahram; Alizadeh, Arsalan

    2012-01-01

    The present study aims to evaluate the effect of bone marrow mesenchymal stem cells (MSCs) grafts on cognition deficit in chemically and age-induced Alzheimer's models of rats. In the first experiments aged animals (30 months) were tested in Morris water maze (MWM) and divided into two groups: impaired memory and unimpaired memory. Impaired groups were divided into two groups and cannulated bilaterally at the CA1 of the hippocampus for delivery of mesenchymal stem cells (500 × 10(3)/μL) and PBS (phosphate buffer saline). In the second experiment, Ibotenic acid (Ibo) was injected bilaterally into the nucleus basalis magnocellularis (NBM) of young rats (3 months) and animals were tested in MWM. Then, animals with memory impairment received the following treatments: MSCs (500 × 10(3)/μL) and PBS. Two months after the treatments, cognitive recovery was assessed by MWM in relearning paradigm in both experiments. Results showed that MSCs treatment significantly increased learning ability and memory in both age- and Ibo-induced memory impairment. Adult bone marrow mesenchymal stem cells show promise in treating cognitive decline associated with aging and NBM lesions.

  15. Transplanted Bone Marrow Mesenchymal Stem Cells Improve Memory in Rat Models of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Parvin Babaei

    2012-01-01

    Full Text Available The present study aims to evaluate the effect of bone marrow mesenchymal stem cells (MSCs grafts on cognition deficit in chemically and age-induced Alzheimer's models of rats. In the first experiments aged animals (30 months were tested in Morris water maze (MWM and divided into two groups: impaired memory and unimpaired memory. Impaired groups were divided into two groups and cannulated bilaterally at the CA1 of the hippocampus for delivery of mesenchymal stem cells (500×103/ and PBS (phosphate buffer saline. In the second experiment, Ibotenic acid (Ibo was injected bilaterally into the nucleus basalis magnocellularis (NBM of young rats (3 months and animals were tested in MWM. Then, animals with memory impairment received the following treatments: MSCs (500×103/ and PBS. Two months after the treatments, cognitive recovery was assessed by MWM in relearning paradigm in both experiments. Results showed that MSCs treatment significantly increased learning ability and memory in both age- and Ibo-induced memory impairment. Adult bone marrow mesenchymal stem cells show promise in treating cognitive decline associated with aging and NBM lesions.

  16. The transition state analog inhibitor of Purine Nucleoside Phosphorylase (PNP) Immucillin-H arrests bone loss in rat periodontal disease models.

    Science.gov (United States)

    Deves, Candida; de Assunção, Thiago Milech; Ducati, Rodrigo Gay; Campos, Maria Martha; Basso, Luiz Augusto; Santos, Diogenes Santiago; Batista, Eraldo L

    2013-01-01

    Purine nucleoside phosphorylase (PNP) is a purine-metabolizing enzyme that catalyzes the reversible phosphorolysis of 6-oxypurine (deoxy)nucleosides to their respective bases and (deoxy)ribose-1-phosphate. It is a key enzyme in the purine salvage pathway of mammalian cells. The present investigation sought to determine whether the PNP transition state analog inhibitor (Immucillin-H) arrests bone loss in two models of induced periodontal disease in rats. Periodontal disease was induced in rats using ligature or LPS injection followed by administration of Immucillin-H for direct analysis of bone loss, histology and TRAP staining. In vitro osteoclast differentiation and activation of T CD4+ cells in the presence of Immucillin-H were carried out for assessment of RANKL expression, PNP and Cathepsin K activity. Immucillin-H inhibited bone loss induced by ligatures and LPS, leading to a reduced number of infiltrating osteoclasts and inflammatory cells. In vitro assays revealed that Immucillin-H could not directly abrogate differentiation of osteoclast precursor cells, but affected lymphocyte-mediated osteoclastogenesis. On the other hand, incubation of pre-activated T CD4+ with Immucillin-H decreased RANKL secretion with no compromise of cell viability. The PNP transition state analog Immucillin-H arrests bone loss mediated by T CD4+ cells with no direct effect on osteoclasts. PNP inhibitor may have an impact in the treatment of diseases characterized by the presence of pathogens and imbalances of bone metabolism.

  17. Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases

    Science.gov (United States)

    2017-03-16

    Severe Combined Immunodeficiency (SCID); Immunodeficiency With Predominant T-cell Defect, Unspecified; Severe Chronic Neutropenia; Chronic Granulomatous Disease (CGD); Hyper IgE Syndromes; Hyper IgM Deficiencies; Wiskott-Aldrich Syndrome; Mendelian Susceptibility to Mycobacterial Disease; Common Variable Immune Deficiency (CVID)

  18. Gaucher disease diagnosed after bone marrow trephine biopsy — a report of two cases

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    Bożena Sokołowska

    2011-07-01

    Full Text Available The hematologist is at the forefront of specialists to whom patients with Gaucher disease presentbecause of cytopenia and hepatosplenomegaly. Usually, patients with such symptoms have undergone trephinebiopsy. We present the cases of two patients in whom Gaucher disease was suspected because of the discovery ofGaucher cells in trephine biopsy, and subsequently confirmed via enzymatic and molecular investigations.

  19. Intramyocardial Bone Marrow Cell Injection : Clinical and Functional Effects in Ischemic Heart Disease

    NARCIS (Netherlands)

    Ramshorst, Jan van

    2014-01-01

    Coronary artery disease is a major cause of mortality and morbidity in the western world. Despite successive revascularization procedures, a large number of patients ends up with end-stage coronary artery disease, not amenable for conventional revascularization. These patients often have stress-indu

  20. A novel and feasible way to cultivate and purify endothelial progenitor cells from bone marrow of children with congenital heart diseases

    Institute of Scientific and Technical Information of China (English)

    WU Yong-tao; LI Jing-xing; LIU Shuo; XIN Yi; WANG Zi-jian; GAO Jin; JI Bing-yang; FAN Xiang-ming; ZHOU Qi-wen

    2012-01-01

    Background Endothelial progenitor cells (EPCs) are used in vascular tissue engineering and clinic therapy.Some investigators get EPCs from the peripheral blood for clinic treatment,but the number of EPCs is seldom enough.We have developed the cultivation and purification of EPCs from the bone marrow of children with congenital heart disease,to provide enough seed cells for a small calibre vascular tissue engineering study.Methods The 0.5-ml of bone marrow was separated from the sternum bone,and 5-ml of peripheral blood was collected from children with congenital heart diseases who had undergone open thoracic surgery.CD34+ and CD34+/VEGFR+cells in the bone marrow and peripheral blood were quantified by flow cytometry.CD34+NEGFR+ cells were defined as EPCs.Mononuclear cells in the bone marrow were isolated by Ficoll(R) density gradient centrifugation and cultured by the EndoCult Liquid Medium KitTM.Colony forming endothelial cells was detected.Immunohistochemistry staining for Dil-ac-LDL and FITC-UEA-1 confirmed the endothelial lineage of these cells.Results CD34+ and CD34+NEGFR+ cells in peripheral blood were (0.07±0.05)% and (0.05±0.02)%,respectively.The number of CD34+ and CD34+NEGFR+ cells in bone marrow were significantly higher than in blood,(4.41±1.47)% and (0.98±0.65)%,respectively (P <0.0001).Many colony forming units formed in the culture.These cells also expressed high levels of Dil-ac-LDL and FITC-UEA-1.Conclusion This is a novel and feasible approach that can cultivate and purify EPCs from the bone marrow of children with congenital heart disease,and provide seed cells for small calibre vascular tissue engineering.

  1. Inhibition of p38-MAPK signaling pathway attenuates breast cancer induced bone pain and disease progression in a murine model of cancer-induced bone pain

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    Vanderah Todd W

    2011-10-01

    Full Text Available Abstract Background Mechanisms driving cancer-induced bone pain are poorly understood. A central factor implicated to be a key player in the process of tumorigenesis, osteoclastogenesis and nociception is p38 MAPK. We determined the role of p38 MAPK in a mouse model of breast cancer induced bone pain in which mixed osteolytic and osteoblastic remodeling occurs. Results In cancer-treated mice, acute as well as chronic inhibition of p38 MAPK with SB203580 blocked flinching and guarding behaviors in a dose-dependent manner whereas no effect on thresholds to tactile stimuli was observed. Radiographic analyses of bones demonstrated that chronic inhibition of p38 MAPK reduced bone loss and incidence of spontaneous fracture in cancer-treated mice. Histological analysis of bones collected from mice treated with the p38 MAPK inhibitor showed complete absence of osteoblastic growth in the intramedullary space as well as significantly reduced tumor burden. Conclusions Blockade of non-evoked pain behaviors but not hypersensitivity suggests differences in the underlying mechanisms of specific components of the pain syndrome and a possibility to individualize aspects of pain management. While it is not known whether the role of p38 MAPK signaling can be expanded to other cancers, the data suggest a need for understanding molecular mechanisms and cellular events that initiate and maintain cancer-induced bone pain for effective management for both ongoing pain as well as breakthrough pain.

  2. Elevated interferon-gamma in CNS inflammatory disease: a potential complication for bone marrow reconstitution in MS

    DEFF Research Database (Denmark)

    Hassan-Zahraee, M; Tran, E H; Bourbonnière, L;

    2000-01-01

    Bone marrow transplantation (BMT) is increasingly used to treat Multiple Sclerosis (MS) a CNS inflammatory disease with elevated CNS and systemic IFNgamma levels. We wished to determine the effect of IFNgamma on BM graft survival in a transgenic mouse model for chronic MS. BM transplantation...... into transgenic mice which express elevated levels of IFNgamma in the CNS was unsuccessful. By contrast, there was 100% survival of even fully allogeneic, T-depleted transplants to transgenics that over express TNFalpha in the CNS, using the same MBP promoter. IFNgamma was detectable in spleen of irradiated mice...... but levels were higher in IFNgamma transgenics. BM transplantation into IFNgamma-deficient recipients also had a high failure rate. Transplants of BM from mice lacking expression of IFNgamma-receptor failed, whereas IFNgamma-deficient grafts survived, suggesting that IFNgamma response status of the graft can...

  3. Molecular Characterization of Three Canine Models of Human Rare Bone Diseases: Caffey, van den Ende-Gupta, and Raine Syndromes.

    Science.gov (United States)

    Hytönen, Marjo K; Arumilli, Meharji; Lappalainen, Anu K; Owczarek-Lipska, Marta; Jagannathan, Vidhya; Hundi, Sruthi; Salmela, Elina; Venta, Patrick; Sarkiala, Eva; Jokinen, Tarja; Gorgas, Daniela; Kere, Juha; Nieminen, Pekka; Drögemüller, Cord; Lohi, Hannes

    2016-05-01

    One to two percent of all children are born with a developmental disorder requiring pediatric hospital admissions. For many such syndromes, the molecular pathogenesis remains poorly characterized. Parallel developmental disorders in other species could provide complementary models for human rare diseases by uncovering new candidate genes, improving the understanding of the molecular mechanisms and opening possibilities for therapeutic trials. We performed various experiments, e.g. combined genome-wide association and next generation sequencing, to investigate the clinico-pathological features and genetic causes of three developmental syndromes in dogs, including craniomandibular osteopathy (CMO), a previously undescribed skeletal syndrome, and dental hypomineralization, for which we identified pathogenic variants in the canine SLC37A2 (truncating splicing enhancer variant), SCARF2 (truncating 2-bp deletion) and FAM20C (missense variant) genes, respectively. CMO is a clinical equivalent to an infantile cortical hyperostosis (Caffey disease), for which SLC37A2 is a new candidate gene. SLC37A2 is a poorly characterized member of a glucose-phosphate transporter family without previous disease associations. It is expressed in many tissues, including cells of the macrophage lineage, e.g. osteoclasts, and suggests a disease mechanism, in which an impaired glucose homeostasis in osteoclasts compromises their function in the developing bone, leading to hyperostosis. Mutations in SCARF2 and FAM20C have been associated with the human van den Ende-Gupta and Raine syndromes that include numerous features similar to the affected dogs. Given the growing interest in the molecular characterization and treatment of human rare diseases, our study presents three novel physiologically relevant models for further research and therapy approaches, while providing the molecular identity for the canine conditions.

  4. Mesenchymal bone marrow cell therapy in a mouse model of chagas disease. Where do the cells go?

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    Jasmin

    Full Text Available BACKGROUND: Chagas disease, resulting from infection with the parasite Trypanosoma cruzi (T. cruzi, is a major cause of cardiomyopathy in Latin America. Drug therapy for acute and chronic disease is limited. Stem cell therapy with bone marrow mesenchymal cells (MSCs has emerged as a novel therapeutic option for cell death-related heart diseases, but efficacy of MSC has not been tested in Chagas disease. METHODS AND RESULTS: We now report the use of cell-tracking strategies with nanoparticle labeled MSC to investigate migration of transplanted MSC in a murine model of Chagas disease, and correlate MSC biodistribution with glucose metabolism and morphology of heart in chagasic mice by small animal positron emission tomography (microPET. Mice were infected intraperitoneally with trypomastigotes of the Brazil strain of T. cruzi and treated by tail vein injection with MSC one month after infection. MSCs were labeled with near infrared fluorescent nanoparticles and tracked by an in vivo imaging system (IVIS. Our IVIS results two days after transplant revealed that a small, but significant, number of cells migrated to chagasic hearts when compared with control animals, whereas the vast majority of labeled MSC migrated to liver, lungs and spleen. Additionally, the microPET technique demonstrated that therapy with MSC reduced right ventricular dilation, a phenotype of the chagasic mouse model. CONCLUSIONS: We conclude that the beneficial effects of MSC therapy in chagasic mice arise from an indirect action of the cells in the heart rather than a direct action due to incorporation of large numbers of transplanted MSC into working myocardium.

  5. Bone health and risk factors of cardiovascular disease--a cross-sectional study in healthy young adults.

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    Satu Pirilä

    Full Text Available OBJECTIVE: Both osteoporosis and cardiovascular disease (CVD are diseases that comprise a growing medical and economic burden in ageing populations. They share many risk factors, including ageing, low physical activity, and possibly overweight. We aimed to study associations between individual risk factors for CVD and bone mineral density (BMD and turnover markers (BTMs in apparently healthy cohort. DESIGN: A cross-sectional assessment of 155 healthy 32-year-old adults (74 males was performed for skeletal status, CVD risk factors and lifestyle factors. METHODS: We analysed serum osteocalcin, procollagen I aminoterminal propeptide (P1NP, collagen I carboxy-terminal telopeptide (ICTP and urine collagen I aminoterminal telopeptide (U-NTX, as well as serum insulin, plasma glucose, triglyceride and HDL-cholesterol levels. BMD, fat and lean mass were assessed using DXA scanning. Associations were tested with partial correlations in crude and adjusted models. Bone status was compared between men with or without metabolic syndrome (defined according to the NCEP-ATPIII criteria with multivariate analysis. RESULTS: Osteocalcin and P1NP correlated inversely with insulin (R = -0.243, P = 0.003 and R = -0.187, P = 0.021 and glucose (R = -0.213, P = 0.009 and R = -0.190, P = 0.019, but after controlling for fat mass and lifestyle factors, the associations attenuated with insulin (R = -0.162, P = 0.053 and R = -0.093, P = 0.266 and with glucose (R = -0.099, P = 0.240 and R = -0.133, P = 0.110, respectively. Whole body BMD associated inversely only with triglycerides in fully adjusted model. In men with metabolic syndrome, whole body BMD, osteocalcin and P1NP were lower compared to healthy men, but these findings disappeared in fully adjusted model. CONCLUSIONS: In young adults, inverse associations between BTM/BMD and risk factors of CVD appeared in crude models, but after adjusting for fat mass

  6. Minimal residual disease in bone marrow and peripheral blood of patients with metastatic breast cancer.

    Science.gov (United States)

    Bischoff, Joachim; Rosenberg, Robert; Dahm, Michael; Janni, Wolfgang; Gutschow, Klaus

    2003-01-01

    The presence of occult micrometastases in bone marrow (BM) of patients with early breast cancer increases the risk of relapse. Detection of circulation tumor cells in peripheral blood (PB) may also influence the patient's prognosis. Few data are available on the correlation between tumor cell dissemination in BM and PB in solid epithelial tumors. Twenty-milliliter blood samples were collected from PB of 42 patients with advanced breast cancer and centrifuged using the density gradient OncoQuick (OncoQuick Greiner BioOne, Frickenhausen, Germany). The BM aspirates available from 11 of the 42 patients were centrifuged using density centrifugation Ficoll. Tumor cell detection was performed by microscopy after cytospin preparation and immunocytochemical staining with the monoclonal antibody A45-B/B3. Cytokeratin-positive cells were detected in 23 patients (55%) in the PB and in three patients (27%) in the BM. A cohort with bone lesions as the only metastatic side showed a correlation as follows: 7 of the 11 patients (64%) had negative findings in BM and PB, whereas cytokeratin-positive cells in PB were present in 3 of these 11 patients (27%). The presence of visceral metastases was associated with the detection of cytokeratin-positive cells in the PB in 20 of the 31 patients (65%) in this subgroup. The density gradient OncoQuick in combination with immunocytochemical staining allows the detection of cytokeratin-positive cells in PB of patients with advanced breast cancer. The immunocytochemical detection of cytokeratin-positive cells in PB seems to be associated with the site of metastatic manifestation.

  7. Bone Biopsy

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Bone Biopsy Bone biopsy uses a needle and imaging ... the limitations of Bone Biopsy? What is a Bone Biopsy? A bone biopsy is an image-guided ...

  8. Serum levels of parathyroid hormone and markers of bone metabolism in patients with rheumatoid arthritis. Relationship to disease activity and glucocorticoid treatment

    DEFF Research Database (Denmark)

    Jensen, Tonny Joran; Hansen, M; Madsen, J C;

    2001-01-01

    OBJECTIVE: To evaluate the influence of inflammatory activity and glucocorticoid (GC) treatment on serum parathyroid hormone (s-PTH) and bone metabolism in patients with rheumatoid arthritis (RA). Furthermore, in patients with active RA, to examine the PTH secretion and Ca2+ set point before...... and after treatment with GC. METHODS: A range of biochemical markers of bone metabolism and calcium homeostasis were measured in 95 patients with definite RA stratified into groups according to disease activity and GC treatment. In a subgroup of 12 patients with active disease, initiating slow...... groups. The levels of urine pyridinoline (Pyr) and s-albumin-corrected calcium (s-AlbCorrCa2+) were elevated in patients with active disease and patients treated with GC. S-PTH and s-phosphate were within normal ranges. S-TAP, s-ICTP, Pyr and s-AlbCorrCa2+ correlated positively with indices of disease...

  9. Gaucher disease diagnosed after bone marrow trephine biopsy — a report of two cases

    Directory of Open Access Journals (Sweden)

    Anna Dmoszyńska

    2011-07-01

    Full Text Available The hematologist is at the forefront of specialists to whom patients with Gaucher disease present because of cytopenia and hepatosplenomegaly. Usually, patients with such symptoms have undergone trephine biopsy. We present the cases of two patients in whom Gaucher disease was suspected because of the discovery of Gaucher cells in trephine biopsy, and subsequently confirmed via enzymatic and molecular investigations. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 2, pp. 352–356

  10. Effects of recombinant human erythropoietin on the haemopoietic bone marrow monitored by magnetic resonance spectroscopy in patients with end-stage renal disease

    DEFF Research Database (Denmark)

    Jensen, K E; Stenver, D; Jensen, M;

    1990-01-01

    Volume selective magnetic resonance (MR) proton spectroscopy was used to investigate changes in the haemopoietic bone marrow in patients with end-stage renal disease undergoing treatment with recombinant human erythropoietin (rHuEPO). Significant changes could be detected in the spectra 14 days...

  11. Increased technetium-99 m hydroxy diphosphonate soft tissue uptake on bone scintigraphy in chronic kidney disease patients with secondary hyperparathyroidism

    DEFF Research Database (Denmark)

    Enevoldsen, Lotte Hahn; Heaf, James Goya; Højgaard, Liselotte

    2017-01-01

    In bone scan patients with dialysis-treated chronic kidney disease (CKD) and hyperparathyroidism, soft tissue accumulation of technetium-99 m hydroxy/methylene diphosphonate (Tc-99 m-HDP/MDP) has been reported primarily in case reports and usually explained by hypercalcaemia and/or hyperphosphata......In bone scan patients with dialysis-treated chronic kidney disease (CKD) and hyperparathyroidism, soft tissue accumulation of technetium-99 m hydroxy/methylene diphosphonate (Tc-99 m-HDP/MDP) has been reported primarily in case reports and usually explained by hypercalcaemia and...... patients diagnosed with secondary hyperparathyroidism admitted for Tc-99 m-HDP bone scan. Baseline characteristics and mean concentrations of biochemical markers (including P-calcium and P-phosphate) taken 0-3 months prior to the bone scans were collected. Soft tissue uptake was detected on bone scans...... of the 36 patients without myocardial uptake. In conclusion, dialysis-treated CKD patients with secondary hyperparathyroidism have a high incidence of soft tissue uptake, and this finding is strongly correlated with elevated phosphate, but not calcium values....

  12. Exploring the role of FDG-PET in the assessment of bone marrow involvement in lymphoma patients as interpreted by qualitative and semiquantitative disease metabolic activity parameter

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    P G Kand

    2010-01-01

    Full Text Available Bone marrow biopsy (BMB is currently the standard method to evaluate marrow involvement in malignant lymphomas. However, there exist a number of pitfalls in this technique that can have important implications for initial staging, prognostification, and treatment of the disease. The present study was undertaken to investigate the utility of FDG-PET imaging in the detection of bone marrow involvement in untreated lymphoma patients. Forty untreated patients (36 males and 12 females with either Hodgkin′s disease (HD (n = 17 or non-Hodgkin′s lymphoma (NHL (n = 31 underwent whole body FDG-PET study for disease evaluation. Bone marrow uptake of FDG was graded as absence or presence of disease activity at marrow sites by qualitative assessment. Semiquantitative analysis involved deriving disease metabolic index (DMI using the following formula: DMI = SUV max of suitable circular ROI over PSIS or trochanteric region/ SUVmax of similar ROI over adjoining background. Findings of BMB and FDG-PET were compared for final analysis. Eleven out of 17 HD patients (12 males and 5 females demonstrated concordance between FDG PET findings and BMB reports. Remaining 6 cases showed discordance of FDG-PET demonstrating presence of marrow involvement at marrow sites and uninvolved marrow on BMB. Twenty six of the 31 NHL cases (24 males and 7 females demonstrated concordance between FDG PET findings and BMB reports. Remaining 5 cases showed discordance of FDG-PET demonstrating presence of marrow involvement at marrow sites and uninvolved marrow on BMB. All the BMB positive patients (2 of HD and 5 of NHL demonstrated disease activity in bone marrow on FDG-PET study. All patients with absence of disease activity at marrow sites on FDG-PET scan (9 of HD and 21 of NHL had histology proven uninvolved marrow. The quantitative assessment by DMI showed a mean of >2.5 in HD and NHL patients at the PSIS region and the trochanteric region bilaterally in cases of bone marrow

  13. Staphylococcal enterotoxin A regulates bone marrow granulocyte trafficking during pulmonary inflammatory disease in mice

    Energy Technology Data Exchange (ETDEWEB)

    Takeshita, W.M.; Gushiken, V.O.; Ferreira-Duarte, A.P.; Pinheiro-Torres, A.S.; Roncalho-Buck, I.A. [Department of Biology and Physiology, Faculty of Medicine of Jundiai (FMJ), Jundiai, SP (Brazil); Squebola-Cola, D.M.; Mello, G.C.; Anhê, G.F.; Antunes, E. [Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP (Brazil); DeSouza, I.A., E-mail: ivanidesouza@uol.com.br [Department of Biology and Physiology, Faculty of Medicine of Jundiai (FMJ), Jundiai, SP (Brazil)

    2015-09-15

    Pulmonary neutrophil infiltration produced by Staphylococcal enterotoxin A (SEA) airway exposure is accompanied by marked granulocyte accumulation in bone marrow (BM). Therefore, the aim of this study was to investigate the mechanisms of BM cell accumulation, and trafficking to circulating blood and lung tissue after SEA airway exposure. Male BALB/C mice were intranasally exposed to SEA (1 μg), and at 4, 12 and 24 h thereafter, BM, circulating blood, bronchoalveolar lavage (BAL) fluid and lung tissue were collected. Adhesion of BM granulocytes and flow cytometry for MAC-1, LFA1-α and VLA-4 and cytokine and/or chemokine levels were assayed after SEA-airway exposure. Prior exposure to SEA promoted a marked PMN influx to BAL and lung tissue, which was accompanied by increased counts of immature and/or mature neutrophils and eosinophils in BM, along with blood neutrophilia. Airway exposure to SEA enhanced BM neutrophil MAC-1 expression, and adhesion to VCAM-1 and/or ICAM-1-coated plates. Elevated levels of GM-CSF, G-CSF, INF-γ, TNF-α, KC/CXCL-1 and SDF-1α were detected in BM after SEA exposure. SEA exposure increased production of eosinopoietic cytokines (eotaxin and IL-5) and BM eosinophil VLA-4 expression, but it failed to affect eosinophil adhesion to VCAM-1 and ICAM-1. In conclusion, BM neutrophil accumulation after SEA exposure takes place by integrated action of cytokines and/or chemokines, enhancing the adhesive responses of BM neutrophils and its trafficking to lung tissues, leading to acute lung injury. BM eosinophil accumulation in SEA-induced acute lung injury may occur via increased eosinopoietic cytokines and VLA-4 expression. - Highlights: • Airway exposure to SEA causes acute lung inflammation. • SEA induces accumulation of bone marrow (BM) in immature and mature neutrophils. • SEA increases BM granulocyte or BM PMN adhesion to ICAM-1 and VCAM-1, and MAC-1 expression. • SEA induces BM elevations of CXCL-1, INF-γ, TNF-α, GM-CSF, G-CSF and

  14. Effect of phylloquinone (vitamin K1) supplementation for 12 months on the indices of vitamin K status and bone health in adult patients with Crohn's disease.

    Science.gov (United States)

    O'Connor, Eibhlís M; Grealy, Geraldine; McCarthy, Jane; Desmond, Alan; Craig, Orla; Shanahan, Fergus; Cashman, Kevin D

    2014-10-14

    Although epidemiological findings support a role for vitamin K status in the improvement of bone indices in adult patients with Crohn's disease (CD), this needs to be confirmed in double-blind, randomised controlled trials (RCT) with phylloquinone (vitamin K1). By conducting two RCT, the present study aimed to first establish whether supplementation with 1000 μg of phylloquinone daily near-maximally suppresses the percentage of undercarboxylated osteocalcin in serum (%ucOC; marker of vitamin K status) in adult patients with CD currently in remission as it does in healthy adults and second determine the effect of supplementation with phylloquinone at this dose for 12 months on the indices of bone turnover and bone mass. The initial dose-ranging RCT was conducted in adult patients with CD (n 10 per group) using 0 (placebo), 1000 or 2000 μg of phylloquinone daily for 2 weeks. In the main RCT, the effect of placebo v. 1000 μg vitamin K/d (both co-administered with Ca (500 mg/d) and vitamin D3 (10 μg/d)) for 12 months (n 43 per group) on the biochemical indices of bone turnover (determined by enzyme immunoassay) and bone mass (determined by dual-energy X-ray absorptiometry) were investigated. At baseline, the mean %ucOC was 47 %, and this was suppressed upon supplementation with 1000 μg of phylloquinone daily ( - 81 %; P0·1) on bone turnover markers or on the bone mass of the lumbar spine or femur, but modestly increased (Pvitamin D3) had no effect on the indices of bone health in adult CD patients with likely vitamin K insufficiency.

  15. Bone Densitometry (Bone Density Scan)

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Bone Densitometry (DEXA) Bone densitometry, also called dual-energy ... limitations of DEXA Bone Densitometry? What is a Bone Density Scan (DEXA)? Bone density scanning, also called ...

  16. Importance of measuring Bone Mineral Density in Adult Coeliac Disease Patients

    Directory of Open Access Journals (Sweden)

    Dr. DI Hobday

    2007-07-01

    Full Text Available This study was conducted with an aim to confirm the presence of osteoporosis in patients proven to be suffering from Coeliac Disease and compare present practice in the hospital against the guidelines suggested in the published literature. Information was obtained by retrospective analysis by reviewing notes of 73 patients with coeliac disease, who are registered in the database of a busy Gastroenterology Department of Sunderland Royal Hospital. Of the total of 73 patients, 54 patients underwent a DEXA scan at diagnosis and the Osteoporosis (WHO defined criteria of T score below 2.5 SD the mean adult was detected in 15(27.3% of them. 6 of the 15 patients detected to have osteoporosis were less than 53 years of age. Osteoporosis is common in patients with coeliac disease, and need regular monitoring for osteoporosis, as they are at significant risk of developing it.

  17. Bone scintiscanning updated.

    Science.gov (United States)

    Lentle, B C; Russell, A S; Percy, J S; Scott, J R; Jackson, F I

    1976-03-01

    Use of modern materials and methods has given bone scintiscanning a larger role in clinical medicine, The safety and ready availability of newer agents have led to its greater use in investigating both benign and malignant disease of bone and joint. Present evidence suggests that abnormal accumulation of 99mTc-polyphosphate and its analogues results from ionic deposition at crystal surfaces in immature bone, this process being facilitated by an increase in bone vascularity. There is, also, a component of matrix localization. These factors are in keeping with the concept that abnormal scintiscan sites represent areas of increased osteoblastic activity, although this may be an oversimplification. Increasing evidence shows that the bone scintiscan is more sensitive than conventional radiography in detecting focal disease of bone, and its ability to reflect the immediate status of bone further complements radiographic findings. The main limitation of this method relates to nonspecificity of the results obtained.

  18. Ceacam1 separates graft-versus-host-disease from graft-versus-tumor activity after experimental allogeneic bone marrow transplantation.

    Directory of Open Access Journals (Sweden)

    Sydney X Lu

    Full Text Available Allogeneic bone marrow transplantation (allo-BMT is a potentially curative therapy for a variety of hematologic diseases, but benefits, including graft-versus-tumor (GVT activity are limited by graft-versus-host-disease (GVHD. Carcinoembryonic antigen related cell adhesion molecule 1 (Ceacam1 is a transmembrane glycoprotein found on epithelium, T cells, and many tumors. It regulates a variety of physiologic and pathological processes such as tumor biology, leukocyte activation, and energy homeostasis. Previous studies suggest that Ceacam1 negatively regulates inflammation in inflammatory bowel disease models.We studied Ceacam1 as a regulator of GVHD and GVT after allogeneic bone marrow transplantation (allo-BMT in mouse models. In vivo, Ceacam1(-/- T cells caused increased GVHD mortality and GVHD of the colon, and greater numbers of donor T cells were positive for activation markers (CD25(hi, CD62L(lo. Additionally, Ceacam1(-/- CD8 T cells had greater expression of the gut-trafficking integrin α(4β(7, though both CD4 and CD8 T cells were found increased numbers in the gut post-transplant. Ceacam1(-/- recipients also experienced increased GVHD mortality and GVHD of the colon, and alloreactive T cells displayed increased activation. Additionally, Ceacam1(-/- mice had increased mortality and decreased numbers of regenerating small intestinal crypts upon radiation exposure. Conversely, Ceacam1-overexpressing T cells caused attenuated target-organ and systemic GVHD, which correlated with decreased donor T cell numbers in target tissues, and mortality. Finally, graft-versus-tumor survival in a Ceacam1(+ lymphoma model was improved in animals receiving Ceacam1(-/- vs. control T cells.We conclude that Ceacam1 regulates T cell activation, GVHD target organ damage, and numbers of donor T cells in lymphoid organs and GVHD target tissues. In recipients of allo-BMT, Ceacam1 may also regulate tissue radiosensitivity. Because of its expression on both the

  19. Psychological Impact of Predictive Genetic Testing in VCP Inclusion Body Myopathy, Paget Disease of Bone and Frontotemporal Dementia.

    Science.gov (United States)

    Surampalli, Abhilasha; Khare, Manaswitha; Kubrussi, Georgette; Wencel, Marie; Tanaja, Jasmin; Donkervoort, Sandra; Osann, Kathryn; Simon, Mariella; Wallace, Douglas; Smith, Charles; M McInerney-Leo, Aideen; Kimonis, Virginia

    2015-10-01

    Inclusion Body Myopathy associated with Paget's disease of bone and Fronto-temporal Dementia, also known as multisystem proteinopathy is an autosomal dominant, late onset neurodegenerative disorder caused by mutations in Valosin containing protein (VCP) gene. This study aimed to assess uptake and decision making for predictive genetic testing and the impact on psychological well-being. Individuals who had participated in the gene discovery study with a 50 % a priori risk of inheriting VCP disease were sent a letter of invitation offering genetic counseling and testing and were also invited to participate in this psychosocial study. A total of 102 individuals received an invitation and 33 individuals participated in genetic counseling and testing (32.3 %) with 29 completing baseline questionnaires. Twenty completed the follow-up post-test Hospital Anxiety and Depression Scale questionnaire including 13 of the 18 who had tested positive. Mean risk perception at baseline was 50.1 %. Reasons for testing included planning for the future, relieving uncertainty, informing children and satisfying curiosity. At baseline, one quarter of the participants had high levels of anxiety. However, scores were normal one year following testing. In this small cohort, one third of individuals at 50 % risk chose pre-symptomatic testing. Although one quarter of those choosing testing had high anxiety at baseline, this was not evident at follow-up.

  20. Relationship between body mass index, bone mineral density, and oral hygiene with periodontal disease in a Mexican elderly group.

    Directory of Open Access Journals (Sweden)

    José Francisco Murrieta

    2016-05-01

    Full Text Available The aim of this study was to evaluate the relationship of body mass index (BMI, bone mineral density (BMD, and oral hygiene with periodontal disease (PD in a group of elderly adults in Mexico City. Material and Methods: A cross-sectional study with a convenience sample of 151 elderly adults was conducted. Before applying the epidemiological survey, each subject was asked to sign an informed consent. Standardization for measuring Ramfjord’s Periodontal Disease Index (PDI, BMI, and Green and Vermilion’s OHI-S was carried out. Descriptive statistics and linear regression models were performed. Results: The 93.4% of the group had PD, 33.8% showed severe gingivitis and 20.5% mild gingivitis. A 28.5% five percent of the group had osteopenia and 18.5% had osteoporosis, being more common in people over 69 years. The 38.4% percent of the group was underweight and 53.0% had poor oral hygiene. Oral hygiene accounted for 63.1% of the PD variance (p=0.0001, figure that did not increase considerably by adding BMD and BMI variables to the regression model. Conclusion: The frequency of PD in this group of elderly adults was high and significantly associated with BMD, BMI, and mainly oral hygiene.

  1. Increased IL-6 expression in osteoclasts is necessary but not sufficient for the development of Paget's disease of bone.

    Science.gov (United States)

    Teramachi, Jumpei; Zhou, Hua; Subler, Mark A; Kitagawa, Yukiko; Galson, Deborah L; Dempster, David W; Windle, Jolene J; Kurihara, Noriyoshi; Roodman, G David

    2014-06-01

    Measles virus nucleocapsid protein (MVNP) expression in osteoclasts (OCLs) and mutation of the SQSTM1 (p62) gene contribute to the increased OCL activity in Paget's disease (PD). OCLs expressing MVNP display many of the features of PD OCLs. Interleukin-6 (IL-6) production is essential for the pagetic phenotype, because transgenic mice with MVNP targeted to OCLs develop pagetic OCLs and lesions, but this phenotype is absent when MVNP mice are bred to IL-6(-/-) mice. In contrast, mutant p62 expression in OCL precursors promotes receptor activator of NF-κB ligand (RANKL) hyperresponsivity and increased OCL production, but OCLs that form have normal morphology, are not hyperresponsive to 1,25-dihydroxyvitamin D3 (1,25-(OH)2 D3 ), nor produce elevated levels of IL-6. We previously generated p62(P394L) knock-in mice (p62KI) and found that although OCL numbers were increased, the mice did not develop pagetic lesions. However, mice expressing both MVNP and p62KI developed more exuberant pagetic lesions than mice expressing MVNP alone. To examine the role of elevated IL-6 in PD and determine if MVNP mediates its effects primarily through elevation of IL-6, we generated transgenic mice that overexpress IL-6 driven by the tartrate-resistant acid phosphatase (TRAP) promoter (TIL-6 mice) and produce IL-6 at levels comparable to MVNP mice. These were crossed with p62KI mice to determine whether IL-6 overexpression cooperates with mutant p62 to produce pagetic lesions. OCL precursors from p62KI/TIL-6 mice formed greater numbers of OCLs than either p62KI or TIL-6 OCL precursors in response to 1,25-(OH)2 D3 . Histomorphometric analysis of bones from p62KI/TIL-6 mice revealed increased OCL numbers per bone surface area compared to wild-type (WT) mice. However, micro-quantitative CT (µQCT) analysis did not reveal significant differences between p62KI/TIL-6 and WT mice, and no pagetic OCLs or lesions were detected in vivo. Thus, increased IL-6 expression in OCLs from p62KI mice

  2. Autologous bone marrow mononuclear cell transplantation in patients with decompensated alcoholic liver disease: a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Laurent Spahr

    Full Text Available OBJECTIVE: Impaired liver regeneration is associated with a poor outcome in patients with decompensated alcoholic liver disease (ALD. We assessed whether autologous bone marrow mononuclear cell transplantation (BMMCT improved liver function in decompensated ALD. DESIGN: 58 patients (mean age 54 yrs; mean MELD score 19, all with cirrhosis, 81% with alcoholic steatohepatitis at baseline liver biopsy were randomized early after hospital admission to standard medical therapy (SMT alone (n = 30, including steroids in patients with a Maddrey's score ≥32, or combined with G-CSF injections and autologous BMMCT into the hepatic artery (n = 28. Bone marrow cells were harvested, isolated and reinfused the same day. The primary endpoint was a ≥3 points decrease in the MELD score at 3 months, corresponding to a clinically relevant improvement in liver function. Liver biopsy was repeated at week 4 to assess changes in Ki67+/CK7+ hepatic progenitor cells (HPC compartment. RESULTS: Both study groups were comparable at baseline. After 3 months, 2 and 4 patients died in the BMMCT and SMT groups, respectively. Adverse events were equally distributed between groups. Moderate alcohol relapse occurred in 31% of patients. The MELD score improved in parallel in both groups during follow-up with 18 patients (64% from the BMMCT group and 18 patients (53% from the SMT group reaching the primary endpoint (p = 0.43 (OR 1.6, CI 0.49-5.4 in an intention to treat analysis. Comparing liver biopsy at 4 weeks to baseline, steatosis improved (p<0.001, and proliferating HPC tended to decrease in both groups (-35 and -33%, respectively. CONCLUSION: Autologous BMMCT, compared to SMT is a safe procedure but did not result in an expanded HPC compartment or improved liver function. These data suggest either insufficient regenerative stimulation after BMMCT or resistance to liver regenerative drive in patients with decompensated alcoholic cirrhosis. TRIAL REGISTRATION

  3. Multiparameter MRI assessment of normal-appearing and diseased vertebral bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Biffar, Andreas; Dietrich, Olaf [LMU University Hospitals Munich-Grosshadern, Josef Lissner Laboratory for Biomedical Imaging, Institute of Clinical Radiology, Munich (Germany); Baur-Melnyk, Andrea; Schmidt, Gerwin P. [LMU University Hospitals Munich-Grosshadern, Institute of Clinical Radiology, Munich 81377 (Germany); Reiser, Maximilian F. [LMU University Hospitals Munich-Grosshadern, Josef Lissner Laboratory for Biomedical Imaging, Institute of Clinical Radiology, Munich (Germany); LMU University Hospitals Munich-Grosshadern, Institute of Clinical Radiology, Munich 81377 (Germany)

    2010-11-15

    To evaluate spin-lattice (T1) and spin-spin (T2) relaxation times as well as apparent diffusion coefficients (ADCs) of the fat and water components in the vertebral bone marrow (vBM) of patients with benign and malignant lesions. Forty-four patients were examined at 1.5 T: there were 24 osteoporotic vertebral fractures (15 women, 9 men; median age: 73, 48-86 years) and 20 malignant vertebral infiltrations (9 women, 11 men; median age: 60, 25-87). Relaxation times were determined separately for the water and the fat component using a saturation-recovery technique for T1 and measurements with variable echo times for T2. ADCs were determined with a diffusion-weighted (DW) echo-planar imaging (EPI) and a single-shot turbo-spin-echo (ssTSE) sequence. T1 of the water component and ADCs were significantly increased in the lesions compared with normal-appearing vBM (malignant: 1,252 vs. 828 ms, osteoporotic: 1,315 vs. 872 ms). ADCs determined with the DW-ssTSE were significantly increased compared with the DW-EPI. ADCs determined with the DW-ssTSE differed significantly between osteoporotic and malignant lesions (1.74vs1.35 x 10{sup -3}mm{sup 2}/s). All parameters exhibit significant differences between normal-appearing vBM and the lesions. However, only the ADCs determined with the DW-ssTSE differed significantly between osteoporotic fractures and malignant lesions, potentially allowing for a differential diagnosis of these two entities. (orig.)

  4. Bone loss in unclassified polyarthritis and early rheumatoid arthritis is better detected by digital x ray radiogrammetry than dual x ray absorptiometry: relationship with disease activity and radiographic outcome

    DEFF Research Database (Denmark)

    Jensen, T; Klarlund, Mette; Hansen, M

    2004-01-01

    every six months. RESULTS: DXR BMD decreased significantly only in patients with RA from month 6 and was associated with the mean disease activity. Patients with RA and erosive as well as non-erosive disease showed a significant decrease in the rate of bone loss, greatest in those with erosive disease...... is better than DXA for detecting and monitoring periarticular osteoporosis of the metacarpal bone. Udgivelsesdato: 2004-Jan...

  5. Impact of cytomegalovirus and grafts versus host disease on the dynamics of CD57+CD28-CD8+ T cells after bone marrow transplant

    Directory of Open Access Journals (Sweden)

    Ana Verena Almeida Mendes

    2008-01-01

    Full Text Available OBJECTIVES: The present study aimed to evaluate the dynamics of CD28 and CD57 expression in CD8+ T lymphocytes during cytomegalovirus viremia in bone marrow transplant recipients. METHODS: In a prospective study, blood samples were obtained once weekly once from 33 healthy volunteers and weekly from 33 patients. To evaluate the expression of CD57 and CD28 on CD8+ T lymphocytes, flow cytometry analysis was performed on blood samples for four months after bone marrow transplant, together with cytomegalovirus antigenemia assays. RESULTS: Compared to cytomegalovirus-seronegative healthy subjects, seropositive healthy subjects demonstrated a higher percentage of CD57+ and a lower percentage of CD28+ cells (p<0.05. A linear regression model demonstrated a continuous decrease in CD28+ expression and a continuous increase in CD57+ expression after bone marrow transplant. The occurrence of cytomegalovirus antigenemia was associated with a steep drop in the percentage of CD28+ cells (5.94%, p<0.01 and an increase in CD57+ lymphocytes (5.60%, p<0.01. This cytomegalovirus-dependent effect was for the most part concentrated in the allogeneic bone marrow transplant patients. The development of acute graft versus host disease, which occurred at an earlier time than antigenemia (day 26 vs. day 56 post- bone marrow transplant, also had an impact on the CD57+ subset, triggering an increase of 4.9% in CD57+ lymphocytes (p<0.05. CONCLUSION: We found continuous relative changes in the CD28+ and CD57+ subsets during the first 120 days post- bone marrow transplant, as part of immune system reconstitution and maturation. A clear correlation was observed between the expansion of the CD57+CD28-CD8+ T lymphocyte subpopulation and the occurrence of graft versus host disease and cytomegalovirus viremia.

  6. Enfermedad metastásica ósea: Diagnóstico y tratamiento Metastatic bone disease: Diagnosis and treatment

    Directory of Open Access Journals (Sweden)

    A.J. Garbayo

    2004-01-01

    classic tests of detection and evaluation of the spread of the metastatic disease, simple radiology and gammagraphy, are today complemented by others such as computerised tomography (CT and magnetic resonance (MR, improving the information on the characteristics of the lesion both inside and outside the bone. On the other hand, positron emission tomography (PET is showing a far higher sensitivity than gammagraphy and will probably be the test of the future for the early detection of metastasis and of silent primary tumours. The possibilities of treatment of bone metastasis are based on the use of bone regenerators, radiotherapy and surgery. The former two are indicated in lesions already detected in radiography, whether symptomatic or not, if there is no foreseeable risk of fracture. Surgery is indicated in situations of poor or null response to those treatments, when the risk of fracture is high or a pathological fracture has been produced. Before any therapeutic planning, a detailed evaluation of the patient must be carried out, both at a local level (size, site, extension of the metastasis and general (type of primary tumour, phase of treatment and response, estimated survival.

  7. Shockwave treatment for musculoskeletal diseases and bone consolidation: qualitative analysis of the literature

    Directory of Open Access Journals (Sweden)

    Paulo Kertzman

    2015-02-01

    Full Text Available Shockwave treatment is an option within orthopedics. The exact mechanism through which shockwaves function for treating musculoskeletal diseases is unknown. The aim of this study was to make a qualitative analysis on the effectiveness of shockwave treatment among patients with musculoskeletal pathological conditions and pseudarthrosis. Searches were conducted in the Cochrane Library, Medline and Lilacs databases. Thirty-nine studies that reported using shockwave treatment for musculoskeletal diseases were found. Their results varied greatly, as did the types of protocol used. The studies that evaluated the effectiveness of shockwave treatment for lateral epicondylitis, shoulder tendinopathy, knee osteoarthrosis, femoral head osteonecrosis and trochanteric bursitis reported inconsistent results for most of their patients. Those that evaluated patients with calcifying tendinopathy, plantar fasciitis, Achilles tendinopathy, patellar tendinopathy and pseudarthrosis showed benefits. Shockwave treatment is a safe and non-invasive method for chronic cases in which conventional techniques have been unsatisfactory and should be used in association with other treatment methods for tendinopathy. Further quality studies are needed.

  8. Shockwave treatment for musculoskeletal diseases and bone consolidation: qualitative analysis of the literature.

    Science.gov (United States)

    Kertzman, Paulo; Lenza, Mario; Pedrinelli, André; Ejnisman, Benno

    2015-01-01

    Shockwave treatment is an option within orthopedics. The exact mechanism through which shockwaves function for treating musculoskeletal diseases is unknown. The aim of this study was to make a qualitative analysis on the effectiveness of shockwave treatment among patients with musculoskeletal pathological conditions and pseudarthrosis. Searches were conducted in the Cochrane Library, Medline and Lilacs databases. Thirty-nine studies that reported using shockwave treatment for musculoskeletal diseases were found. Their results varied greatly, as did the types of protocol used. The studies that evaluated the effectiveness of shockwave treatment for lateral epicondylitis, shoulder tendinopathy, knee osteoarthrosis, femoral head osteonecrosis and trochanteric bursitis reported inconsistent results for most of their patients. Those that evaluated patients with calcifying tendinopathy, plantar fasciitis, Achilles tendinopathy, patellar tendinopathy and pseudarthrosis showed benefits. Shockwave treatment is a safe and non-invasive method for chronic cases in which conventional techniques have been unsatisfactory and should be used in association with other treatment methods for tendinopathy. Further quality studies are needed.

  9. [Resection of the first row of carpal bones: post-traumatic wrist and Kienbock's disease].

    Science.gov (United States)

    Welby, F; Alnot, J Y

    2003-06-01

    This study reports the outcomes of 27 proximal row carpectomies for stage II (Watson) scapholunate--(10 Slac) and scaphoid non union--(8 Snac) advanced collapse and stage III (Lichtman) Kienböck's disease (9 cases) followed for an average of respectively 72 and 50 months. Following surgical treatment, more than 80% of patients in both groups were pain free. The total arc of motion averaged 67 degrees (unchanged), for the post-traumatic arthritis, and 59 degrees for Kienböck's, a decrease of 17%. Grip strength averaged a 17% increase in comparison to the opposite size for both groups. Proximal row carpectomy showed a high degree of patient satisfaction and is a motion-preserving and grip-preserving procedure used in stage II post-traumatic arthritis but Lichtman III stage in Kienböck's disease had a comparatively poor result. Proximal row carpectomy simplifies the structure of the radiocarpal joint. When the cartilage on the capitate head and the radial lunate facet are not worn, this procedure provides a good result with respect to pain, range of motion and strength which is stable with time.

  10. Kinetics of lymphocyte reconstitution after allogeneic bone marrow transplantation: markers of graft-versus-host disease.

    Science.gov (United States)

    Zinöcker, Severin; Sviland, Lisbet; Dressel, Ralf; Rolstad, Bent

    2011-07-01

    GVHD causes extensive morbidity and mortality in patients who receive alloHCT. Predictive and reliable markers for GVHD are currently lacking but required to improve the safety and accessibility of alloHCT. We present an experimental rat model of myeloablative total body irradiation and fully mismatched major and minor histoincompatible, T cell-depleted BMT, followed by delayed infusion of donor lymphocytes. This treatment, in contrast to marrow transplantation alone, resulted in severe aGVHD and 100% lethality within 2-6 weeks. We investigated the reconstitution kinetics and phenotypes of donor leukocyte subpopulations as well as the histopathology of selected organs that may correlate with GVHD, with the goal to find potential disease-related markers. We observed histological changes mainly confined to the skin, with degenerative changes in the basal layer. LNs and spleen showed deranged architecture with markedly increased accumulation of lymphocytes, whereas the gut, liver, and lungs appeared normal. Of the lymphocyte markers tested, donor-derived CD62L(+) T cells were markedly decreased in animals suffering from GVHD. Furthermore, we observed peripheral depletion of CD4(+)CD25(hi)FoxP3(+) T(reg), which was in contrast to controls. The relative frequency of these lymphocyte subpopulations in blood may therefore serve as accessible cellular markers of aGVHD. We propose that the animal model presented is instructive for the identification of clinically relevant markers of GVHD, which could improve disease diagnosis and management in alloHCT.

  11. Evaluation of bone marrow infiltration in non-neuropathic Gaucher disease patients with use of whole-body MRI. A retrospective data analysis

    Energy Technology Data Exchange (ETDEWEB)

    Laudemann, K.; Moos, L.; Lollert, A.; Wagner, D.; Staatz, G. [University Medical Center of the Johannes Gutenberg University, Mainz (Germany). Section of Pediatric Radiology; Mengel, K.E.; Reinke, J.; Brixius-Huth, M. [University Medical Center of the Johannes Gutenberg University, Mainz (Germany). Clinic for Metabolic Diseases; Dueber, C. [University Medical Center of the Johannes Gutenberg University, Mainz (Germany). Dept. of Diagnostic and Interventional Radiology

    2015-12-15

    To evaluate whole-body magnetic resonance imaging (WB-MRI) for the assessment of bone marrow infiltration in patients with confirmed Gaucher disease type 1 under long-term enzyme replacement therapy (ERT). This retrospective data analysis included 38 patients in two subgroups. Group A: 10 females, 9 males, 15-29 years, mean age 22 years and Group B: 11 females, 8 males, 29-77 years, mean age 49 years, all treated with alglucerase or imiglucerase for at least 12.5 years. Whole-body MRI was carried out in all patients using a standard MRI protocol. Two radiologists assessed all MR images retrospectively with the use of three different MRI score systems: The bone marrow burden (BMB) score, the Duesseldorf-Gaucher score (DGS) and the vertebra disc ratio (VDR). As a clinical component, severity score index type 1 (GD-DS3) was determined. In both groups the MR scores showed low to moderate pathologic levels but no statistically significant difference was found between both groups. The median scores in group A/group B were 7.00/9.00 for the BMB score (p=0.07), 4.00/3.00 for the DGS score (p=0.062) and 1.54/1.62 for the VDR score (p=0.267). The GD-DS3 score was statistically significantly different between both groups (1.6/3.9, p=0.000) and osseous Gaucher disease complications were only found in group B. Bone marrow involvement and typical clinical manifestations are reduced to a minimum, when ERT starts immediately after the confirmed diagnosis of Gaucher disease type 1. The applied MR scores are useful markers to control bone marrow infiltration under enzyme replacement therapy in older patients. Pathologic MR scores in young patients may reflect postponed fat conversion of the juvenile bone marrow. This issue has to be examined in further studies.

  12. Lower fibroblast growth factor 23 levels in young adults with Crohn disease as a possible secondary compensatory effect on the disturbance of bone and mineral metabolism.

    Science.gov (United States)

    Oikonomou, Konstantinos A; Orfanidou, Timoklia I; Vlychou, Marianna K; Kapsoritakis, Andreas N; Tsezou, Aspasia; Malizos, Konstantinos N; Potamianos, Spyros P

    2014-01-01

    Fibroblast growth factor 23 (FGF-23) is a bone-derived circulating phosphaturic factor that decreases serum concentration of phosphate and vitamin D, suggested to actively participate in a complex renal-gastrointestinal-skeletal axis. Serum FGF-23 concentrations, as well as various other laboratory parameters involved in bone homeostasis, were measured and analyzed with regard to various diseases and patients' characteristics in 44 patients with Crohn disease (CD) and 20 healthy controls (HCs) included in this cross-sectional study. Serum FGF-23 levels were significantly lower in patients with CD (900.42 ± 815.85pg/mL) compared with HC (1410.94 ± 1000.53pg/mL), p = 0.037. Further analyses suggested FGF-23 as a factor independent from various parameters including age (r = -0.218), body mass index (r = -0.115), 25-hydroxy vitamin D (r = 0.126), parathyroid hormone (r = 0.084), and bone mineral density (BMD) of hip and lumbar (r = 0.205 and r = 0.149, respectively). This observation remained even after multivariate analyses, exhibiting that BMD was not affected by FGF-23, although parameters such as age (p = 0.026), cumulative prednisolone dose (p vitamin D levels, showing no impact on BMD determination of young adults with CD. The downregulation of serum FGF-23 levels in CD appears as a secondary compensatory effect on the bone and mineral metabolism induced by chronic intestinal inflammation.

  13. Skeletal blood flow in Paget's disease of bone and its response to calcitonin therapy.

    Science.gov (United States)

    Wootton, R; Reeve, J; Spellacy, E; Tellez-Yudilevich, M

    1978-01-01

    1. Blood flow to the skeleton was measured by the 18F clearance method of Wooton, Reeve & Veall (1976) in 24 patients with untreated Paget's disease. In every patient but one, resting skeletal blood flow was increased. There was a significant positive correlation between skeletal blood flow and serum alkaline phosphatase and between skeletal blood flow and urinary total hydroxyproline excretion. 2. Fourteen patients were re-studied after they had received short-term (7 days or less) or long-term (7 weeks or more) calcitonin. Skeletal blood flow, alkaline phosphatase and urinary hydroxy-proline excretion fell towards normal in every case. There was some evidence from the short-term studies that calcitonin produced a more rapid fall in skeletal blood flow than in alkaline phosphatase. 3. Glomerular filtration rate appeared to increase transiently in response to calcitonin.

  14. Inclusion body myopathy, Paget's disease of the bone and fronto-temporal dementia: a disorder of autophagy.

    Science.gov (United States)

    Ju, Jeong-Sun; Weihl, Conrad C

    2010-04-15

    Inclusion body myopathy associated with Paget's disease of the bone and fronto-temporal dementia (IBMPFD) is a progressive autosomal dominant disorder caused by mutations in p97/VCP (valosin-containing protein). p97/VCP is a member of the AAA+ (ATPase associated with a variety of activities) protein family and participates in multiple cellular processes. One particularly important role for p97/VCP is facilitating intracellular protein degradation. p97/VCP has traditionally been thought to mediate the ubiquitin-proteasome degradation of proteins; however, recent studies challenge this dogma. p97/VCP clearly participates in the degradation of aggregate-prone proteins, a process principally mediated by autophagy. In addition, IBMPFD mutations in p97/VCP lead to accumulation of autophagic structures in patient and transgenic animal tissue. This is likely due to a defect in p97/VCP-mediated autophagosome maturation. The following review will discuss the evidence for p97/VCP in autophagy and how a disruption in this process contributes to IBMPFD pathogenesis.

  15. Hydatid disease of scapula and upper third of humerus treated by en bloc excision and fibular bone grafting

    Directory of Open Access Journals (Sweden)

    Chari P

    2007-01-01

    Full Text Available 35-year-old male patient presented with gradually increasing painful swelling of the right shoulder, which was incised and drained and wound persisted as a discharging sinus on the anterolateral aspect of the deltoid region with seropurulent discharge. A clinical diagnosis of tuberculosis of the shoulder was made. Plain skiagram of the right shoulder revealed multicystic lesion involving the entire scapula and upper third of the humerus with loss of joint space and pathological fracture at the junction of upper one-third and lower two-thirds of the humerus. A clinico-radiological diagnosis of hydatid disease was made. In view of the extensive involvement of the scapula with stiff shoulder and an active sinus, a two-stage surgical procedure was performed. Stage 1 consisted of en bloc excision of the scapula, upper half of the humerus and lateral end of the clavicle. Stage II surgery, consisting of fibular bone grafting. Tablet albendazole (400 mg, thrice daily was given as systemic scolicidal agent. This case is reported in view of it′s rarity and to highlight the management.

  16. Bone marrow involvement in Gaucher disease at MRI: what long-term evolution can we expect under enzyme replacement therapy?

    Energy Technology Data Exchange (ETDEWEB)

    Fedida, Benjamin; Touraine, Sebastien; Laredo, Jean-Denis [Hopital Lariboisiere, AP-HP, Department of Musculoskeletal Imaging, Paris (France); Stirnemann, Jerome [Universite Paris-Diderot Hopital Bichat, AP-HP, Department of Biostatistics and Medical Data Processing, INSERM UMR 738, Paris (France); Geneva University Hospital, Division of General Internal Medicine, Faculty of Medicine, Geneva (Switzerland); Belmatoug, Nadia [Hopital Beaujon, AP-HP, Referral Center for Lysosomal Diseases (RCLD), Clichy (France); Hopital Beaujon, AP-HP, Department of Internal Medicine, Clichy (France); Petrover, David [Hopital Lariboisiere, AP-HP, Department of Musculoskeletal Imaging, Paris (France); Hopital Beaujon, AP-HP, Referral Center for Lysosomal Diseases (RCLD), Clichy (France)

    2015-10-15

    To study the long-term evolution of the bone marrow burden (BMB) score at MRI in patients with Gaucher disease (GD) under enzyme replacement therapy (ERT). Forty patients treated for GD were retrospectively studied in a referral centre. BMB scores were assessed on spine and femur MR examinations performed between January 2003 and June 2014. The long-term evolution of the BMB scores was analyzed using a linear mixed model. A total of 121 MRI examinations were performed during the study period with a mean follow-up of 7.1 years ± 5.6, an average rate of 3.1 MR examinations ± 1.7 per patient and an interval of 2.3 years ± 1.1 between examinations. Patients had received ERT during 12 years on average ± 6.7. The trend of BMB scores with time decreased significantly by 15 % (P = 0.008) during the total study period and 39 % (P = 0.01) during the first 5 years of treatment. No changes in BMB scores were observed after five years of treatment. In Gaucher patients, the trend of MRI BMB scores with time decreased significantly under ERT the first 5 years of treatment before a long-term stabilization. (orig.)

  17. Intravenous transplantation of bone marrow-derived mononuclear cells prevents memory impairment in transgenic mouse models of Alzheimer's disease.

    Science.gov (United States)

    Kanamaru, Takuya; Kamimura, Naomi; Yokota, Takashi; Nishimaki, Kiyomi; Iuchi, Katsuya; Lee, Hyunjin; Takami, Shinya; Akashiba, Hiroki; Shitaka, Yoshitsugu; Ueda, Masayuki; Katsura, Ken-Ichiro; Kimura, Kazumi; Ohta, Shigeo

    2015-04-24

    Stem cell transplantation therapy is currently in clinical trials for the treatment of ischemic stroke, and several beneficial aspects have been reported. Similarly, in Alzheimer's disease (AD), stem cell therapy is expected to provide an efficient therapeutic approach. Indeed, the intracerebral transplantation of stem cells reduced amyloid-β (Aβ) deposition and rescued memory deficits in AD model mice. Here, we show that intravenous transplantation of bone marrow-derived mononuclear cells (BMMCs) improves cognitive function in two different AD mouse models, DAL and APP mice, and prevents neurodegeneration. GFP-positive BMMCs were isolated from tibiae and femurs of 4-week-old mice and then transplanted intravenously into DAL and APP mice. Transplantation of BMMCs suppressed neuronal loss and restored memory impairment of DAL mice to almost the same level as in wild-type mice. Transplantation of BMMCs to APP mice reduced Aβ deposition in the brain. APP mice treated with BMMCs performed significantly better on behavioral tests than vehicle-injected mice. Moreover, the effects were observed even with transplantation after the onset of cognitive impairment in DAL mice. Together, our results indicate that intravenous transplantation of BMMCs has preventive effects against the cognitive decline in AD model mice and suggest a potential therapeutic effect of BMMC transplantation therapy.

  18. Mineral and Bone Disorder and Its Association with Cardiovascular Parameters in Chinese Patients with Chronic Kidney Disease

    Science.gov (United States)

    Zhou, Chu; Wang, Fang; Wang, Jin-Wei; Zhang, Lu-Xia; Zhao, Ming-Hui

    2016-01-01

    Background: Mineral and bone disorder (MBD), especially hyperphosphatemia, is an independently risk factor for adverse prognosis in patients with chronic kidney disease (CKD). However, CKD-MBD among Chinese population was poorly studied. This study aimed to investigate the status of MBD and its association with cardiovascular parameters in Chinese patients with predialysis CKD. Methods: Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE) is a prospective multicenter cohort study involving predialysis CKD patients in China. Markers of MBD, including serum phosphorus, calcium, and intact parathyroid hormone, were measured in baseline samples at the patients’ entry. The association between serum phosphorus and abdominal aortic calcification (AAC), left ventricular hypertrophy (LVH) were examined by logistic regression models. Results: Altogether 3194 predialysis patients with mean estimated glomerular filtration of 51.8 ± 33.1 ml·min−1.1.73 m−2 were included. The proportion of patients with hyperphosphatemia were 2.6%, 2.9%, 6.8%, and 27.1% in CKD Stages 3a, 3b, 4, and 5, respectively. Moreover, 71.6% of the patients with hyperphosphatemia did not receive any phosphate-binder (PB). Lateral abdominal X-rays were obtained in 2280 patients, 9.8% of the patients were diagnosed as having AAC. Altogether 2219 patients had data of echocardiography, and 13.2% of them were diagnosed with LVH. Multivariate logistic regression analysis showed that serum phosphorus was independently associated with the presence of AAC and LVH. Conclusions: In Chinese patients with CKD, the percentage of hyperphosphatemia is comparable to that of other countries while the usage of PBs is suboptimal. The prevalence of vascular calcification in Chinese patients is relatively lower compared with the Caucasian population. PMID:27647184

  19. Mineral and Bone Disorder and Its Association with Cardiovascular Parameters in Chinese Patients with Chronic Kidney Disease

    Institute of Scientific and Technical Information of China (English)

    Chu Zhou; Fang Wang; Jin-Wei Wang; Lu-Xia Zhang; Ming-Hui Zhao

    2016-01-01

    Background:Mineral and bone disorder (MBD),especially hyperphosphatemia,is an independently risk factor for adverse prognosis in patients with chronic kidney disease (CKD).However,CKD-MBD among Chinese population was poorly studied.This study aimed to investigate the status of MBD and its association with cardiovascular parameters in Chinese patients with predialysis CKD.Methods:Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE) is a prospective multicenter cohort study involving predialysis CKD patients in China.Markers of MBD,including serum phosphorus,calcium,and intact parathyroid hormone,were measured in baseline samples at the patients' entry.The association between serum phosphorus and abdominal aortic calcification (AAC),left ventricular hypertrophy (LVH) were examined by logistic regression models.Results:Altogether 3194 predialysis patients with mean estimated glomerular filtration of 51.8 ± 33.1 ml·min 1· 1.73 m 2 were included.The proportion of patients with hyperphosphatemia were 2.6%,2.9%,6.8%,and 27.1% in CKD Stages 3a,3b,4,and 5,respectively.Moreover,71.6% of the patients with hyperphosphatemia did not receive any phosphate-binder (PB).Lateral abdominal X-rays were obtained in 2280 patients,9.8% of the patients were diagnosed as having AAC.Altogether 2219 patients had data of echocardiography,and 13.2% of them were diagnosed with LVH.Multivariate logistic regression analysis showed that serum phosphorus was independently associated with the presence of AAC and LVH.Conclusions:In Chinese patients with CKD,the percentage of hyperphosphatemia is comparable to that of other countries while the usage of PBs is suboptimal.The prevalence of vascular calcification in Chinese patients is relatively lower compared with the Caucasian population.

  20. Bone within a bone

    Energy Technology Data Exchange (ETDEWEB)

    Williams, H.J.; Davies, A.M. E-mail: wendy.turner@roh.nhs.uk; Chapman, S

    2004-02-01

    The 'bone within a bone' appearance is a well-recognized radiological term with a variety of causes. It is important to recognize this appearance and also to be aware of the differential diagnosis. A number of common conditions infrequently cause this appearance. Other causes are rare and some remain primarily of historical interest, as they are no longer encountered in clinical practice. In this review we illustrate some of the conditions that can give the bone within a bone appearance and discuss the physiological and pathological aetiology of each where known.

  1. Chinese expert consensus statement on clinical diagnosis and treatment of malignant tumor bone metastasis and bone related diseases%恶性肿瘤骨转移及骨相关疾病临床诊疗中国专家共识

    Institute of Scientific and Technical Information of China (English)

    Shiying Yu; Zefei Jiang; Li Zhang; Xiaohui Niu; Lvhua Wang; Ning Wu; Jianhui Ma

    2010-01-01

    @@ Clinical diagnosis and treatment of malignant tumor bone metastases Overview Bone is the most common place of metastases in ad vanced malignant diseases. Constant improvement in the treatment of malignant tumors has resulted in prolonged survival time, and so as an increased incidence of osseous metastases and skeletal complications.

  2. Peripheral blood minimal residual disease may replace bone marrow minimal residual disease as an immunophenotypic biomarker for impending relapse in acute myeloid leukemia.

    Science.gov (United States)

    Zeijlemaker, W; Kelder, A; Oussoren-Brockhoff, Y J M; Scholten, W J; Snel, A N; Veldhuizen, D; Cloos, J; Ossenkoppele, G J; Schuurhuis, G J

    2016-03-01

    As relapses are common in acute myeloid leukemia (AML), early relapse prediction is of high importance. Although conventional minimal residual disease (MRD) measurement is carried out in bone marrow (BM), peripheral blood (PB) would be an advantageous alternative source. This study aims to investigate the specificity of leukemia-associated immunophenotypes used for MRD detection in blood samples. Consistency of PB MRD as compared with BM MRD was determined in flow cytometric data of 205 paired BM and PB samples of 114 AML patients. A significant correlation was found between PB and BM MRD (r=0.67, P<0.001), while median PB MRD percentage was factor 4-5 lower compared with BM MRD. Primitive blast (CD34+/CD117+/CD133+) frequency was significantly lower in PB (median factor 23.7), indicating that PB MRD detection is more specific than BM. Cumulative incidence of relapse 1 year after induction therapy was 29% for PB MRD-negative and 89% for PB MRD-positive patients (P<0.001). Three-year OS was 52% for MRD-negative and 15% for MRD-positive patients (P=0.034). Similar differences were found after consolidation therapy. As PB MRD appeared to be an independent predictor for response duration, the highly specific PB MRD assay may have a prominent role in future MRD assessment in AML.

  3. The effect of intrathecal delivery of bone marrow stromal cells on hippocampal neurons in rat model of Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Mina Eftekharzadeh

    2015-05-01

    Full Text Available Objective(s: Intracerebral injection of bone marrow stromal cells (BMSCs is being investigated as a therapeutic tool to prevent Alzheimer's disease (AD. Our aim was to investigate the effects of BMSCs by intrathecal injection in AD rat model. Materials and Methods: BMSCs were obtained from the bone marrow of Wistar rat and transplanted into AD rat model via intrathecal injection. The rat model had received an injection of β amyloid into the hippocampus for histological and immunohistochemical studies. Results: Histological examination of the brains in transplanted rats compared to controls demonstrated the migration of BrdU-labeled BMSCs from the site of delivery, confirmed the differentiation of BMSCs transplanted cells into the cholinergic neurons, and increased number of healthy and decreased number of dark neurons. Conclusion: Our results showed that BMSCs intratechal administration could be a promising method for treatment ofAlzheimer’s disease in rat model.

  4. 早产儿代谢性骨病防治进展%Metabolic bone disease in the preterm newborn:an update on prevention and treatment

    Institute of Scientific and Technical Information of China (English)

    王丹虹(综述); 陈平洋(审校)

    2014-01-01

    Metabolic bone disease is one of the common complications in preterm neonates,which has important influence on the quality of life,even increases the risk of adulthood osteoporosis. Early diagnosis and therapy are important for the improvement of outcome of preterm neonates. This article reviews the progress of prevention and treatment of metabolic bone disease in preterm neonates.%早产儿代谢性骨病是早产儿常见的并发症,对其生存质量会造成重要影响,甚至增加成年期骨质疏松的风险。早期干预能有效地减少代谢性骨病的发生,改善早产儿预后。该文对早产儿代谢性骨病的防治进展作一综述。

  5. Tapentadol prolonged release for patients with multiple myeloma suffering from moderate-to-severe cancer pain due to bone disease

    Directory of Open Access Journals (Sweden)

    Coluzzi F

    2015-05-01

    Full Text Available Flaminia Coluzzi,1,2 Robert B Raffa,3 Joseph Pergolizzi,4 Alessandra Rocco,1 Pamela Locarini,1 Natalia Cenfra,5 Giuseppe Cimino,5 Consalvo Mattia1,2 1Department of Medical and Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine, Unit of Anaesthesiology, Intensive Care Medicine and Pain Therapy, Polo Pontino, Sapienza University of Rome, Latina, Italy; 2SIAARTI Study Group on Acute and Chronic Pain, Rome, Italy; 3Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA, USA; 4Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 5Department of Cellular Biotechnology and Hematology, Sapienza University of Rome, Rome, Italy Context: Myeloma bone disease (MBD is a devastating complication of multiple myeloma that leads to severe pain. Objectives: The aim of this study was to evaluate the efficacy and tolerability of tapentadol prolonged release (PR in the management of patients with MBD suffering from moderate-to-severe cancer pain. Methods: A 12-week prospective study was carried out in 25 opioid-naïve MBD patients. Patients initially received twice-daily doses of tapentadol PR 50 mg. Doses were then managed to maintain adequate relief or dose-limiting toxicity. The following parameters were recorded at weekly intervals for 4 weeks, and then at weeks 8 and 12: pain, opioid-related adverse effects, use of other analgesics, DN4 (Douleur Neuropathique 4 score. Quality of life (SF-36 [36-item short-form health survey] was measured at baseline and at final evaluation. Results: Of 25 patients, 22 completed the study. Pain intensity significantly decreased from baseline to all the week intervals (P<0.01. Quality of life significantly improved with respect to all SF-36 subscale parameters (P<0.01, and so did both the physical and mental status (P<0.01. Tapentadol PR significantly reduced DN4 mean value (P<0.01 and the number of patients with neuropathic component

  6. [Structural and functional characteristics of bone tissue and blood cytokines in health and disease of the joints].

    Science.gov (United States)

    Kariakina, E V; Norkin, I A; Gladkova, E V; Persova, E A; Matveeva, O V; Puchin'ian, D M

    2014-02-01

    Change of structural and functional state of bone in patients with primary osteoarthrosis of the hip joint compared to healthy individuals is characterized by decreased bone formation with a relative predominance of resorption. Osteopenic syndrome develops in the background of evident imbalance of a blood cytokine profile with increasing the level of proinflammatory and the variability of the level of anti-inflammatory cytokines.

  7. Clinical practice guidelines for the prevention, diagnosis, evaluation and treatment of mineral and bone disorders in chronic kidney disease (CKD-MBD) in adults.

    Science.gov (United States)

    Bellorin-Font, Ezequiel; Ambrosoni, Pablo; Carlini, Raúl G; Carvalho, Aluizio B; Correa-Rotter, Ricardo; Cueto-Manzano, Alfonso; Jara, Aquiles; Jorgetti, Vanda; Negri, Armando L; Negri, Armando; Olaizola, Inés; Salusky, Isidro; Slatopolsky, Eduardo; Weisinger, José R

    2013-01-01

    The clinical practice guidelines for the prevention, diagnosis, evaluation and treatment of chronic kidney disease mineral and bone disorders (CKD-BMD) in adults, of the Latin American Society of Nephrology and Hypertension (SLANH) comprise a set of recommendations developed to support the doctor in the management of these abnormalities in adult patients with stages 3-5 kidney disease. This excludes changes associated with renal transplantation. The topics covered in the guidelines are divided into four chapters: 1) Evaluation of biochemical changes, 2) Evaluation of bone changes, 3) Evaluation of vascular calcifications, and 4) Treatment of CKD-MBD. The guidelines are based on the recommendations proposed and published by the Kidney Disease: Improving Global Outcomes (KDIGO) for the prevention, diagnosis, evaluation and treatment of CKD-MBD (KDIGO Clinical practice guidelines for the diagnosis, evaluation, prevention and treatment of Chronic Kidney Disease Mineral and Bone Disorder [CKD-MBD]), adapted to the conditions of patients, institutions and resources available in Latin America, with the support of KDIGO. In some cases, the guidelines correspond to management recommendations directly defined by the working group for their implementation in our region, based on the evidence available in the literature. Each chapter contains guidelines and their rationale, supported by numerous updated references. Unfortunately, there are few controlled studies with statistically sufficient weight in Latin America to support specific recommendations for the region, and as such, most of the references used correspond to studies carried out in other regions. This highlights the need to plan research studies designed to establish the current status of mineral and bone metabolism disorders in Latin America as well as defining the best treatment options for our population.

  8. A case of Paget's disease of bone with mycosis fungoides%Paget's骨病伴皮肤蕈样霉菌病一例报告

    Institute of Scientific and Technical Information of China (English)

    卓勤俭; 王瑞明; 苏小芳; 孟彩云; 郑恂; 段京明; 况成国

    2008-01-01

    @@ Paget's骨病(Paget's disease of bone,PDB),又称畸形性骨炎,系原因不明骨吸收增加的缓慢、局限性骨骼病变.可致骨再建异常,新形成不正常骨质增加,局部骨骼膨大、疏松、血管增多,易畸形和骨折.

  9. Bone biomarkers help grading severity of coronary calcifications in non dialysis chronic kidney disease patients.

    Directory of Open Access Journals (Sweden)

    Marion Morena

    Full Text Available BACKGROUND: Osteoprotegerin (OPG and fibroblast growth factor-23 (FGF23 are recognized as strong risk factors of vascular calcifications in non dialysis chronic kidney disease (ND-CKD patients. The aim of this study was to investigate the relationships between FGF23, OPG, and coronary artery calcifications (CAC in this population and to attempt identification of the most powerful biomarker of CAC: FGF23? OPG? METHODOLOGY/PRINCIPAL FINDINGS: 195 ND-CKD patients (112 males/83 females, 70.8 [27.4-94.6] years were enrolled in this cross-sectional study. All underwent chest multidetector computed tomography for CAC scoring. Vascular risk markers including FGF23 and OPG were measured. Logistic regression analyses were used to study the potential relationships between CAC and these markers. The fully adjusted-univariate analysis clearly showed high OPG (≥10.71 pmol/L as the only variable significantly associated with moderate CAC ([100-400[ (OR = 2.73 [1.03;7.26]; p = 0.04. Such association failed to persist for CAC scoring higher than 400. Indeed, severe CAC was only associated with high phosphate fractional excretion (FEPO(4 (≥38.71% (OR = 5.47 [1.76;17.0]; p = 0.003 and high FGF23 (≥173.30 RU/mL (OR = 5.40 [1.91;15.3]; p = 0.002. In addition, the risk to present severe CAC when FGF23 level was high was not significantly different when OPG was normal or high. Conversely, the risk to present moderate CAC when OPG level was high was not significantly different when FGF23 was normal or high. CONCLUSIONS: Our results strongly suggest that OPG is associated to moderate CAC while FGF23 rather represents a biomarker of severe CAC in ND-CKD patients.

  10. Genetic epidemiology of Paget's disease of bone in italy: sequestosome1/p62 gene mutational test and haplotype analysis at 5q35 in a large representative series of sporadic and familial Italian cases of Paget's disease of bone.

    Science.gov (United States)

    Falchetti, Alberto; Di Stefano, Marco; Marini, Francesca; Ortolani, Sergio; Ulivieri, Massimo Fabio; Bergui, Simona; Masi, Laura; Cepollaro, Chiara; Benucci, Maurizio; Di Munno, Ombretta; Rossini, Maurizio; Adami, Silvano; Del Puente, Antonio; Isaia, Giancarlo; Torricelli, Francesca; Brandi, Maria Luisa

    2009-01-01

    Families affected by Paget's disease of bone frequently harbor mutations in the SQSTM1/p62 gene. In this multicentric study we collected 345 sporadic and 12 familial PDB cases throughout Italy, identifying 12 different mutations, 5 of which are newly reported and 3, D335E, A381V, and Y383X, external to the UBA domain. Subjects with truncating mutations, E396X, showed a significantly younger age at clinical diagnosis, while the Y383X subjects had a higher average number of affected skeletal sites. All the mutants exhibited the CGTG-H2 haplotype. In two pairs and one triad of unrelated Italian PDB families from different Italian regions, we detected a common SQSTM1/p62 mutation for each P392L, M404V, and G425R group. Since the CGTG-H2 haplotype frequency was also high in normal subjects, and genetic influence due to migratory fluxes of different ethnic groups exists in the Italian population, to refine the search for a more geographically specific founder effect, we extended the haplotype analysis in these families using polymorphic microsatellite repeat markers, within and flanking the SQSTM1/p62 locus, from chromosome 5q35, other than the exon 6 and 3'UTR polymorphisms. All mutant carriers from two of the three M404V families and from the G425R families exhibited common extended chromosome 5q35 haplotypes, IT01 and IT02, respectively, which may be reflecting influences of past migrations. This may be helpful in estimating the true rate of de novo mutations. We confirm the data on the existence of both a mutational hotspot at the UBA domain of SQSTM1/p62 and a founder effect in the PDB population.

  11. Evaluation of the mineral content of peripheral bones (radius) by photon-absorption technique in normals as well as in patients with various types of bone diseases

    Energy Technology Data Exchange (ETDEWEB)

    Runge, H.; Fengler, F.; Franke, J.; Koall, W.

    1980-10-01

    The evaluation of the mineral content of peripheral bones by measuring the photon absorption of the radius has proven to be a valuable method for routine clinical work: for diagnosis, follow-up and control of therapy. While there was a significant difference in the findings of normal persons compared with those of patients suffering from osteoporosis, renal osteodystrophy, osteogenesis imperfecta and skeletal fluorosis, there was no difference between normals and these patients suffering from Bechterew, Scheuermann, coxarthrosis, spondylosis, skoliosis and rheumatoid arthritis. Normal values for the mineral content and the width of the radius at the junction of the middle and lower third - based on 8000 examinations - are mentioned.

  12. Metabolic bone disease and central retinal degeneration in a kitten due to nutritional inadequacy of an all-meat raw diet

    Directory of Open Access Journals (Sweden)

    Catherine Lenox

    2015-05-01

    Full Text Available A 5-month-old castrated male Sphynx kitten presented with left hindlimb lameness shortly after adoption. Prior to adoption, the breeder had fed the kitten an exclusively raw chicken diet. Radiographs revealed generalized osteopenia and a left tibia–fibula fracture. Ophthalmic examination revealed corneal vascularization and opacity in the right eye, and lesions suggestive of feline central retinal degeneration in the left eye. The patient’s diagnoses included metabolic bone disease and feline central retinal degeneration, which can result from taurine deficiency. The kitten’s nutritional diseases were managed with a complete and balanced canned diet designed for kitten growth and with taurine supplementation.

  13. Causal assessment of dietary acid load and bone disease: a systematic review & meta-analysis applying Hill's epidemiologic criteria for causality

    Directory of Open Access Journals (Sweden)

    Lyon Andrew W

    2011-04-01

    Full Text Available Abstract Background Modern diets have been suggested to increase systemic acid load and net acid excretion. In response, alkaline diets and products are marketed to avoid or counteract this acid, help the body regulate its pH to prevent and cure disease. The objective of this systematic review was to evaluate causal relationships between dietary acid load and osteoporosis using Hill's criteria. Methods Systematic review and meta-analysis. We systematically searched published literature for randomized intervention trials, prospective cohort studies, and meta-analyses of the acid-ash or acid-base diet hypothesis with bone-related outcomes, in which the diet acid load was altered, or an alkaline diet or alkaline salts were provided, to healthy human adults. Cellular mechanism studies were also systematically examined. Results Fifty-five of 238 studies met the inclusion criteria: 22 randomized interventions, 2 meta-analyses, and 11 prospective observational studies of bone health outcomes including: urine calcium excretion, calcium balance or retention, changes of bone mineral density, or fractures, among healthy adults in which acid and/or alkaline intakes were manipulated or observed through foods or supplements; and 19 in vitro cell studies which examined the hypothesized mechanism. Urine calcium excretion rates were consistent with osteoporosis development; however calcium balance studies did not demonstrate loss of whole body calcium with higher net acid excretion. Several weaknesses regarding the acid-ash hypothesis were uncovered: No intervention studies provided direct evidence of osteoporosis progression (fragility fractures, or bone strength as measured using biopsy. The supporting prospective cohort studies were not controlled regarding important osteoporosis risk factors including: weight loss during follow-up, family history of osteoporosis, baseline bone mineral density, and estrogen status. No study revealed a biologic mechanism

  14. Assessment of bone microarchitecture in chronic kidney disease: a comparison of 2D bone texture analysis and high-resolution peripheral quantitative computed tomography at the radius and tibia.

    Science.gov (United States)

    Bacchetta, Justine; Boutroy, Stéphanie; Vilayphiou, Nicolas; Fouque-Aubert, Anne; Delmas, Pierre D; Lespessailles, Eric; Fouque, Denis; Chapurlat, Roland

    2010-11-01

    Bone microarchitecture can be studied noninvasively using high-resolution peripheral quantitative computed tomography (HR-pQCT). However, this technique is not widely available, so more simple techniques may be useful. BMA is a new 2D high-resolution digital X-ray device, allowing for bone texture analysis with a fractal parameter (H(mean)). The aims of this study were (1) to evaluate the reproducibility of BMA at two novel sites (radius and tibia) in addition to the conventional site (calcaneus), (2) to compare the results obtained with BMA at all of those sites, and (3) to study the relationship between H(mean) and trabecular microarchitecture measured with an in vivo 3D device (HR-pQCT) at the distal tibia and radius. BMA measurements were performed at three sites (calcaneus, distal tibia, and radius) in 14 healthy volunteers to measure the short-term reproducibility and in a group of 77 patients with chronic kidney disease to compare BMA results to HR-pQCT results. The coefficient of variation of H(mean) was 1.2, 2.1, and 4.7% at the calcaneus, radius, and tibia, respectively. We found significant associations between trabecular volumetric bone mineral density and microarchitectural variables measured by HR-pQCT and H(mean) at the three sites (e.g., Pearson correlation between radial trabecular number and radial H(mean) r = 0.472, P technique with few technical constraints. Thus, it may represent an interesting tool for evaluating bone structure, in association with biological parameters and DXA.

  15. miR-29b negatively regulates human osteoclastic cell differentiation and function: implications for the treatment of multiple myeloma-related bone disease.

    Science.gov (United States)

    Rossi, Marco; Pitari, Maria Rita; Amodio, Nicola; Di Martino, Maria Teresa; Conforti, Francesco; Leone, Emanuela; Botta, Cirino; Paolino, Francesco Maria; Del Giudice, Teresa; Iuliano, Eleonora; Caraglia, Michele; Ferrarini, Manlio; Giordano, Antonio; Tagliaferri, Pierosandro; Tassone, Pierfrancesco

    2013-07-01

    Skeletal homeostasis relies upon a fine tuning of osteoclast (OCL)-mediated bone resorption and osteoblast (OBL)-dependent bone formation. This balance is unsettled by multiple myeloma (MM) cells, which impair OBL function and stimulate OCLs to generate lytic lesions. Emerging experimental evidence is disclosing a key regulatory role of microRNAs (miRNAs) in the regulation of bone homeostasis suggesting the miRNA network as potential novel target for the treatment of MM-related bone disease (BD). Here, we report that miR-29b expression decreases progressively during human OCL differentiation in vitro. We found that lentiviral transduction of miR-29b into OCLs, even in the presence of MM cells, significantly impairs tartrate acid phosphatase (TRAcP) expression, lacunae generation, and collagen degradation, which are relevant hallmarks of OCL activity. Accordingly, expression of cathepsin K and metalloproteinase 9 (MMP9) as well as actin ring rearrangement were impaired in the presence of miR-29b. Moreover, we found that canonical targets C-FOS and metalloproteinase 2 are suppressed by constitutive miR-29b expression which also downregulated the master OCL transcription factor, NAFTc-1. Overall, these data indicate that enforced expression of miR-29b impairs OCL differentiation and overcomes OCL activation triggered by MM cells, providing a rationale for miR-29b-based treatment of MM-related BD.

  16. From “Kidneys Govern Bones” to Chronic Kidney Disease, Diabetes Mellitus, and Metabolic Bone Disorder: A Crosstalk between Traditional Chinese Medicine and Modern Science

    Directory of Open Access Journals (Sweden)

    Xiao-Qin Wang

    2016-01-01

    Full Text Available Although traditional Chinese medicine (TCM and Western medicine have evolved on distinct philosophical foundations and reasoning methods, an increasing body of scientific data has begun to reveal commonalities. Emerging scientific evidence has confirmed the validity and identified the molecular mechanisms of many ancient TCM theories. One example is the concept of “Kidneys Govern Bones.” Here we discuss the molecular mechanisms supporting this theory and its potential significance in treating complications of chronic kidney disease (CKD and diabetes mellitus. Two signaling pathways essential for calcium-phosphate metabolism can mediate the effect of kidneys in bone homeostasis, one requiring renal production of bioactive vitamin D and the other involving an endocrine axis based on kidney-expressed Klotho and bone-secreted fibroblast growth factor 23. Disruption of either pathway can lead to calcium-phosphate imbalance and vascular calcification, accelerating metabolic bone disorder. Chinese herbal medicine is an adjunct therapy widely used for treating CKD and diabetes. Our results demonstrate the therapeutic effects and underlying mechanisms of a Chinese herbal formulation, Shen-An extracts, in diabetic nephropathy and renal osteodystrophy. We believe that the smart combination of Eastern and Western concepts holds great promise for inspiring new ideas and therapies for preventing and treating complications of CKD and diabetes.

  17. [Literature review and presentation of our own research results regarding the effects on bone of tyrosine kinase inhibitors imatinib and nilotinib used in the treatment of oncohematological diseases].

    Science.gov (United States)

    Kirschner, Gyöngyi; Balla, Bernadett; Kósa, János; Horváth, Péter; Kövesdi, Andrea; Lakatos, Gergely; Takács, István; Nagy, Zsolt; Tóbiás, Bálint; Árvai, Kristóf; Lakatos, Péter

    2016-09-01

    Tyrosine kinase inhibitors are widely used for treatment of certain oncohematological diseases. Several clinical studies have confirmed that specific BCR-ABL tyrosine kinase inhibitors alter the physiological process of bone tissue in a complex and unclearly identified manner. Since these treatments are being given to more and more patients, and the therapy takes decades or lasts even lifelong, it is justifiable to obtain more detailed knowledge of the molecular background of these mechanisms. In this article the authors summarize preliminary research results and human clinical observations on imatinib and nilotinib which are related to bone metabolism, and present the results of their own experiments in in vitro osteoblast cultures. Based on the presented results, the effects of imatinib and nilotinib on bone cells depend on the concentration of imatinib and nilotinib, the maturation stage of the cells and the distribution ratio of receptor tyrosine kinase signaling pathways. In this study the authors firstly prepared a stop-gap, comprehensive review in the Hungarian literature, regarding the effects of tyrosine kinase inhibitors on bone metabolism. In addition they firstly performed whole transcriptome analysis on osteoblasts in order to obtain a better understanding of the cellular molecular mechanisms. Orv. Hetil., 2016, 157(36), 1429-1437.

  18. Tapentadol prolonged release for patients with multiple myeloma suffering from moderate-to-severe cancer pain due to bone disease

    Science.gov (United States)

    Coluzzi, Flaminia; Raffa, Robert B; Pergolizzi, Joseph; Rocco, Alessandra; Locarini, Pamela; Cenfra, Natalia; Cimino, Giuseppe; Mattia, Consalvo

    2015-01-01

    Context Myeloma bone disease (MBD) is a devastating complication of multiple myeloma that leads to severe pain. Objectives The aim of this study was to evaluate the efficacy and tolerability of tapentadol prolonged release (PR) in the management of patients with MBD suffering from moderate-to-severe cancer pain. Methods A 12-week prospective study was carried out in 25 opioid-naïve MBD patients. Patients initially received twice-daily doses of tapentadol PR 50 mg. Doses were then managed to maintain adequate relief or dose-limiting toxicity. The following parameters were recorded at weekly intervals for 4 weeks, and then at weeks 8 and 12: pain, opioid-related adverse effects, use of other analgesics, DN4 (Douleur Neuropathique 4) score. Quality of life (SF-36 [36-item short-form health survey]) was measured at baseline and at final evaluation. Results Of 25 patients, 22 completed the study. Pain intensity significantly decreased from baseline to all the week intervals (P<0.01). Quality of life significantly improved with respect to all SF-36 subscale parameters (P<0.01), and so did both the physical and mental status (P<0.01). Tapentadol PR significantly reduced DN4 mean value (P<0.01) and the number of patients with neuropathic component (DN4 ≥4) (P<0.01). After 8 weeks of treatment, all patients were negative for the DN4 score. Tapentadol PR was well tolerated, and the use of other analgesics was reduced during the study period. Conclusion Tapentadol PR started in doses of 100 mg/day was effective and well tolerated in opioid-naïve MBD patients with moderate-to-severe pain. Tapentadol PR can be considered a first-choice opioid in cancer patients suffering from mixed pain with a neuropathic component. PMID:26064064

  19. Paget disease of bone-associated UBA domain mutations of SQSTM1 exert distinct effects on protein structure and function

    Science.gov (United States)

    Goode, Alice; Long, Jed E.; Shaw, Barry; Ralston, Stuart H.; Visconti, Micaela Rios; Gianfrancesco, Fernando; Esposito, Teresa; Gennari, Luigi; Merlotti, Daniela; Rendina, Domenico; Rea, Sarah L.; Sultana, Melanie; Searle, Mark S.; Layfield, Robert

    2014-01-01

    SQSTM1 mutations are common in patients with Paget disease of bone (PDB), with most affecting the C-terminal ubiquitin-associated (UBA) domain of the SQSTM1 protein. We performed structural and functional analyses of two UBA domain mutations, an I424S mutation relatively common in UK PDB patients, and an A427D mutation associated with a severe phenotype in Southern Italian patients. Both impaired SQSTM1's ubiquitin-binding function in pull-down assays and resulted in activation of basal NF-κB signalling, compared to wild-type, in reporter assays. We found evidence for a relationship between the ability of different UBA domain mutants to activate NF-κB signalling in vitro and number of affected sites in vivo in 1152 PDB patients from the UK and Italy, with A427D-SQSTM1 producing the greatest level of activation (relative to wild-type) of all PDB mutants tested to date. NMR and isothermal titration calorimetry studies were able to demonstrate that I424S is associated with global structural changes in the UBA domain, resulting in 10-fold weaker UBA dimer stability than wild-type and reduced ubiquitin-binding affinity of the UBA monomer. Our observations provide insights into the role of SQSTM1-mediated NF-κB signalling in PDB aetiology, and demonstrate that different mutations in close proximity within loop 2/helix 3 of the SQSTM1 UBA domain exert distinct effects on protein structure and stability, including indirect effects at the UBA/ubiquitin-binding interface. PMID:24642144

  20. MC1288, a vitamin D analog, prevents acute graft-versus-host disease in rat bone marrow transplantation.

    Science.gov (United States)

    Pakkala, I; Taskinen, E; Pakkala, S; Räisänen-Sokolowski, A

    2001-04-01

    The major obstacle to successful bone marrow transplantation (BMT) is graft-versus-host disease (GVHD). Vitamin D analogs have shown their efficacy in solid organ transplantation. The purpose of this study was to investigate the suitability of a novel vitamin D analog, MC1288, in the prevention of acute GVHD in a rat BMT model. Allogeneic BMT were performed from Lewis to BN rats (n = 18). The animals were divided into four groups: an untreated control group, MC1288, cyclosporin A (CsA), and MC1288 + CsA-treated groups. Rats were harvested for histology and immunohistochemistry on day 20 after BMT. Histological changes for GVHD in liver, skin, and spleen were scored. Positivity in immunostaining was quantified as the number of positive cells/high power field. Treatment with MC1288 decreased clinical signs of GVHD compared with untreated or CsA-treated rats. Histological manifestations of GVHD, expressed as mean total increment, were significantly lower (1.4 +/- 0.5) in MC1288 than in untreated (5.0 +/- 1.6) or CsA (3.5 +/- 1.0) groups. Combining MC1288 and CsA further improved histology (1.1 +/- 0.6). The expression of CD4, CD8, MHC class II, interleukin-2 receptor, nitric oxide 2, and NKR-P1A (NK cells) positivity was significantly decreased in the liver and skin of BMT rats by MC1288. MC1288 was effective in preventing clinical and histological signs and symptoms of GVHD. This novel vitamin D analog could be used as an immunomodulating agent in BMT.

  1. Bone scintigraphy and metabolic disorders

    Energy Technology Data Exchange (ETDEWEB)

    Mari' , C.; Catafau, A.; Carrio' , I. [Hospital de Sant Pau, Barcelone (Spain). Serv. of Nuclear Medicine

    1999-09-01

    The paper discusses the main clinical value of bone scan in metabolic bone disease: its detection of focal conditions or focal complications of such generalized disease, its most common use of being the detection of fractures in osteoporosis, pseudo fractures in osteomalacia and the evaluation of Paget's disease.

  2. Biochemical parameters of bone metabolism in bone metastases of solid tumors (Review)

    NARCIS (Netherlands)

    Meijer, Wilhelmus; van der Veer, E; Willemse, P H

    1998-01-01

    The role of biochemical markers of bone metabolism in the diagnosis and monitoring of bone metastases in solid tumors is reviewed. Emphasis is on the recently developed markers, which may provide a more accurate quantitation of bone metabolism. In metastatic bone disease, bone formation and resorpti

  3. Trends of elevated parathormone serum titers in hemodialysis patients on intensive therapy for bone disease: A multicenter study

    Directory of Open Access Journals (Sweden)

    Ayman Karkar

    2014-01-01

    Full Text Available To determine the prevalence of controlled parathyroid hormone (PTH serum levels with intensified therapy for chronic kidney disease mineral and bone disorder (CKD-MBD in the dialysis population, we studied 563 chronic hemodialysis patients recruited from three different dialysis centers from three different major cities in the Kingdom of Saudi Arabia. The trend of the routine monthly chemistries related to CKD-MBD was evaluated besides the whole-molecule PTH serum levels over 28 months (January 2011 to April 2013. The cost ratios of the medications to the estimated dialysis total cost were calculated. There were 323 (57.4% males in the study, and the mean age of the patients was 50.2 ± 15.2 years; 371 (65.9% patients were initiated on dialysis before 2011. The causes of the original kidney disease included diabetes mellitus in 163 (29% patients. Parathyroidectomy was performed in 23 (4.1% patients and only six (23% patients underwent the operation during the study period; most of the parathyroidectomies (69% were performed before 2011. The trend of the medians of monthly serum levels of calcium, phosphorus, albumin, bicarbonate, alkaline phosphatase, serum levels of PTH and vitamin D25 assays showed better control of the levels with time. The added cost of cinacalcet was more significant than the other drugs, including vitamin D and phosphate binders, but the cost was minimal in comparison with the whole dialysis bill. The ratios of the discontinuation rates to the total patient-months of treatment for the different drugs were in the range of 3-4% and mostly due to transient overdosing of medications. We conclude that the trends of the median serum levels of PTH and related minerals in the CKD patients in our dialysis patients suggested a good inclination toward control and prevention of the vascular calcifications prevalent in the CKD-MBD. The popularity of use of new drugs such as cinacalcet is promising and does not seem to add much to the

  4. Lower Limb Metaphyseal Bone Is Lost in Men with Coeliac Disease and Does Not Relate to Parathyroid Status

    Directory of Open Access Journals (Sweden)

    Michael W. J. Davie

    2016-01-01

    Full Text Available Aims. To investigate regional lower limb bone density and associations with weight, PTH, and bone breakdown in coeliac men. Methods. From whole body DXA scans bone mineral density (BMD was measured in 28 coeliac men, in the lower limb (subdivided into 6 regions, 3 being metaphyseal (mainly trabecular and 2 diaphyseal (mainly cortical. BMD at femoral neck (FN and lumbar spine L2–4, body weight, height, serum calcium, alkaline phosphatase, parathyroid hormone (PTH, and urinary calcium and NTx/Cr, a measure of bone breakdown, were also measured. Age matched healthy men provided values for BMD calculation of z and T scores and for biochemical measurements. Results. Low BMD z scores were found at metaphyseal regions in the leg (p<0.001 and in the FN (p<0.05. The distal metaphyseal region BMD in the leg was lower than spine or FN (p<0.05. PTH, urinary calcium/creatinine, and urinary NTx/Cr were similar to controls. Both metaphyseal and diaphyseal BMD z scores were associated with body weight (p<0.02, but not with either PTH or urinary NTx/Cr. Conclusions. Low BMD lower limb regions comprising mostly trabecular bone occur early in CD and in the absence of elevated PTH or increased bone resorption. Low BMD is associated with low body weight.

  5. Lower Limb Metaphyseal Bone Is Lost in Men with Coeliac Disease and Does Not Relate to Parathyroid Status

    Science.gov (United States)

    Evans, Sally F.

    2016-01-01

    Aims. To investigate regional lower limb bone density and associations with weight, PTH, and bone breakdown in coeliac men. Methods. From whole body DXA scans bone mineral density (BMD) was measured in 28 coeliac men, in the lower limb (subdivided into 6 regions, 3 being metaphyseal (mainly trabecular) and 2 diaphyseal (mainly cortical)). BMD at femoral neck (FN) and lumbar spine L2–4, body weight, height, serum calcium, alkaline phosphatase, parathyroid hormone (PTH), and urinary calcium and NTx/Cr, a measure of bone breakdown, were also measured. Age matched healthy men provided values for BMD calculation of z and T scores and for biochemical measurements. Results. Low BMD z scores were found at metaphyseal regions in the leg (p < 0.001) and in the FN (p < 0.05). The distal metaphyseal region BMD in the leg was lower than spine or FN (p < 0.05). PTH, urinary calcium/creatinine, and urinary NTx/Cr were similar to controls. Both metaphyseal and diaphyseal BMD z scores were associated with body weight (p < 0.02), but not with either PTH or urinary NTx/Cr. Conclusions. Low BMD lower limb regions comprising mostly trabecular bone occur early in CD and in the absence of elevated PTH or increased bone resorption. Low BMD is associated with low body weight. PMID:27672477

  6. Gene expression profiling suggests a pathological role of human bone marrow-derived mesenchymal stem cells in aging-related skeletal diseases.

    Science.gov (United States)

    Jiang, Shih Sheng; Chen, Chung-Hsing; Tseng, Kuo-Yun; Tsai, Fang-Yu; Wang, Ming Jen; Chang, I-Shou; Lin, Jiunn-Liang; Lin, Shankung

    2011-07-01

    Aging is associated with bone loss and degenerative joint diseases, in which the aging of bone marrow-derived mesenchymal stem cell (bmMSC)[1] may play an important role. In this study, we analyzed the gene expression profiles of bmMSC from 14 donors between 36 and 74 years old, and obtained age-associated genes (in the background of osteoarthritis) and osteoarthritis-associated genes (in the background of old age). Pathway analysis of these genes suggests that alterations in glycobiology might play an important role in the aging of human bmMSC. On the other hand, antigen presentation and signaling of immune cells were the top pathways enriched by osteoarthritis-associated genes, suggesting that alteration in immunology of bmMSC might be involved in the pathogenesis of osteoarthritis. Most intriguingly, we found significant age-associated differential expression of HEXA, HEXB, CTSK, SULF1, ADAMTS5, SPP1, COL8A2, GPNMB, TNFAIP6, and RPL29; those genes have been implicated in the bone loss and the pathology of osteoporosis and osteoarthritis in aging. Collectively, our results suggest a pathological role of bmMSC in aging-related skeletal diseases, and suggest the possibility that alteration in the immunology of bmMSC might also play an important role in the etiology of adult-onset osteoarthritis.

  7. Rationale and Design for the Intramyocardial Injection of Autologous Bone Marrow Mononuclear Cells for Patients with Chronic Ischemic Heart Disease and Left Ventricular Dysfunction Trial (FOCUS)

    Science.gov (United States)

    Willerson, James T.; Perin, Emerson C.; Ellis, Stephen G.; Pepine, Carl J.; Henry, Timothy D.; Zhao, David X.M.; Lai, Dejian; Penn, Marc S.; Byrne, Barry J.; Silva, G; Gee, Adrian; Traverse, Jay H.; Hatzopoulos, Antonis K.; Forder, John R.; Martin, Daniel; Kronenberg, Marvin; Taylor, Doris A.; Cogle, Christopher R.; Baraniuk, Sarah; Westbrook, Lynette; Sayre, Shelly L.; Vojvodic, Rachel W.; Gordon, David J.; Skarlatos, Sonia I.; Moyé, Lemuel A.; Simari, Robert D.

    2010-01-01

    Background The increasing worldwide prevalence of coronary artery disease (CAD) continues to challenge the medical community. Management options include medical and revascularization therapy. Despite advances in these methods, CAD is a leading cause of recurrent ischemia and heart failure, posing significant morbidity and mortality risks along with increasing health costs in a large patient population worldwide. Trial Design The Cardiovascular Cell Therapy Research Network (CCTRN) was established by the National Institutes of Health to investigate the role of cell therapy in the treatment of chronic cardiovascular disease. FOCUS is a CCTRN-designed randomized Phase II, placebo-controlled clinical trial that will assess the effect of autologous bone marrow mononuclear cells delivered transendocardially to patients with left ventricular (LV) dysfunction and symptomatic heart failure or angina. All patients need to have limiting ischemia by reversible ischemia on SPECT assessment. Results After thoughtful consideration of both statistical and clinical principles, we will recruit 87 patients (58 cell treated and 29 placebo) to receive either bone marrow–derived stem cells or placebo. Myocardial perfusion, LV contractile performance, and maximal oxygen consumption are the primary outcome measures. Conclusions The designed clinical trial will provide a sound assessment of the effect of autologous bone marrow mononuclear cells in improving blood flow and contractile function of the heart. The target population is patients with CAD and LV dysfunction with limiting angina or symptomatic heat failure. Patient safety is a central concern of the CCTRN, and patients will be followed for at least 5 years. PMID:20691824

  8. Whole-body skeletal imaging in mice utilizing microPET: optimization of reproducibility and applications in animal models of bone disease

    Energy Technology Data Exchange (ETDEWEB)

    Berger, Frank [The Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California School of Medicine, 700 Westwood Blvd., Los Angeles, CA 90095 (United States); Department of Nuclear Medicine, Ludwig-Maximilians-University, Munich (Germany); Lee, Yu-Po; Lieberman, Jay R. [Department of Orthopedic Surgery, University of California School of Medicine, Los Angeles, California (United States); Loening, Andreas M.; Chatziioannou, Arion [The Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California School of Medicine, 700 Westwood Blvd., Los Angeles, CA 90095 (United States); Freedland, Stephen J.; Belldegrun, Arie S. [Department of Urology, University of California School of Medicine, Los Angeles, California (United States); Leahy, Richard [University of Southern California School of Bioengineering, Los Angeles, California (United States); Sawyers, Charles L. [Department of Medicine, University of California School of Medicine, Los Angeles, California (United States); Gambhir, Sanjiv S. [The Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California School of Medicine, 700 Westwood Blvd., Los Angeles, CA 90095 (United States); UCLA-Jonsson Comprehensive Cancer Center and Department of Biomathematics, University of California School of Medicine, Los Angeles, California (United States)

    2002-09-01

    The aims were to optimize reproducibility and establish [{sup 18}F]fluoride ion bone scanning in mice, using a dedicated small animal positron emission tomography (PET) scanner (microPET) and to correlate functional findings with anatomical imaging using computed tomography (microCAT). Optimal tracer uptake time for [{sup 18}F]fluoride ion was determined by performing dynamic microPET scans. Quantitative reproducibility was measured using region of interest (ROI)-based counts normalized to (a) the injected dose, (b) integral of the heart time-activity curve, or (c) ROI over the whole skeleton. Bone lesions were repetitively imaged. Functional images were correlated with X-ray and microCAT. The plateau of [{sup 18}F]fluoride uptake occurs 60 min after injection. The highest reproducibility was achieved by normalizing to an ROI over the whole skeleton, with a mean percent coefficient of variation [(SD/mean) x 100] of <15%-20%. Benign and malignant bone lesions were successfully repetitively imaged. Preliminary correlation of microPET with microCAT demonstrated the high sensitivity of microPET and the ability of microCAT to detect small osteolytic lesions. Whole-body [{sup 18}F]fluoride ion bone imaging using microPET is reproducible and can be used to serially monitor normal and pathological changes to the mouse skeleton. Morphological imaging with microCAT is useful to display correlative changes in anatomy. Detailed in vivo studies of the murine skeleton in various small animal models of bone diseases should now be possible. (orig.)

  9. Bone building with bortezomib

    Science.gov (United States)

    Roodman, G. David

    2008-01-01

    In this issue of the JCI, Mukherjee et al. report that bortezomib, a clinically available proteasome inhibitor active against myeloma, induces the differentiation of mesenchymal stem/progenitor cells (MSCs) — rather than mature osteoprogenitor cells — into osteoblasts, resulting in new bone formation (see the related article beginning on page 491). These results were observed when MSCs were implanted subcutaneously in mice or were used to treat a mouse model of postmenopausal bone loss. Others have reported that immunomodulatory drugs (e.g., thalidomide and lenalidomide), which are active against myeloma, also block the activity of bone-resorbing osteoclasts. These results reflect the utility of targeting endogenous MSCs for the purpose of tissue repair and suggest that combining different classes of agents that are antineoplastic and also inhibit bone destruction and increase bone formation should be very beneficial for myeloma patients suffering from severe bone disease. PMID:18219395

  10. Diagnostic Workup for Disorders of Bone and Mineral Metabolism in Patients with Chronic Kidney Disease in the Era of KDIGO Guidelines

    Directory of Open Access Journals (Sweden)

    Luigi Francesco Morrone

    2011-01-01

    Full Text Available KDIGO (Kidney Disease: Improving Global Outcomes is an international nonprofit organization devoted to “improve the care and outcomes of kidney disease patients worldwide through promoting coordination, collaboration, and integration of initiatives to develop and implement clinical practice guidelines.” The mineral and bone disorder (MBD in patients with chronic kidney disease (CKD has been the first area of interest of KDIGO international initiative. KDIGO guidelines on CKD-MBD were published in 2009 with the intent to modify the previous KDOQI guidelines that had failed to consistently change the global outcome of CKD patients. After the publication of KDOQI guidelines for bone metabolism and disease in 2003, a large number of observational data emerged in literature linking disordered mineral metabolism with adverse clinical outcomes. Notwithstanding this large body of observational data, a paucity of evidence from high-quality clinical trials was available for the development of KDIGO guidelines. Herein, a summary will be provided of the most important findings of KDIGO guidelines regarding the diagnostic workup and clinical monitoring of CKD-MBD patients.

  11. [Vascular Calcification - Pathological Mechanism and Clinical Application - . Vascular calcification in chronic kidney disease-mineral and bone disorder (CKD-MBD)].

    Science.gov (United States)

    Omata, Momoyo; Fukagawa, Masafumi; Kakuta, Takatoshi

    2015-05-01

    Chronic kidney disease-mineral and bone disorder (CKD-MBD), is sequential pathophysiology that starts in the very early stages of CKD. Three major aspects of CKD-MBD are laboratory abnormalities, bone abnormalities and vascular calcification. In dialysis patients, the prevalence of death due to cardiovascular disease accounts for more than 40% of all-cause mortality. Therefore, arteriosclerosis with vascular calcification may be an important pathophysiological mechanism in the development of cardiovascular disease. Vascular calcification is known to be an important risk factor influencing mortality in CKD patients. A number of studies have suggested a close association between serum FGF23 concentration and the risks of mortality, cardiovascular disease vascular calcification as well as CKD progression. Renal insufficiency leads to decline in klotho level and impaired phosphate excretion. However serum phosphate levels are maintained in the normal range by up regulation of FGF23 and PTH in early CKD stage. Early treatment intervention is necessary to improve the prognosis of the CKD patient.

  12. Gaucher disease

    OpenAIRE

    POSPÍŠILOVÁ, Iva

    2012-01-01

    This thesis is about the disease called Gaucher disease, or Morbus Gaucher. There is described the history of the disease, various forms of disease, effect of bones, visceral organs, hematological changes, changes in metabolism etc.; differential diagnosis, diagnosis and therapy.

  13. Gaucher disease: MR evaluation of bone marrow features during treatment with enzyme replacement; Morbus Gaucher: Analyse der Knochenmarkveraenderungen in der MRT waehrend Enzymersatztherapie

    Energy Technology Data Exchange (ETDEWEB)

    Poll, L.W.; Koch, J.A.; Boerner, D.; Cohnen, M.; Jung, G.; Scherer, A.; Moedder, U. [Duesseldorf Univ. (DF). Inst. fuer Diagnostische Radiologie; Dahl, S. vom; Haeussinger, D. [Duesseldorf Univ. (Germany). Klinik fuer Gastroenterologie, Hepatologie und Infektiologie; Willers, R. [Rechenzentrum, Heinrich-Heine-Univ. Duesseldorf (Germany); Niederau, C. [Innere Abt., St. Josef-Hospital Oberhausen, Akademisches Lehrkrankenhaus der Univ. Essen (Germany)

    2001-10-01

    Purpose: Enzyme replacement therapy (ERT) arrests and reverses the hematological and visceral symptoms of adult Gaucher disease, the most frequent lysosomal storage disorder. There are only a few studies available evaluating bone disease during ERT. The aim of this study was to investigate the features of bone marrow (bm) by magnetic resonance imaging (MRI) in these patients during ERT. Materials and Methods: MRI was performed prospectively in thirty adult type I Gaucher patients before and during ERT with a mean follow-up of 3 years. Spin-echo sequences (T{sub 1}/T{sub 2}) of the lower extremities were obtained and the reconversion (response) or lack of reconversion (non-response) to fatty marrow during treatment was analyzed. The morphological features of bm involvement, a homogeneous or non-homogeneous distribution of bm changes and focal bone lesions surrounded by a rim of reduced signal intensity (SI), were analyzed. Results: Infiltration of bm by Gaucher cells is characterized by a reduction of Sl on both T{sub 1}- and T{sub 2}-weighted sequences. Bone marrow responses were seen in 19 patients (63%) during treatment. Focal bone lesions, surrounded by a rim of reduced Sl, did not respond to ERT and correlated with a non-homogenous distribution of bone involvement and splenectomy. (orig.) [German] Ziel: Unter Enzymersatztherapie (enzyme replacement therapy = ERT) zeigen Patienten mit adulter Form des Morbus Gaucher, der haeufigsten lysosomalen Speicherkrankheit, eine deutliche Besserung der haematologischen und visceralen Symptome. Bislang liegen nur wenige Untersuchungen zur Analyse der Knochenveraenderungen waehrend der ERT vor. Ziel war es, die Knochenmarkveraenderungen bei Gaucher-Patienten waehrend der Enzymersatztherapie mit Alglucerase/Imiglucerase in der Magnetresonanztomographie (MRT) zu evaluieren. Material und Methoden: In einer prospektiven Untersuchung wurden 30 adulte Patienten mit gesichertem Morbus Gaucher vor und waehrend der ERT in der MRT

  14. Extent of Surgery Does Not Influence 30-Day Mortality in Surgery for Metastatic Bone Disease: An Observational Study of a Historical Cohort.

    Science.gov (United States)

    Sørensen, Michala Skovlund; Hindsø, Klaus; Hovgaard, Thea Bechmann; Petersen, Michael Mørk

    2016-04-01

    Estimating patient survival has hitherto been the main focus when treating metastatic bone disease (MBD) in the appendicular skeleton. This has been done in an attempt to allocate the patient to a surgical procedure that outlives them. No questions have been addressed as to whether the extent of the surgery and thus the surgical trauma reduces survival in this patient group. We wanted to evaluate if perioperative parameters such as blood loss, extent of bone resection, and duration of surgery were risk factors for 30-day mortality in patients having surgery due to MBD in the appendicular skeleton. We retrospectively identified 270 consecutive patients who underwent joint replacement surgery or intercalary spacing for skeletal metastases in the appendicular skeleton from January 1, 2003 to December 31, 2013. We collected intraoperative (duration of surgery, extent of bone resection, and blood loss), demographic (age, gender, American Society of Anesthesiologist score [ASA score], and Karnofsky score), and disease-specific (primary cancer) variables. An association with 30-day mortality was addressed using univariate and multivariable analyses and calculation of odds ratio (OR). All patients were included in the analysis. ASA score 3 + 4 (OR 4.16 [95% confidence interval, CI, 1.80-10.85], P = 0.002) and Karnofsky performance status below 70 (OR 7.34 [95% CI 3.16-19.20], P < 0.001) were associated with increased 30-day mortality in univariate analysis. This did not change in multivariable analysis. No parameters describing the extent of the surgical trauma were found to be associated with 30-day mortality. The 30-day mortality in patients undergoing surgery for MBD is highly dependent on the general health status of the patients as measured by the ASA score and the Karnofsky performance status. The extent of surgery, measured as duration of surgery, blood loss, and degree of bone resection were not associated with 30-day mortality.

  15. Increased technetium-99 m hydroxy diphosphonate soft tissue uptake on bone scintigraphy in chronic kidney disease patients with secondary hyperparathyroidism: correlation with hyperphosphataemia.

    Science.gov (United States)

    Enevoldsen, Lotte Hahn; Heaf, James; Højgaard, Liselotte; Zerahn, Bo; Hasbak, Philip

    2017-03-01

    In bone scan patients with dialysis-treated chronic kidney disease (CKD) and hyperparathyroidism, soft tissue accumulation of technetium-99 m hydroxy/methylene diphosphonate (Tc-99 m-HDP/MDP) has been reported primarily in case reports and usually explained by hypercalcaemia and/or hyperphosphataemia. As human vascular smooth muscle cells produce hydroxyapatite during cell culture with increased phosphate levels and as Tc-99 m-HDP/MDP primarily binds to hydroxyapatite, we hypothesized that soft tissue accumulation would be found in patients with hyperphosphataemia. We identified 63 CKD patients diagnosed with secondary hyperparathyroidism admitted for Tc-99 m-HDP bone scan. Baseline characteristics and mean concentrations of biochemical markers (including P-calcium and P-phosphate) taken 0-3 months prior to the bone scans were collected. Soft tissue uptake was detected on bone scans in 37 of 63 (59%) patients. Primary locations were in the heart (27/37 = 73%), muscles (12/37 = 32%), lung (9/37 = 24%) and gastrointestinal tract (6/37 = 16%), and 13 of 37 (35%) patients had simultaneous uptake in more than one location. Regarding biochemical markers, patients with soft tissue uptake only differed from patients without in terms of plasma phosphate levels (1·95 ± 0·15 (n = 37) versus 1·27 ± 0·08 (n = 26), P = 0·0012). All patients with myocardial uptake (n = 27) had a coronary arteriography-verified history of coronary artery disease (CAD), whereas CAD was only present in six of the 36 patients without myocardial uptake. In conclusion, dialysis-treated CKD patients with secondary hyperparathyroidism have a high incidence of soft tissue uptake, and this finding is strongly correlated with elevated phosphate, but not calcium values.

  16. Bone scanning in otolaryngology.

    Science.gov (United States)

    Noyek, A M

    1979-09-01

    Modern radionuclide bone scanning has introduced a new concept in physiologic and anatomic diagnostic imaging to general medicine. As otolaryngologists must diagnose and treat disease in relation to the bony and/or cartilaginous supporting structures of the neurocranium and upper airway, this modality should be included in the otolaryngologist's diagnostic armamentarium. It is the purpose of this manuscript to study the specific applications of bone scanning to our specialty at this time, based on clinical experience over the past three years. This thesis describes the development of bone scanning in general (history of nuclear medicine and nuclear physics; history of bone scanning in particular). General concepts in nuclear medicine are then presented; these include a discussion of nuclear semantics, principles of radioactive emmissions, the properties 99mTc as a radionuclide, and the tracer principle. On the basis of these general concepts, specific concepts in bone scanning are then brought forth. The physiology of bone and the action of the bone scan agents is presented. Further discussion considers the availability and production of the bone scan agent, patient factors, the gamma camera, the triphasic bone scan and the ultimate diagnostic principle of the bone scan. Clinical applications of bone scanning in otolaryngology are then presented in three sections. Proven areas of application include the evaluation of malignant tumors of the head and neck, the diagnosis of temporomandibular joint disorders, the diagnosis of facial fractures, the evaluation of osteomyelitis, nuclear medicine imaging of the larynx, and the assessment of systemic disease. Areas of adjunctive or supplementary value are also noted, such as diagnostic imaging of meningioma. Finally, areas of marginal value in the application of bone scanning are described.

  17. Bone scan

    Science.gov (United States)

    ... legs, or spine fractures) Diagnose a bone infection (osteomyelitis) Diagnose or determine the cause of bone pain, ... 2015:chap 43. Read More Broken bone Metabolism Osteomyelitis Review Date 12/10/2015 Updated by: Jatin ...

  18. Bone Cancer

    Science.gov (United States)

    Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another ... more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 and ...

  19. Emerging therapeutic targets in cancer induced bone disease: A focus on the peripheral type 2 cannabinoid receptor.

    Science.gov (United States)

    Marino, Silvia; Idris, Aymen I

    2017-03-05

    Skeletal complications are a common cause of morbidity in patients with primary bone cancer and bone metastases. The type 2 cannabinoid (Cnr2) receptor is implicated in cancer, bone metabolism and pain perception. Emerging data have uncovered the role of Cnr2 in the regulation of tumour-bone cell interactions and suggest that agents that target Cnr2 in the skeleton have potential efficacy in the reduction of skeletal complications associated with cancer. This review aims to provide an overview of findings relating to the role of Cnr2 receptor in the regulation of skeletal tumour growth, osteolysis and bone pain, and highlights the many unanswered questions and unmet needs. This review argues that development and testing of peripherally-acting, tumour-, Cnr2-selective ligands in preclinical models of metastatic cancer will pave the way for future research that will advance our knowledge about the basic mechanism(s) by which the endocannabinoid system regulate cancer metastasis, stimulate the development of a safer cannabis-based therapy for the treatment of cancer and provide policy makers with powerful tools to assess the science and therapeutic potential of cannabinoid-based therapy. Thus, offering the prospect of identifying selective Cnr2 ligands, as novel, alternative to cannabis herbal extracts for the treatment of advanced cancer patients.

  20. Connective tissue metabolism in patients with unclassified polyarthritis and early rheumatoid arthritis. Relationship to disease activity, bone mineral density, and radiographic outcome

    DEFF Research Database (Denmark)

    Jensen, Trine; Klarlund, Mette; Hansen, Michael;

    2004-01-01

    tissue metabolism were measured in 72 patients with symmetrically swollen and tender second and third metacarpophalangeal or proximal interphalangeal joints for at least 4 weeks and less than 2 years. At 2 years, 51 patients fulfilled the American College Rheumatology criteria for rheumatoid arthritis...... (RA) and 21 patients had unclassified polyarthritis. Patients with RA were divided into groups according to the mean disease activity and to magnetic resonance imaging and radiographically detected bone erosions in the hands. RESULTS: Patients with RA had significantly higher serum concentrations...... of matrix metalloproteinase-3 (MMP-3) at baseline and higher mean concentrations of serum MMP-3 and pyridinoline (Pyd) during the first 6 and 12 months than patients with unclassified polyarthritis. RA patients with persistent disease activity and erosive disease had significantly higher concentrations...

  1. A multicenter, retrospective epidemiologic survey of the clinical features and management of bone metastatic disease in China

    Institute of Scientific and Technical Information of China (English)

    Yunpeng Yang; Li Zhang; Yuxiang Ma; Jin Sheng; Yan Huang; Yuanyuan Zhao; Wenfeng Fang; Shaodong Hong; Ying Tian; Cong Xue

    2016-01-01

    Background: Bone metastases are common in patients with advanced cancer. Bisphosphonates (BPs) could prevent or delay the development of skeleton-related events (SREs). The present study aimed to identify the clinical features of and treatment strategies for Chinese patients with bone metastases. Methods: Consecutive cancer patients who had bone metastases and received BP treatment were enrolled. A ques-tionnaire was developed to collect the patients’clinical data, as well as information on the diagnosis and manage-ment of bone metastases. Physicians’awareness of the guidelines and knowledge of the application of BP were also assessed. Results: A total of 3223 patients with lung cancer (36.5%), breast cancer (30.9%), prostate cancer (8.5%), and gas-trointestinal cancer (5.7%) were included in this study. The sites of bone metastases were the thoracic spine (56.0 %), lumbar spine (47.1%), ribs (32.6%), and pelvis (23.2%). The SRE frequency was the highest in patients with multiple myeloma (36.6%), followed by those with lung cancer (25.9%), breast cancer (20.2%), prostate cancer (18.2%), and gas-trointestinal cancer (17.3%). Irradiation to the bone was the most frequent SRE (58% in lung cancer patients, 45% in breast cancer patients, and 48% in prostate cancer patients). Our survey also showed that 45.5% of patients received BP within 3 months after their diagnosis of bone metastases, whereas the remaining 54.5% of patients did not receive BP treatment until at least 3 months after their diagnosis of bone metastases. The SRE frequency in the former group was significantly lower than that in the latter group (4.0% vs. 42.3%, P < 0.05). In patients with more than 6 months of continuous BP treatment, the mean time to the first SRE was significantly longer than that in patients with less than 6 months of continuous BP treatment (7.2 vs. 3.4 months, P < 0.05). In addition, 12.2% of the physicians were not aware of the efcacy of BP in preventing and delaying SRE. Only

  2. Metabolic bone disease as a presenting manifestation of primary Sjögren′s syndrome: Three cases and review of literature

    Directory of Open Access Journals (Sweden)

    Deepak Khandelwal

    2011-01-01

    Full Text Available Primary Sjögren′s syndrome (pSS is a chronic autoimmune disease characterized by a progressive lymphocytic infiltration of the exocrine glands with varying degrees of systemic involvement. Chronic inflammation compromises the glands′ function that leads to dry symptoms in the mouth/eyes. Renal involvement is a well recognized extraglandular manifestation of pSS. Metabolic bone disease (MBD, however, rarely occurs as the primary manifestation of a renal tubule disorder due to pSS. To the best of our knowledge there are only 6 reported cases of metabolic bone disease as the primary manifestation of pSS to date. Four of these had distal renal tubular acidosis (RTA, and 2 had a combined picture of distal and proximal tubular dysfunction. We herein present our experience of 3 cases who presented to us with a clinical picture suggestive of MBD. While investigating these patients, we found evidence of RTA, which was found to be secondary to pSS.

  3. APOE3, but not APOE4, bone marrow transplantation mitigates behavioral and pathological changes in a mouse model of Alzheimer disease.

    Science.gov (United States)

    Yang, Yue; Cudaback, Eiron; Jorstad, Nikolas L; Hemingway, Jake F; Hagan, Catherine E; Melief, Erica J; Li, Xianwu; Yoo, Tom; Khademi, Shawn B; Montine, Kathleen S; Montine, Thomas J; Keene, C Dirk

    2013-09-01

    Apolipoprotein E4 (APOE4) genotype is the strongest genetic risk factor for late-onset Alzheimer disease and confers a proinflammatory, neurotoxic phenotype to microglia. Here, we tested the hypothesis that bone marrow cell APOE genotype modulates pathological progression in experimental Alzheimer disease. We performed bone marrow transplants (BMT) from green fluorescent protein-expressing human APOE3/3 or APOE4/4 donor mice into lethally irradiated 5-month-old APPswe/PS1ΔE9 mice. Eight months later, APOE4/4 BMT-recipient APPswe/PS1ΔE9 mice had significantly impaired spatial working memory and increased detergent-soluble and plaque Aβ compared with APOE3/3 BMT-recipient APPswe/PS1ΔE9 mice. BMT-derived microglia engraftment was significantly reduced in APOE4/4 recipients, who also had correspondingly less cerebral apoE. Gene expression analysis in cerebral cortex of APOE3/3 BMT recipients showed reduced expression of tumor necrosis factor-α and macrophage migration inhibitory factor (both neurotoxic cytokines) and elevated immunomodulatory IL-10 expression in APOE3/3 recipients compared with those that received APOE4/4 bone marrow. This was not due to detectable APOE-specific differences in expression of microglial major histocompatibility complex class II, C-C chemokine receptor (CCR) type 1, CCR2, CX3C chemokine receptor 1 (CX3CR1), or C5a anaphylatoxin chemotactic receptor (C5aR). Together, these findings suggest that BMT-derived APOE3-expressing cells are superior to those that express APOE4 in their ability to mitigate the behavioral and neuropathological changes in experimental Alzheimer disease.

  4. Chronic Kidney Disease-Mineral Bone Disorder in Korean Patients: a Report from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD).

    Science.gov (United States)

    Kim, Chang Seong; Bae, Eun Hui; Ma, Seong Kwon; Han, Seung Hyeok; Lee, Kyu Beck; Lee, Joongyub; Oh, Kook Hwan; Chae, Dong Wan; Kim, Soo Wan

    2017-02-01

    This study examined the characteristics of biochemical parameters, bone diseases, and vascular calcification in Korean patients with chronic kidney disease (CKD) not yet on dialysis. Serum levels of fibroblast growth factor 23 (FGF23), intact parathyroid hormone (iPTH), 25-hydroxyvitamin D3 (25D), and 1,25-dihydroxyvitamin D3 (1,25D); lumbar spine, total hip, and femur neck bone mineral densities; and brachial-to-ankle pulse wave velocity (baPWV) representing vascular calcification were measured at baseline for 2,238 CKD patients in the KoreaN Cohort Study for Outcomes in Patients With CKD (KNOW-CKD). Increases in serum FGF23 and iPTH preceded changes in serum calcium and phosphate, similar to Western populations. However, the 25D and 1,25D levels decreased earlier than serum FGF23 or iPTH increased, with a decreased estimated glomerular filtration rate (eGFR) in Korean CKD patients. Vitamin D deficiency occurred in 76.7% of patients with CKD stage 1. Bone mineral densities were lowest in CKD stage 5 (lumbar spine, -0.64 ± 1.67; total hip, -0.49 ± 1.21; femur neck, -1.02 ± 1.25). Osteoporosis was more prevalent in patients with higher CKD stages. The mean baPWV, abdominal aortic calcification (AAC), and coronary calcium score also increased, with declined eGFR. In conclusion, a decline in serum vitamin D levels was observed in early CKD stages before significant increases of FGF23 and iPTH in the Korean CKD population compared with that in Western populations. Increased bone disease and vascular calcification occurred in early-stage CKD.

  5. Characterization of bone pathologies in the ins2+/akita mouse, a new model for diabetes insulindependent: contribution for a better understanding of the disease in humans

    OpenAIRE

    Carvalho, Filipe Ricardo Pires de

    2016-01-01

    Tese de Doutoramento, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2016 In the past 30 years developed and developing countries faced significant lifestyle changes that made the incidence of diabetes mellitus to reach pandemic proportion worldwide. This increase, seen in both types of the disease, made diabetes mellitus one of the leading causes of morbidity and mortality of our times. Bone is one t of several organs that are aff...

  6. Follicular lymphoma (in situ) pattern in the bone marrow: does it indicate an early stage in disease evolution?

    Science.gov (United States)

    Alobeid, Bachir; Mears, John Gregory; Bhagat, Govind

    2015-01-01

    Key Clinical Message Bone marrow involvement by an isolated interstitial lymphoid aggregate exhibiting the pattern and phenotype described for follicular lymphoma in situ (FLIS) has not been reported before. The detection of clinically silent FL in this case highlights the necessity of complete staging workup when such lesions are encountered in biopsies. PMID:26185645

  7. Phenotypic differences and similarities in fibro-osseous tumours of bone : implications for clinical practice and disease management

    NARCIS (Netherlands)

    Hauben, Esther Irène

    2006-01-01

    Non-haematogenic tumours arising primarily in the bone are rare. They are classified based on their histomorphology. Within the osteofibrous group the spectrum ranges from benign, exclusively fibrous lesions to high-grade osteosarcoma. These osteofibrous tumours show histological variability in a gi

  8. Prednisone treatment of elderly-onset rheumatoid arthritis: Disease activity and bone mass in comparison with chloroquine treatment

    NARCIS (Netherlands)

    D. van Schaardenburg (Dirkjan); R. Valkema (Roelf); B.A.C. Dijkmans (Ben); S.E. Papapoulos (Socrates); A.H. Zwinderman (Ailko); K.H. Han (Hubert); E.K.J. Pauwels (Ernest K.J); F.C. Breedveld (Ferdinand)

    1995-01-01

    textabstractObjective. Prednisone is frequently used in the treatment of elderly-onset rheumatoid arthritis (RA), but the balance between efficacy and toxicity, including the effect on bone mass, has not been investigated in long-term studies. This prospective, randomized study was undertaken to com

  9. HLA-DP and bone marrow transplantation: DP-incompatibility and severe acute graft versus host disease

    DEFF Research Database (Denmark)

    Ødum, Niels; Platz, P; Jakobsen, B K;

    1987-01-01

    Thirteen recipients of HLA-haploidentical, DR compatible bone marrow (BM) and the corresponding BM donors were HLA-DP typed using primed lymphocyte typing (PLT). Severe acute GVHD (greater than or equal to grade 2) developed within 3 months after BM-transplantation in all of eight recipients of DP...... a role as transplantation antigens....

  10. Adrenal gland and bone.

    Science.gov (United States)

    Hardy, Rowan; Cooper, Mark S

    2010-11-01

    The adrenal gland synthesizes steroid hormones from the adrenal cortex and catecholamines from the adrenal medulla. Both cortisol and adrenal androgens can have powerful effects on bone. The overproduction of cortisol in Cushing's disease leads to a dramatic reduction in bone density and an increase risk of fracture. Overproduction of adrenal androgens in congenital adrenal hyperplasia (CAH) leads to marked changes in bone growth and development with early growth acceleration but ultimately a significant reduction in final adult height. The role of more physiological levels of glucocorticoids and androgens on bone metabolism is less clear. Cortisol levels measured in elderly individuals show a weak correlation with measures of bone density and change in bone density over time with a high cortisol level associated with lower bone density and more rapid bone loss. Cortisol levels and the dynamics of cortisol secretion change with age which could also explain some age related changes in bone physiology. It is also now clear that adrenal steroids can be metabolized within bone tissue itself. Local synthesis of cortisol within bone from its inactive precursor cortisone has been demonstrated and the amount of cortisol produced within osteoblasts appears to increase with age. With regard to adrenal androgens there is a dramatic reduction in levels with aging and several studies have examined the impact that restoration of these levels back to those seen in younger individuals has on bone health. Most of these studies show small positive effects in women, not men, but the skeletal sites where benefits are seen varies from study to study.

  11. The role of 18FDG, 18FDOPA PET/CT and 99mTc bone scintigraphy imaging in Erdheim–Chester disease

    Energy Technology Data Exchange (ETDEWEB)

    García-Gómez, F.J., E-mail: javier191185@gmail.com [Department of Nuclear Medicine, Virgen del Rocío Universitary Hospital, Seville (Spain); Acevedo-Báñez, I.; Martínez-Castillo, R.; Tirado-Hospital, J.L.; Cuenca-Cuenca, J.I.; Pachón-Garrudo, V.M.; Álvarez-Pérez, R.M.; García-Jiménez, R. [Department of Nuclear Medicine, Virgen del Rocío Universitary Hospital, Seville (Spain); Rivas-Infante, E. [Department of Pathology, Virgen del Rocío Universitary Hospital, Seville (Spain); García-Morillo, J.S. [Department of Internal Medicine, Virgen del Rocío Universitary Hospital, Seville (Spain); Borrego-Dorado, I. [Department of Nuclear Medicine, Virgen del Rocío Universitary Hospital, Seville (Spain)

    2015-08-15

    Highlights: • Erdheim–Chester disease (ECD) is a rare non-Langerhans cell histiocitosis, characterized by multisystemic xanthogranulomatous infiltration by foamy histiocytes. Etiology and pathogenesis are still unknown and only about 500 cases are related in the literature. • Multifocal nature of involvement in ECD can produce a wide variety of clinical signs. In our experience, neurological involvement is associated with mortality in all cases. Characteristic long bone osteosclerosis was a quasi-pathognomonic finding in bone scintigraphy. • To the best of our knowledge, the 18FDOPA-PET/CT not seem useful in the initial staging of ECD based on a single case report. • Bone scintigraphy and the 18FDG-PET/CT that were particularly useful in despite systemic involvement, locate the optimum site for biopsy and treatment response evaluation. In this context, a baseline 18FDG-PET/CT with an optional bone scintigraphy may help in monitoring the disease and could be considered when patients were incidentally diagnosed and periodically follow-up 18FDG-PET/CT must be performed in the follow up to evaluate the treatment response. - Abstract: Erdheim–Chester disease (ECD) is a rare non-Langerhans cell histiocitosis, characterized by multisystemic xanthogranulomatous infiltration by foamy histiocytes that stain positively for CD68 marker but not express CD1a and S100 proteins. Etiology and pathogenesis are still unknown and only about 500 cases are related in the literature. Multisystemic involvement leads to a wide variety of clinical manifestations that results in a poor prognosis although recent advances in treatment. We present the clinical, nuclear medicine findings and therapeutic aspects of a serie of 6 patients with histopathological diagnosis of ECD, who have undergone both bone scintigraphy (BS) and 18F-fluorodeoxyglucose (18FDG)-PET/CT scans in our institution. A complementary 18F-fluorodopa (18FDOPA)-PET/CT was performed in one case. Three different

  12. Aspects of osteo-articular complications in sickle-cell disease on planar bone scintigraphy (infection excluded). Apropos of three cases; Aspects des complications osteoarticulaires de la drepanocytose en scintigraphie osseuse planaire (infection exclue). A propos de trois observations

    Energy Technology Data Exchange (ETDEWEB)

    Oufroukhi, Y.; Biyi, A.; Zekri, A.; Doudouh, A. [HMI Med-V, Service de Medecine Nucleaire, Rabat (Morocco)

    2008-06-15

    Skeletal complications of sickle-cell anemia are multiple and can appear on the acute (osseous infarction, acute osteomyelitis) or chronic mode (osteonecrosis, chronic osteomyelitis). The radio-labelled diphosphonate bone scintigraphy remains an important tool in the early diagnosis and in the follow-up of these complications and must form part of the initial assessment of the disease. Through clinical observations, the authors undertake to sum up the bone scintigraphy aspects of these complications. (author)

  13. Bone Densitometry (Bone Density Scan)

    Science.gov (United States)

    ... of DXA Bone Densitometry? What is a Bone Density Scan (DXA)? Bone density scanning, also called dual-energy x-ray absorptiometry ( ... is today's established standard for measuring bone mineral density (BMD). An x-ray (radiograph) is a noninvasive ...

  14. Spinal-cord syndrome due to non-compressive Paget's disease of bone: a spinal-artery steal phenomenon reversible with calcitonin.

    Science.gov (United States)

    Herzberg, L; Bayliss, E

    1980-07-05

    A 76-year-old man had progressive low back pain, leg weakness, and sensory loss. Radiology showed changes consistent with wide-spread Paget's disease, but no cord compression or involvement of nerve roots was detected by myelography or computerised axial tomography. His symptoms were relieved within 12 days of starting 100 MRC units of subcutaneous salmon calcitonin and recurred when calcitonin was discontinued for 5 days. The improvement continued on calcitonin treatment for 1 year, with falls in serum alkaline phosphatase and urinary hydroxyproline excretion. It is suggested that calcitonin treatment, in reducing the abnormally high metabolic activity of the diseased bone, and hence its vascular perfusion, allows more blood to reach the spinal cord.

  15. Neuronal-like differentiation of bone marrow-derived mesenchymal stem cells induced by striatal extracts from a rat model of Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    Xiaoling Qin; Wang Han; Zhigang Yu

    2012-01-01

    A rat model of Parkinson's disease was established by 6-hydroxydopamine injection into the medial forebrain bundle. Bone marrow-derived mesenchymal stem cells (BMSCs) were isolated from the femur and tibia, and were co-cultured with 10% and 60% lesioned or intact striatal extracts. The results showed that when exposed to lesioned striatal extracts, BMSCs developed bipolar or multi-polar morphologies, and there was an increase in the percentage of cells that expressed glial fibrillary acidic protein (GFAP), nestin and neuron-specific enolase (NSE). Moreover, the percentage of NSE-positive cells increased with increasing concentrations of lesioned striatal extracts. However, intact striatal extracts only increased the percentage of GFAP-positive cells. The findings suggest that striatal extracts from Parkinson's disease rats induce BMSCs to differentiate into neuronal-like cells in vitro.

  16. Immunomodulation and neuroprotection with mesenchymal bone marrow stem cells (MSCs): a proposed treatment for multiple sclerosis and other neuroimmunological/neurodegenerative diseases.

    Science.gov (United States)

    Karussis, Dimitrios; Kassis, Ibrahim; Kurkalli, Basan Gowda S; Slavin, Shimon

    2008-02-15

    Bone marrow (BM) derived mesenchymal stem cells (MSCs) (non-hematopoietic, stromal cells) can differentiate under certain circumstances into cells from various neuronal and glial type lineages; they also exert immunomodulatory effects. For potential clinical applications, BM-MSCs offer significant practical advantages over other types of stem cells, since they can be obtained from the adult BM (the patient himself being the donor) and can be easily cultured and expanded posing in parallel a very low risk for development of malignancies. We have shown that BM-MSCs cultured with a cocktail of growth factors (containing FGF and BDNF) differentiate into neuronal/glial lineage cells with a predominance of cells expressing astrocytes' markers. BM-MSCs were effective in suppression of chronic EAE in mice and induced neuroprotection, preserving most of the axons in the CNS of successfully-treated animals. Histopathological studies revealed that MSCs could efficiently migrate into the CNS inflamed tissue (both when administered intravenously and intraventricularly) and differentiated into cells expressing neural-glial lineage markers. Our preclinical results indicate that bone marrow can provide a source of stem cells with a potential for migration into inflamed CNS tissue and differentiation into cells expressing neuronal and glial cell markers. Such an approach may provide a feasible and practical way for in situ immunomodulation, neuroprotection and possibly remyelination/regeneration in diseases like multiple sclerosis. We therefore developed a explorative protocol for the evaluation of this therapeutic approach in a small group of patients with MS and other neurodegenerative diseases.

  17. Adaptation of subchondral bone in osteoarthritis

    DEFF Research Database (Denmark)

    Ding, Ming

    2004-01-01

    never been proven. Recent studies showing reduced chemical and mechanical properties of subchondral bone in various stages of the disease have invigorated interest in the role of subchondral bone in the development and progression of the disease. The current study showed that the concept of bone...

  18. Bone marrow aspiration

    Science.gov (United States)