Can bone metabolism markers be adopted as an alternative to scintigraphic imaging in monitoring bone metastases from breast cancer?

International Nuclear Information System (INIS)

Bombardieri, E.; Martinetti, A.; Castellani, M.R.; Seregni, E.; Miceli, R.; Mariani, L.

1997-01-01

Bone scintigraphy plays a major role in the diagnosis of bone metastases. The clinical utility of new biochemical markers of bone metabolism has recently been investigated in various bone diseases. This study evaluated the role of some bone metabolism markers in comparison with bone scan in the follow-up of breast cancer patients. We studied 149 patients with breast cancer, 33 (22%) of whom had bone metastases. IRMAs were used for the evaluation of blood levels of osteocalcin, bone alkaline phosphatase (BAP), the C-terminal propeptide of type I procollagen and the C-terminal cross-linked telopeptide of type I collagen (ICTP). Multivariate regression analysis showed that menopausal status (P=0.007) and metastatic bone lesions (P=0.001) affected bone marker levels. When considering post-menopausal women, the only subset in which bone metabolism marker behaviour could be reliably investigated, we found a high degree of overlap in marker distribution for scan-positive and scan-negative patients. Discrimination between scan-negative and scan-positive patients based on the above markers, taken singly or jointly, was assessed by means of logistic discriminant analysis. The best discrimination was achieved with BAP, closely followed by ICTP. BAP and ICTP together gave a slight improvement over the use of the two markers separately. However, even in this case the degree of discrimination was poor and its clinical utility was limited. In fact, to achieve a specificity of 95%, the sensitivity of the test was about 20%; conversely, with a sensitivity of 95%, the specificity was below 10%. In conclusion, based on our findings, we believe that blood levels of the investigated markers cannot replace bone scintigraphy in the follow-up of breast cancer patients for the early detection of bone metastases. (orig.)

Comparison in bone turnover markers during early healing of femoral neck fracture and trochanteric fracture in elderly patients

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Shota Ikegami

2009-10-01

Full Text Available Healing of fractures is different for each bone and bone turnover markers may reflect the fracture healing process. The purpose of this study was to determine the characteristic changes in bone turnover markers during the fracture healing process. The subjects were consecutive patients with femoral neck or trochanteric fracture who underwent surgery and achieved bone union. There were a total of 39 patients, including 33 women and 6 men. There were 18 patients (16 women and 2 men with femoral neck fracture and 21 patients (17 women and 4 men with trochanteric fracture. Serum bone-specific alkaline phosphatase (BAP was measured as a bone formation marker. Urine and serum levels of N-terminal telopeptide of type I collagen (NTX, as well as urine levels of C-terminal telopeptide of type I collagen (CTX and deoxypyridinoline (DPD, were measured as markers of bone resorption. All bone turnover markers showed similar changes in patients with either type of fracture, but significantly higher levels of both bone formation and resorption markers were observed in trochanteric fracture patients than in neck fracture patients. BAP showed similar levels at one week after surgery and then increased. Bone resorption markers were increased after surgery in patients with either fracture. The markers reached their peak values at three weeks (BAP and urinary NTX, five weeks (serum NTX and DPD, and 2-3 weeks (CTX after surgery. The increase in bone turnover markers after hip fracture surgery and the subsequent decrease may reflect increased bone formation and remodeling during the healing process. Both fractures had a similar bone turnover marker profile, but the extent of the changes differed between femoral neck and trochanteric fractures.

Comparison in bone turnover markers during early healing of femoral neck fracture and trochanteric fracture in elderly patients.

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Ikegami, Shota; Kamimura, Mikio; Nakagawa, Hiroyuki; Takahara, Kenji; Hashidate, Hiroyuki; Uchiyama, Shigeharu; Kato, Hiroyuki

2009-10-10

Healing of fractures is different for each bone and bone turnover markers may reflect the fracture healing process. The purpose of this study was to determine the characteristic changes in bone turnover markers during the fracture healing process. The subjects were consecutive patients with femoral neck or trochanteric fracture who underwent surgery and achieved bone union. There were a total of 39 patients, including 33 women and 6 men. There were 18 patients (16 women and 2 men) with femoral neck fracture and 21 patients (17 women and 4 men) with trochanteric fracture. Serum bone-specific alkaline phosphatase (BAP) was measured as a bone formation marker. Urine and serum levels of N-terminal telopeptide of type I collagen (NTX), as well as urine levels of C-terminal telopeptide of type I collagen (CTX) and deoxypyridinoline (DPD), were measured as markers of bone resorption. All bone turnover markers showed similar changes in patients with either type of fracture, but significantly higher levels of both bone formation and resorption markers were observed in trochanteric fracture patients than in neck fracture patients. BAP showed similar levels at one week after surgery and then increased. Bone resorption markers were increased after surgery in patients with either fracture. The markers reached their peak values at three weeks (BAP and urinary NTX), five weeks (serum NTX and DPD), and 2-3 weeks (CTX) after surgery. The increase in bone turnover markers after hip fracture surgery and the subsequent decrease may reflect increased bone formation and remodeling during the healing process. Both fractures had a similar bone turnover marker profile, but the extent of the changes differed between femoral neck and trochanteric fractures.

Sequential analysis of biochemical markers of bone resorption and bone densitometry in multiple myeloma

DEFF Research Database (Denmark)

Abildgaard, Niels; Brixen, K; Eriksen, E.F

2004-01-01

BACKGROUND AND OBJECTIVES: Bone lesions often occur in multiple myeloma (MM), but no tests have proven useful in identifying patients with increased risk. Bone marker assays and bone densitometry are non-invasive methods that can be used repeatedly at low cost. This study was performed to evaluate...... 6 weeks, DEXA-scans performed every 3 months, and skeletal radiographs were done every 6 months as well as when indicated. RESULTS: Serum ICTP and urinary NTx were predictive of progressive bone events. Markers of bone formation, bone mineral density assessments, and M component measurements were...... changes, and our data do not support routine use of sequential DEXA-scans. However, lumbar DEXA-scans at diagnosis can identify patients with increased risk of early vertebral collapses. Sequential analyses of serum ICTP and urinary NTx are useful for monitoring bone damage....

[Biochemical markers of bone remodeling: pre-analytical variations and guidelines for their use. SFBC (Société Française de Biologie Clinique) Work Group. Biochemical markers of bone remodeling].

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Garnero, P; Bianchi, F; Carlier, M C; Genty, V; Jacob, N; Kamel, S; Kindermans, C; Plouvier, E; Pressac, M; Souberbielle, J C

2000-01-01

Biochemical markers of bone turnover have been developed over the past 20 years that are more specific for bone tissue than conventional ones such as total alkaline phosphatase and urinary hydroxyproline. They have been widely used in clinical research and in clinical trials of new therapies as secondary end points of treatment efficacy. Most of the interest has been devoted to their use in postmenopausal osteoporosis, a condition characterized by subtle modifications of bone metabolism that cannot be detected readily by conventional markers of bone turnover. Although several recent studies have suggested that biochemical markers may be used for the management of the individual patient in routine clinical practice, this has not been clearly defined and is a matter of debate. Because of the crucial importance to clarify this issue, the Société Francaise de Biologie Clinique prompted an expert committee to summarize the available data and to make recommendations. The following paper includes a review on the biochemical and analytical aspects of the markers of bone formation and resorption and on the sources of variability such as sex, age, menstrual cycle, pregnancy and lactation, physical activity, seasonal variation and effects of diseases and treatments. We will also describe the effects of pre-analytical factors on the measurements of the different markers. Finally based on that review, we will make practical recommendations for the use of these markers in order to minimize the variability of the measurements and improve the clinical interpretation of the data.

Association of Glycemic Status with Bone Turnover Markers in Type 2 Diabetes Mellitus.

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Kulkarni, Sweta Vilas; Meenatchi, Suruthi; Reeta, R; Ramesh, Ramasamy; Srinivasan, A R; Lenin, C

2017-01-01

Type 2 diabetes mellitus has profound implications on the skeleton. Even though bone mineral density is increased in type 2 diabetes mellitus patients, they are more prone for fractures. The weakening of bone tissue in type 2 diabetes mellitus can be due to uncontrolled blood sugar levels leading to high levels of bone turnover markers in blood. The aim of this study is to find the association between glycemic status and bone turnover markers in type 2 diabetes mellitus. This case-control study was carried out in a tertiary health care hospital. Fifty clinically diagnosed type 2 diabetes mellitus patients in the age group between 30 and 50 years were included as cases. Fifty age- and gender-matched healthy nondiabetics were included as controls. Patients with complications and chronic illness were excluded from the study. Depending on glycated hemoglobin (HbA1c) levels, patients were grouped into uncontrolled (HbA1c >7%, n = 36) and controlled (HbA1c diabetics. Based on duration of diabetes, patients were grouped into newly diagnosed, 1-2 years, 3-5 years, and >5 years. Serum osteocalcin (OC), bone alkaline phosphatase (BAP), acid phosphatase (ACP), and HbA1c levels were estimated. OC/BAP and OC/ACP ratio was calculated. Student's t -test, analysis of variance, and Chi-square tests were used for analysis. Receiver operating characteristic (ROC) curve analysis was done for OC/BAP and OC/ACP ratios. Serum OC, HbA1c, and OC/BAP ratio were increased in cases when compared to controls and were statistically significant ( P type 2 diabetes mellitus and was statistically significant ( P = 0.01). In patients with >5-year duration of diabetes, HbA1c level was high and was statistically significant ( P 2). BAP levels were high in uncontrolled diabetics but statistically not significant. ROC curve showed OC/BAP ratio better marker than OC/ACP ratio. Uncontrolled type 2 diabetes mellitus affects bone tissue resulting in variations in bone turnover markers. Bone turnover

Image findings and bone metabolic markers of bone involvement by oral squamous cell carcinoma

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Kameta, Ayako; Tsuchimochi, Makoto; Harada, Mikiko; Katada, Tsutomu; Sasaki, Yoshihiko; Hayama, Kazuhide

2000-01-01

Recently it has been reported that the circulating pyridinoline cross-linked carboxyl-terminal telopeptide of type I collagen (ICTP) and carboxyl-terminal propeptide of type I procollagen (PICP) are useful markers for detecting metastasis of malignancies to bone. Since ICTP and PICP are related to collagen metabolism, respectively breaking down and synthesizing type I collagen, elevated blood concentrations of these markers may reflect direct jaw bone destruction by oral cancer. The purpose of this study was to clarify the relationship between serum ICTP and PICP levels and bone invasion associated with oral cancer. Bone invasion was evaluated in 41 patients with oral squamous cell carcinoma (SCC) by panoramic radiography and 99m Tc-methylene diphosphonate (MDP) scintigraphy. We also assayed serum levels of parathyroid hormone-related protein (PTHrP) and compared them with concentrations of bone metabolic markers and imaging findings. There was no significant relationship between serum ICTP and PICP levels and bone invasion. However, in three of the five cases that showed remarkably high serum ICTP levels, 99m Tc-MDP uptake in the lesion was intensely increased. This suggests that serum ICTP levels may be elevated when bone metabolic changes caused by cancer involving the bone are extensive. We could find no significant correlation among serum levels of ICTP, PICP, and PTHrP. ICTP and PICP do not appear to be good indicators of direct bone invasion by oral SCC in early stages. (author)

Bone Turnover Markers and Lean Mass in Pubescent Boys: Comparison Between Elite Soccer Players and Controls.

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Nebigh, Ammar; Abed, Mohamed Elfethi; Borji, Rihab; Sahli, Sonia; Sellami, Slaheddine; Tabka, Zouhair; Rebai, Haithem

2017-11-01

The aim of this study was to examine the relationship between bone mass and bone turnover markers with lean mass (LM) in pubescent soccer players. Two groups participated in this study, which included 65 elite young soccer players who trained for 6-8 hours per week and 60 controls. Bone mineral density; bone mineral content in the whole body, lower limbs, lumbar spine, and femoral neck; biochemical markers of osteocalcin; bone-specific alkaline phosphatase; C-telopeptide type I collagen; and total LM were assessed. Young soccer players showed higher bone mineral density and bone mineral content in the whole body and weight-bearing sites (P soccer players compared with the control group, but no significant difference in C-telopeptide type I collagen was observed between the 2 groups. This study showed a significant positive correlation among bone-specific alkaline phosphatase, osteocalcin, and total LM (r = .29; r = .31; P soccer players. Findings of this study highlight the importance of soccer practice for bone mineral parameters and bone turnover markers during the puberty stage.

Biochemical markers of bone turnover in diagnosis of myeloma bone disease.

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Dizdar, Omer; Barista, Ibrahim; Kalyoncu, Umut; Karadag, Omer; Hascelik, Gulsen; Cila, Aysenur; Pinar, Asli; Celik, Ismail; Kars, Ayse; Tekuzman, Gulten

2007-03-01

This study was designed to explore the value of markers of bone turnover, macrophage inflammatory protein-1alpha (MIP-1alpha), and osteopontin (OPN) in the diagnosis of myeloma bone disease. Twenty-five patients with newly diagnosed and untreated multiple myeloma (MM), and 22 age-, sex-, and bone mineral density-matched control subjects were enrolled. Levels of MIP-1alpha, OPN, carboxy-terminal telopeptide of Type-1 collagen (C-telopeptide or Ctx), deoxypyridinoline (DPD), Type-1 collagen propeptide (T1Pro), and bone-specific alkaline phosphatase (BALP) were assessed in both groups. Twenty-two of the patients had bone involvement documented by skeletal surveys and lumbar spinal magnetic resonance imaging. Levels of serum Ctx, OPN, MIP-1alpha, and urine DPD were significantly higher in MM patients with bone disease than in controls (P<0.01). Serum Ctx levels were elevated in 90.9% of patients with MM and 40.9% of controls (P<0.001). Urine DPD levels were elevated in 90.4% of the patients and 31.8% of the controls (P<0.001). The serum OPN and MIP-1alpha levels of the patients were significantly correlated with beta2-microglobulin and lactate dehydrogenase levels (P<0.05). Our study indicates that Ctx and DPD are sensitive markers of bone disease in MM, and higher than normal values suggest presence of bone disease rather than benign osteoporosis in MM. The utility of OPN and MIP-1alpha needs to be further investigated. Copyright (c) 2006 Wiley-Liss, Inc.

Markers of bone pain in the hemodialysis patients with renal insufficiency

International Nuclear Information System (INIS)

Oka, Fumitoshi; Sagawa, Hitoshi; Yabe, Kinji

1988-01-01

The patients receiving maintenance hemodialysis were divided into two groups in the absence and the presence of bone pain and investigated the markers of bone pain in these patients. These results suggested that the duration of receiving hemodialysis, serum contrations of alkaline phosphatase, osteocalcin and parathyroid hormone became to be the markers of bone pain. (author)

The influence of vegan diet on bone mineral density and biochemical bone turnover markers.

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Ambroszkiewicz, Jadwiga; Klemarczyk, Witold; Gajewska, Joanna; Chełchowska, Magdalena; Franek, Edward; Laskowska-Klita, Teresa

2010-01-01

Vegetarian diets can be healthy when they are well balanced and if a variety of foods is consumed. However, elimination of animal products from the diet (vegan diets) decreases the intake of some essential nutrients and may influence the bone metabolism. This is especially important in childhood and adolescence, when growth and bone turnover are most intensive. The aim of the study was to assess the effect of vegan diet on bone density (BMD) density and serum concentrations of bone metabolism markers. We examined a family on vegan diet which consisted of parents and two children. Dietary constituents were analysed using a nutritional program. Total and regional BMD were measured by dual-energy X-ray absorptiometry. Concentrations of calcium and phosphate in serum obtained from fasting patients were determined by colorimetric methods, 25-hydroxyvitamin D by the chemiluminescence method and bone turnover markers by specific enzyme immunoassays. In studied vegans, the dietary intake of phosphate was adequate while calcium and vitamin D were below the recommended range. Concentrations of calcium, phosphate and bone turnover markers in the serum of all subjects were within the physiological range, but 25-hydroxyvitamin D level was low. Age-matched Z-score total BMD was between -0.6 and 0.3 in adults, however in children it was lower (-0.9 and -1.0). Z-score BMD lumbar spine (L2-L4) was between -0.9 to -1.9 in parents and -1.5 to -1.7 in children. Our results suggest that an inadequate dietary intake of calcium and vitamin D may impair the bone turnover rate and cause a decrease in bone mineral density in vegans. The parameters of bone density and bone metabolism should be monitored in vegans, especially children, in order to prevent bone abnormalities.

Bone turnover markers in patients with type 1 Gaucher disease

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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.

Age-related changes in bone biochemical markers and their relationship with bone mineral density in normal Chinese women.

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Pi, Yin-Zhen; Wu, Xian-Ping; Liu, Shi-Ping; Luo, Xiang-Hang; Cao, Xing-Zhi; Xie, Hui; Liao, Er-Yuan

2006-01-01

Measurements of bone biochemical markers are increasingly being used to evaluate the state of bone turnover in the management of bone metabolic diseases, especially osteoporosis. However, changes in the bone turnover rate vary with age. The aim of this study was to establish the laboratory reference range of serum bone-specific alkaline phosphatase (sBAP), serum type I collagen cross-linked C-terminal telopeptide (sCTx), and urine CTx (uCTx), based on values from 665 healthy Chinese women aged 20-80 years. We measured the levels of sBAP, sCTx, serum alkaline phosphatase (sALP), and uCTx and evaluated the age-related changes and their relationship with bone mineral density (BMD) in the anteroposterior (AP) lumbar spine, hip, and left forearm. We found significant correlations between biochemical markers and age, with coefficients of determination (R (2)) of 0.358 for sBAP, 0.126 for sCTx, 0.125 for uCTx, and 0.336 for sALP. The net changes in different biochemical markers were inversely correlated with the rates of BMD loss in the AP lumbar spine. After correction for age, body weight, and height, the levels of the markers had significant negative correlations with the BMD of the AP lumbar spine, femoral neck, and ultradistal forearm. All four biochemical markers had the highest negative correlation with BMD of the AP lumbar spine (partial correlation coefficients of -0.366, -0.296, -0.290, and -0.258 for sBAP, sCTx, uCTx, and sALP, respectively). The mean and SD values of these markers in premenopausal and postmenopausal women with normal BMD values were used as the normal reference ranges. The reference ranges of sBAP, sCTx, and uCTx for pre- vs postmenopausal women were 17.3 +/- 6.23 vs 18.9 +/- 7.52 U/l, 3.18 +/- 1.49 vs 3.23 +/- 1.57 nmol/l, and 15.5 +/- 11.4 vs 16.2 +/- 12.4 nM bone collagen equivalents/mM urinary creatinine, respectively. Levels of the bone formation marker (sBAP) and bone resorption markers (sCTx, uCTx) increased rapidly in women with

Effect of zoledronic acid on bone density and markers of bone turnover in a community clinic.

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Lim, Ria; Zailskas, Susan; Goldsby, Tashauna U; Lukens, Carrie; Muravev, Rostislav; Dulipsingh, Latha

2013-01-01

This study aims to document the efficacy of zoledronic acid by comparing bone densities and markers of bone turnover, in patients with osteoporosis. Bone mineral density (BMD) and urinary N-telopeptide, a marker of bone turnover, were compared before and after treatment with intravenous zoledronic acid. 52 participants had atleast two doses of zoledronic acid over 36 months. Significant increases in BMD were found in the spine (t=4.38, Pturnover marker N-telopeptide (t=3.30, P=0.002). Small but significant correlations were determined between prior steroid use and change in BMD in the spine (r=0.35, P<0.05), and family history of osteoporosis and change in BMD in the right femur (r=0.38, P<0.05). Annual infusions of zoledronic acid for at least two years, revealed a significant increase in bone density at the spine and a decrease in urinary N-telopeptide in patients treated at our center.

The effect of semelil (angipars® on bone resorption and bone formation markers in type 2 diabetic patients

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Hasani-Ranjbar Shirin

2012-12-01

Full Text Available Abstract Background and purpose of the study Diabetes mellitus has been recognized as a major risk factor for osteoporosis in which bone turnover is affected by different mechanisms. As the morbidity, mortality and financial cost related to osteoporosis are expected to rise in Iran in coming years, and considering the efficacy of Angipars® for improvement of different ulcers which made it a new herbal drug in diabetic foot ulcer, there is a need to evaluate the effect of this new drug on different organs including bone resorption and bone formation markers. Methods In this randomized, double- blind clinical trial, 61 diabetic patients were included. The subjects were randomly divided into intervention and control groups. Subjects of intervention group received 100 mg of Angipars® twice a day. Laboratory tests including bone resorption and bone formation markers were performed at baseline and after 3 months. Result 31 patients in study group and 30 patients in control group finished the study. The mean age of the study population and the mean disease duration was respectively 51.8 ± 6.2 and 7.5 ± 4.7 years with no significant differences between intervention and control patients. No statistically significant differences between patients and controls were observed in pyridinoline, osteocalcin, urine calcium, bone alkaline phosphatase and tumor necrosis factor (TNF-α. Only urine creatinine level significantly changed between two groups after 3 month of treatment (p-value: 0.029 Conclusion In conclusion, the findings of this study indicate that Semelil (Angipars® had no beneficial or harmful effects on bone. It might be other effects of this new component on bone turnover process which need more studies and more time to be discovered.

Biochemical markers of bone turnover in the clinical development of drugs for osteoporosis and metastatic bone disease: potential uses and pitfalls.

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Cremers, Serge; Garnero, Patrick

2006-01-01

Biochemical markers of bone turnover are used increasingly during the clinical development of drugs for the treatment of metabolic bone diseases such as Paget's disease, osteoporosis and cancer that has metastasised to the bone. However, assessing the optimal value of these markers is often complicated, and such an assessment is an obvious prerequisite for rational use of the markers and, consequently, potential improvement of clinical drug development. Biochemical markers of bone turnover are substances in the blood or urine that are produced or released during bone remodelling. They provide semiquantitative information on bone remodelling, and are often the most adequate tool to describe the pharmacodynamics of the drug. Their use has increased considerably because of dose-effect relationships that have been seen with certain drugs, but also because they have proven relationships with clinical outcomes in several metabolic bone diseases. However, there is a lack of information on the kinetics of these markers, and the immunoassays that are frequently used in their monitoring often measure a mixture of fragments rather than a single molecular entity. For drug development it should also be realised that different markers, but also different assays for the same marker, may provide different results, considerably limiting the ability to compare results. In postmenopausal osteoporosis, relationships have been shown between several biochemical markers of bone turnover, and either fracture risk and/or the antifracture efficacy of drugs. Such relationships can be used for the development of drugs with similar mechanisms of action, but also for the development of these drugs for closely related indications, such as corticosteroid-induced osteoporosis. In both of these instances, data on effects on biochemical markers of bone turnover are usually employed in combination with information about effects on bone mineral density. However, the relationships of these parameters

Biochemical markers predictive for bone marrow involvement in systemic mastocytosis

NARCIS (Netherlands)

Donker, Marjolein L.; van Doormaal, Jasper J.; van Doormaal, Frederiek F.; Kluin, Philip M.; van der Veer, Eveline; de Monchy, Jan G. R.; Kema, Ido P.; Kluin-Nelemans, Hanneke C.

Systemic mastocytosis is characterized by bone marrow involvement, which requires a bone marrow biopsy for diagnostic work-up. We questioned whether bone marrow involvement could be predicted using biochemical markers. We selected patients with various symptoms suggestive of indolent systemic

Can tumour marker assays be a guide in the prescription of bone scan for breast and lung cancers?

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Buffaz, P.-D.; Gauchez, A.S.; Caravel, J.P.; Vuillez, J.P.; Cura, C.; Agnius-Delord, C.; Fagret, D. [Service de Medecine Nucleaire, Centre Hospitalier Universitaire de Grenoble (France)

1999-01-01

Considering the current need to improve cost-effectiveness in cancer patient management, a prospective study was undertaken in order to define the optimal combination of bone scan and tumour marker assays in breast and lung cancer strategies, as has been done in the case of prostate cancer. All patients with breast or lung cancer referred to the Nuclear Medicine Department of the Grenoble Teaching Hospital between December 1995 and April 1997 were included. A blood sample was drawn in each case for marker assay (CA15-3 or CEA and CYFRA 21-1) on the same day as the bone scan. Two hundred and seventy-five patients were included: 118 with lung cancer and 157 with breast cancer. With regard to lung cancer, no information useful for guiding bone scan prescription was obtained through CEA and CYFRA 21-1 assays. For breast cancer, the results suggest that in asymptomatic patients, a CA15-3 level of less than 25 U/ml (upper normal value chosen as the threshold) is strongly predictive of a negative bone scan; by contrast, high tumour marker levels are predictive of neoplastic bone involvement. When a doubtful bone scan is obtained in a patient with breast cancer, a normal marker level makes it highly probable that bone scan abnormalities are not related to malignancy. (orig.) With 3 figs., 21 refs.

Thalassemic osteopathy: a new marker of bone deposition.

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Baldini, M; Forti, S; Orsatti, A; Marcon, A; Ulivieri, F M; Airaghi, L; Zanaboni, L; Cappellini, M D

2014-01-01

Osteopathy represents a prominent cause of morbidity in patients with beta-thalassemia major (TM) and manifests as osteopenia/osteoporosis. Biochemical turnover markers (BTMs) are considered a useful, non-invasive tool for the clinical follow-up of osteoporotic patients; they can provide a dynamic view of the remodeling process and give information on the metabolic activity of bone tissue as well as on the pathogenesis of bone loss. The amino-terminal pro-peptide of type I procollagen (P1NP) is a recently introduced marker that is considered the most sensitive index of bone formation. Although demonstrated in several categories of patients with bone disease, there is little information on the clinical usefulness of this bone formation index in thalassemic patients. We evaluated the P1NP levels of 53 adult patients with b-thalassemia major (21 males and 32 females, mean age 34.5 ± 5.7, range 22-46 years) and associated osteopathy. We investigated the correlation between P1NP and bone condition as examined by dual X-ray photon absorptiometry and with BTMs expressing bone resorption and bone mineralization (carboxyterminal collagen cross-linked (CTX) terminal regions of type I collagen and osteocalcin, respectively). P1NP serum levels were correlated with CTX levels (r=0.545, p<0.001); the results were unchanged when males and females, as well as osteoporotic and osteopenic subgroups, were considered separately. No correlation was demonstrated neither between OC and CTX (r=0.17, p=ns), nor between P1NP and OC levels (r=0.11, p=ns). No correlation was demonstrated among the P1NP/CTX ratio and age, OC or densitometric values and no difference was found in the same ratio between osteopenic (0.19 ± 0.16) and osteoporotic (0.15 ± 0.14) patients. Similar results were obtained for the OC/CTX ratio, as it was not correlated with age, P1NP or densitometric values. This is the first report of circulating P1NP in patients with TM-associated osteoporosis. P1NP and CTX assays

The Relationship Between the FRAX Tool and Bone Turnover Markers in Postmenopausal Osteoporosis

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Murat Uludağ

2013-08-01

Full Text Available Aim: In this study, we aimed to show the correlation between the ten-year fracture risk, calculated with FRAX and bone turnover markers (BTM in a group of postmenopausal women with osteoporosis. Material and Methods: Twenty-four postmenopausal women diagnosed as osteoporosis were included. Patients were assessed for duration of menopause, secondary diseases, medication, habits of nutrition, previous fracture, and family history of fracture. Weight and height measurements were obtained. Bone mineral density (BMD was measured by dual-energy X-ray absorptiometry (DXA, with a Hologic-QDR 4500 plus device. The ten-year risk for major as well as hip fractures were calculated with the FRAX tool. Serum calcium, phosphorus, magnesium, 25-OH Vitamin D, parathormone (PTH, alkaline phosphatase (ALP, and biochemical markers of bone formation (Osteocalcin, Bone-ALP and resorption ( N-terminal collagen type 1 and C terminal collagen type 1 were determined. Results: The mean age of patients was 64.3±8.6 (46-80 years. The mean ten-year major fracture and hip fracture risks were 19.5±6.2% and 16.0±5.1%, respectively. There was a strong correlation between the duration of menopause and hip fracture risk (r: 0.878, p=0.022. There was also a strong relationship between hip fracture risk and NTX (r: 0.759, p=0.042. Conclusion: Resorption markers of bone turnover are relevant components in determining fracture risk. Rate of bone remodeling is a parameter which is not included in the FRAX tool. Since FRAX is an established tool for assessing the ten-year fracture risk, we assessed and found a correlation between hip fracture risk and NTX. Further studies, in larger groups of patients need to make clear the impact of BTM in this tool. (Turkish Journal of Osteoporosis 2013;19: 38-41

Noninvasive markers of bone metabolism in the rhesus monkey: normal effects of age and gender

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Cahoon, S.; Boden, S. D.; Gould, K. G.; Vailas, A. C.

1996-01-01

Measurement of bone turnover in conditions such as osteoporosis has been limited by the need for invasive iliac bone biopsy to reliably determine parameters of bone metabolism. Recent advances in the area of serum and urinary markers of bone metabolism have raised the possibility for noninvasive measurements; however, little nonhuman primate data exist for these parameters. The purpose of this experiment was to define the normal range and variability of several of the newer noninvasive bone markers which are currently under investigation in humans. The primary intent was to determine age and gender variability, as well as provide some normative data for future experiments in nonhuman primates. Twenty-four rhesus macaques were divided into equal groups of male and female according to the following age groupings: 3 years, 5-10 years, 15-20 years, and > 25 years. Urine was collected three times daily for a four-day period and measured for several markers of bone turnoverm including pyridinoline (PYD), deoxypyrodinoline (DPD), hydroxyproline, and creatinine. Bone mineral density measurements of the lumbar spine were performed at the beginning and end of the study period. Serum was also obtained at the time of bone densitometry for measurement of osteocalcin levels by radioimmunoassay. There were no significant differences in bone mineral density, urine PYD, or urine DPD based on gender. Bone density was lowest in the youngest animals, peaked in the 15-20-year group, but again decreased in the oldest animals. The osteocalcin, PYD, and DPD levels followed an inversely related pattern to bone density. The most important result was the relative age insensitivity of the ratio of PYD:DPD in monkeys up to age 20 years. Since bone density changes take months or years to become measurable and iliac biopsies are invasive, the PYD/DPD marker ratio may have important implications for rapid noninvasive measurement of the effects of potential treatments for osteoporosis in the non

Bone turnover markers in sheep and goat: A review of the scientific literature

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JOSÉ A. CAMASSA

Full Text Available ABSTRACT Bone turnover markers (BTMs are product of bone cell activity and are generally divided in bone formation and bone resorption markers. The purpose of this review was to structure the available information on the use of BTMs in studies on small ruminants, especially for monitoring their variations related to diet, exercise, gestation and metabolic lactation state, circadian and seasonal variations, and also during skeletal growth. Pre-clinical and translational studies using BTMs with sheep and goats as animal models in orthopaedic research studies to help in the evaluation of the fracture healing process and osteoporosis research are also described in this review. The available information from the reviewed studies was systematically organized in order to highlight the most promising BTMs in small ruminant research, as well as provide a wide view of the use of sheep and goat as animal models in orthopaedic research, type of markers and commercial assay kits with cross-reactivity in sheep and goat, method of sample and storage of serum and urine for bone turnover markers determination and the usefulness and limitations of bone turnover markers in the different studies, therefore an effective tool for researchers that seek answers to different questions while using BTMs in small ruminants.

The influence of ibandronate treatment on bone density and biochemical bone markers in patients with osteogenesis imperfecta

Directory of Open Access Journals (Sweden)

Ingmar Ipach

2012-09-01

Full Text Available Osteogenesis imperfecta (OI is characterized by different signs including increased bone fragility, short stature, blue sclera, abnormal tooth growth and often secondary immobility. No curative therapy has been found for this rare disease up to now, and different pharmacological substances have been tried as treatment for severe forms of OI. Promising results were seen with intravenous bisphosphonates in the treatment of patients with OI. The aim of present study was to show the effect of intravenous ibandronate therapy on bone density and bone metabolism markers. We analyzed the data of 27 patients with the diagnosis of OI who were treated off-label with intravenous ibandronate. Ibandronate was administered by intravenous infusion every three months at a dosage of 0.3-2 mg. Bone turnover markers and bone density were measured before starting therapy and every three months during treatment. Bone density was measured by using an ultrasound imaging system providing an accurate image of the calcaneus and by evaluating broadband ultrasound attenuation (BUA. Twenty-seven patients were treated with intravenous iban- dronate during the observation period. 18 were female. The mean age of all patients was 23.9 years ± 19.6 (range 4-63. Seventeen patients were categorized to have OI Type I, 5 patients to have OI Type III and 5 patients to have OI Type IV. There was a statistically significant decrease in total alkaline phosphatase (P<0.0001. We detected also a statistically significant decrease in the ratio urinary deoxypyridinoline/urinary creatinine (P=0.0048 and the ratio urinary pyridinoline/urinary creatinine (P<0.0001 respectively. There was also a statistically significant increase in serum magnesium (P=0.034 and BUA (P=0.0071. No statistically significant changes were seen for total serum calcium (P=0.16, the ratio of urine calcium/urine creatinine (P=0.29, alkaline phosphatase (isoform bone (P=0.3, procollagen-I-peptide (P=0.5, osteocalcin (P=0

Genetic and environmental variances of bone microarchitecture and bone remodeling markers: a twin study.

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Bjørnerem, Åshild; Bui, Minh; Wang, Xiaofang; Ghasem-Zadeh, Ali; Hopper, John L; Zebaze, Roger; Seeman, Ego

2015-03-01

All genetic and environmental factors contributing to differences in bone structure between individuals mediate their effects through the final common cellular pathway of bone modeling and remodeling. We hypothesized that genetic factors account for most of the population variance of cortical and trabecular microstructure, in particular intracortical porosity and medullary size - void volumes (porosity), which establish the internal bone surface areas or interfaces upon which modeling and remodeling deposit or remove bone to configure bone microarchitecture. Microarchitecture of the distal tibia and distal radius and remodeling markers were measured for 95 monozygotic (MZ) and 66 dizygotic (DZ) white female twin pairs aged 40 to 61 years. Images obtained using high-resolution peripheral quantitative computed tomography were analyzed using StrAx1.0, a nonthreshold-based software that quantifies cortical matrix and porosity. Genetic and environmental components of variance were estimated under the assumptions of the classic twin model. The data were consistent with the proportion of variance accounted for by genetic factors being: 72% to 81% (standard errors ∼18%) for the distal tibial total, cortical, and medullary cross-sectional area (CSA); 67% and 61% for total cortical porosity, before and after adjusting for total CSA, respectively; 51% for trabecular volumetric bone mineral density (vBMD; all p accounted for 47% to 68% of the variance (all p ≤ 0.001). Cross-twin cross-trait correlations between tibial cortical porosity and medullary CSA were higher for MZ (rMZ  = 0.49) than DZ (rDZ  = 0.27) pairs before (p = 0.024), but not after (p = 0.258), adjusting for total CSA. For the remodeling markers, the data were consistent with genetic factors accounting for 55% to 62% of the variance. We infer that middle-aged women differ in their bone microarchitecture and remodeling markers more because of differences in their genetic factors than

Repeatability of quantitative parameters of 18F-fluoride PET/CT and biochemical tumour and specific bone remodelling markers in prostate cancer bone metastases.

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Wassberg, Cecilia; Lubberink, Mark; Sörensen, Jens; Johansson, Silvia

2017-12-01

18F-fluoride PET/CT exhibits high sensitivity to delineate and measure the extent of bone metastatic disease in patients with prostate cancer. 18F-fluoride PET/CT could potentially replace traditional bone scintigraphy in clinical routine and trials. However, more studies are needed to assess repeatability and biological uptake variation. The aim of this study was to perform test-retest analysis of quantitative PET-derived parameters and blood/serum bone turnover markers at the same time point. Ten patients with prostate cancer and verified bone metastases were prospectively included. All underwent two serial 18F-fluoride PET/CT at 1 h post-injection. Up to five dominant index lesions and whole-body 18F-fluoride skeletal tumour burden were recorded per patient. Lesion-based PET parameters were SUVmax, SUVmean and functional tumour volume applying a VOI with 50% threshold (FTV 50% ). The total skeletal tumour burden, total lesion 18F-fluoride (TLF), was calculated using a threshold of SUV of ≥15. Blood/serum biochemical bone turnover markers obtained at the time of each PET were PSA, ALP, S-osteocalcin, S-beta-CTx, 1CTP and BAP. A total of 47 index lesions and a range of 2-122 bone metastases per patient were evaluated. Median time between 18F-fluoride PET/CT was 7 days (range 6-8 days). Repeatability coefficients were for SUVmax 26%, SUVmean 24%, FTV 50% for index lesions 23% and total skeletal tumour burden (TLF) 35%. Biochemical bone marker repeatability coefficients were for PSA 19%, ALP 23%, S-osteocalcin 18%, S-beta-CTx 22%, 1CTP 18% and BAP 23%. Quantitative 18F-fluoride uptake and simultaneous biochemical bone markers measurements are reproducible for prostate cancer metastases and show similar magnitude in test-retest variation.

A hospital based study of biochemical markers of bone turnovers & bone mineral density in north Indian women

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Kumar, Ashok; Devi, Salam Gyaneshwori; Mittal, Soniya; Shukla, Deepak Kumar; Sharma, Shashi

2013-01-01

Background & objectives: The osteoporotic risk for women increases soon after menopause. Bone turnover markers are known to be associated with bone loss and fracture risk. This study was aimed to assess bone turnover using bone markers and their correlation with bone mineral density (BMD) in pre- and post-menopausal women. Methods: A total of 255 healthy women (160 pre- and 95 post-menopausal) were enrolled. Serum bone alkaline phosphatase (sBAP) and serum N-terminal telopeptide of type I collagen (NTX) were measured to evaluate the bone formation and resorption, respectively. Bone mineral density was determined at lumbar spine (L2-L4) anteroposteriorly, femoral neck and Ward's triangle using Prodigy dual-energy X-ray absorptiometry (DXA) system. The comparison of years since menopause with respect to BMD and bone markers was also evaluated. Results: NTX and sBAP showed significant negative correlation with BMD of femur neck and Ward's triangle in postmenopausal women. BMD of all three sides were significant variables for NTX and BMD of femur neck and Ward's triangle for sBAP in postmenopausal women. BMD lumbar spine was a significant variable for sBAP in premenopausal women. The mean values of NTX increased significantly with increase in the duration of years since menopause. The BMD of all three sides decreased significantly with increase in the duration of years since menopause. Interpretation & conclusions: Serum NTX and sBAP were inversely correlated to BMD of femur neck and Ward's triangle in post-menopausal women. Simultaneous measurements of NTX and BMD in the north Indian women, suggest that bone resorption in women with low BMD remains high after menopause. PMID:23481051

[Association between bone turnover markers, bone mineral density and vitamin D in Moroccan postmenopausal women].

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Elmaataoui, A; Elmachtani Idrissi, S; Dami, A; Bouhsain, S; Chabraoui, L; Ouzzif, Z

2014-02-01

The aim of the study is to find the correlation between bone turnover markers and bone mineral density in a cohort of Moroccan postmenopausal women. A cross-sectional study, conducted over a period of 12 months from October 2008 to November 2009. Five hundred Moroccan postmenopausal women volunteers participated in this study and we included only 185. In this cohort of 185 women, average age 60 years, the percentage of osteoporotic women was 35.7%, they were older 62.09 (9.13) years and they had an average of the body mass index (BMI), the lowest 29.58 (4.45). The values of the bone mineral density (BMD) measured at the lumbar spine correlated positively and significantly with BMI (P<0.001), serum calcium (P=0.026), negatively with age (P<0.001) and osteocalcin (OC) (P=0.0033). As for the results of BMD measured at the femoral neck, they show a negative and highly significant correlation with age (P<0.001) and osteocalcin. Looking for an association between the biochemical markers of bone remodeling, a weak positive correlation was found between the calcium (Ca) and alkaline phosphatase (PAL) on the one hand and Ca and intact parathyroid hormone (PTHi) in the other hand. And a significant positive correlation was found between PTHi and PAL, and between PTHi and OC. Finally, a significant positive correlation was found between the cross-laps (β-CTX) and Ca and between PAL and OC. Our results are in agree to some international studies and disagree to others. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

[Bone metabolism, biochemical markers of bone resorption and formation processes and interleukine 6 cytokin level during coeliac disease].

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Fekih, Monia; Sahli, Hela; Ben Mustapha, Nadia; Mestiri, Imen; Fekih, Moncef; Boubaker, Jalel; Kaabachi, Naziha; Sellami, Mohamed; Kallel, Lamia; Filali, Azza

2013-01-01

Celiac disease (CD) is characterized by a malabsorption syndrom. The bone anomalies are one of the principal complications of this disease. The osteoporosis frequency is high: 3.4% among patients having with CD versus 0.2% in the general population. To study the bone mineral density during the CD, to compare it to a control group and to determine the anomalies of biochemical markers of bone turn over and level of interleukin 6 cytokin (IL6) in these patients. All patients with CD have a measurement of bone mineral density by dual-energy x-ray absorptiometry (DXA), a biological exam with dosing calcemia, vitamin D, parathormone (PTH), the osteoblastic bone formation markers (serum osteocalcin, ALP phosphates alkaline), bone osteoclastic activity (C Télopeptide: CTX) and of the IL6. 42 patients were included, with a median age of 33.6 years. 52. 8% of the patients had a low level of D vitamine associated to a high level of PTH. An osteoporosis was noted in 21.5% of patients. No case of osteoporosis was detected in the control group. The mean level of the CTX, ostéocalcine and the IL6 was higher among patients having an osteoporosis or ostéopenia compared to patients with normal bone (p = 0,017). The factors associated with an bone loss (osteopenia or osteoporosis) were: an age > 30 years, a weight 90 UI/ml, an hypo albuminemia < 40 g/l and a level of CTX higher than 1.2. Our study confirms the impact of the CD on the bone mineral statute. The relative risk to have an osteopenia or an osteoporosis was 5 in our series. The measurement of the osseous mineral density would be indicated among patients having a CD.

Calcium homestasis markers of bone metabolism in feline hyperthyroidism - A review

OpenAIRE

Cardoso, M. J L; Muniz, L. M R [UNESP; Gasparini, T. J.; Melussi, M.

2007-01-01

Hyperthyroidism is the most frequent endocrine disease in old-aged cats. It is a illness provoked by the excess of circulating thyroid hormones. Hyperthyroidism causes alteration in bone metabolism with predominance of activity resorption. The evaluation of bone metabolism can be made by measuring serum and urinary markers of bone metabolism or bone mineral densitometry. Osteoblasts are responsible cells for bone formation while the osteoclasts are for resorption. In physiological situation o...

Relationship of cytokines and bone metabolic markers to osteoporosis in aged males

International Nuclear Information System (INIS)

Luo Nanping; Hu Chengjin; Li Jinhua; Chen Yingjian; Wang Ruishan; Yin Qiuxia

2003-01-01

Objective: To observe the relationship of cytokines and bone metabolic markers to osteoporosis in aged men. Methods: Serum interleukin-4 (IL-4), IL-6, IL-10, bone glaprotein (BGP), testosterone (T), alkaline phosphatase (AKP), Ca and bone density of aged men with osteoporosis or bone mass loss were assessed and compared with those of middle-aged and aged healthy men. Results: The levels of serum IL-4 and IL-6 increased with severity of osteoporosis and the differences were significant compared with normal controls (P<0.05, P<0.01). The levels of IL-10, BGP, AKP and T decreased at different degrees and also had significant differences compared with normal controls (P<0.05). Bone density of aged men with osteoporosis and bone mass loss was lower than that of middle-aged healthy men (P<0.01), and bone density of aged men with osteoporosis was apparently lower than that of men with bone mass loss (P<0.05). Conclusions: From bone mass loss to osteoporosis, the deteriorating process presents as bone absorption increasing and osteogenesis decreasing. IL-4, IL-6 and IL-10 and other bone metabolic markers may play a role in diagnosis of osteoporosis

Development of Raman spectral markers to assess metastatic bone in breast cancer

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Ding, Hao; Nyman, Jeffry S.; Sterling, Julie A.; Perrien, Daniel S.; Mahadevan-Jansen, Anita; Bi, Xiaohong

2014-11-01

Bone is the most common site for breast cancer metastases. One of the major complications of bone metastasis is pathological bone fracture caused by chronic bone loss and degeneration. Current guidelines for the prediction of pathological fracture mainly rely on radiographs or computed tomography, which are limited in their ability to predict fracture risk. The present study explored the feasibility of using Raman spectroscopy to estimate pathological fracture risk by characterizing the alterations in the compositional properties of metastatic bones. Tibiae with evident bone destruction were investigated using Raman spectroscopy. The carbonation level calculated by the ratio of carbonate/phosphate ν1 significantly increased in the tumor-bearing bone at all the sampling regions at the proximal metaphysis and diaphysis, while tumor-induced elevation in mineralization and crystallinity was more pronounced in the metaphysis. Furthermore, the increased carbonation level is positively correlated to bone lesion size, indicating that this parameter could serve as a unique spectral marker for tumor progression and bone loss. With the promising advances in the development of spatially offset Raman spectroscopy for deep tissue measurement, this spectral marker can potentially be used for future noninvasive evaluation of metastatic bone and prediction of pathological fracture risk.

Clinical value of combined detection of serum tumor markers and whole body bone scan for diagnosis of bone metastases from breast cancer

International Nuclear Information System (INIS)

Gao Chao; Zhao Jing; Liu Desheng; Zhang Jingchuan; Ji Xuejing; Hou Xiancun

2007-01-01

Objective: To study the clinical value of serum tumor marker determination and whole body bone scan for diagnosis of bone metastases from breast cancer. Methods: Serum tumor markers (CA15-3, CEA, TSGF)were detected with GLIA and whole body bone scan were investigated by SPECT in 124 breast cancer patients. Results: In 124 patients, 38 patients were diagnosed as positive for bone metastases with whole body bone scan. The positive predicting values of CA15-3, CEA, TSGF were 76.78%, 80% and 82.14%, and the negative predicting values of CA15-3, GEA, TSGF were 82.41%, 86.74% and 84.29% respectively. The levels of CA15-3, CEA, TSGF in patients with bone metastases were significantly higher than those in patients without metastasis and the controls (P<0.01). Conclusion: Determination of levels of serum tumor markers CA15-3, CEA, TSGF is helpful for diagnosis of bone metastases from breast cancer. Combined detection of GA15-3, CEA, TSGF could increase the sensitivity and accuracy of diagnosing bone metastases. (authors)

Collagen-derived markers of bone metabolism in osteogenesis imperfecta

DEFF Research Database (Denmark)

Lund, A M; Hansen, M; Kollerup, Gina Birgitte

1998-01-01

)] were measured in 78 osteogenesis imperfecta (OI) patients to investigate bone metabolism in vivo and relate marker concentrations to phenotype and in vitro collagen I defects, as shown by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). PICP and PINP were generally low....... The in vivo findings correlated with in vitro results of collagen I SDS-PAGE. Bone turnover is reduced in OI children and mildly affected OI adults, whereas bone resorption is elevated in severely affected adults. These findings may prove helpful for diagnosis and decision-making regarding therapy in OI....

Bone turnover and oxidative stress markers in estrogen- deficient ...

African Journals Online (AJOL)

Bone turnover and oxidative stress markers in estrogen- ... reproduction in any medium, provided the original work is properly credited. ..... Institute for Laboratory Animal Research: Guide for the ... American Veterinary Medical Association.

Significance of CEA, CA15-3 and biochemical markers of bone turnover in the diagnosis of bone metastasis from breast cancer

International Nuclear Information System (INIS)

Fan Guanglei; Wan Renming; Peng Mingya; Luan Yufen; Zhao Jun; Liu Jianwen; Xu Longbao

2013-01-01

Objective: To evaluate the significance of tumor markers CEA and CA15-3, and biochemical markers of bone turnover (total procollagen type Ⅰ amino-terminal propeptide (TP Ⅰ NP), β-isomerized carboxyterminal propeptide (β-CTx), ALP and PTH) in the diagnosis of bone metastasis from breast cancer. Methods: A total of 78 patients (all females) with mean age (56.72 ± 10.76) years, who were diagnosed with breast cancer, were included in this study. The patients were divided into two groups based on radionuclide bone imaging: with bone metastasis (n=32) and without bone metastasis (n=46). The serum concentrations of CEA, CA15-3, TP Ⅰ NP, β-CTx, PTH, ALP were measured. Gleason scores were evaluated. The diagnostic value was evaluated by ROC curve.The two groups were compared using two-sample t test. The correlations between bone metastasis and tumor markers, bone metastasis and biochemical markers of bone turnover were analyzed with Pearson correlation and logistic analysis. Results: The serum levels of CEA, CA15-3, TP Ⅰ NP, β-CTx, PTH and ALP were significantly higher in the group with bone metastasis than those in the group without bone metastasis (t: 4.16-7.56, all P<0.05). For the diagnosis of bone metastasis from breast cancer, the AUC of CEA, CA15-3, TP Ⅰ NP, [β-CTx, PTH and ALP was 0.815, 0.887, 0.869, 0.852, 0.844, 0.731, respectively. Using the cut-off values of 4.18 μg/L for CEA, 0.04 U/L for CA15-3, 49.70 μg/L for TP Ⅰ NP, 0.47 pg/L for β-CTx,54.90 ng/L for PTH and 49.90 U/L for ALP, the sensitivities were 56.3% (18/32), 75.0% (24/32), 78.1% (25/32), 81.3% (26/32), 78.1% (25/32), 68.8% (22/32) and the specificities were 80.4% (37/46), 84.8% (39/46), 76.1% (35/46), 78.3% (36/46), 69.6% (32/46), 58.7% (27/46), respectively. CEA, CA15-3, TP Ⅰ NP, β-CTx, PTH, ALP and Gleason score were positively correlated with the presence of bone metastasis (r: 0.267-0.636, all P<0.05). CEA, CA15-3, TP Ⅰ NP, β-CTx, PTH and Gleason score were independent

Clinical study on bone mineral density and bone metabolism biochemical marker in hyperthyroidism

International Nuclear Information System (INIS)

Xu Ying; Xu Xiaohui

2004-01-01

To investigate the mechanism and relationship between hyperthyroidism and osteoporosis, bone mineral density was observed using dual-energy X-ray absorptiometry in 149 cases of hyperthyroidism, while serum FT 3 , FT 4 , TSH, alkaline phosphatase (ALP), BGP, and D-pyd levels were measured in 81 cases of hyperthyroidism. The osteopenia rate is 30.2% and the osteoporosis rate is 24.1% in hyperthyroidism patients. Compare with control group, bone metabolic biochemical markers in all cases of hyperthyroidism showed a significant increase, which displays high turnover osteoporosis. In order to find out the case of osteoporosis as soon as possible, bone mineral density of all patients with hyperthyroidism should be measured in the period of treatment. (authors)

Bone status in patients with epilepsy: relationship to markers of bone remodeling

Directory of Open Access Journals (Sweden)

Sherifa Ahmed Hamed

2014-08-01

Full Text Available Patients with epilepsy and treated with antiepileptic drugs (AEDs may develop metabolic bone disease, however, the exact pathogenesis of bone loss with AEDs is still unclear. Included were 75 adults with epilepsy (mean age: 31.90±5.62years; duration of treatment with AEDs: 10.57±3.55years and 40 matched healthy controls. Bone mineral content (BMC and densities (BMD of the femoral neck and lumbar spine were measured using dual energy X-ray absorptiometry (DEXA. Blood samples were analyzed for calcium, magnesium, phosphate, alkaline phosphatase (ALP, 25-hydroxy vitamin D (25OHD, soluble receptor activator of nuclear factor kB ligand (sRANKL, osteoprotegerin (OPG and OPG/RANKL ratio (markers of bone remodeling. Compared to controls, patients had lower BMD, BMC, Z-score and T-score at the femoral neck and lumbar spine (all p<0.001. 72% and 29.33% of patients had osteoporosis of the lumbar spine and femoral neck. Patients had significantly lower serum calcium, 25(OHD and OPG and higher ALP, sRANKL levels and sRANKL/OPG (all p<0.001. 52% of patients had hypocalcemia, 93% had hypovitaminosis D, 31% had high levels of sRANKL and 49% had low levels of OPG. No differences were identified between DEXA and laboratory results in relation to the type, dose or serum levels of AEDs. BMD at the femoral neck and lumbar spine were found to be correlated with the duration of illness (p=0.043; p=0.010, duration of treatment with AEDs (p<0.001; p=0.012 and serum levels of 25(OHD (p<0.042; p=0.010, sRANKLs (p=0.005; p=0.01 and OPG (p<0.006; p<0.01. In linear regression analysis and after adjusting for gender, age, weight, duration and number of AEDs, we observed an association between BMD, 25(OHD (p=0.04 and sRANKL (p=0.03 concentrations. We conclude that AEDs may compromise bone health through disturbance of mineral metabolism and acceleration of bone turnover mechanisms.

Measurement of bone mineral density using DEXA and biochemical markers of bone turnover in 5-year survivors after orthotopic liver transplantation

International Nuclear Information System (INIS)

Xu Hao; Eichstaedt, H.

1998-01-01

Purpose: To observe bone loss and bone metabolism status in 5-year survivors after orthotopic liver transplantation (OLT). Methods: Measurement of bone mineral density (BMD) of the lumbar spine (L2∼L4) and femoral neck using dual energy X-ray absorptiometry (DEXA) and analysis of biochemical markers of bone turnover, such as ostecalcin (OSC), bone alkaline phosphatase (BAP), carboxy-terminal propeptide of type I procollagen (PICP), carboxy-terminal cross-linked telo-peptide of type I collagen (ICTP), PTH and 25-hydroxy-vitamin D (25-OH-D). These markers were measured in 31 5-year survivors after OLT, 34 patients with chronic liver failure (CLF) before OLT and 38 normal subjects. Results: Age-matched Z-score of BMD (Z-score) at L2∼L4 was significantly higher in 5-year survivors than that in patients with CLF before OLT. Incidence of osteoporosis (Z-score<-2.0) in 5-year survivors was significantly lower than that in patients with CLF before OLT. Although serum concentrations of bone formation and bone resorption markers in 5-year survivors were high than those of normal subjects, as compared to patients with CLF before OLT, serum OSC was increased, serum ICTP and BAP were reduced, serum PICP was unchanged. Serum PTH and 25-OH-D level was normal. Conclusions: In 5-year survivors following liver transplantation there was a reduction in bone loss and incidence of osteoporosis and an improvement of bone metabolism

Are bone turnover markers associated with volumetric bone density, size, and strength in older men and women? The AGES-Reykjavik study.

Science.gov (United States)

Marques, E A; Gudnason, V; Sigurdsson, G; Lang, T; Johannesdottir, F; Siggeirsdottir, K; Launer, L; Eiriksdottir, G; Harris, T B

2016-05-01

Association between serum bone formation and resorption markers and bone mineral, structural, and strength variables derived from quantitative computed tomography (QCT) in a population-based cohort of 1745 older adults was assessed. The association was weak for lumbar spine and femoral neck areal and volumetric bone mineral density. The aim of this study was to examine the relationship between levels of bone turnover markers (BTMs; osteocalcin (OC), C-terminal cross-linking telopeptide of type I collagen (CTX), and procollagen type 1N propeptide (P1NP)) and quantitative computed tomography (QCT)-derived bone density, geometry, and strength indices in the lumbar spine and femoral neck (FN). A total of 1745 older individuals (773 men and 972 women, aged 66-92 years) from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik cohort were studied. QCT was performed in the lumbar spine and hip to estimate volumetric trabecular, cortical, and integral bone mineral density (BMD), areal BMD, bone geometry, and bone strength indices. Association between BTMs and QCT variables were explored using multivariable linear regression. Major findings showed that all BMD measures, FN cortical index, and compressive strength had a low negative correlation with the BTM levels in both men and women. Correlations between BTMs and bone size parameters were minimal or not significant. No associations were found between BTMs and vertebral cross-sectional area in women. BTMs alone accounted for only a relatively small percentage of the bone parameter variance (1-10 %). Serum CTX, OC, and P1NP were weakly correlated with lumbar spine and FN areal and volumetric BMD and strength measures. Most of the bone size indices were not associated with BTMs; thus, the selected bone remodeling markers do not reflect periosteal bone formation. These results confirmed the limited ability of the most sensitive established BTMs to predict bone structural integrity in older adults.

The relationship between biological marker factors and the bone metastasis in breast cancer

International Nuclear Information System (INIS)

Xiong Lingjing; Liang Changhua; Li Xinhui; Deng Haoyu; Hu Shuo; Duan Huaxin

2003-01-01

Objective: To investigate the relationship between biological marker factors and the bone metastasis in breast cancer to instruct the follow-up of breast cancer patients. Methods: One hundred and fifteen breast cancer patients proved by histological examination after surgery were involved. To detect nm23 protein, C-erbB-2 protein, estrogen receptor (ER), progestogen receptor (PR) expression of their excised breast cancer tissue, immunohistochemical procedures were used. The relationship between biological marker factors and the bone metastasis in breast cancer was analyzed. All patients were examined by radioisotope whole body bone imaging during the follow-up. Results: The results were that the clinical staging, the status of axillary lymph nodes, the expression of nm23 protein, C-erbB-2 protein, ER were related to the bone metastasis in breast cancer, while the age, the mode of operation and the expression of PR were not. Conclusion: Colligating analysis of clinical, pathological status and biological marker factors is very important for the prediction of the prognosis and the direction of the follow-up in breast cancer patients after surgery

The use of biochemical markers of bone remodeling in multiple myeloma: a report of the International Myeloma Working Group

DEFF Research Database (Denmark)

Terpos, E; Dimopoulos, M A; Sezer, O

2010-01-01

progression and overall survival. Bone markers have also been used for the early diagnosis of bone lesions. This International Myeloma Working Group report summarizes the existing data for the role of bone markers in assessing the extent of MM bone disease and in monitoring bone turnover during anti...

Collagen-derived markers of bone metabolism in osteogenesis imperfecta

DEFF Research Database (Denmark)

Lund, A M; Hansen, M; Kollerup, Gina Birgitte

1998-01-01

)] were measured in 78 osteogenesis imperfecta (OI) patients to investigate bone metabolism in vivo and relate marker concentrations to phenotype and in vitro collagen I defects, as shown by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). PICP and PINP were generally low...

Effects of calcium-fortified ice cream on markers of bone health.

Science.gov (United States)

Ferrar, L; van der Hee, R M; Berry, M; Watson, C; Miret, S; Wilkinson, J; Bradburn, M; Eastell, R

2011-10-01

Premenopausal women with low calcium intakes consumed calcium-fortified ice cream daily for 28 days. Bone markers, NTX, CTX and PTH decreased significantly by 7 days, with some evidence of a calcium dose-dependent effect. Bone marker responses were observed within 1 h of consuming ice cream. Body weight remained constant over 28 days. Dietary calcium is important for lifelong bone health. Milk is a good source of bioavailable calcium, but consumption has declined among young adults. The aims were to determine whether calcium-fortified ice cream, a palatable source of calcium, produces significant, sustainable changes in bone turnover markers and parathyroid hormone (PTH) in premenopausal women with calcium intake below recommended UK levels. Eighty women, ages 20-39 years (calcium intake ice cream containing 96, 244, 459 or 676 mg calcium daily for 28 days. Urinary NTX/Cr, serum CTX, PINP, 1,25D and PTH were measured (baseline, days 1, 7 and 28). Acute changes in CTX and PTH were measured over 5 h (n = 29 women). There were significant mean decreases by 7 days in NTX/Cr, CTX, PTH and 1,25D and increases in PINP (one sample t tests), with a significant dose-dependent effect on CTX analysis of covariance. Only CTX remained suppressed at 28 days. Serum CTX and PTH decreased within 1 h. Body weight did not change significantly between baseline and 28 days. Daily consumption of calcium-fortified ice cream by premenopausal women may significantly reduce levels of the bone resorption marker serum CTX, without stimulating weight gain. The ice cream could be incorporated into the diet to replace low-calcium snacks and thus help individuals with habitually low calcium intakes to meet recommended intakes. The 244 mg calcium preparation would provide more than a quarter of the UK daily recommended nutrient intake for premenopausal women.

Serum 25-hydroxyvitamin D and bone turnover markers in Palestinian postmenopausal osteoporosis and normal women.

Science.gov (United States)

Kharroubi, Akram; Saba, Elias; Smoom, Riham; Bader, Khaldoun; Darwish, Hisham

2017-12-01

This study evaluated the association of vitamin D and bone markers with the development osteoporosis in Palestinian postmenopausal women. Even though vitamin D deficiency was very high for the recruited subjects, it was not associated with osteoporosis except for bones of the hip. Age and obesity were the strongest determining factors of the disease. The purpose of this study was to investigate the association of bone mineral density (BMD) with serum vitamin D levels, parathyroid hormone (PTH), calcium, obesity, and bone turnover markers in Palestinian postmenopausal women. Three hundred eighty-two postmenopausal women (≥45 years) were recruited from various women clinics for BMD assessment (131 women had osteoporosis and 251 were normal and served as controls). Blood samples were obtained for serum calcium, PTH, 25(OH)D, bone formation (N-terminal propeptide (PINP)), and bone resorption (serum C-terminal telopeptide of type I collagen (CTX1)) markers. Women with osteoporosis had statistically significant lower mean weight, height, body mass index (BMI), and serum calcium (p osteoporosis decreased with increasing BMI (overweight OR = 0.11, p = 0.053; obese OR = 0.05, p = 0.007). There was no direct correlation between BMD and PTH, bone turnover markers, and vitamin D except at the lumbar spine. A negative correlation between BMD and age and a positive correlation with BMI were observed. The protective effect of obesity on osteoporosis was complicated by the effect of obesity on vitamin D and PTH.

Quantification of the 3D relative movement of external marker sets vs. bones based on magnetic resonance imaging.

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Sangeux, M; Marin, F; Charleux, F; Dürselen, L; Ho Ba Tho, M C

2006-11-01

Most in vivo knee kinematic analyses are based on external markers attached to the shank and the thigh. Literature data show that markers positioning and soft tissues artifacts affect the kinematic parameters of the bones true movement. Most of the techniques of quantification used were invasive. The aim of the present study was to develop and apply a non-invasive methodology to compute the relative movement between the bones and the markers. Magnetic resonance imaging acquisitions were performed on the right knee of eleven volunteers without knee injury. The subjects were equipped with external magnetic resonance imaging-compatible marker sets. A foot drive device allowed the subjects to perform an actively loaded knee extension. The whole volume of the subject's knee was processed for four sequentially held knee flexion positions during the knee movement. The bones and external marker sets geometry were reconstructed from magnetic resonance imaging images. Then a registration algorithm was applied to the bones and the relative movement of the thigh and shank marker sets with respect to their underlying bones was computed. The protocol resulted in a good geometrical accuracy and reproducibility. Marker sets movement differ from that of the bones with a maximum of 22 mm in translation and 15 degrees in rotation and it affects the knee kinematics. Marker sets relative movement modify the knee movement finite helical axes direction (range 10-35 degrees ) and localization (range 0-40 mm). The methodology developed can evaluate external marker set system to be used for kinematic analysis in a clinical environment.

Bone turnover markers are correlated with total skeletal uptake of 99mTc-methylene diphosphonate (99mTc-MDP)

International Nuclear Information System (INIS)

Lenora, Janaka; Norrgren, Kristina; Thorsson, Ola; Wollmer, Per; Obrant, Karl J; Ivaska, Kaisa K

2009-01-01

Skeletal uptake of 99m Tc labelled methylene diphosphonate ( 99m Tc-MDP) is used for producing images of pathological bone uptake due to its incorporation to the sites of active bone turnover. This study was done to validate bone turnover markers using total skeletal uptake (TSU) of 99m Tc-MDP. 22 postmenopausal women (52–80 years) volunteered to participate. Scintigraphy was performed by injecting 520 MBq of 99m Tc-MDP and taking whole body images after 3 minutes, and 5 hours. TSU was calculated from these two images by taking into account the urinary loss and soft tissue uptake. Bone turnover markers used were bone specific alkaline phosphatase (S-Bone ALP), three different assays for serum osteocalcin (OC), tartrate resistant acid phosphatase 5b (S-TRACP5b), serum C-terminal cross-linked telopeptides of type I collagen (S-CTX-I) and three assays for urinary osteocalcin (U-OC). The median TSU of 99m Tc-MDP was 23% of the administered activity. All bone turnover markers were significantly correlated with TSU with r-values from 0.52 (p = 0.013) to 0.90 (p < 0.001). The two resorption markers had numerically higher correlations (S-TRACP5b r = 0.90, S-CTX-I r = 0.80) than the formation markers (S-Total OC r = 0.72, S-Bone ALP r = 0.66), but the difference was not statistically significant. TSU did not correlate with age, weight, body mass index or bone mineral density. In conclusion, bone turnover markers are strongly correlated with total skeletal uptake of 99m Tc-MDP. There were no significant differences in correlations for bone formation and resorption markers. This should be due to the coupling between formation and resorption

Sclerostin and bone metabolism markers in hyperthyroidism before treatment and interrelations between them.

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Sarıtekin, İlker; Açıkgöz, Şerefden; Bayraktaroğlu, Taner; Kuzu, Fatih; Can, Murat; Güven, Berrak; Mungan, Görkem; Büyükuysal, Çağatay; Sarıkaya, Selda

2017-01-01

Sclerostin, which is a glycoprotein produced by osteocytes, reduces the formation of bones by inhibiting the Wnt signal pathway. Thyroid hormones are related with Wnt signal pathway and it has been reported that increased thyroid hormones in hyperthyroidism fasten epiphysis maturation in childhood, and increase the risk of bone fractures by stimulating the bone loss in adults. The aim of this study was to examine the sclerostin serum levels, the relation between sclerostin and thyroid hormones as well as the biochemical markers of the bone metabolism in patients with hyperthyroidism (including multinodular goiter and Graves' disease), whose treatments have not started yet. No difference was found in the serum sclerostin levels between the hyperthyroidism group (n=24) and the control group (n=24) (p=0.452). The serum osteocalcin levels and 24-hour urinary phosphorus excretion were found to be higher in the hyperthyroid group than in the control group (p0.05). Therefore, we consider that a long-term study that covers the pre-post treatment stages of hyperthyroidism, including both the destruction and construction of the skeleton would be more enlightening. Moreover, the assessment of the synthesis of sclerostin in the bone tissue and in the serum level might show differences.

Bone turnover markers in medicamentous and physiological hyperprolactinemia in female rats

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Radojković Danijela

2014-01-01

Full Text Available Background/Aim. There is a lack of data on the effects of prolactin on calcium metabolism and bone turnover in hyperprolactinemia of various origins. The aim of this study was to compare the influence of medicamentous and physiological hyperprolactinemia on bone turnover in female rats. Methods. Experimental animals (18 weeks old, Wistar female rats were divided as follows: the group P - 9 rats, 3 weeks pregnant; the group M3-10 rats that were intramuscularly administrated sulpirid (10 mg/kg twice daily for 3 weeks, the group M6 - 10 rats that were intramuscularly administrated with sulpirid (10 mg/kg twice daily for 6 weeks, and age matched nulliparous rats as the control group: 10 rats, 18-week-old (C1 and 7 rats, 24 weeks old (C2. Laboratory investigations included serum ionized calcium and phosphorus, urinary calcium and phosphorous excretion, osteocalcin and serum procollagen type 1 N-terminal propeptide (P1NP. Results. Experimental animals in the group P compared to the control group, displayed lower mean serum ionized calcium (0.5 ± 0.2 vs 1.12 ± 0.04 mmol/L; p < 0.001; higher mean serum phosphorus (2.42 ± 0.46 vs 2.05 ± 0.2 mmol/L; p < 0.05; increased urinary calcium (3.90 ± 0.46 vs 3.05 ± 0.58; p < 0.01 and significantly increased P1NP (489,22 ± 46,77 vs 361.9 ± 53,01 pg/mL; p < 0.001. Experimental animals in the group M3 had significantly decreased P1NP, compared to the control group. Prolongated medicamentous hyperprolactinemia (the group M6 induced increased serum ionized calcium (1.21 ± 0.03 vs 1.15 ± 0.02 mmol/L; p < 0.001; decreased serum phosphorus (1.70 ± 0.13 vs 1.89 ± 0.32 mmol/L; p < 0.001; decreased osteocalcin and P1NP. Conclusions. Physiological hyperprolactinemia does not have such harmful effect on bone metabolism as medicamentous hyperprolactinemia. Chronic medicamentous hyperprolactinemia produces lower serum levels of bone formation markers. Assessment of bone turnover markers in prolongated medicamentous

Comparison of bone scintigraphy with serum tumor markers of CA 15-3 and carcinoembryonic antigen in patients with breast carcinoma

International Nuclear Information System (INIS)

Gedik, G. K.; Kiratli, P.O.; Aras, T.; Tascioglu, B.

2006-01-01

To compare the bone scintigraphy findings with a carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA 15-3) levels in breast carcinoma patients. We also investigated the relationship between anatomical bone type and its effect on tumor marker levels. The study was consisted of retrospective evaluation of 120 bone scans of patients with breast carcinoma admitted to the Nuclear Medicine Department, Medical Faculty, Hacettepe University, Ankara, Turkey between January 2003 and December 2004. The mean age of the patients was 54.7 years. We grouped the results of the bone scans into 3 as normal, equivocal and metastatic. Carcinoembryonic antigen and CA 15-3 levels were recorded from the files of the patients. Upper cut levels of 4.8 U/ml for CEA and 38 U/ml for CA 15-3 was accepted. Metastatic bone areas were distributed according to their anatomical location as long, short, flat, irregular and sesamoid and effect of bone type on tumor marker was investigated. In 16 of the patients, bone scintigraphy revealed metastases. Sixty-one patients had normal scans and in 47 patients metastases could not be ruled out. In patients with metastases, CA 15-3 was elevated in 8 and CEA was higher than the upper limit in 6. For CEA and CA 15-3, the anatomical type of bone has no any effect on serum tumor marker concentration between patients with normal and elevated levels of tumor markers in metastatic patients. Tumor markers are not solely enough in predicting bone metastases. Bone scintigraphy and tumor markers should be both used in management of patients with breast carcinoma. The anatomical type of bone has no any effect on elevation of serum tumor marker concentration. (author)

Tumor markers and bone scan in breast cancer patients

International Nuclear Information System (INIS)

Ugrinska, A.; Vaskova, O.; Kraleva, S.; Petrova, D.; Smickova, S.

2004-01-01

Full text: The objective of this study was to compare the levels of CA15-3 and CEA with the bone scan findings in patients with breast cancer. Retrospective analysis of 76 bone scans from 61 patients diagnosed with breast cancer in the last 5 years was performed by two nuclear medicine specialists. All bone scans were performed after surgical treatment of the disease. Patients with loco-regional residual disease or distant metastases in the liver, lung or the brain were excluded from the study. According to the bone scan the patients were divided in 5 groups: normal bone scan (N), equivocal bone scan (E), single metastasis (1MS), three metastases (3MS) and multiple metastases (MMS). Tumor markers were determined within a month before or after the bone scan was performed. Cut-off value for CA 15-3 was 35 U/ml, and for CEA 3 ng/ml. Statistical analysis was performed using descriptive statistic and Kolmogorov-Smirnov test. Bone metastases were revealed in 38% of the patients referred for bone scintigraphy out of which 26% had MMS, 7.8% had single MS and 4% had 3MS. The results of 6.5% of the patients were determined as equivocal. The values of CA15-3 were higher in all patient groups compared with the group that had normal bone scan, but this difference reached statistical significance only in groups with 3MS and MMS (p < 0.01). The values of CEA were significantly higher only in patients with multiple metastases when compared with group N (p < 0.01). Values higher than cut-off value for CA 15-3 was found in 9 patients out of 42 in the group with normal bone scan. The highest value of CA 15-3 in this group was 47 U/ml. Only one patient in this group showed elevated levels for CEA. Three patients in the group with single metastasis had normal CA 15-3, while CEA was elevated only in one patient. All patients in the group with 3MS had elevated levels of CA 15-3 while CEA was in the normal range. All patients with MMS had elevated CA 15-3 values while CEA was elevated in

Diet-induced obesity, gut microbiota and bone, including alveolar bone loss.

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Eaimworawuthikul, Sathima; Thiennimitr, Parameth; Chattipakorn, Nipon; Chattipakorn, Siriporn C

2017-06-01

Obesity is a major risk factor for several pathologies, including jaw bone resorption. The underlying mechanisms involved in pathological conditions resulting from obesity include chronic systemic inflammation and the development of insulin resistance. Although numerous studies have indicated the importance of the role of gut microbiota in the pathogenesis of inflammation and insulin resistance in obesity, only a few studies have established a relationship between obesity, gut microbiota and status of the jaw bone. This review aims to summarize current findings relating to these issues, focusing on the role of obesity and gut microbiota on jaw bone health, including possible mechanisms which can explain this link. Copyright © 2017 Elsevier Ltd. All rights reserved.

Feasibility of measurement of bone turnover markers in female patients with systemic lupus erythematosus.

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Bogaczewicz, Jaroslaw; Karczmarewicz, Elzbieta; Pludowski, Pawel; Zabek, Jakub; Kowalski, Jan; Lukaszkiewicz, Jacek; Wozniacka, Anna

2015-01-01

To investigate the feasibility of bone turnover markers (BTMs) for the assessment of bone metabolism in patients with systemic lupus erythematosus (SLE), according to the guidelines of the International Osteoporosis Foundation and the International Federation of Clinical Chemistry and Laboratory Medicine. The study included 43 female SLE patients. Serum procollagen type I N propeptide (PINP), C-terminal telopeptide of type I collagen (CTX), osteocalcin, PTH, 25(OH)D, anti-cardiolipin, anti-dsDNA, and anti-nucleosome levels were measured. PINP and CTX levels were elevated in SLE patients aged > 45 in comparison to those aged 45 (p < 0.001). No significant difference in PINP, osteocalcin or CTX levels was found with respect to season, neither in the entire SLE group, nor in the under-45 or over-45 groups. Previous glucocorticoid treatment was not associated with difference in BTMs. Increased BTMs in SLE appear to predominantly reflect the pattern of bone remodeling related to age. Increased PINP is expected to be the most frequent outcome among BTMs. Better diagnoses of bone disturbances with BTMs performed in accordance with international reference standards need to be included in the approach to SLE patients, in addition to bone mineral density assessment. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

Effects of Vitamin D Supplementation on Bone Turnover Markers: A Randomized Controlled Trial

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Verena Schwetz

2017-04-01

Full Text Available Bone turnover markers (BTMs are used to evaluate bone health together with bone mineral density and fracture assessment. Vitamin D supplementation is widely used to prevent and treat musculoskeletal diseases but existing data on vitamin D effects on markers of bone resorption and formation are inconsistent. We therefore examined the effects of vitamin D supplementation on bone-specific alkaline phosphatase (bALP, osteocalcin (OC, C-terminal telopeptide (CTX, and procollagen type 1 N-terminal propeptide (P1NP. This is a post-hoc analysis of the Styrian Vitamin D Hypertension Trial, a single-center, double-blind, randomized, placebo-controlled trial (RCT performed at the Medical University of Graz, Austria (2011–2014. Two hundred individuals with arterial hypertension and 25-hydroxyvitamin D (25[OH]D levels <75 nmol/L were randomized to 2800 IU of vitamin D daily or placebo for eight weeks. One hundred ninety-seven participants (60.2 ± 11.1 years; 47% women were included in this analysis. Vitamin D had no significant effect on bALP (mean treatment effect (MTE 0.013, 95% CI −0.029 to 0.056 µg/L; p = 0.533, CTX (MTE 0.024, 95% CI −0.163 to 0.210 ng/mL, p = 0.802, OC (MTE 0.020, 95% CI −0.062 to 0.103 ng/mL, p = 0.626, or P1NP (MTE −0.021, 95% CI −0.099 to 0.057 ng/mL, p = 0.597. Analyzing patients with 25(OHD levels <50 nmol/L separately (n = 74 left results largely unchanged. In hypertensive patients with low 25(OHD levels, we observed no significant effect of vitamin D supplementation for eight weeks on BTMs.

Biological effects of drinking-water mineral composition on calcium balance and bone remodeling markers.

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Roux, S; Baudoin, C; Boute, D; Brazier, M; De La Guéronniere, V; De Vernejoul, M C

2004-01-01

To compare the effects of 2 drinking waters containing similar calcium (Ca) concentration in order to analyze the role of ions other than Ca on bone metabolism. These mineral drinking-waters differed by their mineral composition primarily concerning the concentration of bicarbonate (HCO3-), high in the HB, and sulfate, high in HS water. Of 60 included women, 39 completed the study. Patients were randomly assigned to an intake of 1 liter per day of mineral water HB or HS for 28 d, followed by cross-over to the alternative drinking-water for a further 28 d. At baseline and after each period of one month, Ca metabolism parameters, acid-base status, and bone remodeling markers were measured. Changes in Ca metabolism were significant in the HB group where the ionized Ca increased and the PTH decreased. Serum pH showed a similar increase whatever the used drinking water compared to baseline. In the HB group, significant increase in urine pH, and significant decrease in AT-HCO3- and NH4+ were observed. Bone resorption markers, urinary CTx/Cr, Pyr/Cr, and D-Pyr/Cr, significantly decreased in the HB group compared to baseline, and were not significantly modified in the HS group. These results showed a beneficial effect of the bicarbonaterich HB water on bone metabolism. This may account for a better bioavailability of the Ca, a greater alkalinization, and a larger decrease in PTH level secondary to a higher ionized Ca level. The higher content of silica in HB water may have also participated to the positive action on bone balance that was observed. In this short term study, these data underlined the potential role of the mineral drinking water composition on bone metabolism.

Analysis of the results of serum tumor markers in patients with multiple abnormal concentrations in bone imagines

International Nuclear Information System (INIS)

Wu Xingyong; Jiang Min; Geng Jun; Hu Desheng; He Jian; Fan Xiandong

2008-01-01

To study the serum tumor markers in patients with multiple abnormal concentration of radiopharmaceuticals in whole body bone imagine, 73 patients with malignancy were under a whole body bone scan. The serum tumor markers levels of AFP, CEA, CA125, CA15-3 and CA19-9 were measured in 73 patients and 37 normal people. The results showed that there was significant difference only on serum CEA level (P<0.005), and no significant difference on CA125, CA15-3 and CA19-9 levels (P<0.05) between 36 patients with multiple abnormal concentration and the others with normal bone imagine. The serum levels of CEA, CA125 and CA19-9 in patients were significant higher than that of normal controls (P<0.005). Combined the whole body bone scan and detection of serum tumor markers might be regarded as clinical significance for the diagnosis of bone metastases. (authors)

Effects of Alendronate and Raloxifene on Bone Density and Bone Turnover Markers in Postmenopausal Women

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Ebru Zülfikaroğlu

2011-04-01

CONCLUSION: ALN 70 mg once- weekly significantly produced greater increases in spine and greater but not significantly increases in hip BMD and significantly greater reductions in markers of bone turnover than RLX in 1 yr treatment period. Both ALN and RLX treatment groups have similar safety and tolerability profiles.

Steroid implants and markers of bone turnover in steers | Knetter ...

African Journals Online (AJOL)

The current study was designed to test the hypothesis that recently identified indicators of bone and cartilage turnover could be detected in the peripheral circulation, and that these markers might reflect accelerated ageing effects of the widely used steroidal implants, trenbolone acetate (TBA) and estradiol-17β (E2).

Bone turnover markers: Emerging tool in the management of osteoporosis

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Sahana Shetty

2016-01-01

Full Text Available Bone is a dynamic tissue which undergoes constant remodeling throughout the life span. Bone turnover is balanced with coupling of bone formation and resorption at various rates leading to continuous remodeling of bone. A study of bone turnover markers (BTMs provides an insight of the dynamics of bone turnover in many metabolic bone disorders. An increase in bone turnover seen with aging and pathological states such as osteoporosis leads to deterioration of bone microarchitecture and thus contributes to an increase in the risk of fracture independent of low bone mineral density (BMD. These microarchitectural alterations affecting the bone quality can be assessed by BTMs and thus may serve as a complementary tool to BMD in the assessment of fracture risk. A systematic search of literature regarding BTMs was carried out using the PubMed database for the purpose of this review. Various reliable, rapid, and cost-effective automated assays of BTMs with good sensitivity are available for the management of osteoporosis. However, BTMs are subjected to various preanalytical and analytical variations necessitating strict sample collection and assays methods along with utilizing ethnicity-based reference standards for different populations. Estimation of fracture risk and monitoring the adherence and response to therapy, which is a challenge in a chronic, asymptomatic disease such as osteoporosis, are the most important applications of measuring BTMs. This review describes the physiology of bone remodeling, various conventional and novel BTMs, and BTM assays and their role in the assessment of fracture risk and monitoring response to treatment with antiresorptive or anabolic agents.

Relationship among panoramic radiography findings, biochemical markers of bone turnover and hip bone mineral density in the diagnosis of postmenopausal osteoporosis

International Nuclear Information System (INIS)

Johari Khatoonabad, M.; Aghamohammadzade, N.; Taghilu, H.; Esmaeili, F.; Jabbari Khamnei, H.

2011-01-01

Recent investigations have shown that panoramic radiography might be a useful tool in the early diagnosis of osteoporosis. In addition, bone turnover biochemical marker might be valuable in predicting osteoporosis and fracture risks in the elderly, especially in post-menopausal women. The aim of the present study was to evaluate the relationship among the radio morphometric indices of the mandible, biochemical markers of the bone turnover and hip bone mineral density in a group of post-menopausal women. Patients and Methods: Evaluations of mandibular cortical width, mandibular cortical index, panoramic index and alveolar crest resorption ration (M/M ration) were carried out on panoramic radiographs of 140 post-menopausal women with an age range of 44-82 years. Hip bone mineral density was measured by dual-energy X-ray absorptiometry method. Bone mineral density values were divided into three groups of normal (T score>-1.0), Osteopenic (T score, -2.5 to -1.0) and Osteoporotic (T score<-2.5). Serum alkaline phosphatase and 25(OH) D3 were measured. Results: A decrease in mandibular cortical width by 1 mm increases the likelihood of osteopenia or osteoporosis up to 40%, having taken into consideration the effect of menopause duration. A 1 mm decrease in mandibular cortical width increased the likelihood of moderate or severe erosion of the lower cortex of the mandible up to 28% by taking age into consideration. The results did not demonstrate a statistically significant relationship between bone turnover markers and mandibular radio morphometric indices. Conclusion: Panoramic radiography gives sufficient information to make an early diagnosis regarding osteoporosis in post-menopausal women. Panoramic radiographs may be valuable in the prevention of osteoporotic fractures in elderly women.

Effect of Quercetin on Bone Mineral Status and Markers of Bone Turnover in Retinoic Acid-Induced Osteoporosis

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Oršolić Nada

2018-06-01

Full Text Available Retinoic acid-induced osteoporosis (RBM is one of the most common causes of secondary osteoporosis. This study tested the anti-osteoporetic effect of quercetin in RBM-induced bone loss model (RBM. After 14-day supplementation of 13cRA to induce RBM, rats were administered with quercetin (100 mg/kg or alendronate (40 mg/kg. We analysed changes in body and uterine weight of animals, femoral geometric characteristics, calcium and phosphorus content, bone weight index, bone hystology, bone mineral density (BMD, markers of bone turnover, lipid peroxidation, glutathione levels and SOD, CAT activity of liver, kidney spleen, and ovary as well as biochemical and haematological variables. In comparison to the control RBM rats, the treatment with quercetin increased bone weight index, BMD, osteocalcin level, femoral geometric characteristics, calcium and phosphorus content in the 13cRA-induced bone loss model. Histological results showed its protective action through promotion of bone formation. According to the results, quercetin could be an effective substitution for alendronate in 13cRA-induced osteoporosis. Good therapeutic potential of quercetin on rat skeletal system is based partly on its antioxidant capacity and estrogenic activity.

Relation between body composition and biochemical markers of bone turnover among early postmenopausal women

DEFF Research Database (Denmark)

Hla, M M; Davis, J W; Ross, P D

2000-01-01

, and whole body bone mineral content (BMC) with biochemical markers of bone formation (serum osteocalcin) and resorption (urinary type I collagen crosslinked N-telopeptides [NTX]). Per interquartile range (IQR) (the difference between 75th and 25th percentiles) increase in fat mass and whole body BMC...

Impact of bone turnover markers and/or educational information on persistence to oral bisphosphonate therapy: a community setting-based trial.

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Silverman, S L; Nasser, K; Nattrass, S; Drinkwater, B

2012-03-01

We examined how the use of bone turnover markers and educational information affects persistence of bisphosphonate use in osteoporotic patients. We found that reporting bone turnover results and/or educational information did not affect persistence. Long-term adherence and persistence to osteoporosis medication are poor. We examined whether reporting of bone turnover marker results, education about osteoporosis, or a combination of both would increase persistence to oral bisphosphonates. Two hundred and forty women who were 5 years postmenopausal with BMD at least 2.0 standard deviations below normal were recruited for the study. All women were given a new prescription for alendronate and randomly assigned to one of four groups: (1) bone marker results at baseline, 3 and 12 months; (2) educational materials every month and a membership in the National Osteoporosis Foundation; (3) bone marker and educational information; and (4) control, no information other than usual care. Persistence among randomization groups was tested using survival analysis adjusting for the delay between intervention methods. Of those filling their initial prescription, 95.5% refilled their prescription at the end of the first month, 87% at 3 months, 82% at 6 months, and 78% at 10 months. Overall persistence through 12 months was 54%. There was no difference found among the four groups for persistence time using (p > 0.58). Providing bone turnover marker results is not an effective way to enhance early compliance and persistence with drug therapy. While the women in our study felt that bone marker results and educational information were helpful to them, there was no difference in persistence between those who received either bone marker information and/or educational information and those who did not. Because of the unexpected rate of primary nonadherence, this study may be underpowered.

Clinical significance of biochemical markers of bone metabolism in patients with type 2 diabetes mellitus

International Nuclear Information System (INIS)

Zhang Bashan; Zeng Longhong; Lai Fudi

2004-01-01

Objective: To investigate the clinical significance of changes of levels of biochemical markers of bone metabolism in patients with type 2 diabetes mellitus. Methods: Serum osteocalcin (BGP, with RIA), Ca alkaline phosphatase (ALP) and random specimen urinary deoxypyridinoline (DPD, with chemiluminescence assay), Ca, creatinine levels were measured in 40 patients with type 2 diabetes mellitus and 31 controls. Results: Serum BGP levels in diabetic patients were much lower than those in the controls (P<0.05); while urinary DPD/Cr ratio and Ca/Cr ratio were significantly higher in the patients than those in the controls (P<0.05, P<0.05). Serum Ca and ALP levels were about the same in the two groups. Conclusion: Loss of bone mass in diabetic patients are due to both decreased bone formation and increased bone resorption. Determination of the levels of the biochemical markers of bone metabolism (BGP, DPD......) could be applied for early detection of osteoporosis. (authors)

The Assessment of Bone Regulatory Pathways, Bone Turnover, and Bone Mineral Density in Vegetarian and Omnivorous Children.

Science.gov (United States)

Ambroszkiewicz, Jadwiga; Chełchowska, Magdalena; Szamotulska, Katarzyna; Rowicka, Grażyna; Klemarczyk, Witold; Strucińska, Małgorzata; Gajewska, Joanna

2018-02-07

Vegetarian diets contain many beneficial properties as well as carry a risk of inadequate intakes of several nutrients important to bone health. The aim of the study was to evaluate serum levels of bone metabolism markers and to analyze the relationships between biochemical bone markers and anthropometric parameters in children on vegetarian and omnivorous diets. The study included 70 prepubertal children on a lacto-ovo-vegetarian diet and 60 omnivorous children. Body composition, bone mineral content (BMC), and bone mineral density (BMD) were assessed by dual-energy X-ray absorptiometry. Biochemical markers-bone alkaline phosphatase (BALP), C-terminal telopeptide of type I collagen (CTX-I), osteoprotegerin (OPG), nuclear factor κB ligand (RANKL), sclerostin, and Dickkopf-related protein 1 (Dkk-1)-were measured using immunoenzymatic assays. In vegetarians, we observed a significantly higher level of BALP ( p = 0.002) and CTX-I ( p = 0.027), and slightly lower spine BMC ( p = 0.067) and BMD ( p = 0.060) than in omnivores. Concentrations of OPG, RANKL, sclerostin, and Dkk-1 were comparable in both groups of children. We found that CTX-I was positively correlated with BMC, total BMD, and lumbar spine BMD in vegetarians, but not in omnivores. A well-planned vegetarian diet with proper dairy and egg intake does not lead to significantly lower bone mass; however, children following a lacto-ovo-vegetarian diet had a higher rate of bone turnover and subtle changes in bone regulatory markers. CTX-I might be an important marker for the protection of vegetarians from bone abnormalities.

The effect of cholecalciferol and calcitriol on biochemical bone markers in HIV type 1-infected males

DEFF Research Database (Denmark)

Bang, Ulrich Christian; Kolte, Lilian; Hitz, Mette

2013-01-01

HIV-1-infected patients have an increased risk of osteoporosis and fractures. The main objective of this study was to evaluate the bone metabolism in HIV-1-infected patients exposed to calcitriol and cholecalciferol. We also investigated the relationship between T cells and bone markers. We...... conducted a placebo-controlled randomized study running for 16 weeks including 61 HIV-1-infected males, of whom 51 completed the protocol. Nineteen participants were randomized to daily treatment with (A) 0.5-1.0 μg calcitriol and 1,200 IU (30 μg) cholecalciferol, 17 participants to (B) 1,200 IU...

Urinary hydroxyproline excretion as a marker of bone metastasis in prostatic cancer, 2

International Nuclear Information System (INIS)

Nemoto, Shin-ichi; Rinsho, Kenji

1984-01-01

In 25 patients with prostatic cancer confirmed histologically, 24 patients had bone metastasis on the whole body bone scintigraphy. The extent of bone metastasis was estimated quantitatively by the computerized digitizer. At the same time, the number of the metastatic lesions was counted. The correlations between the area of metastatic lesions on the sup(99m)Tc-MDP bone scintigrams and ESR, LDH, total acid phosphatase, prostatic acid phosphatase, ALP and urinary hydroxyproline/creatinine levels were further investigated. The number of the metastatic lesions was also investigated with the same tumor markers. The results are as follows: 1) The extent of the metastatic lesions was showed more accurately by the area measured with the computerized digitalizer than by the number of metastatic lesions. 2) The correlation between the area of metastatic lesions and serum ALP levels was relatively high (γ = 0.75). But almost all were within normal limits. 3) As for the relation between the area of the metastatic lesions and the urinary hydroxyproline/creatinine levels, the correlation was high (γ = 0.78). And the hydroxyproline/creatinine levels were almost over the upper limit. Therefore, the urinary hydroxyproline/creatinine was considered as a good marker of the extent of bone metastasis. (author)

Healthy looking hospital nurses showing vitamin d deficiency: correlation of vitamin d levels with their levels of parathhyroid hormone and bone turnover markers

International Nuclear Information System (INIS)

Nasim, A.; Salim, B.; Niazi, S.; Fatima, N.

2015-01-01

To evaluate the correlation of low vitamin D levels with parathyroid hormone (PTH) levels and bone turn over markers among apparently healthy hospital nurses. Methods: Screening was done on 50 recruited healthy female nursing staff, aged between 18 to 35 years, for vitamin D levels. Among them 31 were found to be deficient in vitamin D. These 31 nurses were selected for further evaluation in trance. Their vitamin D levels were calculated by using the electrochemiluminescence immunoassay. Blood samples were drawn to estimate serum PTH levels accordingly. Samples were also collected from these recruited subjects to evaluate their bone turn over markers, including, osteocalcin, procollagen type 1 N propeptide and Beta-Crosslaps. Results: Out of 50 subjects, 31 subjects were found to have Vitamin D levels below 50 nmol/l. Out of these 31 subjects, 13 subjects, 41.9%, showed vitamin D levels below 20 nmol/l. Among these 13 subjects, all had significantly raised PTH levels (p-value: <0.001, r-value: -0.781). In rest of all the subjects, including those having Vitamin D levels above 20nmol/l, inordinately, PTH levels were normal. No reciprocity was found between low Vitamin D and raised PTH levels with bone turnover markers, except with P1NP (r-value 0.022). Conclusion: PTH levels show a steep augmentation in serum, when vitamin D levels hit the trough below 20 nmol/l. These are the subjects who should be treated prior to the development of complications of bone resorption. Moreover we could not find any significant correlation of Vitamin D and PTH with any bone turnover marker except P1NP. (author)

Changes in markers of bone formation and resorption in a bed rest model of weightlessness

Science.gov (United States)

Lueken, S. A.; Arnaud, S. B.; Taylor, A. K.; Baylink, D. J.

1993-01-01

To study the mechanism of bone loss in physical unloading, we examined indices of bone formation and bone resorption in the serum and urine of eight healthy men during a 7 day -6 degrees head-down tilt bed rest. Prompt increases in markers of resorption--pyridinoline (PD), deoxypyridinoline (DPD), and hydroxyproline (Hyp)/g creatinine--during the first few days of inactivity were paralleled by tartrate-resistant acid phosphatase (TRAP) with significant increases in all these markers by day 4 of bed rest. An index of formation, skeletal alkaline phosphatase (SALP), did not change during bed rest and showed a moderate 15% increase 1 week after reambulation. In contrast to SALP, serum osteocalcin (OC) began increasing the day preceding the increase in Hyp, remained elevated for the duration of the bed rest, and returned to pre-bed rest values within 5 days of reambulation. Similarly, DPD increased significantly at the onset of bed rest, remained elevated for the duration of bed rest, and returned to pre-bed rest levels upon reambulation. On the other hand, the other three indices of resorption, Hyp, PD, and TRAP, remained elevated for 2 weeks after reambulation. The most sensitive indices of the levels of physical activity proved to be the noncollagenous protein, OC, and the collagen crosslinker, DPD. The bed rest values of both these markers were significantly elevated compared to both the pre-bed rest values and the post-bed rest values. The sequence of changes in the circulating markers of bone metabolism indicated that increases in serum OC are the earliest responses of bone to head-down tilt bed rest.

Use of CTX-I and PINP as bone turnover markers: National Bone Health Alliance recommendations to standardize sample handling and patient preparation to reduce pre-analytical variability.

Science.gov (United States)

Szulc, P; Naylor, K; Hoyle, N R; Eastell, R; Leary, E T

2017-09-01

The National Bone Health Alliance (NBHA) recommends standardized sample handling and patient preparation for C-terminal telopeptide of type I collagen (CTX-I) and N-terminal propeptide of type I procollagen (PINP) measurements to reduce pre-analytical variability. Controllable and uncontrollable patient-related factors are reviewed to facilitate interpretation and minimize pre-analytical variability. The IOF and the International Federation of Clinical Chemistry (IFCC) Bone Marker Standards Working Group have identified PINP and CTX-I in blood to be the reference markers of bone turnover for the fracture risk prediction and monitoring of osteoporosis treatment. Although used in clinical research for many years, bone turnover markers (BTM) have not been widely adopted in clinical practice primarily due to their poor within-subject and between-lab reproducibility. The NBHA Bone Turnover Marker Project team aim to reduce pre-analytical variability of CTX-I and PINP measurements through standardized sample handling and patient preparation. Recommendations for sample handling and patient preparations were made based on review of available publications and pragmatic considerations to reduce pre-analytical variability. Controllable and un-controllable patient-related factors were reviewed to facilitate interpretation and sample collection. Samples for CTX-I must be collected consistently in the morning hours in the fasted state. EDTA plasma is preferred for CTX-I for its greater sample stability. Sample collection conditions for PINP are less critical as PINP has minimal circadian variability and is not affected by food intake. Sample stability limits should be observed. The uncontrollable aspects (age, sex, pregnancy, immobility, recent fracture, co-morbidities, anti-osteoporotic drugs, other medications) should be considered in BTM interpretation. Adopting standardized sample handling and patient preparation procedures will significantly reduce controllable pre

Changes in Inflammatory and Bone Turnover Markers After Periodontal Disease Treatment in Patients With Diabetes.

Science.gov (United States)

Izuora, Kenneth E; Ezeanolue, Echezona E; Neubauer, Michael F; Gewelber, Civon L; Allenback, Gayle L; Shan, Guogen; Umpierrez, Guillermo E

2016-06-01

The underlying mechanisms for increased osteopenia and fracture rates in patients with diabetes are not well understood, but may relate to chronic systemic inflammation. We assessed the effect of treating periodontal disease (POD), a cause of chronic inflammation, on inflammatory and bone turnover markers in patients with diabetes. Using an investigator-administered questionnaire, we screened a cross-section of patients presenting for routine outpatient diabetes care. We recruited 22 subjects with POD. Inflammatory and bone turnover markers were measured at baseline and 3 months following POD treatment (scaling, root planing and subantimicrobial dose doxycycline). There were nonsignificant reductions in high-sensitivity C-reactive protein (6.34-5.52mg/L, P = 0.626) and tumor necrosis factor-alpha (10.37-10.01pg/mL, P = 0.617). There were nonsignificant increases in urinary C-terminal telopeptide (85.50-90.23pg/mL, P = 0.684) and bone-specific alkaline phosphatase (7.45-8.79pg/mL, P = 0.074). Patients with >90% adherence with doxycycline were 6.4 times more likely to experience reduction in tumor necrosis factor-alpha (P = 0.021) and 2.8 times more likely to experience reductions in high-sensitivity C-reactive protein (P = 0.133). Treatment of POD in patients with diabetes resulted in nonsignificant lowering of inflammatory markers and nonsignificant increase in bone turnover markers. However, adherence to doxycycline therapy resulted in better treatment effects. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Marker for the pre-clinical development of bone substitute materials

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de Wild Michael

2017-09-01

Full Text Available Thin mechanically stable Ti-cages have been developed for the in-vivo application as X-ray and histology markers for the optimized evaluation of pre-clinical performance of bone graft materials. A metallic frame defines the region of interest during histological investigations and supports the identification of the defect site. This standardization of the procedure enhances the quality of pre-clinical experiments. Different models of thin metallic frameworks were designed and produced out of titanium by additive manufacturing (Selective Laser Melting. The productibility, the mechanical stability, the handling and suitability of several frame geometries were tested during surgery in artificial and in ex-vivo bone before a series of cages was preclinically investigated in the female Göttingen minipigs model. With our novel approach, a flexible process was established that can be adapted to the requirements of any specific animal model and bone graft testing.

Sclerostin as a novel marker of bone turnover in athletes

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A Zagrodna

2016-02-01

Full Text Available Sclerostin is a protein secreted by osteocytes that acts as an inhibitor of bone formation. It has been shown that physical activity affects sclerostin concentration and thus bone remodelling. The aim of the study was to evaluate serum concentrations of sclerostin, selected bone turnover markers (PTH, P1NP, 25(OH D3 and the intake of calcium and vitamin D in physically active versus sedentary men. A total of 59 healthy men aged 17-37 were enrolled in the study (43 athletes and 16 non-athletes. The mean sclerostin concentration in the group of athletes (A was significantly higher than in non-athletes (NA (35.3±8.9 vs 28.0±5.6 pmol• l-1, p= 0.004. A compared with NA had higher concentrations of P1NP (145.6±77.5 vs 61.2±22.3 ng• ml-1, p= <0.0001 and 25(OHD3 (16.9±8.4 vs 10.3±4.3 ng • ml-1, p= 0.004 and lower concentrations of PTH (25.8±8.3 vs 38.2±11.5 pg• ml-1, p= <0.0001. Vitamin D deficiency was found in 77% of A and 100% of NA. A and NA had similar daily energy intake. They did not differ as to the intake of calcium and vitamin D. We observed a negative correlation between the serum concentrations of sclerostin and calcium in the studied subjects. Our results suggest that regular, long-lasting physical training may be associated with higher concentration of sclerostin. It seems that increased sclerostin is not related to other bone turnover markers (PTH, P1NP.

Bone mineral content and bone metabolism in young adults with severe periodontitis

DEFF Research Database (Denmark)

Wowern von, N.; Westergaard, J.; Kollerup, G.

2001-01-01

Bone loss, bone markers, bone metabolism, bone mineral content, osteoporosis, severe periodontitis......Bone loss, bone markers, bone metabolism, bone mineral content, osteoporosis, severe periodontitis...

Secretory IgA, albumin level, and bone density as markers of biostimulatory effects of laser radiation

Science.gov (United States)

Kucerova, Hana; Dostalova, Tatjana; Himmlova, Lucia; Bartova, Jirina; Mazanek, Jiri

1998-12-01

The aim of contribution is to evaluate the effects of low- level laser radiation on healing process after human molars extraction in lower jaw using frequency 5 Hz, 292 Hz and 9000 Hz. Changes in bone density and monitoring of secretory IgA and albumin levels in saliva were used as a marker of biostimulatory effect. Bone density after extraction and 6 month after surgical treatment was examined using the dental digital radiography. Bone healing was followed by osseointegration of bone structure in extraction wound. Changes of bone density, secretory IgA and albumin levels were compared in groups of patients with laser therapy and control group without laser therapy. Differences in levels of the saliva markers (sIgA and albumin) were found to be significant comparing irradiated and non-irradiated groups, as well as comparing groups irradiated by various modulatory frequencies. Density of alveolar bone (histogram) was examined on five slices acquired from every RVG image. Histograms were evaluated with computer program for microscopic image analysis. Differences of density were verified in area of the whole slice. There were no significant differences found between the bone density in irradiated and non irradiated groups perhaps due to our used therapeutical diagram.

Effects of Curcumin on Bone Loss and Biochemical Markers of Bone Turnover in Patients with Spinal Cord Injury.

Science.gov (United States)

Hatefi, Masoud; Ahmadi, Mohammad Reza Hafezi; Rahmani, Asghar; Dastjerdi, Masoud Moghadas; Asadollahi, Khairollah

2018-06-01

Osteoporosis is one of the most common problems of patients with spinal cord injuries (SCIs). The current study aimed to evaluate the antiosteoporotic effects of curcumin on densitometry parameters and biomarkers of bone turnovers among patients with SCI. The current controlled clinical trial was conducted among 100 patients with SCI referred to an outpatient clinic of rehabilitation in Ilam City, Iran, in 2013-2015. The intervention group received 110/mg/kg/day curcumin for 6 months and the control group received placebo. Bone mineral density (BMD) was measured in all patients. The level of procollagen type I N-terminal propeptide, serum carboxy-terminal telopeptide of type I collagen, osteocalcin, and bone-specific alkaline phosphates were compared before and after study. BMD indicators of lumbar, femoral neck, and total hip in the control group significantly decreased compared with the beginning of study. However, in the curcumin group, a significant increase was observed in BMD indicators of lumbar, femoral neck, and hip at the end of study compared with the beginning. There was also a significant difference between interventional and control groups for the mean BMD of femoral neck and hip at the end of study (0.718 ± 0.002 g/cm 2 vs. 0.712 ± 0.003 g/cm 2 and 0.742 ± 0.031 g/cm 2 vs. 0.692 ± 0.016 g/cm 2 , respectively). Curcumin, via modulation of densitometry indices and bone resorption markers, showed inhibitory effects on the process of osteoporosis. Treatment with curcumin was significantly associated with a decrease in the osteoporosis progression and bone turnover markers of patients with SCI after 6 months. Copyright © 2018 Elsevier Inc. All rights reserved.

Effect of adiponectin and sex steroid hormones on bone mineral density and bone formation markers in postmenopausal women with subclinical hyperthyroidism.

Science.gov (United States)

Ahn, Ki Hoon; Lee, Seung Hyeun; Park, Hyun Tae; Kim, Tak; Hur, Jun Young; Kim, Young Tae; Kim, Sun Haeng

2010-04-01

The relationship between adiponectin and sex hormones with bone mineral density (BMD) and bone formation markers was investigated in postmenopausal women with subclinical hyperthyroidism (SCH). Seventy-five postmenopausal women were selected among the patients who participated in a health screening program in 2007. Thirty-seven control women with normal thyroid function were matched to 38 women with SCH by age, body mass index (BMI), and years since menopause (YSM). The associations between adiponectin and sex hormones with lumbar spine BMD and bone turnover markers were investigated. Adiponectin, testosterone (T; total and free forms), and thyroid-stimulating hormone were significantly different between the women with SCH and euthyroid. After adjusting for age, BMI, and YSM, free T (r = 0.351; P = 0.029) and estradiol (E2; r = -0.368; P = 0.024) had significant associations with bone alkaline phosphatase (B-ALP). Total T (r = 0.388; P = 0.021) and E2 (r = -0.376; P = 0.026) had significant associations with osteocalcin. However, there were no significant associations between adiponectin and sex hormones with the BMD levels in the SCH subjects. There were correlations between sex hormones with B-ALP and osteocalcin, but no associations between adiponectin and sex hormones with the lumbar spine BMD in postmenopausal SCH patients.

Clinical usefulness of bone turnover marker concentrations in osteoporosis

DEFF Research Database (Denmark)

Morris, H A; Eastell, R; Jorgensen, N R

2017-01-01

Current evidence continues to support the potential for bone turnover markers (BTM) to provide clinically useful information particularly for monitoring the efficacy of osteoporosis treatment. Many of the limitations identified earlier remain, principally in regard to the relationship between BTM...... of combining such data for meta-analyses. Harmonization of units for reporting serum/plasma CTX (ng/L) and PINP (μg/L) is recommended. The development of international collaborations continues with an important initiative to combine BTM results from clinical trials in osteoporosis in a meta...

The association between bone turnover markers and kyphosis in community-dwelling older adults

Directory of Open Access Journals (Sweden)

Corinne R. McDaniels-Davidson

2016-12-01

Full Text Available Purpose: Hyperkyphosis, accentuated curvature of the thoracic spine, is often attributed to osteoporosis, yet its underlying pathophysiology is not well understood. Bone turnover markers (BTM reflect the dynamic process of bone formation and resorption. This study examined the association between serum BTM levels and kyphosis in community-dwelling older adults. Methods: Between 2003 and 2006, 760 men and women in the Rancho Bernardo Study age 60 and older had blood drawn and kyphosis measured. Fasting serum was assayed for N-telopeptide (NTX and procollagen type 1 n-terminal propeptide (P1NP, markers of bone resorption and formation, respectively. Participants requiring two or more 1.7 cm blocks under their head to achieve a neutral supine position were classified as having accentuated kyphosis. Analyses were stratified by sex and use of estrogen therapy (ET. Odds of accentuated kyphosis were calculated for each standard deviation increase in log-transformed BTM. Results: Mean age was 75 years. Overall, 51% of 341 non-ET using women, 41% of 111 ET-using women, and 75% of 308 men had accentuated kyphosis. In adjusted models, higher P1NP and NTX were associated with decreased odds of accentuated kyphosis in non-ET using women (P1NP: OR = 0.78 [95% CI, 0.58–0.92]; NTX: OR = 0.68 [95% CI, 0.54–0.86], but not in men or ET-using women (p > 0.05. Conclusions: The selective association of higher bone turnover with reduced odds of accentuated kyphosis in non-ET using women suggests that elevated BTM were associated with a lower likelihood of hyperkyphosis only in the low estrogen/high BTM environment characteristic of postmenopausal women who are not using ET. Keywords: Kyphosis, Hyperkyphosis, Bone turnover, Bone remodeling, P1NP, NTX

Bone mineral density and bone markers in patients with a recent low-energy fracture: effect of 1 y of treatment with calcium and vitamin D

DEFF Research Database (Denmark)

Hitz, Mette F; Jensen, Jens-Erik B; Eskildsen, Peter C

2007-01-01

BACKGROUND: Low-energy fractures of the hip, forearm, shoulder, and spine are known consequences of osteoporosis. OBJECTIVE: We evaluated the effect of 1 y of treatment with calcium and vitamin D on bone mineral density (BMD) and bone markers in patients with a recent low-energy fracture. DESIGN...

Correlation of bone mineral density with biochemical markers in different menopausal statuses of Pakistani women

International Nuclear Information System (INIS)

Maqsood, A.; Nadia, N.; Farzana, A.; Bashir, A.

2005-01-01

Aim: The present study is aimed to use bone mineral density (BMD) and various biochemical markers to predict the fracture risk at different menopausal statuses in Pakistani women. Method: Seventy women aged between 28-80 years at various menopausal statuses participated in this study. BMD (T score) of right calcaneus was determined using SAHARA ultrasound bone densitometer that measures the transmission of high frequency from heel. Various biochemical markers such as alkaline phosphates, calcium and inorganic phosphorus were measured from the serum of venous blood using standard kits of Randox. Results: Alkaline phosphates was raised in per menopausal, postmenopausal and postmenopausal with hysterectomy and ligation groups of women as compared to premenopausal women but did not achieve significance (P>0.05). Serum calcium level was significantly lower in postmenopausal women than premenopausal women and inorganic phosphorus decrease significantly when compared with premenopausal and postmenopausal with ligation and hysterectomy. BMD (T score) values of postmenopausal osteopenic and postmenopausal osteoprotic women were significantly lower than those of premenopausal women. BMD values of women under study have negative correlation with age, alkaline phosphates and calcium. Conclusion: Our study conclude that in addition to BMD, serum levels of alkaline phosphate, calcium and inorganic phosphorus can be valuable biochemical markers in predicting bone fracture risk at different menopausal states. (author)

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...... turnover state in children with chronic kidney disease. Growth hormone induces an osteoanabolic pattern and normalizes osteocyte activity. The osteocyte markers cFGF23 and sclerostin are associated with standardized height, and the markers of bone turnover predict height velocity......./min/ 1.73m2. 41 children receiving recombinant growth hormone therapy were compared to an untreated matched control group. Results: Standardized levels of BAP, TRAP5b and cFGF-23 were increased whereas sclerostin was reduced. BAP was correlated positively and cFGF-23 inversely with eGFR. Intact serum...

Palmitic Acid Reduces Circulating Bone Formation Markers in Obese Animals and Impairs Osteoblast Activity via C16-Ceramide Accumulation.

Science.gov (United States)

Alsahli, Ahmad; Kiefhaber, Kathryn; Gold, Tziporah; Muluke, Munira; Jiang, Hongfeng; Cremers, Serge; Schulze-Späte, Ulrike

2016-05-01

Obesity and impaired lipid metabolism increase circulating and local fatty acid (FA) levels. Our previous studies showed that a high high-saturated -fat diet induced greater bone loss in mice than a high high-unsaturated-fat diet due to increased osteoclast numbers and activity. The impact of elevated FA levels on osteoblasts is not yet clear. We induced obesity in 4 week old male mice using a palmitic acid (PA)- or oleic acid (OA)-enriched high fat high-fat diet (HFD) (20 % of calories from FA), and compared them to mice on a normal (R) caloric diet (10 % of calories from FA). We collected serum to determine FA and bone metabolism marker levels. Primary osteoblasts were isolated; cultured in PA, OA, or control (C) medium; and assessed for mineralization activity, gene expression, and ceramide levels. Obese animals in the PA and OA groups had significantly lower serum levels of bone formation markers P1NP and OC compared to normal weight animals (*p < 0.001), with the lowest marker levels in animals on an PA-enriched HFD (*p < 0.001). Accordingly, elevated levels of PA significantly reduced osteoblast mineralization activity in vitro (*p < 0.05). Elevated PA intake significantly increased C16 ceramide accumulation. This accumulation was preventable through inhibition of SPT2 (serine palmitoyl transferase 2) using myriocin. Elevated levels of PA reduce osteoblast function in vitro and bone formation markers in vivo. Our findings suggest that saturated PA can compromise bone health by affecting osteoblasts, and identify a potential mechanism through which obesity promotes bone loss.

Markers of bone resorption and calcium metabolism are related to dietary intake patterns in male and female bed rest subjects

Science.gov (United States)

Smith, Scott M.; Zwart, S. R.; Hargens, A. r.

2006-01-01

Dietary potassium and protein intakes predict net endogenous acid production in humans. Intracellular buffers, including exchangeable bone mineral, play a crucial role in balancing chronic acid-base perturbations in the body; subsequently, chronic acid loads can potentially contribute to bone loss. Bone is lost during space flight, and a dietary countermeasure would be desirable for many reasons. We studied the ability of diet protein and potassium to predict levels of bone resorption markers in males and females. Identical twin pairs (8 M, 7 F) were assigned to 2 groups: bed rest (sedentary, SED) or bed rest with supine treadmill exercise in a lower body negative pressure chamber (EX). Diet was controlled for 3 d before and 30 d of bed rest (BR). Urinary Ca, N-telopeptide (NTX), and pyridinium crosslinks (PYD) were measured before and on days 5, 12, 19, and 26 of BR. Data were analyzed by Pearson correlation (Pdietary animal protein/potassium intake was not correlated with NTX before BR for males or females, but they were positively correlated in both groups of males during bed rest. Dietary animal protein/potassium and urine Ca were correlated before and during bed rest for the males, and only during bed rest for the females. Conversely, the ratio of dietary vegetable protein/potassium intake was negatively correlated with urinary calcium during bed rest for the females, but there was no relationship between vegetable protein/potassium intake and bone markers for the males. These data suggest that the ratio of animal protein/potassium intake may affect bone, particularly in bed rest subjects. These data show that the type of protein and gender may be additional factors that modulate the effect of diet on bone metabolism during bed rest. Altering this ratio may help prevent bone loss on Earth and during space flight.

Markers of bone resorption and calcium metabolism are related to dietary intake patterns in male and female bed rest subjects

Science.gov (United States)

Smith, Scott M.; Zwart, S. R.; Hargens, A. r.

2006-01-01

Dietary potassium and protein intakes predict net endogenous acid production in humans. Intracellular buffers, including exchangeable bone mineral, play a crucial role in balancing chronic acid-base perturbations in the body; subsequently, chronic acid loads can potentially contribute to bone loss. Bone is lost during space flight, and a dietary countermeasure would be desirable for many reasons. We studied the ability of diet protein and potassium to predict levels of bone resorption markers in males and females. Identical twin pairs (8 M, 7 F) were assigned to 2 groups: bed rest (sedentary, SED) or bed rest with supine treadmill exercise in a lower body negative pressure chamber (EX). Diet was controlled for 3 d before and 30 d of bed rest (BR). Urinary Ca, N-telopeptide (NTX), and pyridinium crosslinks (PYD) were measured before and on days 5, 12, 19, and 26 of BR. Data were analyzed by Pearson correlation (P<0.05). The ratio of dietary animal protein/potassium intake was not correlated with NTX before BR for males or females, but they were positively correlated in both groups of males during bed rest. Dietary animal protein/potassium and urine Ca were correlated before and during bed rest for the males, and only during bed rest for the females. Conversely, the ratio of dietary vegetable protein/potassium intake was negatively correlated with urinary calcium during bed rest for the females, but there was no relationship between vegetable protein/potassium intake and bone markers for the males. These data suggest that the ratio of animal protein/potassium intake may affect bone, particularly in bed rest subjects. These data show that the type of protein and gender may be additional factors that modulate the effect of diet on bone metabolism during bed rest. Altering this ratio may help prevent bone loss on Earth and during space flight.

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

Science.gov (United States)

Doyon, Anke; Fischer, Dagmar-Christiane; Bayazit, Aysun Karabay; Canpolat, Nur; Duzova, Ali; Sözeri, Betül; Bacchetta, Justine; Balat, Ayse; Büscher, Anja; Candan, Cengiz; Cakar, Nilgun; Donmez, Osman; Dusek, Jiri; Heckel, Martina; Klaus, Günter; Mir, Sevgi; Özcelik, Gül; Sever, Lale; Shroff, Rukshana; Vidal, Enrico; Wühl, Elke; Gondan, Matthias; Melk, Anette; Querfeld, Uwe; Haffner, Dieter; Schaefer, Franz

2015-01-01

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 chronic kidney disease cohort. 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/min/1.73 m2. 41 children receiving recombinant growth hormone therapy were compared to an untreated matched control group. Standardized levels of BAP, TRAP5b and cFGF-23 were increased whereas sclerostin was reduced. BAP was correlated positively and cFGF-23 inversely with eGFR. Intact serum parathormone was an independent positive predictor of BAP and TRAP5b and negatively associated with sclerostin. BAP and TRAP5B were negatively affected by increased C-reactive protein levels. In children receiving recombinant growth hormone, BAP was higher and TRAP5b lower than in untreated controls. Sclerostin levels were in the normal range and higher than in untreated controls. Serum sclerostin and cFGF-23 independently predicted height standard deviation score, and BAP and TRAP5b the prospective change in height standard deviation score. Markers of bone metabolism indicate a high-bone turnover state in children with chronic kidney disease. Growth hormone induces an osteoanabolic pattern and normalizes osteocyte activity. The osteocyte markers cFGF23 and sclerostin are associated with standardized height, and the markers of bone turnover predict height velocity.

Markers of bone resorption and calcium metabolism are related to dietary intake patterns in male and female bed rest subjects

Science.gov (United States)

Smith, Scott M.; Zwart, S. R.; Hargens, A. r.

2006-01-01

Dietary potassium and protein intakes predict net endogenous acid production in humans. Intracellular buffers, including exchangeable bone mineral, play a crucial role in balancing chronic acid-base perturbations in the body; subsequently, chronic acid loads can potentially contribute to bone loss. Bone is lost during space flight, and a dietary countermeasure would be desirable for many reasons. We studied the ability of diet protein and potassium to predict levels of bone resorption markers in males and females. Identical twin pairs (8 M, 7 F) were assigned to 2 groups: bed rest (sedentary, SED) or bed rest with supine treadmill exercise in a lower body negative pressure chamber (EX). Diet was controlled for 3 d before and 30 d of bed rest (BR). Urinary Ca, N-telopeptide (NTX), and pyridinium crosslinks (PYD) were measured before and on days 5, 12, 19, and 26 of BR. Data were analyzed by Pearson correlation (Pdiet on bone metabolism during bed rest. Altering this ratio may help prevent bone loss on Earth and during space flight.

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

Changes in calcitropic hormones, bone markers and insulin-like growth factor I (IGF-I) during pregnancy and postpartum: a controlled cohort study.

Science.gov (United States)

Møller, U K; Streym, S; Mosekilde, L; Heickendorff, L; Flyvbjerg, A; Frystyk, J; Jensen, L T; Rejnmark, L

2013-04-01

Pregnancy and lactation cause major changes in calcium homeostasis and bone metabolism. This population-based cohort study presents the physiological changes in biochemical indices of calcium homeostasis and bone metabolism during pregnancy and lactation We describe physiological changes in calcium homeostasis, calcitropic hormones and bone metabolism during pregnancy and lactation. We studied 153 women planning pregnancy (n=92 conceived) and 52 non-pregnant, age-matched female controls. Samples were collected prior to pregnancy, once each trimester and 2, 16 and 36 weeks postpartum. The controls were followed in parallel. P-estradiol (E2), prolactin and 1,25-dihydroxyvitamin D (1,25(OH)2D) increased (phormone (P-PTH) and calcitonin decreased (pgrowth factor I (IGF-I) was suppressed (pbone resorption and formation rose and fall, respectively (pbone formation markers increased in association with IGF-I changes (pbone turnover markers were associated with lactation status (pbone markers indicated a negative bone balance. The rise in bone formation in late pregnancy may be initiated by a spike in IGF-I levels. The high bone turnover in lactating women may be related to high prolactin and PTH levels, low E2 levels and perhaps increased parathyroid hormone-related protein levels.

The Incidence and Topographic Distribution of Sutures Including Wormian Bones in Human Skulls.

Science.gov (United States)

Cirpan, Sibel; Aksu, Funda; Mas, Nuket

2015-07-01

The Wormian Bones are accessory bones located within the cranial sutures and fontanelles. The present article examines the incidence of Wormian Bones and compares the number and topographic distribution between the sutures including Wormian Bones in skulls of West Anatolian Population. One hundred fifty crania were examined. The parameters evaluated in the present study were as follows: the rate of skulls including Wormian Bones; the topographic distribution and frequencies of the sutures including Wormian Bones; the number of these sutures for each skull; the name and number of sutures that were bilaterally and symmetrically located on the right and left side of skull (paired sutures) and which coincidentally had Wormian Bones for each skull; the differences of frequencies between the paired sutures including Wormian Bones. The rate of skulls including Wormian Bones was determined as 59.3%. The maximum and minimum numbers of sutures, including Wormian Bones, were 6 in 1 skull and 1 in each of 30 skulls, respectively. The maximum and minimum rates of sutures that had Wormian Bones were found in left lambdoid 40.7% and right occipitomastoid 1.3% sutures, respectively. There was only a significant difference between the rate of right and left squamous sutures (P = 0.04). Forty-five skulls were including 55 pairs of bilaterally and symmetrically located sutures that coincidentally had Wormian Bones in each pair. Each of 35 skulls had 1 pair of sutures including Wormian Bones and each of 10 skulls had 2 pairs. In the present study, the rate of Wormian Bones was determined as 59.3% in West Anatolian Population. This incidence rate is considerably lower than the other reports, and it may be as a result of racial variations. These divergent bones were more frequently found in left lambdoid sutures (40.7%) and less frequently in right occipitomastoid sutures (1.3%). This study may guide the investigators dealing with the neurosurgery, orthopedy, radiology, anatomy, and

The effects of a 6-month resistance training and dried plum consumption intervention on strength, body composition, blood markers of bone turnover, and inflammation in breast cancer survivors.

Science.gov (United States)

Simonavice, Emily; Liu, Pei-Yang; Ilich, Jasminka Z; Kim, Jeong-Su; Arjmandi, Bahram; Panton, Lynn B

2014-06-01

The purpose of this study was to examine the effects of resistance training (RT) and dried plum (DP) consumption on strength, body composition, blood markers of bone, and inflammation in breast cancer survivors (BCS). Twenty-three BCS (RT, n = 12; RT+DP, n = 11), aged 64 ± 7 years, were evaluated at baseline and after 6 months of intervention on the following: muscular strength (chest press and leg extension) via 1-repetition maximums (1RMs); body composition, specifically bone mineral density (BMD) by dual energy X-ray absorptiometry; biochemical markers of bone turnover (bone-specific alkaline phosphatase (BAP), tartrate resistant acid phosphatase (TRAP-5b)); and inflammation (C-reactive protein (CRP)). Target RT prescription was 2 days/week of 10 exercises, including 2 sets of 8-12 repetitions at ∼60%-80% of 1RM. RT+DP also consumed 90 g of DP daily. There were no baseline differences between groups or any group-by-time interactions for any of the variables. BCS increased upper (p body strength. Body composition and BMD improvements were not observed. TRAP-5b decreased in the RT group (p body composition and biochemical markers of inflammation.

Biochemical markers of bone metabolism in draught and warmblood horses.

Science.gov (United States)

Lepage, O M; Hartmann, D J; Eicher, R; Uebelhart, B; Tschudi, P; Uebelhart, D

1998-11-01

Concentrations of the cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and osteocalcin (OC) have been determined in the serum of one hundred clinically healthy adult Draught or Warmblood horses. The correlation between these two markers has been evaluated and the influence of gender, age and type of horse described. No significant variations were observed between animals of different sex, but a significant inverse correlation (P Draught [adjusted least square mean (LSM) = 6.612 micrograms.L-1] than in Warmblood horses (adjusted LSM = 8.596 micrograms.L-1), whereas levels of ICTP were higher in Draughts (adjusted LSM = 8.035 micrograms.L-1) than in Warmbloods (adjusted LSM = 6.643 micrograms.L-1). A significant correlation (P Draught horses might reflect a higher bone remodelling level of horses submitted to regular daily work. It was concluded that ICTP and OC are influenced by the type of horse, and probably reflect a physiological difference in bone remodelling between these animals.

Effects of vildagliptin on postprandial markers of bone resorption and calcium homeostasis in recently diagnosed, well-controlled type 2 diabetes patients

NARCIS (Netherlands)

Bunck, M.C.M.; Poelma, M.; Eekhoff, E.M.; Schweizer, A.; Heine, R.J.; Nijpels, G.; Foley, J.E.; Diamant, M.

2012-01-01

Background: Bone metabolism is a dynamic process that is influenced by food ingestion. Endogenous incretins have been shown to be important regulators of bone turnover. The aim of the present study was to assess whether a dipeptidylpeptidase (DPP)-4 inhibitor affects markers of bone resorption and

Tantalum markers in radiography

International Nuclear Information System (INIS)

Aronson, A.S.; Jonsson, N.; Alberius, P.

1985-01-01

The biocompatibility of two types of radiopaque tantalum markers was evaluated histologically. Reactions to pin markers (99.9% purity) and spherical markers (95.2% purity) were investigated after 3-6 weeks in rabbits and 5-48 weeks in children with abnormal growth. Both marker types were firmly attached to bone trabeculae; this was most pronounced in rabbit bone, and no adverse macroscopic reactions were observed. Microscopically, no reactions or only slight fibrosis of bone tissue were detected, while soft tissues only demonstrated a minor inflammatory reaction. Nevertheless, the need for careful preparation and execution of marker implantations is stressed, and particularly avoidance iof the use of emery in sharpening of cannulae. The bioinertness of tantalum was reconfirmed as was its suitability for use as skeletal and soft tissue radiographic markers. (orig.)

Inhibition of markers of bone resorption by consumption of vitamin D and calcium-fortified soft plain cheese by institutionalised elderly women.

Science.gov (United States)

Bonjour, Jean-Philippe; Benoit, Valérie; Pourchaire, Olivier; Ferry, Monique; Rousseau, Brigitte; Souberbielle, Jean-Claude

2009-10-01

Acceleration of bone remodelling increases the risk of fragility fractures. The objective of the present study was to explore in elderly women whether a vitamin D and Ca-fortified dairy product providing about 17-25 % of the recommended intakes in vitamin D, Ca and proteins would reduce secondary hyperparathyroidism and bone remodelling in a way that may attenuate age-related bone loss in the long term. Thirty-seven institutionalised women, aged 84.8 (sd 8.1) years, with low serum 25-hydroxyvitamin D (5.5 (sd 1.7) ng/ml) were enrolled into a multicentre open trial to consume during 1 month two servings of soft plain cheese made of semi-skimmed milk providing daily 686 kJ (164 kcal), 2.5 microg vitamin D, 302 mg Ca and 14.2 g proteins. The primary endpoint was the change in serum carboxy terminal cross-linked telopeptide of type I collagen (CTX), selected as a marker of bone resorption. Thirty-five subjects remained compliant. Mean serum changes were: 25-hydroyvitamin D, +14.5 % (P = 0.0051); parathyroid hormone (PTH), - 12.3 % (P = 0.0011); CTX, - 7.5 % (P = 0.01); tartrate-resistant acid phosphatase isoform 5b (TRAP 5b), - 9.9 % (P elderly women with vitamin D insufficiency can reduce bone resorption markers by positively influencing Ca and protein economy, as expressed by decreased PTH and increased IGF-I, respectively. The rise in the bone formation marker P1NP could be explained by a protein-mediated increase in IGF-I. Thus, such a dietary intervention might uncouple, at least transiently, bone resorption from bone formation and thereby attenuate age-related bone loss.

Systematic review of the use of bone turnover markers for monitoring the response to osteoporosis treatment: the secondary prevention of fractures, and primary prevention of fractures in high-risk groups.

Science.gov (United States)

Burch, Jane; Rice, Stephen; Yang, Huiqin; Neilson, Aileen; Stirk, Lisa; Francis, Roger; Holloway, Paul; Selby, Peter; Craig, Dawn

2014-02-01

There is currently no standard practice for the monitoring of patients receiving treatment for osteoporosis. Repeated dual-energy X-ray absorptiometry (DXA) is commonly used for monitoring treatment response, but it has its limitations. Bone turnover markers have advantages over DXA as they are non-invasive, relatively cheap and can detect changes in bone turnover rates earlier. However, they do have disadvantages, particularly high within- and between-patient variability. The ability of bone turnover markers to identify treatment non-responders and predict future fracture risk has yet to be established. We aimed to determine the clinical effectiveness, test accuracy, reliability, reproducibility and cost-effectiveness of bone turnover markers for monitoring the response to osteoporosis treatment. We searched 12 electronic databases (including MEDLINE, EMBASE, The Cochrane Library and trials registries) without language restrictions from inception to March 2012. We hand-searched three relevant journals for the 12 months prior to May 2012, and websites of five test manufacturers and the US Food and Drug Administration (FDA). Reference lists of included studies and relevant reviews were also searched. A systematic review of test accuracy, clinical utility, reliability and reproducibility, and cost-effectiveness of two formation and two resorption bone turnover markers, in patients being treated for osteoporosis with any of bisphosphonate [alendronate (Fosamax, MSD), risedronate (Actonel, Warner Chilcott Company), zolendronate (Zometa, Novartis)], raloxifene (Evista, Eli Lilly and Company Ltd), strontium ranelate (Protelos, Servier Laboratories Ltd), denosumab (Prolia, Amgen Ltd) or teriparatide (Forsteo, Eli Lilly and Company Ltd), was undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Given the breadth of the review question, a range of study designs and outcome measures were eligible. The development

Non-invasive markers of bone turnover and plasma cytokines differ in osteoporotic patients with multiple myeloma and monoclonal gammopathies of undetermined significance

International Nuclear Information System (INIS)

Diamond, T.; Levy, S.; Smith, A.; Day, P.; Manoharan, A.

2001-01-01

Multiple myeloma (MM) is a common malignancy manifest by bone marrow infiltration with malignant plasma cells, the production of a paraprotein and lytic bone lesions. Monoclonal gammopathy of undetermined significance (MGUS) is assumed to be the precursor of clinically apparent myeloma, with one or more additional genetic events being required for progression to MM. Elderly patients presenting with osteoporosis and skeletal fractures are not infrequently found to have elevated serum paraprotein concentrations suggestive of either MM or MGUS. Differentiating between these two clinical disorders may prove challenging, despite bone marrow biopsy evidence of plasmacytosis. The underlying pathogenesis of bone loss in these conditions is complex and may be attributed to cytokine-induced osteoclastogenesis coupled with increased osteoclastic bone resorption. In the present study, various markers of bone turnover and plasma cytokines were measured in order to determine whether they may be of value in differentiating between these two disorders. It is concluded that the urinary deoxypyridinoline excretion rate is a sensitive marker of bone resorption and of underlying bone disease activity. It may also help to differentiate between MM and MGUS

A phase II clinical trial does not show that high dose simvastatin has beneficial effect on markers of bone turnover in multiple myeloma

DEFF Research Database (Denmark)

Søndergaard, Teis Esben; Pedersen, PT; Levin Andersen, Thomas

2008-01-01

Several studies have evaluated the impact of low dose statin (20-80 mg/day) on bone metabolism with inconclusive results despite promising data of preclinical studies. In this study, we investigated the effect of high dose simvastatin (HD-Sim) on biochemical markers of bone turnover and disease...... acid phosphatase, TRACP); (ii) bone resorption (collagen fragments CTX and NTX); (iii) bone formation (osteocalcin and aminoterminal propeptide of type I collagen PINP); (iv) cholesterol; (v) regulators of bone metabolism [osteoprotegerin (OPG) and Dickkopf-1 (DKK-1)] and (vi) disease activity...... (monoclonal proteins or free light chains in serum). TRACP activity in serum and levels of collagen fragments (NTX) in urine increased for all patients temporarily during the 7 days of treatment with HD-Sim indicating that osteoclasts may have been stimulated rather than inhibited. The other markers of bone...

The effects of improved metabolic risk factors on bone turnover markers after 12 weeks of simvastatin treatment with or without exercise.

Science.gov (United States)

Jiang, Jun; Boyle, Leryn J; Mikus, Catherine R; Oberlin, Douglas J; Fletcher, Justin A; Thyfault, John P; Hinton, Pamela S

2014-11-01

Emerging evidence supports an association between metabolic risk factors and bone turnover. Statins and exercise independently improve metabolic risk factors; however whether improvements in metabolic risk factor affects bone turnover is unknown. The purpose of the present study was to: 1) evaluate the relationship between metabolic risk factors and bone turnover; and 2) determine if improvements in metabolic risk factors after 12 weeks of statin treatment, exercise or the combination affect bone turnover. Fifty participants with ≥2 metabolic syndrome defining characteristics were randomly assigned to one of three groups: statin (STAT: simvastatin, 40 mg/day), exercise (EX: brisk walking and/or slow jogging, 45 minutes/day, 5 days/week), or the combination (STAT+EX). Body composition and whole body bone mineral density were measured with dual energy X-ray absorptiometry. Serum markers of bone formation (bone specific alkaline phosphatase, BAP; osteocalcin, OC), resorption (C-terminal peptide of type I collagen, CTX) and metabolic risk factors were determined. Two-factor (time, group) repeated-measures ANCOVA was used to examine changes of metabolic risk factors and bone turnover. General linear models were used to determine the effect of pre-treatment metabolic risk factors on post-treatment bone turnover marker outcomes. Participants with ≥4 metabolic syndrome defining characteristics had lower pre-treatment OC than those with 3 or fewer. OC was negatively correlated with glucose, and CTX was positively correlated with cholesterol. STAT or STAT+EX lowered total and LDL cholesterol. The OC to CTX ratio decreased in all groups with no other significant changes in bone turnover. Higher pre-treatment insulin or body fat predicted a greater CTX reduction and a greater BAP/CTX increase. Metabolic risk factors were negatively associated with bone turnover markers. Short-term statin treatment with or without exercise lowered cholesterol and all treatments had a small

The association between bone turnover markers and kyphosis in community-dwelling older adults.

Science.gov (United States)

McDaniels-Davidson, Corinne R; Kritz-Silverstein, Donna; Huang, Mei-Hua; Laughlin, Gail A; Johnson, Sarah; Haapalahti, Jouko; Schneider, Diane L; Barrett-Connor, Elizabeth; Kado, Deborah M

2016-12-01

Hyperkyphosis, accentuated curvature of the thoracic spine, is often attributed to osteoporosis, yet its underlying pathophysiology is not well understood. Bone turnover markers (BTM) reflect the dynamic process of bone formation and resorption. This study examined the association between serum BTM levels and kyphosis in community-dwelling older adults. Between 2003 and 2006, 760 men and women in the Rancho Bernardo Study age 60 and older had blood drawn and kyphosis measured. Fasting serum was assayed for N-telopeptide (NTX) and procollagen type 1 n-terminal propeptide (P1NP), markers of bone resorption and formation, respectively. Participants requiring two or more 1.7 cm blocks under their head to achieve a neutral supine position were classified as having accentuated kyphosis. Analyses were stratified by sex and use of estrogen therapy (ET). Odds of accentuated kyphosis were calculated for each standard deviation increase in log-transformed BTM. Mean age was 75 years. Overall, 51% of 341 non-ET using women, 41% of 111 ET-using women, and 75% of 308 men had accentuated kyphosis. In adjusted models, higher P1NP and NTX were associated with decreased odds of accentuated kyphosis in non-ET using women (P1NP: OR = 0.78 [95% CI, 0.58-0.92]; NTX: OR = 0.68 [95% CI, 0.54-0.86]), but not in men or ET-using women ( p  > 0.05). The selective association of higher bone turnover with reduced odds of accentuated kyphosis in non-ET using women suggests that elevated BTM were associated with a lower likelihood of hyperkyphosis only in the low estrogen/high BTM environment characteristic of postmenopausal women who are not using ET.

Predictive implications of bone turnover markers after palliative treatment with 186Re-HEDP in hormone-refractory prostate cancer patients with painful osseous metastases

International Nuclear Information System (INIS)

Zafeirakis, Athanasios; Papatheodorou, Georgios; Arhontakis, Athanasios; Gouliamos, Athanasios; Vlahos, Lambros; Limouris, Georgios S.

2010-01-01

To prospectively evaluate the predictive value of various bone formation and resorption markers in patients with bone metastases from prostate cancer after palliative treatment with 186 Re-1,1-hydroxyethylidene diphosphonate ( 186 Re-HEDP). Included in the study were 36 men with prostate cancer, suffering from painful osseous metastases and treated with 186 Re-HEDP. None had received any treatment that would have interfered with bone metabolism before 186 Re-HEDP treatment or throughout the follow-up period. For each patient, pretreatment and posttreatment serum levels of osteocalcin (OC), bone alkaline phosphatase (BALP), aminoterminal (PINP) and carboxyterminal (PICP) propeptides of type I collagen, amino-terminal (NTx) and carboxyterminal (CTx) telopeptides of type I collagen and their combinations were compared with the level and duration of pain response to radionuclide treatment. Pain response was correlated only with pretreatment ΝΤx/PINP, PICP/PINP and NTx/CTx ratios and posttreatment decrease in baseline NTx and PICP values (p=0.0025-0.035). According to multivariate and ROC analyses, the best marker-derived predictors of better and longer duration of response to 186 Re-HEDP treatment were a posttreatment decrease in NTx of ≥20% (RR=3.44, p=0.0005) and a pretreatment NTx/PINP ratio of ≥1.2 (RR=3.04, p=0.036) NTx, a potent collagenous marker of bone resorption, along with the novel NTx/PINP ratio provide useful cut-off values for identifying a group of patients suffering from painful osseous metastases from hormone-refractory prostatic carcinoma who do not respond to palliative treatment with 186 Re-HEDP. This information could help avoid an inefficient and expensive radionuclide treatment. Also, in the cohort of patients who will eventually undergo such treatment, the medium-term posttreatment changes in NTx offer valuable predictive information regarding long-term palliative response. (orig.)

Prospective assessment of bone turnover and clinical bone diseases after allogeneic hematopoietic stem-cell transplantation.

Science.gov (United States)

Petropoulou, Anna D; Porcher, Raphael; Herr, Andrée-Laure; Devergie, Agnès; Brentano, Thomas Funck; Ribaud, Patricia; Pinto, Fernando O; Rocha, Vanderson; Peffault de Latour, Régis; Orcel, Philippe; Socié, Gérard; Robin, Marie

2010-06-15

Bone complications after hematopoietic stem-cell transplantation (HSCT) are relatively frequent. Evaluation of biomarkers of bone turnover and dual energy x-ray absorptiometry (DEXA) are not known in this context. We prospectively evaluated bone mineral density, biomarkers of bone turnover, and the cumulative incidence of bone complications after allogeneic HSCT. One hundred forty-six patients were included. Bone mineral density was measured by DEXA 2-month and 1-year post-HSCT. The markers of bone turnover were serum C-telopeptide (C-TP), 5 tartrate-resistant acid phosphatase (bone resorption), and osteocalcin (bone formation) determined pre-HSCT and 2 months and 1 year thereafter. Potential association between osteoporosis at 2 months, osteoporotic fracture or avascular necrosis and, individual patient's characteristics and biologic markers were tested. C-TP was high before and 2 months after transplant. At 2 months, DEXA detected osteoporosis in more than half the patients tested. Male sex, median age less than or equal to 15 years, and abnormal C-TP before HSCT were risk factors significantly associated with osteoporosis. Three-year cumulative incidences of fractures and avascular necrosis were 8% and 11%, respectively. Children were at higher risk of fracture, whereas corticosteroid treatment duration was a significant risk factor for developing a clinical bone complication post-HSCT. Bone complications and osteoporosis are frequent after HSCT. Bone biologic markers and DEXA showed that subclinical bone abnormalities appeared early post-HSCT. The risk factors, age, gender, and C-TP easily available at the time of transplantation were identified. Biphosphonates should probably be given to patients with those risk factors.

Associations of total, dairy, and meat protein with markers for bone turnover in healthy, prepubertal boys

DEFF Research Database (Denmark)

Budek, Alicja Zofia; Hoppe, Camilla; Michaelsen, Kim Fleischer

2007-01-01

intake was estimated from a 3-d weighed food record. sIGF-I and its binding protein-3 were assessed (immunoassay) in a subgroup of 56 boys. All statistical models included effects of age, BMI, and energy intake. Dairy protein was negatively associated with sOC (P ¼ 0.05) but not significantly associated......We previously reported that high intake of milk, but not meat, equal in protein content, increased serum insulin-like growth factor-I (sIGF-I) in prepubertal boys. sIGF-I plays a key role in bone metabolism. Therefore, the aim of this cross-sectional study was to investigate associations of total.......04) but not significantly associated with sOC and sCTX. Free sIGF-I was positively associated with total (P , 0.01) and dairy (P ¼ 0.06) protein but not with meat protein. Our results indicate that dairy and meat protein may exhibit a distinct regulatory effect on different markers for bone turnover. Future studies should...

Oxidative Criteria And Somebone Turnover Markers In Beta ...

African Journals Online (AJOL)

Bone disease in beta-thalassemic patients has multifactorial etiology; increased iron stores and per-oxidative stress are involved factors. This study aimed to investigate the relationship between some bone turnover markers and some oxidants, antioxidants parameters of betathalassemic patients. The study included 50 ...

Bone marrow-derived mesenchymal stem cells express the pericyte marker 3G5 in culture and show enhanced chondrogenesis in hypoxic conditions.

Science.gov (United States)

Khan, Wasim S; Adesida, Adetola B; Tew, Simon R; Lowe, Emma T; Hardingham, Timothy E

2010-06-01

Bone marrow-derived mesenchymal stem cells are a potential source of cells for the repair of articular cartilage defects. Hypoxia has been shown to improve chondrogenesis in some cells. In this study, bone marrow-derived stem cells were characterized and the effects of hypoxia on chondrogenesis investigated. Adherent bone marrow colony-forming cells were characterized for stem cell surface epitopes, and then cultured as cell aggregates in chondrogenic medium under normoxic (20% oxygen) or hypoxic (5% oxygen) conditions. The cells stained strongly for markers of adult mesenchymal stem cells, and a high number of cells were also positive for the pericyte marker 3G5. The cells showed a chondrogenic response in cell aggregate cultures and, in lowered oxygen, there was increased matrix accumulation of proteoglycan, but less cell proliferation. In hypoxia, there was increased expression of key transcription factor SOX6, and of collagens II and XI, and aggrecan. Pericytes are a candidate stem cell in many tissue, and our results show that bone marrow-derived mesenchymal stem cells express the pericyte marker 3G5. The response to chondrogenic culture in these cells was enhanced by lowered oxygen tension. This has important implications for tissue engineering applications of bone marrow-derived stem cells. (c) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Predictive implications of bone turnover markers after palliative treatment with {sup 186}Re-HEDP in hormone-refractory prostate cancer patients with painful osseous metastases

Energy Technology Data Exchange (ETDEWEB)

Zafeirakis, Athanasios [401 Army Hospital of Athens, Department of Nuclear Medicine, Athens (Greece); Papatheodorou, Georgios [401 Army Hospital of Athens, Clinical Research Unit, Athens (Greece); Arhontakis, Athanasios [401 Army Hospital of Athens, Department of Urology, Athens (Greece); Gouliamos, Athanasios; Vlahos, Lambros [Aretaieion University Hospital, Athens Medical School, Department of Radiology, Athens (Greece); Limouris, Georgios S. [Aretaieion University Hospital, Athens Medical School, Department of Nuclear Medicine, Athens (Greece)

2010-01-15

To prospectively evaluate the predictive value of various bone formation and resorption markers in patients with bone metastases from prostate cancer after palliative treatment with {sup 186}Re-1,1-hydroxyethylidene diphosphonate ({sup 186}Re-HEDP). Included in the study were 36 men with prostate cancer, suffering from painful osseous metastases and treated with {sup 186}Re-HEDP. None had received any treatment that would have interfered with bone metabolism before {sup 186}Re-HEDP treatment or throughout the follow-up period. For each patient, pretreatment and posttreatment serum levels of osteocalcin (OC), bone alkaline phosphatase (BALP), aminoterminal (PINP) and carboxyterminal (PICP) propeptides of type I collagen, amino-terminal (NTx) and carboxyterminal (CTx) telopeptides of type I collagen and their combinations were compared with the level and duration of pain response to radionuclide treatment. Pain response was correlated only with pretreatment {nu}{tau}x/PINP, PICP/PINP and NTx/CTx ratios and posttreatment decrease in baseline NTx and PICP values (p=0.0025-0.035). According to multivariate and ROC analyses, the best marker-derived predictors of better and longer duration of response to {sup 186}Re-HEDP treatment were a posttreatment decrease in NTx of {>=}20% (RR=3.44, p=0.0005) and a pretreatment NTx/PINP ratio of {>=}1.2 (RR=3.04, p=0.036) NTx, a potent collagenous marker of bone resorption, along with the novel NTx/PINP ratio provide useful cut-off values for identifying a group of patients suffering from painful osseous metastases from hormone-refractory prostatic carcinoma who do not respond to palliative treatment with {sup 186}Re-HEDP. This information could help avoid an inefficient and expensive radionuclide treatment. Also, in the cohort of patients who will eventually undergo such treatment, the medium-term posttreatment changes in NTx offer valuable predictive information regarding long-term palliative response. (orig.)

Biochemical relationships between bone turnover markers and blood glucose in patients with type 2 diabetes mellitus.

Science.gov (United States)

Hussein, Rasha M

2017-11-01

Patients with type 2 diabetes mellitus develop many complications including osteopenia, which is associated with high fracture risk. Osteocalcin is a non collagenous protein derived from the osteoblasts. Recently, it was found that osteocalcin enhances the pancreatic beta cell proliferation, insulin secretion and protection against type 2 diabetes. Investigation of the association of serum osteocalcin and other bone turnover markers with blood glucose level and diabetes mellitus duration in type 2 diabetic patients. Twenty diagnosed type 2 diabetic patients together with 20 healthy controls were enrolled in this study. Serum osteocalcin, alkaline phosphatase activity and calcium concentrations were measured by commercial ELISA kits. The results showed that type 2 diabetic patients exhibited a significantly lower serum osteocalcin and calcium (p=0.0001 and 0.002 respectively) and a higher alkaline phosphatase (p=0.008) compared to the controls. Multiple linear regression analysis revealed that serum osteocalcin was inversely associated with fasting blood glucose and Diabetes Mellitus duration (β=- 0.018; p=0.007 and β=- 0.085; p=0.014 respectively) in Type 2 diabetic patients. In addition, alkaline phosphatase was positively associated (β=0.828; p=0.015) while serum calcium was negatively associated (β=- 0.046; p=0.048) with Diabetes Mellitus duration. These results refer to the strong association between diabetes and bone turnover markers and call for monitoring of diabetes-associated osteopenia in type 2 diabetic patients. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Calcium and Bone Turnover Markers in Acromegaly: A Prospective, Controlled Study.

Science.gov (United States)

Constantin, Tina; Tangpricha, Vin; Shah, Reshma; Oyesiku, Nelson M; Ioachimescu, Octavian C; Ritchie, James; Ioachimescu, Adriana G

2017-07-01

Acromegaly has been associated with calcium-phosphate and bone turnover alterations. Controlled studies of these interactions are sparse. To evaluate calcium and bone metabolism in active and treated acromegaly. We conducted a controlled, prospective study at a tertiary referral center. We studied 22 patients with acromegaly referred for surgical or medical therapy (ACM) and 22 with nonfunctioning pituitary adenomas referred for surgery (control). Calcium (serum and urine), phosphorus, parathyroid hormone (PTH), 25-hydroxy- and 1,25-dihydroxy-vitamin D, bone turnover markers [serum C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP)], and cytokines [receptor activator of nuclear factor κB ligand (RANK-L) and osteoprotegerin (OPG)] at baseline and 3 to 6 months after treatment. At baseline, the ACM group had lower PTH levels than controls (36.3 ± 13.9 pg/mL vs 56.0 ± 19.9 pg/mL) and higher phosphorus (4.34 ± 0.71 mg/dL vs 3.55 ± 0.50 mg/dL) (P acromegaly, serum calcium (9.52 ± 0.43 mg/dL to 9.26 ± 0.28 mg/dL), phosphorus (4.34 ± 0.71 mg/dL to 3.90 ± 0.80 mg/dL), and CTX (0.91 ± 0.75 ng/mL to 0.63 ± 0.68 ng/mL) decreased, while PTH increased (36.3 ± 13.9 pg/mL to 48.9 ± 16.7 pg/mL) (P Acromegaly patients exhibited PTH-independent calcium-phosphate alterations and enhanced coupled bone formation and resorption. Within 6 months of treatment, bone resorption decreased, whereas RANK-L/OPG changes were inconsistent. Copyright © 2017 Endocrine Society

Effects on bone metabolism markers and arterial stiffness by switching to rivaroxaban from warfarin in patients with atrial fibrillation.

Science.gov (United States)

Namba, Sayaka; Yamaoka-Tojo, Minako; Kakizaki, Ryota; Nemoto, Teruyoshi; Fujiyoshi, Kazuhiro; Hashikata, Takehiro; Kitasato, Lisa; Hashimoto, Takuya; Kameda, Ryo; Meguro, Kentaro; Shimohama, Takao; Tojo, Taiki; Ako, Junya

2017-08-01

In recent years, direct oral anticoagulants (DOACs) of dabigatran, rivaroxaban, apixaban, edoxaban, which are all alternatives to warfarin, have been released. The use of DOACs is becoming more widespread in the clinical management of thrombotic stroke risk in patients with atrial fibrillation (AF). In large-scale clinical trials of each drug, DOACs were reported to inhibit intracranial hemorrhage, stroke, and death compared to warfarin. Warfarin is an endogenous vitamin K antagonist; therefore, patients who are taking warfarin must be prohibited from taking vitamin K. Vitamin K is an essential cofactor required for the ɤ-carboxylation of vitamin K-dependent proteins including coagulation factors, osteocalcin (OC), matrix Gla protein (MGP), and the growth arrest-specific 6 (GAS6). OC is a key factor for bone matrix formation. MGP is a local inhibitor of soft tissue calcification in the vessel wall. GAS6 prevents the apoptosis of vascular smooth muscle cells. Therefore, decrease of blood vitamin K levels may cause osteoporosis, vascular calcification, and the inhibition of vessels angiogenesis. This study aimed to evaluate the effects of changing from warfarin to rivaroxaban on bone mineral metabolism, vascular calcification, and vascular endothelial dysfunction. We studied 21 consecutive patients with persistent or chronic AF, who were treated with warfarin at least for 12 months. Warfarin administration was changed to rivaroxaban (10 or 15 mg/day) in all patients. Osteopontin (OPN), bone alkaline phosphatase (BAP), and under-carboxylated osteocalcin (ucOC) were measured. Pulse wave velocity (PWV) and augmentation index (AI) were also measured as atherosclerosis assessments. All measurements were done before and six months after the rivaroxaban treatment. There was a significant increase in serum level of BAP compared to baseline (12.5 ± 4.6 to 13.4 ± 4.1 U/L, P warfarin in patients with atrial fibrillation was associated with an increase of bone

Suppressed bone remodeling in black bears conserves energy and bone mass during hibernation.

Science.gov (United States)

McGee-Lawrence, Meghan; Buckendahl, Patricia; Carpenter, Caren; Henriksen, Kim; Vaughan, Michael; Donahue, Seth

2015-07-01

Decreased physical activity in mammals increases bone turnover and uncouples bone formation from bone resorption, leading to hypercalcemia, hypercalcuria, bone loss and increased fracture risk. Black bears, however, are physically inactive for up to 6 months annually during hibernation without losing cortical or trabecular bone mass. Bears have been shown to preserve trabecular bone volume and architectural parameters and cortical bone strength, porosity and geometrical properties during hibernation. The mechanisms that prevent disuse osteoporosis in bears are unclear as previous studies using histological and serum markers of bone remodeling show conflicting results. However, previous studies used serum markers of bone remodeling that are known to accumulate with decreased renal function, which bears have during hibernation. Therefore, we measured serum bone remodeling markers (BSALP and TRACP) that do not accumulate with decreased renal function, in addition to the concentrations of serum calcium and hormones involved in regulating bone remodeling in hibernating and active bears. Bone resorption and formation markers were decreased during hibernation compared with when bears were physically active, and these findings were supported by histomorphometric analyses of bone biopsies. The serum concentration of cocaine and amphetamine regulated transcript (CART), a hormone known to reduce bone resorption, was 15-fold higher during hibernation. Serum calcium concentration was unchanged between hibernation and non-hibernation seasons. Suppressed and balanced bone resorption and formation in hibernating bears contributes to energy conservation, eucalcemia and the preservation of bone mass and strength, allowing bears to survive prolonged periods of extreme environmental conditions, nutritional deprivation and anuria. © 2015. Published by The Company of Biologists Ltd.

The effect of cholecalciferol and calcitriol on biochemical bone markers in HIV type 1-infected males: results of a clinical trial.

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Bang, Ulrich Christian; Kolte, Lilian; Hitz, Mette; Schierbeck, Louise Lind; Nielsen, Susanne Dam; Benfield, Thomas; Jensen, Jens-Erik Beck

2013-04-01

HIV-1-infected patients have an increased risk of osteoporosis and fractures. The main objective of this study was to evaluate the bone metabolism in HIV-1-infected patients exposed to calcitriol and cholecalciferol. We also investigated the relationship between T cells and bone markers. We conducted a placebo-controlled randomized study running for 16 weeks including 61 HIV-1-infected males, of whom 51 completed the protocol. Nineteen participants were randomized to daily treatment with (A) 0.5-1.0 μg calcitriol and 1,200 IU (30 μg) cholecalciferol, 17 participants to (B) 1,200 IU cholecalciferol, and 15 participants to (C) placebo. At baseline and after 16 weeks, we determined collagen type 1 trimeric cross-linked peptide (CTx), procollagen type 1 N-terminal peptide (P1NP), parathyroid hormone (PTH), ionized calcium, 25-hydroxyvitamin D (25OHD), and 1,25-dihydroxyvitamin D [1,25(OH)2D]. We determined naive CD4(+) and CD8(+), activated CD4(+) and CD8(+), and regulatory CD4(+)CD25(+)CD127(low) T lymphocytes. Baseline levels of P1NP and CTx correlated (coefficient 0.5, p<0.001) with each other but not with PTH, 25OHD, or 1,25(OH)2D. In patients receiving calcitriol and cholecalciferol, the mean levels of P1NP (p<0.001) and CTx (p= 0.002) declined significantly compared to our placebo group. Based on changes in P1NP and CTx, we estimated that net bone formation occurred more frequently in group A compared to groups B and C. PTH correlated inversely with naive CD4(+) and CD8(+) cells. Otherwise, no relationships between bone markers and T lymphocytes were demonstrated. Supplementation with calcitriol and cholecalciferol induced biochemical indications of bone formation in HIV-1 patients.

Dosing related effects of zoledronic acid on bone markers and creatinine clearance in patients with multiple myeloma and metastatic breast cancer

DEFF Research Database (Denmark)

Søe, Kent; Delaissé, Jean-Marie; Jakobsen, Erik H

2014-01-01

phase II clinical trial we investigated the effect of Zol treatment on the serum levels of the bone markers collagen type 1 cross-linked C-telopeptide (CTX) and bone specific alkaline phosphatase (bALP) as well as on creatinine clearance (kidney function) in response to dosing and duration of treatment...

Gene expression markers in circulating tumor cells may predict bone metastasis and response to hormonal treatment in breast cancer.

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Wang, Haiying; Molina, Julian; Jiang, John; Ferber, Matthew; Pruthi, Sandhya; Jatkoe, Timothy; Derecho, Carlo; Rajpurohit, Yashoda; Zheng, Jian; Wang, Yixin

2013-11-01

Circulating tumor cells (CTCs) have recently attracted attention due to their potential as prognostic and predictive markers for the clinical management of metastatic breast cancer patients. The isolation of CTCs from patients may enable the molecular characterization of these cells, which may help establish a minimally invasive assay for the prediction of metastasis and further optimization of treatment. Molecular markers of proven clinical value may therefore be useful in predicting disease aggressiveness and response to treatment. In our earlier study, we identified a gene signature in breast cancer that appears to be significantly associated with bone metastasis. Among the genes that constitute this signature, trefoil factor 1 (TFF1) was identified as the most differentially expressed gene associated with bone metastasis. In this study, we investigated 25 candidate gene markers in the CTCs of metastatic breast cancer patients with different metastatic sites. The panel of the 25 markers was investigated in 80 baseline samples (first blood draw of CTCs) and 30 follow-up samples. In addition, 40 healthy blood donors (HBDs) were analyzed as controls. The assay was performed using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) with RNA extracted from CTCs captured by the CellSearch system. Our study indicated that 12 of the genes were uniquely expressed in CTCs and 10 were highly expressed in the CTCs obtained from patients compared to those obtained from HBDs. Among these genes, the expression of keratin 19 was highly correlated with the CTC count. The TFF1 expression in CTCs was a strong predictor of bone metastasis and the patients with a high expression of estrogen receptor β in CTCs exhibited a better response to hormonal treatment. Molecular characterization of these genes in CTCs may provide a better understanding of the mechanism underlying tumor metastasis and identify gene markers in CTCs for predicting disease progression and

Short-term lower-body plyometric training improves whole body BMC, bone metabolic markers, and physical fitness in early pubertal male basketball players.

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Zribi, Anis; Zouch, Mohamed; Chaari, Hamada; Bouajina, Elyes; Ben Nasr, Hela; Zaouali, Monia; Tabka, Zouhair

2014-02-01

The effects of a 9-week lower-body plyometric training program on bone mass, bone markers and physical fitness was examined in 51 early pubertal male basketball players divided randomly into a plyometric group (PG: 25 participants) and a control group (CG: 26 participants). Areal bone mineral density (aBMD), bone mineral content (BMC), and bone area (BA) in the whole body, L2-L4 vertebrae, and in total hip, serum levels of osteocalcin (Oc) and C-terminal telopeptide fragment of Type I collagen (CTx), jump, sprint and power abilities were assessed at baseline and 9 weeks. Group comparisons were done by independent student's t-test between means and analyses of (ANOVA) and covariance (ANCOVA), adjusting for baseline values. PG experienced a significant increase in Oc (p BMC and BA in any measured site, except in whole body BMC of the PG. A positive correlation was observed between percentage increase (Δ%) of physical fitness and those of (Oc) for the PG. In summary, biweekly sessions of lower body plyometric training program were successful for improving whole body BMC, bone formation marker (Oc) and physical fitness in early pubertal male basketball players.

Characterization of an Ex vivo Femoral Head Model Assessed by Markers of Bone and Cartilage Turnover

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Madsen, Suzi Hoegh; Goettrup, Anne Sofie; Thomsen, Gedske; Christensen, Søren Tvorup; Schultz, Nikolaj; Henriksen, Kim; Bay-Jensen, Anne-Christine; Karsdal, Morten Asser

2011-01-01

Objective: The pathophysiology of osteoarthritis involves the whole joint and is characterized by cartilage degradation and altered subchondral bone turnover. At present, there is a need for biological models that allow investigation of the interactions between the key cellular players in bone/cartilage: osteoblasts, osteoclasts, and chondrocytes. Methods: Femoral heads from 3-, 6-, 9-, and 12-week-old female mice were isolated and cultured for 10 days in serum-free media in the absence or presence of IGF-I (100 nM) (anabolic stimulation) or OSM (10 ng/mL) + TNF-α (20 ng/mL) (catabolic stimulation). Histology on femoral heads before and after culture was performed, and the growth plate size was examined to evaluate the effects on cell metabolism. The conditioned medium was examined for biochemical markers of bone and cartilage degradation/formation. Results: Each age group represented a unique system regarding the interest of bone or cartilage metabolism. Stimulation over 10 days with OSM + TNF-α resulted in depletion of proteoglycans from the cartilage surface in all ages. Furthermore, OSM + TNF-α decreased growth plate size, whereas IGF-I increased the size. Measurements from the conditioned media showed that OSM + TNF-α increased the number of osteoclasts by approximately 80% and induced bone and cartilage degradation by approximately 1200% and approximately 2600%, respectively. Stimulation with IGF-I decreased the osteoclast number and increased cartilage formation by approximately 30%. Conclusion: Biochemical markers and histology together showed that the catabolic stimulation induced degradation and the anabolic stimulation induced formation in the femoral heads. We propose that we have established an explant whole-tissue model for investigating cell-cell interactions, reflecting parts of the processes in the pathogenesis of joint degenerative diseases. PMID:26069585

The impact of fish oil and wheat germ oil combination on mineral-bone and inflammatory markers in maintenance hemodialysis patients: a randomized, double-blind, placebo-controlled clinical trial.

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Zakaria, Hadeer; Mostafa, Tarek M; El-Azab, Gamal A; Abd El Wahab, Ahmed M; Elshahawy, Heba; Sayed-Ahmed, Nagy Ah

2017-10-01

This study aimed to examine the impact of combined supplementation of fish oil (FO) with antioxidants like wheat germ oil (WGO) on mineral-bone and inflammatory markers in maintenance HD patients. This randomized, double-blind, placebo-controlled trial involved 46 HD patients who were randomly assigned into two groups to receive daily 3000 mg of FO [1053 mg omega-3 fatty acids (ω-3 FAs)] plus 300 mg of WGO [0.765 mg vitamin E] or placebo for 4 months. Blood concentrations of hemoglobin (Hgb), white blood cells, mineral-bone parameters including serum calcium (Ca), phosphorus, calcium-phosphorus product, parathyroid hormone, alkaline phosphatase, and osteoprotegerin and serum concentrations of inflammatory markers including high-sensitivity C-reactive protein, ferritin, and uric acid were measured before and after the intervention. Eighty-seven percentage of patients in each group completed the study. The mean serum Ca levels increased significantly in the supplemented group at the end of study (p = 0.0016), and this increment was also significant as compared to placebo group (p = 0.0418). No significant alterations were observed in the other measured parameters within each group during the study (as p values were >0.05). FO plus WGO supplementation showed beneficial effect on serum Ca levels of HD patients without any statistically significant effect on other mineral-bone and inflammatory markers. Further investigations are required to confirm it.

Bone density as a marker for local response to radiotherapy of spinal bone metastases in women with breast cancer: a retrospective analysis

International Nuclear Information System (INIS)

Foerster, Robert; Eisele, Christian; Bruckner, Thomas; Bostel, Tilman; Schlampp, Ingmar; Wolf, Robert; Debus, Juergen; Rief, Harald

2015-01-01

We designed this study to quantify the effects of radiotherapy (RT) on bone density as a local response in spinal bone metastases of women with breast cancer and, secondly, to establish bone density as an accurate and reproducible marker for assessment of local response to RT in spinal bone metastases. We retrospectively assessed 135 osteolytic spinal metastases in 115 women with metastatic breast cancer treated at our department between January 2000 and January 2012. Primary endpoint was to compare bone density in the bone metastases before, 3 months after and 6 months after RT. Bone density was measured in Hounsfield units (HU) in computed tomography scans. We calculated mean values in HU and the standard deviation (SD) as a measurement of bone density before, 3 months and 6 months after RT. T-test was used for statistical analysis of difference in bone density as well as for univariate analysis of prognostic factors for difference in bone density 3 and 6 months after RT. Mean bone density was 194.8 HU ± SD 123.0 at baseline. Bone density increased significantly by a mean of 145.8 HU ± SD 139.4 after 3 months (p = .0001) and by 250.3 HU ± SD 147.1 after 6 months (p < .0001). Women receiving bisphosphonates showed a tendency towards higher increase in bone density in the metastases after 3 months (152.6 HU ± SD 141.9 vs. 76.0 HU ± SD 86.1; p = .069) and pathological fractures before RT were associated with a significantly higher increase in bone density after 3 months (202.3 HU ± SD 161.9 vs. 130.3 HU ± SD 129.2; p = .013). Concomitant chemotherapy (ChT) or endocrine therapy (ET), hormone receptor status, performance score, applied overall RT dose and prescription of a surgical corset did not correlate with a difference in bone density after RT. Bone density measurement in HU is a practicable and reproducible method for assessment of local RT response in osteolytic metastases in breast cancer. Our analysis demonstrated an excellent local response within

Disrupted Bone Metabolism in Long-Term Bedridden Patients.

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Eimori, Keiko; Endo, Naoto; Uchiyama, Seiji; Takahashi, Yoshinori; Kawashima, Hiroyuki; Watanabe, Kei

2016-01-01

Bedridden patients are at risk of osteoporosis and fractures, although the long-term bone metabolic processes in these patients are poorly understood. Therefore, we aimed to determine how long-term bed confinement affects bone metabolism. This study included 36 patients who had been bedridden from birth due to severe immobility. Bone mineral density and bone metabolism markers were compared to the bedridden period in all study patients. Changes in the bone metabolism markers during a follow-up of 12 years were studied in 17 patients aged bedridden period. During the follow-up, osteocalcin and parathyroid hormone were decreased, and the 25(OH) vitamin D was increased. NTX at baseline was negatively associated with bone mineral density after 12 years. Unique bone metabolic abnormalities were found in patients who had been bedridden for long periods, and these metabolic abnormalities were altered by further bed confinement. Appropriate treatment based on the unique bone metabolic changes may be important in long-term bedridden patients.

Marcadores séricos do metabolismo ósseo no hipertireoidismo felino Serum markers of bone metabolism in feline hyperthyroidism

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Mauro José Lahm Cardoso

2008-08-01

Full Text Available Os efeitos do hipertireoidismo experimental (150mg kg-1 d-1 42d-1 de levotiroxina sobre os marcadores do metabolismo ósseo foi estudado em 14 gatos sem raça definida, nove fêmeas e cinco machos, não-castrados, com idade entre um e três anos. As variáveis estudadas foram tiroxina total (T4, tiroxina livre (FT4 e o telopeptídeo carboxiterminal do colágeno tipo I (ICTP mensurados por radioimunoensaio, a osteocalcina (OC foi mensurada por ensaio radioimunométrico e a densidade mineral óssea (DMO foi mensurada pela técnica da densitometria óptica. As concentrações séricas da OC apresentaram diferença significativa (PThe effect of experimental hyperthyroidism (150mg kg-1 d-1 42d-1 levothyroxine on markers of bone metabolism was studied in fourteen shorthair intact cats, nine females and five males, from 1 to 3 years of age. Total thyroxine (T4, free thyroxine (FT4, carboxi-terminal telopeptides of collagen type I (ICTP (measured by radioimmunoassay, osteocalcin (OC (measured by immunoradiometric assay and bone mineral density (DMO (measured by the optic densitometria were evaluated. Serum concentrations of OC were significantly different (P<0.05 between all four moments (before the induction, 14, 28 and 42 days. The DMO presented significant difference (P<0.05 at the 14 days in comparison to the initial moment. Bone remodeling was probably caused by the hyperthyroid state, since both OC and ICTP presented strong positive correlation with TT4 and a little lowerth FT4. The FT4 concentrations did not present positive correlation with ICTP, except at 28 days. Correlation between markers of bone metabolism and the bone mineral density was low in all the moments. High correlation was observed between thyroid hormones and markers of bone metabolism. In conclusion, this excess of thyroid hormones in cats may cause an increase of bone remodeling. Moreover, thyrotoxicosis in this study was not enough to raise the serum levels of ICTP, suggesting

In long-term bedridden elderly patients with dietary copper deficiency, biochemical markers of bone resorption are increased with copper supplementation during 12 weeks.

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Kawada, Etsuo; Moridaira, Kazuaki; Itoh, Katsuhiko; Hoshino, Ayami; Tamura, Jun'ichi; Morita, Toyoho

2006-01-01

Although the effect of copper on bone has been tested in animals and healthy subjects, no studies concerning the effect of copper supplementation on bone metabolism in patients with copper deficiency have been reported because of the rarity of these patients. This study was conducted to investigate the effect of copper supplementation on bone metabolism in copper-deficient patients. This study included 10 patients (83.7 +/- 8.3 years) with dietary copper deficiency under long-term bed rest for more than 12 months. They had their diets supplemented with copper sulfate (3 mg/day) over 12 weeks in addition to their diet of only one kind of enteral food with a low concentration of copper. Serum copper and ceruloplasmin, urinary deoxypyridinoline (DPD) and collagen-type 1 N-telopeptide (NTX) (biomarkers of bone resorption), serum osteocalcin (OC) and bone-specific alkaline phosphatase (Bone ALP) (biomarkers of bone formation) were analyzed at baseline, 4 and 12 weeks after copper supplementation. DPD and NTX excretion were significantly increased 4 weeks after copper supplementation (p = 0.009 and p = 0.013, respectively). Serum bone ALP and OC were not significantly changed 12 weeks after copper supplementation (p = 0.051 and p = 0.594). In patients with nutritional copper deficiency, bone resorption markers are increased with copper supplementation. Copyright (c) 2006 S. Karger AG, Basel.

[The effects of oxygen partial pressure changes on the osteometric markers of the bone tissue in rats].

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Berezovs'kyĭ, V Ia; Zamors'ka, T M; Ianko, R V

2013-01-01

Our purpose was to investigate the oxygen partial pressure changes on the osteometric and biochemical markers of bone tissue in rats. It was shown that breathing of altered gas mixture did not change the mass, general length, sagittal diameter and density thigh-bones in 12-month Wistar male-rats. The dosed normobaric hypoxia increased the activity of alkaline phosphatase and decreased the activity of tartrate-resistant acid phosphatase. At the same time normobaric hyperoxia with 40 and 90% oxygen conversely decreased the activity of alkaline phosphatase and increased the activity of tartrate-resistant acid phosphatase.

Pegvisomant-induced serum insulin-like growth factor-I normalization in patients with acromegaly returns elevated markers of bone turnover to normal

DEFF Research Database (Denmark)

Parkinson, C; Kassem, M; Heickendorff, Lene

2003-01-01

Active acromegaly is associated with increased biochemical markers of bone turnover. Pegvisomant is a GH receptor antagonist that normalizes serum IGF-I in 97% of patients with active acromegaly. We evaluated the effects of pegvisomant-induced serum IGF-I normalization on biochemical markers...... of bone and soft tissue turnover, as well as levels of PTH and vitamin D metabolites, in 16 patients (nine males; median age, 52 yr; range, 28-78 yr) with active acromegaly (serum IGF-I at least 30% above upper limit of an age-related reference range). Serum procollagen III amino-terminal propeptide...... (PIIINP) and type I procollagen amino-terminal propeptide, osteocalcin (OC), bone-related alkaline phosphatase, C-terminal cross-linked telopeptide of type I collagen (CTx), albumin-corrected calcium, intact PTH, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D [1,25-(OH)(2) vit D], urinary type 1 collagen...

Role of Galectin-3 in Bone Cell Differentiation, Bone Pathophysiology and Vascular Osteogenesis

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Carla Iacobini

2017-11-01

Full Text Available Galectin-3 is expressed in various tissues, including the bone, where it is considered a marker of chondrogenic and osteogenic cell lineages. Galectin-3 protein was found to be increased in the differentiated chondrocytes of the metaphyseal plate cartilage, where it favors chondrocyte survival and cartilage matrix mineralization. It was also shown to be highly expressed in differentiating osteoblasts and osteoclasts, in concomitance with expression of osteogenic markers and Runt-related transcription factor 2 and with the appearance of a mature phenotype. Galectin-3 is expressed also by osteocytes, though its function in these cells has not been fully elucidated. The effects of galectin-3 on bone cells were also investigated in galectin-3 null mice, further supporting its role in all stages of bone biology, from development to remodeling. Galectin-3 was also shown to act as a receptor for advanced glycation endproducts, which have been implicated in age-dependent and diabetes-associated bone fragility. Moreover, its regulatory role in inflammatory bone and joint disorders entitles galectin-3 as a possible therapeutic target. Finally, galectin-3 capacity to commit mesenchymal stem cells to the osteoblastic lineage and to favor transdifferentiation of vascular smooth muscle cells into an osteoblast-like phenotype open a new area of interest in bone and vascular pathologies.

Disrupted Bone Metabolism in Long-Term Bedridden Patients.

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Keiko Eimori

Full Text Available Bedridden patients are at risk of osteoporosis and fractures, although the long-term bone metabolic processes in these patients are poorly understood. Therefore, we aimed to determine how long-term bed confinement affects bone metabolism.This study included 36 patients who had been bedridden from birth due to severe immobility. Bone mineral density and bone metabolism markers were compared to the bedridden period in all study patients. Changes in the bone metabolism markers during a follow-up of 12 years were studied in 17 patients aged <30 years at baseline.The bone mineral density was reduced (0.58±0.19 g/cm3, and the osteocalcin (13.9±12.4 ng/mL and urine N-terminal telopeptide (NTX levels (146.9±134.0 mM BCE/mM creatinine were greater than the cutoff value for predicting fracture. Among the bone metabolism markers studied, osteocalcin and NTX were negatively associated with the bedridden period. During the follow-up, osteocalcin and parathyroid hormone were decreased, and the 25(OH vitamin D was increased. NTX at baseline was negatively associated with bone mineral density after 12 years.Unique bone metabolic abnormalities were found in patients who had been bedridden for long periods, and these metabolic abnormalities were altered by further bed confinement. Appropriate treatment based on the unique bone metabolic changes may be important in long-term bedridden patients.

AGE-RELATED FEATURES OF PERIPHERAL BLOOD MARKERS IN CHILDREN AND YOUNG ADULTS WITH NORMAL AND PATHOLOGICAL REMODELING OF BONE TISSUE

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M. V. Dvornichenko

2016-01-01

Full Text Available Activities of total alkaline phosphatase (TALP and its bone isoform (BALP was greater in groups of children and adolescents in the late posttraumatic period (pattern of reparative bone remodeling and scoliosis (pathological bone remodeling, than in the control (healthy children and adolescents. The content of collagen type I degradation products (CrossLaps peripheral blood practically was unchanged. Examined group with posttraumatic period had high activity of tartrate-resistant acid phosphatase form (TRACP. TALP activity reached minimum values in all the studied groups. In the process of children growing to 15–18 years old, as compared to 7–10 years old, reducing activity of remodeling was observed under physiological (healthy donors and reparative osteogenesis. It’s changes was recorded by significant decrease of the studied indicators. On the contrary, children 15–18 years old with scoliosis had maximum of the imbalance (activation/inhibition of various signs of osteogenesis of resorptive/synthetic bone processes. Also, for this group we discovered decrease osteocalcin concentration of 4 times in comparison with the group children of 7–10 years old. The detected growth of the correlations number in the correlation matrix of bone remodeling markers in case of scoliosis proposes the reduction of adaptation reserve of 15–18 years old adolescents, suffering from dysplasia of connective tissue. Thus, the pathophysiological and clinical significance of distant markers of bone metabolism screening in peripheral blood the is ambiguous. The interpretation of these indicators is difficult and largely depends on the clinical situation and age of patients. This requires improving the diagnostic approach to assess physiological and pathological remodeling of bone tissue by means of biochemical blood indicators. 

Osteoporosis and Osteopathy Markers in Patients with Mastocytosis

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Nilüfer Alpay Kanıtez

2015-03-01

Full Text Available OBJECTIVE: Osteoporosis, osteosclerosis, and lytic bone lesions have been observed in patients with systemic mastocytosis (SM. We examined bone mineral density (BMD biochemical turnover markers and serum tryptase levels in SM, which is considered a rare disease. METHODS: Seventeen adult patients (5 females, 12 males; median age: 33 years, range: 20-64 with mastocytosis were included in this study. We investigated the value of quantitative ultrasound (QUS of the calcaneus in the assessment of BMD in SM patients, as well as BMD of the lumbar spine (L1-L4, femoral neck, and distal radius using dual energy x-ray absorptiometry (DXA and plasma tryptase levels, biochemical markers of bone turnover. RESULTS: At lumbar spine L1-L4, the femoral neck, and the distal radius or as calcaneus stiffness, 12 of 17 patients had T-scores of less than -1 at least at 1 site, reflecting osteopenia. Three of 17 patients had T-scores showing osteoporosis (T-score <-2.5. There was no relationship between DXA and bone lesion severity. We also found a significant positive correlation between tryptase levels and disease severity, as well as between disease severity and pyridinoline (p<0.01 by Spearman’s test. CONCLUSION: DXA and calcaneal QUS may not be appropriate techniques to assess bone involvement in SM patients because of the effects of osteosclerosis. This study further shows that the osteoclastic marker pyridinoline is helpful in patients with severe disease activity and sclerotic bone lesions to show bone demineralization.

Effect of phylloquinone supplementation on biochemical markers of vitamin K status and bone turnover in postmenopausal women

DEFF Research Database (Denmark)

Bugel, Susanne; Sorensen, A. Dorthe; Hels, Ole

2007-01-01

While current intakes of phylloquinone (vitamin K-1) in many populations are believed to be sufficient to maintain normal blood coagulation, these may be insufficient to cover the requirements for optimal bone metabolism. Therefore, the objective of the present study was to investigate the effect...... of increasing phylloquinone intakes above the usual dietary intake for 6 weeks on biochemical markers of vitamin K status and bone turnover in postmenopausal women. Thirty-one postmenopausal women completed this 3 X 6-week randomised cross-over study, in which volunteers were supplemented with 0 (placebo), 200......, pyridinoline and deoxypyridinoline) and urinary gamma-carboxyglutarnate were unaffected by phylloquinone supplementation. In conclusion, while daily supplementation with 200 and 500 mu g phylloquinone/d for 6 weeks increased vitamin K status in postmenopausal women, it had no effect on bone turnover....

Giant cells around bone biomaterials: Osteoclasts or multi-nucleated giant cells?

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Miron, Richard J; Zohdi, Hamoon; Fujioka-Kobayashi, Masako; Bosshardt, Dieter D

2016-12-01

Recently accumulating evidence has put into question the role of large multinucleated giant cells (MNGCs) around bone biomaterials. While cells derived from the monocyte/macrophage lineage are one of the first cell types in contact with implanted biomaterials, it was originally thought that specifically in bone tissues, all giant cells were bone-resorbing osteoclasts whereas foreign body giant cells (FBGCs) were found associated with a connective tissue foreign body reaction resulting in fibrous encapsulation and/or material rejection. Despite the great majority of bone grafting materials routinely found with large osteoclasts, a special subclass of bone biomaterials has more recently been found surrounded by large giant cells virtually incapable of resorbing bone grafts even years after their implantation. While original hypotheses believed that a 'foreign body reaction' may be taking place, histological data retrieved from human samples years after their implantation have put these original hypotheses into question by demonstrating better and more stable long-term bone volume around certain bone grafts. Exactly how or why this 'special' subclass of giant cells is capable of maintaining long-term bone volume, or methods to scientifically distinguish them from osteoclasts remains extremely poorly studied. The aim of this review article was to gather the current available literature on giant cell markers and differences in expression patterns between osteoclasts and MNGCs utilizing 19 specific markers including an array of CD-cell surface markers. Furthermore, the concept of now distinguishing between pro-inflammatory M1-MNGCs (previously referred to as FBGCs) as well as wound-healing M2-MNGCs is introduced and discussed. This review article presents 19 specific cell-surface markers to distinguish between osteoclasts and MNGCs including an array of CD-cell surface markers. Furthermore, the concept of now distinguishing between pro-inflammatory M1-MNGCs (often

The effect of short-term low-energy ultraviolet B irradiation on bone mineral density and bone turnover markers in postmenopausal women with osteoporosis: A randomized single-blinded controlled clinical trial

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Micić Ivan

2013-01-01

Full Text Available Introduction. The importance of vitamin D on bone health and osteoporosis was studied by many researchers. The main role of the Vitamin D is to absorb calcium and phosphate and increase bone mineralization. Older people are at an increased risk of the inadequate vitamin D production in the skin because of lower sun exposure and reduced ability of the skin to synthesize vitamin D. Objective. The aim of this clinical trial was to evaluate the efficacy and tolerability of short-term (2 weeks low energy UVB irradiation in postmenopausal women with osteoporosis using bone mineral density and bone turnover markers. Methods. A three-month, single-blinded, randomized, placebo-controlled clinical trial was conducted at the University hospital in Daegu, Republic of Korea. Fifty-two postmenopausal Korean women (older than 65 years with osteoporosis were randomly allocated to have either low energy UVB or placebo for 30 minutes a day for two weeks of treatment during winter. Laboratory analysis and physical examination before and 4, 8 and 12 weeks after treatment were carried out and BMD was measured before and 8 and 12 weeks after treatment. The effects of time and treatment interaction between these two groups were evaluated by repeated-measure two-factor analysis, and subgroup analysis was performed to examine UVB effect on the vitamin D insufficient group [serum 25(OHD3 concentration <30 ng/mL]. Results. In vitamin D insufficient group, the effect of UVB irradiation on vitamin D and bone ALP as well as additional benefit on bone formation was confirmed. The vitamin D insufficient group showed statistically significant increment in serum 25(OHD3 compared with the normal group (p<0.05. However, there was no significant difference between two groups in the other bone turnover markers, such as serum calcium, PTH-C, serum osteocalcin, serum CTX and BMD. Conclusion. Low-energy-short-term UVB radiation for postmenopausal women may be of use in vitamin D

Different culture media affect growth characteristics, surface marker distribution and chondrogenic differentiation of human bone marrow-derived mesenchymal stromal cells.

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Hagmann, Sebastien; Moradi, Babak; Frank, Sebastian; Dreher, Thomas; Kämmerer, Peer Wolfgang; Richter, Wiltrud; Gotterbarm, Tobias

2013-07-30

Bone marrow-derived mesenchymal stromal cells (BM-MSCs) play an important role in modern tissue engineering, while distinct variations of culture media compositions and supplements have been reported. Because MSCs are heterogeneous regarding their regenerative potential and their surface markers, these parameters were compared in four widely used culture media compositions. MSCs were isolated from bone marrow and expanded in four established cell culture media. MSC yield/1000 MNCs, passage time and growth index were observed. In P4, typical MSC surface markers were analysed by fluorescence cytometry. Additionally, chondrogenic, adipogenic and osteogenic differentiation potential were evaluated. Growth index and P0 cell yield varied importantly between the media. The different expansion media had a significant influence on the expression of CD10, CD90, CD105, CD140b CD146 and STRO-1. While no significant differences were observed regarding osteogenic and adipogenic differentiation, chondrogenic differentiation was superior in medium A as reflected by GAG/DNA content. The choice of expansion medium can have a significant influence on growth, differentiation potential and surface marker expression of mesenchymal stromal cells, which is of fundamental importance for tissue engineering procedures.

The status of nuclear medicine techniques in the diagnosis of bone metastases in breast cancer

International Nuclear Information System (INIS)

Makaiova, I.; Kausitz, J.; Hupka, S.; Vivodova, M.

1989-01-01

Experience is presented with the diagnosis of bone metastases in patients with breast cancer using bone scintigraphy with 99m TC phosphonate and radioimmunological determination of carcinoembryonic antigen (CEA) and tissue polypeptic antigen (TPA). In a group of 395 patients, there was agreement between tumor markers (CEA, TPA) and the results of bone scintigraphy in 331 cases (84%) - negative in 193 cases (49%) and positive (i.e., in terms of bone scintigraphy results and the presence of at least one tumor marker) in 138 cases (35%). On the basis of this agreement between bone scintigraphy and CEA and TPA levels, the following algorithm is recommended in monitoring patients with breast cancer: a) follow-up of tumor markers at several month intervals and in case of an increase in their levels the patient should be referred to further examination using imaging techniques including bone scintigraphy. (author). 1 fig., 1 tab., 23 refs

FRET-Aptamer Assays for Bone Marker Assessment, C-Telopeptide, Creatinine, and Vitamin D

Science.gov (United States)

Bruno, John G.

2013-01-01

Astronauts lose 1.0 to 1.5% of their bone mass per month on long-duration spaceflights. NASA wishes to monitor the bone loss onboard spacecraft to develop nutritional and exercise countermeasures, and make adjustments during long space missions. On Earth, the same technology could be used to monitor osteoporosis and its therapy. Aptamers bind to targets against which they are developed, much like antibodies. However, aptamers do not require animal hosts or cell culture and are therefore easier, faster, and less expensive to produce. In addition, aptamers sometimes exhibit greater affinity and specificity vs. comparable antibodies. In this work, fluorescent dyes and quenchers were added to the aptamers to enable pushbutton, one-step, bind-and-detect fluorescence resonance energy transfer (FRET) assays or tests that can be freeze-dried, rehydrated with body fluids, and used to quantitate bone loss of vitamin D levels with a handheld fluorometer in the spacecraft environment. This work generated specific, rapid, one-step FRET assays for the bone loss marker C-telopeptide (CTx) when extracted from urine, creatinine from urine, and vitamin D congeners in diluted serum. The assays were quantified in nanograms/mL using a handheld fluorometer connected to a laptop computer to convert the raw fluorescence values into concentrations of each analyte according to linear standard curves. DNA aptamers were selected and amplified for several rounds against a 26- amino acid form of CTx, creatinine, and vitamin D. The commonalities between loop structures were studied, and several common loop structures were converted into aptamer beacons with a fluorophore and quencher on each end. In theory, when the aptamer beacon binds its cognate target (CTx bone peptide, creatinine, or vitamin D), it is forced open and no longer quenched, so it gives off fluorescent light (when excited) in proportion to the amount of target present in a sample. This proportional increase in fluorescence is

Thyrotropin serum levels are differentially associated with biochemical markers of bone turnover and stiffness in women and men: results from the SHIP cohorts.

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Tsourdi, E; Wallaschofski, H; Rauner, M; Nauck, M; Pietzner, M; Rettig, R; Ittermann, T; Völzke, H; Völker, U; Hofbauer, L C; Hannemann, A

2016-02-01

In two large German population-based cohorts, we showed positive associations between serum thyrotropin (TSH) concentrations and the Fracture Risk Assessment score (FRAX) in men and positive associations between TSH concentrations and bone turnover markers in women. The role of thyroid hormones on bone stiffness and turnover is poorly defined. Existing studies are confounded by differences in design and small sample size. We assessed the association between TSH serum concentrations and bone stiffness and turnover in the SHIP cohorts, which are two population-based cohorts from a region in Northern Germany comprising 2654 men and women and 3261 men and women, respectively. We calculated the bone stiffness index using quantitative ultrasound (QUS) at the calcaneus, employed FRAX score for assessment of major osteoporotic fractures, and measured bone turnover markers, N-terminal propeptide of type I procollagen (P1NP), bone-specific alkaline phosphatase (BAP), osteocalcin, and type I collagen cross-linked C-telopeptide (CTX) in all subjects and sclerostin in a representative subgroup. There was no association between TSH concentrations and the stiffness index in both genders. In men, TSH correlated positively with the FRAX score both over the whole TSH range (p < 0.01) and within the reference TSH range (p < 0.01). There were positive associations between TSH concentrations and P1NP, BAP, osteocalcin, and CTX (p < 0.01) in women but not in men. There was no significant association between TSH and sclerostin levels. TSH serum concentrations are associated with gender-specific changes in bone turnover and stiffness.

Prostate Cancer Metastases to Bone: Role of High Bone Turnover Induced by Androgen Deprivation

National Research Council Canada - National Science Library

Padalecki, Susan

2002-01-01

.... Treatment with androgen deprivation therapy leads to an increase in bone turnover as indicated by the loss of bone mineral density and the increase in markers of bone turnover in patients on treatment...

The Cell Surface Markers Expression in Postmenopausal Women and Relation to Obesity and Bone Status.

Science.gov (United States)

Horváthová, Mira; Ilavská, Silvia; Štefíková, Kornélia; Szabová, Michaela; Krivošíková, Zora; Jahnová, Eva; Tulinská, Jana; Spustová, Viera; Gajdoš, Martin

2017-07-11

The age-related changes and hormonal deprivation in postmenopausal women are associated with the immune response alteration. The excessive fat accumulation, local and systemic inflammation may lead to dysregulation in immune function and relevant health problems, including obesity and osteoporosis. We analyzed the expression of cell surface markers in the venous blood specimens, stained with fluorophores-conjugated monoclonal antibodies and analysed by multicolour flow cytometry. The significant changes of cytotoxic, naive, and memory T-lymphocytes, plasmacytoid dendritic cells (DCs) were in postmenopausal women versus fertile women. Body mass index (BMI) affected markedly the cell surface expression of CD265/RANK. Osteoporosis is linked to reduced percentage of plasmacytoid DCs, and elevated natural Treg cells ( p < 0.05). The confounding factors such as women age, BMI, bone mineral density (BMD), waist size and tissue fat affect the expression of RANK on myeloid DCs and CD40L on T-lymphocytes that might be the immunophenotypic modulators after menopause.

The Cell Surface Markers Expression in Postmenopausal Women and Relation to Obesity and Bone Status

Directory of Open Access Journals (Sweden)

Mira Horváthová

2017-07-01

Full Text Available The age-related changes and hormonal deprivation in postmenopausal women are associated with the immune response alteration. The excessive fat accumulation, local and systemic inflammation may lead to dysregulation in immune function and relevant health problems, including obesity and osteoporosis. We analyzed the expression of cell surface markers in the venous blood specimens, stained with fluorophores-conjugated monoclonal antibodies and analysed by multicolour flow cytometry. The significant changes of cytotoxic, naive, and memory T-lymphocytes, plasmacytoid dendritic cells (DCs were in postmenopausal women versus fertile women. Body mass index (BMI affected markedly the cell surface expression of CD265/RANK. Osteoporosis is linked to reduced percentage of plasmacytoid DCs, and elevated natural Treg cells (p < 0.05. The confounding factors such as women age, BMI, bone mineral density (BMD, waist size and tissue fat affect the expression of RANK on myeloid DCs and CD40L on T-lymphocytes that might be the immunophenotypic modulators after menopause.

Bone regeneration and stem cells

DEFF Research Database (Denmark)

Arvidson, K; Abdallah, B M; Applegate, L A

2011-01-01

cells, use of platelet rich plasma for tissue repair, osteogenesis and its molecular markers. A variety of cells in addition to stem cells, as well as advances in materials science to meet specific requirements for bone and soft tissue regeneration by addition of bioactive molecules, are discussed.......This invited review covers research areas of central importance for orthopedic and maxillofacial bone tissue repair, including normal fracture healing and healing problems, biomaterial scaffolds for tissue engineering, mesenchymal and fetal stem cells, effects of sex steroids on mesenchymal stem...

Rigid Body Motion Calculated From Spatial Co-ordinates of Markers ...

African Journals Online (AJOL)

In this paper, we present a unified method for calculating spatial coordinates of markers for a rigid body motion such as in bones. Kinematical analysis of bone movement in cadaveric specimens or living objects had been developed. Here, we show how spatial co-ordinates of markers in or on bone can be calculated from ...

Serum markers of bone turnover change in response to depletion and repletion of fruit and vegetable intake in adults: A 28-wk single-arm experimental feeding intervention

Science.gov (United States)

Data from controlled intervention trials are lacking to support observational evidence suggesting a positive association between intake of fruit and vegetable (FV) and bone health. The objective of this study was to assess serum markers of bone turnover change in response to FV depletion and repleti...

The usefulness of early whole body bone scintigraphy in the detection of bone metastasis from prostatic cancer

International Nuclear Information System (INIS)

Otsuka, Nobuaki; Fukunaga, Masao; Furukawa, Yohji; Tanaka, Hiroyoshi

1994-01-01

Early whole body bone scintigraphy was performed on 25 patients with prostatic cancer (15 cases with bone metastases and 10 cases without bone metastasis) to obtain anterior and posterior whole body images five minutes after administration of 99m Tc-hydroxymethylene diphosphonate(HMDP). The results were compared with the findings of routine bone scintigraphy after three hours, and the usefulness of the above method for the diagnosis of bone metastasis from prostatic cancer was evaluated. In cases in which increased activity was found in the upper and lower lumbar vertebrae by routine bone scintigraphy but no abnormality was seen by early whole body bone scintigraphy, senile degenerative bone changes such as spondylosis deformance were observed by bone radiography. In cases with multiple bone metastases, abnormal multiple accumulations were found by both early whole body bone scintigraphy and routine bone scintigraphy. In addition, in cases showing super bone scan, high accumulation in the skeletal system had already been detected by early whole body bone scintigraphy. When the courses before and after treatment in nine cases of multiple bone metastases were passaged from the results of early whole body bone scintigraphy and from changes in tumor markers (prostatic specific antigen, γ-semino protein and prostatic acid phosphatase), increased activity and the appearance of new hot spots as well as an increase in tumor markers were detected by early whole body scintigraphy in three of the four advanced cases, whereas decreased accumulations and a decrease in and normalization of tumor markers were observed in five improved cases. (author)

The usefulness of early whole body bone scintigraphy in the detection of bone metastasis from prostatic cancer

Energy Technology Data Exchange (ETDEWEB)

Otsuka, Nobuaki; Fukunaga, Masao; Furukawa, Yohji; Tanaka, Hiroyoshi [Kawasaki Medical School, Kurashiki, Okayama (Japan)

1994-06-01

Early whole body bone scintigraphy was performed on 25 patients with prostatic cancer (15 cases with bone metastases and 10 cases without bone metastasis) to obtain anterior and posterior whole body images five minutes after administration of [sup 99m]Tc-hydroxymethylene diphosphonate(HMDP). The results were compared with the findings of routine bone scintigraphy after three hours, and the usefulness of the above method for the diagnosis of bone metastasis from prostatic cancer was evaluated. In cases in which increased activity was found in the upper and lower lumbar vertebrae by routine bone scintigraphy but no abnormality was seen by early whole body bone scintigraphy, senile degenerative bone changes such as spondylosis deformance were observed by bone radiography. In cases with multiple bone metastases, abnormal multiple accumulations were found by both early whole body bone scintigraphy and routine bone scintigraphy. In addition, in cases showing super bone scan, high accumulation in the skeletal system had already been detected by early whole body bone scintigraphy. When the courses before and after treatment in nine cases of multiple bone metastases were passaged from the results of early whole body bone scintigraphy and from changes in tumor markers (prostatic specific antigen, [gamma]-semino protein and prostatic acid phosphatase), increased activity and the appearance of new hot spots as well as an increase in tumor markers were detected by early whole body scintigraphy in three of the four advanced cases, whereas decreased accumulations and a decrease in and normalization of tumor markers were observed in five improved cases. (author).

Changes of serum bone metabolic biochemical markers in elderly subjects with subclinical hypothyroidism

International Nuclear Information System (INIS)

Dai Yaozong; Li Liren

2005-01-01

Objective: To explore the clinical significance of changes of serum bone metabolic biochemical markers levels in elderly subjects with subclinical hypothyroidism. Methods: Serum S-BGP (with RIA), TSH, FT 4 (with ECLIA), total cholesterol (TC), triglyceride (TG), HDL, LDL, ApoA 1 , ApoB and Ca 2+ (with biochemical methods) were measured in 30 elderly subjects with subclinical hypothyroidism and 30 controls. Results: The serum levels of S-BGP and calcium in elderly subjects with subclinical hypothyroidism (2.78 ± 0.96 μg/L and 2.16 ± 0.17 mmol/L respectively) were significantly lower than those in controls (3.9 ± 1.48 μg/L and 2.31 ± 0.21 mmol/L respectively, both P<0.01). TC and LDL levels in the subclinical hypothyroid subjects (5.58 ± 0.41 mmol/L and 3.67 ± 0.36 mmol/L) were significantly higher than those in controls (P<0.01). Conclusion: The lowering of calcium levels in subjects with subclinical hypothyroidism would lead to loss of bone mass. Decreased S-BGP contents might be the chief cause of osteoporosis in these subjects. (authors)

Serum ionized calcium, intact PTH and novel markers of bone turnover in bedridden elderly patients.

Science.gov (United States)

Sorva, A; Välimäki, M; Risteli, J; Risteli, L; Elfving, S; Takkunen, H; Tilvis, R

1994-12-01

Chronic immobilization could markedly affect calcium and bone metabolism in elderly people. To investigate this, and to test the theory of 'type II' osteoporosis in bedridden elderly patients with low vitamin D status, 55 such subjects were examined. Serum concentrations of ionized calcium (Ca++), intact parathyrin (PTH) and two novel markers of bone collagen formation (carboxyterminal propeptide of type I procollagen; PICP) and resorption (carboxyterminal crosslinked telopeptide of type I collagen; ICTP) were measured. The effects on these parameters after 40 weeks of supplementation with vitamin D (1000 IU d-1) and/or calcium (1 g d-1) were subsequently prospectively evaluated. Despite low (mean 11.6 nmoll-1) serum 25-hydroxyvitamin D levels (25-OHD), those of 1,25-dihydroxy-vitamin D (1,25-(OH)2D) were mostly normal. Neither correlated with Ca++ or PTH. PTH correlated negatively not only with Ca++ (r = -0.328, P r = -0.306, P r = 0.268, P = 0.06). Vitamin D supplementation did not change PICP or ICTP considerably, despite slightly increased 1,25-(OH)2D and slightly decreased PTH. Ca++ values were normal and remained stable. In conclusion, Ca++ and PTH are poor indicators of vitamin D status in chronically immobilized elderly subjects. Furthermore, the results suggest that the increased bone resorption is not due to 'type II' secondary hyperparathyroidism; rather the resorption is primarily increased. Correction of vitamin D deficiency does not seem to benefit ageing bones unless adequate mechanical loading is provided.

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.

Abnormalities in biomarkers of mineral and bone metabolism in kidney donors.

Science.gov (United States)

Kasiske, Bertram L; Kumar, Rajiv; Kimmel, Paul L; Pesavento, Todd E; Kalil, Roberto S; Kraus, Edward S; Rabb, Hamid; Posselt, Andrew M; Anderson-Haag, Teresa L; Steffes, Michael W; Israni, Ajay K; Snyder, Jon J; Singh, Ravinder J; Weir, Matthew R

2016-10-01

Previous studies have suggested that kidney donors may have abnormalities of mineral and bone metabolism typically seen in chronic kidney disease. This may have important implications for the skeletal health of living kidney donors and for our understanding of the pathogenesis of long-term mineral and bone disorders in chronic kidney disease. In this prospective study, 182 of 203 kidney donors and 173 of 201 paired normal controls had markers of mineral and bone metabolism measured before and at 6 and 36 months after donation (ALTOLD Study). Donors had significantly higher serum concentrations of intact parathyroid hormone (24.6% and 19.5%) and fibroblast growth factor-23 (9.5% and 8.4%) at 6 and 36 months, respectively, as compared to healthy controls, and significantly reduced tubular phosphate reabsorption (-7.0% and -5.0%) and serum phosphate concentrations (-6.4% and -2.3%). Serum 1,25-dihydroxyvitamin D3 concentrations were significantly lower (-17.1% and -12.6%), while 25-hydroxyvitamin D (21.4% and 19.4%) concentrations were significantly higher in donors compared to controls. Moreover, significantly higher concentrations of the bone resorption markers, carboxyterminal cross-linking telopeptide of bone collagen (30.1% and 13.8%) and aminoterminal cross-linking telopeptide of bone collagen (14.2% and 13.0%), and the bone formation markers, osteocalcin (26.3% and 2.7%) and procollagen type I N-terminal propeptide (24.3% and 8.9%), were observed in donors. Thus, kidney donation alters serum markers of bone metabolism that could reflect impaired bone health. Additional long-term studies that include assessment of skeletal architecture and integrity are warranted in kidney donors. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Does methamphetamine affect bone metabolism?

International Nuclear Information System (INIS)

Tomita, Masafumi; Katsuyama, Hironobu; Watanabe, Yoko; Okuyama, Toshiko; Fushimi, Shigeko; Ishikawa, Takaki; Nata, Masayuki; Miyamoto, Osamu

2014-01-01

There is a close relationship between the central nervous system activity and bone metabolism. Therefore, methamphetamine (METH), which stimulates the central nervous system, is expected to affect bone turnover. The aim of this study was to investigate the role of METH in bone metabolism. Mice were divided into 3 groups, the control group receiving saline injections, and the 5 and 10 mg/kg METH groups (n = 6 in each group). All groups received an injection of saline or METH every other day for 8 weeks. Bone mineral density (BMD) was assessed by X-ray computed tomography. We examined biochemical markers and histomorphometric changes in the second cancellous bone of the left femoral distal end. The animals that were administered 5 mg/kg METH showed an increased locomotor activity, whereas those receiving 10 mg/kg displayed an abnormal and stereotyped behavior. Serum calcium and phosphorus concentrations were normal compared to the controls, whereas the serum protein concentration was lower in the METH groups. BMD was unchanged in all groups. Bone formation markers such as alkaline phosphatase and osteocalcin significantly increased in the 5 mg/kg METH group, but not in the 10 mg/kg METH group. In contrast, bone resorption markers such as C-terminal telopeptides of type I collagen and tartrate-resistant acid phosphatase 5b did not change in any of the METH groups. Histomorphometric analyses were consistent with the biochemical markers data. A significant increase in osteoblasts, especially in type III osteoblasts, was observed in the 5 mg/kg METH group, whereas other parameters of bone resorption and mineralization remained unchanged. These results indicate that bone remodeling in this group was unbalanced. In contrast, in the 10 mg/kg METH group, some parameters of bone formation were significantly or slightly decreased, suggesting a low turnover metabolism. Taken together, our results suggest that METH had distinct dose-dependent effects on bone turnover and that

Does methamphetamine affect bone metabolism?

Science.gov (United States)

Tomita, Masafumi; Katsuyama, Hironobu; Watanabe, Yoko; Okuyama, Toshiko; Fushimi, Shigeko; Ishikawa, Takaki; Nata, Masayuki; Miyamoto, Osamu

2014-05-07

There is a close relationship between the central nervous system activity and bone metabolism. Therefore, methamphetamine (METH), which stimulates the central nervous system, is expected to affect bone turnover. The aim of this study was to investigate the role of METH in bone metabolism. Mice were divided into 3 groups, the control group receiving saline injections, and the 5 and 10mg/kg METH groups (n=6 in each group). All groups received an injection of saline or METH every other day for 8 weeks. Bone mineral density (BMD) was assessed by X-ray computed tomography. We examined biochemical markers and histomorphometric changes in the second cancellous bone of the left femoral distal end. The animals that were administered 5mg/kg METH showed an increased locomotor activity, whereas those receiving 10mg/kg displayed an abnormal and stereotyped behavior. Serum calcium and phosphorus concentrations were normal compared to the controls, whereas the serum protein concentration was lower in the METH groups. BMD was unchanged in all groups. Bone formation markers such as alkaline phosphatase and osteocalcin significantly increased in the 5mg/kg METH group, but not in the 10mg/kg METH group. In contrast, bone resorption markers such as C-terminal telopeptides of type I collagen and tartrate-resistant acid phosphatase 5b did not change in any of the METH groups. Histomorphometric analyses were consistent with the biochemical markers data. A significant increase in osteoblasts, especially in type III osteoblasts, was observed in the 5mg/kg METH group, whereas other parameters of bone resorption and mineralization remained unchanged. These results indicate that bone remodeling in this group was unbalanced. In contrast, in the 10mg/kg METH group, some parameters of bone formation were significantly or slightly decreased, suggesting a low turnover metabolism. Taken together, our results suggest that METH had distinct dose-dependent effects on bone turnover and that METH might

Effect of re-irradiation for painful bone metastases on urinary markers of osteoclast activity (NCIC CTG SC.20U)

International Nuclear Information System (INIS)

Chow, Edward; DeAngelis, Carlo; Chen, Bingshu E.; Azad, Azar; Meyer, Ralph M.; Wilson, Carolyn; Kerba, Marc; Bezjak, Andrea; Wilson, Paula; Nabid, Abdenour; Greenland, Jonathan; Rees, Gareth; Vieth, Reinhold; Wong, Rebecca K.S.; Hoskin, Peter

2015-01-01

Purpose: The NCIC CTG Symptom Control.20 randomized trial (SC.20) confirmed the effectiveness of re-irradiation to painful bone metastases. This companion study correlates urinary markers of osteoclast activity with response to re-irradiation, survival and skeletal related events (SREs). Methods: Pain response was assessed using the International Consensus Endpoints. Urinary markers of bone turnover-pyridinoline (PYD), deoxypyridinoline (DPD), N-telopeptide (NTX), Alpha and Beta cross-laps of C-telopeptide (CTX)-before and 1 month after re-irradiation were correlated to response to re-irradiation and then to both, either or none of the initial and re-irradiation: frequent responders (response to both); eventual responders (response to re-irradiation only); eventual non-responders (response to initial radiation only), and absolute non-responders (no response to both). Results: Significant differences between 40 responders and 69 non-responders to re-irradiation existed for PYD (p = 0.03) and DPD (p = 0.04) at baseline. When patients were categorized as frequent responders (N = 34), eventual responders (6), eventual non-responders (59) and absolute non-responders (10), the mean values of all markers in the absolute non-responders at baseline and the follow-up were about double those for the other three groups with statistically significant difference for DPD (p = 0.03) at baseline. Absolute non-responders had the worst survival. The few occurrences of the SREs did not allow meaningful comparisons among the groups. Conclusion: There were significant differences between responders and non-responders to re-irradiation for PYD and DPD at baseline. The urinary markers in the absolute non-responders were markedly elevated at both baseline and follow-up with a statistically significant difference for DPD at baseline

Bone regeneration and stem cells

Science.gov (United States)

Arvidson, K; Abdallah, B M; Applegate, L A; Baldini, N; Cenni, E; Gomez-Barrena, E; Granchi, D; Kassem, M; Konttinen, Y T; Mustafa, K; Pioletti, D P; Sillat, T; Finne-Wistrand, A

2011-01-01

Abstract This invited review covers research areas of central importance for orthopaedic and maxillofacial bone tissue repair, including normal fracture healing and healing problems, biomaterial scaffolds for tissue engineering, mesenchymal and foetal stem cells, effects of sex steroids on mesenchymal stem cells, use of platelet-rich plasma for tissue repair, osteogenesis and its molecular markers. A variety of cells in addition to stem cells, as well as advances in materials science to meet specific requirements for bone and soft tissue regeneration by addition of bioactive molecules, are discussed. PMID:21129153

Changes in calcitropic hormones, bone markers and insulin-like growth factor I (IGF-I) during pregnancy and postpartum: a controlled cohort study

DEFF Research Database (Denmark)

Liendgaard, Ulla Kristine Møller; við Streym, Susanna; Mosekilde, Leif

2012-01-01

changes in calcium homeostasis, calcitropic hormones and bone metabolism during pregnancy and lactation. METHODS: We studied 153 women planning pregnancy (n = 92 conceived) and 52 non-pregnant, age-matched female controls. Samples were collected prior to pregnancy, once each trimester and 2, 16 and 36...... weeks postpartum. The controls were followed in parallel. RESULTS: P-estradiol (E(2)), prolactin and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) increased (p ..., markers of bone resorption and formation rose and fall, respectively (p 

Analysis of Subclinical Hyperthyroidism Influence on Parameters of Bone Metabolism

Directory of Open Access Journals (Sweden)

I.V. Pankiv

2016-03-01

Full Text Available State of subclinical hypothyroidism can be considered as the optimal model for assessing the significance of thyroid stimulating hormone (TSH for bone tissue in clinical practice. Objective: to make a comparative analysis of the impact of subclinical hyperthyroidism of various origins on the performance of bone mineral density (BMD and bone metabolism parameters. Materials and methods. The study in an outpatient setting included 112 women with a diagnosis of subclinical hyperthyroidism and duration of menopause for at least 5 years. Among the examinees, endogenous subclinical hyperthyroidism has been detected in 78 women (group I, exogenous subclinical hyperthyroidism on the background of suppressive levothyroxine therapy (group II — in 34. The control group (group III included 20 women without thyroid dysfunction. Results. The study first conducted a comparative analysis of bone metabolism, BMD indicators, as well as parameters of phosphorus and calcium, blood lipids in women with subclinical hyperthyroidism of various origins. A positive correlation between markers of bone metabolism and free triiodothyronine (fT3 as hormones necessary for the development of the skeleton and to maintain its homeostasis indicates a physiological effect of parathyroid hormone and fT3 on bone tissue. It is shown that the bone metabolism and BMD depend not only on the content of TSH, but also on the causes of subclinical hyperthyroidism.Conclusions. In postmenopausal women with endogenous subclinical hyperthyroidism, there is a significant decline in BMD indices, more pronounced in the bones with the cortical structure. A negative correlation between markers of bone metabolism and TSH has been observed among all patients included in the study.

Instrumental and laboratory assessment of stressful remodelling processes in bone tissue at total hip replacement

Directory of Open Access Journals (Sweden)

E.V. Karjakina

2010-06-01

Full Text Available Research objective is to estimate stressful remodelling features of bone tissue according to the densitometry data and to the level of biochemical markers of bone resorption and formation in total hip replacement (THR. Bone tissue mineral density (BTMD, condition of calcium-phosphoric metabolism and biochemical markers of bone formation (osteocalcin and bone isoenzyme of alkaline phosphatase and resorption (С-terminal bodypeptide of the I type collagen have been determined in 52 patients with coxarthrosis of ll-lll stages with marked joint dysfunction before and after THR. The control group included 24 donors. The data were considered to be reliable when the probability index was р<0,05. The reliable (р<0,05 change of BTMD was determined only in 3-6 months after the operation, whereas the change of biochemical markers of remodeling had already been done after 1,5-3 months, allowing to define the group of patients with obvious negative bone balance: strong predominance of resorption processes without compensation of the subsequent adequate osteogenesis, that subsequently could lead to significant bone tissue deficiency in the area adjacent to the endoprosthesis. Changes of indices of calcium-phosphoric metabolism were not certain during the investigation term. ln conclusion it is to state that biochemical markers of remodeling in comparison with BTMD allow to estimate objectively features of adaptive bone tissue remodeling after THR in earlier periods and to define group of patients with sharp intensification of metabolism and obvious negative bone balance

Reduced bone formation markers, and altered trabecular and cortical bone mineral densities of non-paretic femurs observed in rats with ischemic stroke: A randomized controlled pilot study.

Directory of Open Access Journals (Sweden)

Karen N Borschmann

Full Text Available Immobility and neural damage likely contribute to accelerated bone loss after stroke, and subsequent heightened fracture risk in humans.To investigate the skeletal effect of middle cerebral artery occlusion (MCAo stroke in rats and examine its utility as a model of human post-stroke bone loss.Twenty 15-week old spontaneously hypertensive male rats were randomized to MCAo or sham surgery controls. Primary outcome: group differences in trabecular bone volume fraction (BV/TV measured by Micro-CT (10.5 micron istropic voxel size at the ultra-distal femur of stroke affected left legs at day 28. Neurological impairments (stroke behavior and foot-faults and physical activity (cage monitoring were assessed at baseline, and days 1 and 27. Serum bone turnover markers (formation: N-terminal propeptide of type 1 procollagen, PINP; resorption: C-terminal telopeptide of type 1 collagen, CTX were assessed at baseline, and days 7 and 27.No effect of stroke was observed on BV/TV or physical activity, but PINP decreased by -24.5% (IQR -34.1, -10.5, p = 0.046 at day 27. In controls, cortical bone volume (5.2%, IQR 3.2, 6.9 and total volume (6.4%, IQR 1.2, 7.6 were higher in right legs compared to left legs, but these side-to-side differences were not evident in stroke animals.MCAo may negatively affect bone formation. Further investigation of limb use and physical activity patterns after MCAo is required to determine the utility of this current model as a representation of human post-stroke bone loss.

Study on the serum levels of relevant cytokines IL-β, IL-6, IL-8 and tumor markers CEA, CA15-3, PRL in breast cancer patients with bone metastatic lesions shown on SPECT radio-nuclide bone scan

International Nuclear Information System (INIS)

Zhu Bao

2009-01-01

Objective: To explore the correlationship between SPECT radionuclide bone scan and serum levels of three tumor markers as well as three cytokines in patients with breast cancer. Methods: Serum levels of IL-1β, IL-6, IL-8, CEA, CA15-3(with RIA) and PRL(with CLIA) were determined in 1)20 breast cancer patients with definite bone metastatic lesions shown on radio-nuclide bone scan 2) 20 breast cancer patients without bone metastasis 3) 30 patients with benign breast disorders and 4) 35 controls. Results: The serum tumor markers levels in patients osseous metastasis were significantly higher than those in the other three groups (P 0.05). The serum levels of IL-6, IL-8, IL-1β in patients with osseous metastasis were also significantly higher than those in other groups(P<0.05). Conclusion: Over expression of CEA, CA15-3 and PRL as well as IL-6, IL-8, IL-1β were related with osseous metastasis from breast cancer. Determination of the levels of these six parameters would be helpful for dynamic monitoring of the extent of metastasis. (authors)

Bone Density Characteristics and Major Depressive Disorder in Adolescents

Science.gov (United States)

Fazeli, Pouneh K.; Mendes, Nara; Russell, Melissa; Herzog, David B.; Klibanski, Anne; Misra, Madhusmita

2013-01-01

Objective Major depressive disorder (MDD) is common during adolescence, a time period characterized by rapid bone mineral accrual. MDD has recently been associated with lower bone mineral density in adults. Our objective was to determine whether MDD is associated with bone mineral density (BMD), bone turnover markers, vitamin D and gonadal steroids in adolescents. Methods Sixty five adolescents 12 to 18 years of age (32 boys: 16 with MDD and 16 controls, and 33 girls: 17 with MDD and 16 controls) were included in a cross-sectional study. BMD and body composition were obtained by dual energy x-ray absorptiometry. Estradiol, testosterone, 25-OH vitamin D levels and P1NP, a marker of bone formation, and CTX, a marker of bone resorption, were measured. Results Boys with MDD had significantly lower BMD at the hip (Mean [SD] of 0.99 [0.17] vs. 1.04 [0.18] g/cm2; BMI-adjusted p=0.005) and femoral neck (0.92 [0.17] vs. 0.94 [0.17] g/cm2; adjusted; BMI-adjusted p=0.024) compared to healthy controls after adjusting for BMI. This significant finding was maintained after also adjusting for lean mass and bone age (hip: p=0.007; femoral neck: p=0.020). In girls, there were no significant differences in BMD between the girls with MDD and the controls after adjusting for BMI (p-values>.17). Conclusions Male adolescents with MDD have significantly lower BMD as compared to healthy controls after adjusting for body mass and maturity. This association is not observed in girls. PMID:23362498

N-glycosylation profile of undifferentiated and adipogenically differentiated human bone marrow mesenchymal stem cells: towards a next generation of stem cell markers.

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Hamouda, Houda; Ullah, Mujib; Berger, Markus; Sittinger, Michael; Tauber, Rudolf; Ringe, Jochen; Blanchard, Véronique

2013-12-01

Mesenchymal stem cells (MSCs) are multipotent cells that are easy to isolate and expand, develop into several tissues, including fat, migrate to diseased organs, have immunosuppressive properties and secrete regenerative factors. This makes MSCs ideal for regenerative medicine. For application and regulatory purposes, knowledge of (bio)markers characterizing MSCs and their development stages is of paramount importance. The cell surface is coated with glycans that possess lineage-specific nature, which makes glycans to be promising candidate markers. In the context of soft tissue generation, we aimed to identify glycans that could be markers for MSCs and their adipogenically differentiated progeny. MSCs were isolated from human bone marrow, adipogenically stimulated for 15 days and adipogenesis was verified by staining the lipid droplets and quantitative real time polymerase chain reaction of the marker genes peroxisome proliferator-activated receptor gamma (PPARG) and fatty acid binding protein-4 (FABP4). Using matrix-assisted laser desorption-ionization-time of flight mass spectrometry combined with exoglycosidase digestions, we report for the first time the N-glycome of MSCs during adipogenic differentiation. We were able to detect more than 100 different N-glycans, including high-mannose, hybrid, and complex N-glycans, as well as poly-N-acetyllactosamine chains. Adipogenesis was accompanied by an increased amount of biantennary fucosylated structures, decreased amount of fucosylated, afucosylated tri- and tetraantennary structures and increased sialylation. N-glycans H6N5F1 and H7N6F1 were significantly overexpressed in undifferentiated MSCs while H3N4F1 and H5N4F3 were upregulated in adipogenically differentiated MSCs. These glycan structures are promising candidate markers to detect and distinguish MSCs and their adipogenic progeny.

Osterix enhances proliferation and osteogenic potential of bone marrow stromal cells

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Tu Qisheng; Valverde, Paloma; Chen, Jake

2006-01-01

Osterix (Osx) is a zinc-finger-containing transcription factor that is expressed in osteoblasts of all endochondral and membranous bones. In Osx null mice osteoblast differentiation is impaired and bone formation is absent. In this study, we hypothesized that overexpression of Osx in murine bone marrow stromal cells (BMSC) would be able to enhance their osteoblastic differentiation and mineralization in vitro. Retroviral transduction of Osx in BMSC cultured in non-differentiating medium did not affect expression of Runx2/Cbfa1, another key transcription factor of osteoblast differentiation, but induced an increase in the expression of other markers associated with the osteoblastic lineage including alkaline phosphatase, bone sialoprotein, osteocalcin, and osteopontin. Retroviral transduction of Osx in BMSC also increased their proliferation, alkaline phosphatase activity, and ability to form bone nodules. These events occurred without significant changes in the expression of α1(II) procollagen or lipoprotein lipase, which are markers of chondrogenic and adipogenic differentiation, respectively

Assessment of bone metabolism in premenopausal females with hyperthyroidism and hypothyroidism.

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Tuchendler, Dominika; Bolanowski, Marek

2013-01-01

Osteoporosis is one of the commonest metabolic diseases of bone. Its possible causes may include thyroid hormonal dysfunction. The objective of this study was to evaluate the effects of hyperthyroidism and hypothyroidism on osseous tissue metabolism in premenopausal women. 38 women with hyperthyroidism, 40 with hypothyroidism and 41 healthy women participated in this study. Initially after 6 and 12 months, each patient underwent selected hormonal, immunological and biochemical tests, measurement of concentrations of bone turnover markers and densitometry were also performed. On initial evaluation, lower cortical bone density was found in patients with hyperthyroidism (femoral neck). After 12 months, an increase in BMD was seen, but it was still lower than in the control group. Statistically significantly higher concentrations of bone turnover markers, decreasing from the sixth month of treatment, were noted only in the group with hyperthyroidism. Statistically significant differences were not noted in the femoral neck nor in the lumbar spine BMD in patients with hypothyroidism. Hyperthyroidism poses a negative effect on bone metabolism. Hypothyroidism in premenopausal females does not have any influence on bone density.

Marker of Bone Resorption in Acute Response to Exogenous or Endogenous Parathyroid Hormone

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Vit Zikan

2008-01-01

Full Text Available Parathyroid hormone (PTH changes morphology of osteoclasts within minutes after its systemic administration. The aim of our study was to test in healthy men whether both exogenous and endogenous PTH could change acutely (minutes to hours the serum cross-linked C-telopeptide of type I collagen (beta CTX, which is released during osteoclastic resorption of bone. Twelve healthy men (age range 24–34 yr were each studied during 180 min on a control period, after a single subcutaneous injection of teriparatide, and after 30 min EDTA infusion to stimulate endogenous PTH secretion. The tests were started after overnight fast, 3 h after a standard calcium load. The EDTA infusion induced a significant decrease in serum ionized calcium (by 8.5% at 33 min and a significant increase in plasma PTH (by 305% at 33 min. Both the EDTA and teriparatide resulted in a significant increase in beta CTX (p < 0.001 with maximum increases of 64% and 80%, respectively. A mild, but significant decrease in beta CTX was observed during the control test period. In conclusion, single-dose teriparatide injection as well as a stimulation of endogenous PTH in healthy men results in an acute increase of the bone resorption marker.

Effects of Resistive Vibration Exercise Combined with Whey Protein and KHCO3 on Bone Tturnover Markers in Head-down Tilt Bed Rest (MTBR-MNX Study)

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Graf, Sonja; Baecker, Natalie; Buehlmeier, Judith; Fischer, Annelie; Smith, Scott M.; Heer, Martina

2014-01-01

High protein intake further increases bone resorption markers in head-down tilt bed rest (HDBR), most likely induced by low-grade metabolic acidosis. Adding an alkaline salt to a diet with high protein content prevents this additional rise of bone resorption markers in HDBR. In addition, high protein intake, specifically whey protein, increases muscle protein synthesis and improves glucose tolerance, which both are affected by HDBR. Resistive vibration exercise (RVE) training counteracts the inactivity-induced bone resorption during HDBR. To test the hypothesis that WP plus alkaline salt (KHCO3) together with RVE during HDBR will improve bone turnover markers, we conducted a randomized, three-campaign crossover design study with 12 healthy, moderately fit male subjects (age 34+/-8 y, body mass [BM] 70 +/- 8 kg). All study campaigns consisted of a 7-d ambulatory period, 21days of -6 deg. head-down tilt bed rest (HDBR), and a 6-d recovery period. Diet was standardized and identical across phases. In the control (CON) campaign, subjects received no supplement or RVE. In the intervention campaigns, subjects received either RVE alone or combined with WP and KHCO3 (NEX). WP was applied in 3 doses per day of 0.6 g WP/kg BM together with 6 doses of 15 mmol KHCO3 per day. Eleven subjects completed the RVE and CON campaign, 8 subjects completed all three campaigns. On day 21 of HDBR excretion of the bone resorption marker C-telopeptide (CTX) was 80+/-28% (p<0.001) higher than baseline, serum calcium concentrations increased by 12 +/- 29% (p<0.001) and serum osteocalcin concentrations decreased by 6+/-12% (p=0.001). Urinary CTX excretion was 11+/- 25% (p=0.02) lower on day 21 of HDBR in the RVE- and tended to decrease by 3+/- 22% (p=0.06) in the NEX campaign compared to CON. Urinary calcium excretion was higher on day 21 in HDBR in the RVE and NEX (24+/- 43% p=0.01; 25+/- 37% p=0.03) compared to the CON campaign. We conclude that combination of RVE with WP/KHCO3 was not

Investigations of Diabetic Bone Disease

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Linde, Jakob Starup

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 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...... 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...

Greater milk intake is associated with lower bone turnover, higher bone density, and higher bone microarchitecture index in a population of elderly Japanese men with relatively low dietary calcium intake: Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Study.

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Sato, Y; Iki, M; Fujita, Y; Tamaki, J; Kouda, K; Yura, A; Moon, J-S; Winzenrieth, R; Iwaki, H; Ishizuka, R; Amano, N; Tomioka, K; Okamoto, N; Kurumatani, N

2015-05-01

The effects of milk intake on bone health are not clear in elderly Asian men with low dietary calcium intake. This study showed that greater milk intake is associated with lower bone turnover, higher bone density, and higher bone microarchitecture index in community-dwelling elderly Japanese men. The consumption of milk or dairy products is widely recommended for maintaining bone health regardless of gender or age. However, little evidence exists on the beneficial effects of milk intake on bone health in elderly Japanese men characterized with relatively low dietary calcium intake. Here we examined whether or not greater milk intake was associated with lower bone turnover, higher bone density, and stronger bone microarchitecture in community-dwelling elderly Japanese men. Interviews were conducted to obtain information on medical history and lifestyle, including the amount of habitual milk intake, nutrient intake calculations based on a 1-week food diary, and measurements of areal bone mineral density (aBMD) at the lumbar spine (LS), total hip (TH), and femoral neck (FN) by dual-energy x-ray absorptiometry (DXA), trabecular bone score (TBS) using DXA images at LS, and biochemical markers of bone turnover in sera. Participants with a history of diseases or medications that affect bone metabolism, or with missing data, were excluded from the analysis. The median intake of milk in the 1479 participants (mean age, 73.0 ± 5.1 years) was one glass of milk per day. Bone turnover markers showed a decreasing trend (p turnover, higher aBMD, and higher TBS in community-dwelling elderly Japanese men.

Posttranslational heterogeneity of bone alkaline phosphatase in metabolic bone disease.

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Langlois, M R; Delanghe, J R; Kaufman, J M; De Buyzere, M L; Van Hoecke, M J; Leroux-Roels, G G

1994-09-01

Bone alkaline phosphatase is a marker of osteoblast activity. In order to study the posttranscriptional modification (glycosylation) of bone alkaline phosphatase in bone disease, we investigated the relationship between mass and catalytic activity of bone alkaline phosphatase in patients with osteoporosis and hyperthyroidism. Serum bone alkaline phosphatase activity was measured after lectin precipitation using the Iso-ALP test kit. Mass concentration of bone alkaline phosphatase was determined with an immunoradiometric assay (Tandem-R Ostase). In general, serum bone alkaline phosphatase mass and activity concentration correlated well. The activity : mass ratio of bone alkaline phosphatase was low in hyperthyroidism. Activation energy of the reaction catalysed by bone alkaline phosphatase was high in osteoporosis and in hyperthyroidism. Experiments with neuraminidase digestion further demonstrated that the thermodynamic heterogeneity of bone alkaline phosphatase can be explained by a different glycosylation of the enzyme.

Bone turnover, calcium homeostasis, and vitamin D status in Danish vegans.

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Hansen, Tue H; Madsen, Marie T B; Jørgensen, Niklas R; Cohen, Arieh S; Hansen, Torben; Vestergaard, Henrik; Pedersen, Oluf; Allin, Kristine H

2018-01-23

A vegan diet has been associated with increased bone fracture risk, but the physiology linking nutritional exposure to bone metabolism has only been partially elucidated. This study investigated whether a vegan diet is associated with increased bone turnover and altered calcium homeostasis due to insufficient intake of calcium and vitamin D. Fractionated and total 25-hydroxyvitamin D (25(OH)-D), parathyroid hormone (PTH), calcium, and four bone turnover markers (osteocalcin, N-terminal propeptide of type I procollagen (PINP), bone-specific alkaline phosphatase (BAP), and C-terminal telopeptide of type I collagen (CTX)) were measured in serum from 78 vegans and 77 omnivores. When adjusting for seasonality and constitutional covariates (age, sex, and body fat percentage) vegans had higher concentrations of PINP (32 [95% CI: 7, 64]%, P = 0.01) and BAP (58 [95% CI: 27, 97]%, P Vegans had higher serum PTH concentration (38 [95% CI: 19, 60]%; P Vegans have higher levels of circulating bone turnover markers compared to omnivores, which may in the long-term lead to poorer bone health. Differences in dietary habits including intake of vitamin D and calcium may, at least partly, explain the observed differences.

Optimizing Bone Health in Duchenne Muscular Dystrophy

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Jason L. Buckner

2015-01-01

Full Text Available Duchenne muscular dystrophy (DMD is an X-linked recessive disorder characterized by progressive muscle weakness, with eventual loss of ambulation and premature death. The approved therapy with corticosteroids improves muscle strength, prolongs ambulation, and maintains pulmonary function. However, the osteoporotic impact of chronic corticosteroid use further impairs the underlying reduced bone mass seen in DMD, leading to increased fragility fractures of long bones and vertebrae. These serious sequelae adversely affect quality of life and can impact survival. The current clinical issues relating to bone health and bone health screening methods in DMD are presented in this review. Diagnostic studies, including biochemical markers of bone turnover and bone mineral density by dual energy X-ray absorptiometry (DXA, as well as spinal imaging using densitometric lateral spinal imaging, and treatment to optimize bone health in patients with DMD are discussed. Treatment with bisphosphonates offers a method to increase bone mass in these children; oral and intravenous bisphosphonates have been used successfully although treatment is typically reserved for children with fractures and/or bone pain with low bone mass by DXA.

Short Duration Small Sided Football and to a Lesser Extent Whole Body Vibration Exercise Induce Acute Changes in Markers of Bone Turnover

DEFF Research Database (Denmark)

Bowtell, J. L.; Jackman, S. R.; Scott, S.

2016-01-01

We aimed to study whether short-duration vibration exercise or football sessions of two different durations acutely changed plasma markers of bone turnover and muscle strain. Inactive premenopausal women (n = 56) were randomized to complete a single bout of short (FG15) or long duration (FG60) sm...

Characteristics of bone turnover in the long bone metaphysis fractured patients with normal or low Bone Mineral Density (BMD.

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Christoph Wölfl

Full Text Available The incidence of osteoporotic fractures increases as our population ages. Until now, the exact biochemical processes that occur during the healing of metaphyseal fractures remain unclear. Diagnostic instruments that allow a dynamic insight into the fracture healing process are as yet unavailable. In the present matched pair analysis, we study the time course of the osteoanabolic markers bone specific alkaline phosphatase (BAP and transforming growth factor β1 (TGFβ1, as well as the osteocatabolic markers crosslinked C-telopeptide of type-I-collagen (β-CTX and serum band 5 tartrate-resistant acid phosphatase (TRAP5b, during the healing of fractures that have a low level of bone mineral density (BMD compared with fractures that have a normal BMD. Between March 2007 and February 2009, 30 patients aged older than 50 years who suffered a metaphyseal fracture were included in our study. BMDs were verified by dual energy Xray absorptiometry (DXEA scans. The levels of BTMs were examined over an 8-week period. Osteoanabolic BAP levels in those with low levels of BMD were significantly different from the BAP levels in those with normal BMD. BAP levels in the former group increased constantly, whereas the latter group showed an initial strong decrease in BAP followed by slowly rising values. Osteocatabolic β-CTX increased in the bone of the normal BMD group constantly, whereas these levels decreased significantly in the bone of the group with low BMD from the first week. TRAP5b was significantly reduced in the low level BMD group. With this work, we conduct first insights into the molecular biology of the fracture healing process in patients with low levels of BMD that explains the mechanism of its fracture healing. The results may be one reason for the reduced healing qualities in bones with low BMD.

The carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen in serum as a marker of bone resorption

DEFF Research Database (Denmark)

Hassager, C; Jensen, L T; Pødenphant, J

1994-01-01

Carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) in serum has recently been proposed as a new biochemical marker of bone resorption. In the present study we compared serum ICTP with radiopharmaceutical and histomorphometric measurements of bone turnover...... in postmenopausal women with mild osteoporosis, and assessed the effect of hormone replacement therapy (HRT) (2 mg 17 beta-estradiol plus 1 mg norethisterone daily) and anabolic steroid therapy (50 mg nandrolone decanoate (ND) i.m. every 3 weeks) on serum ICTP in two double-blind placebo-controlled studies with 55...... to 75-year-old women. Serum ICTP measured by radioimmunoassay (RIA) correlated significantly with the 24-hour whole body retention of 99m-technetium diphosphonate (Rho = 0.47, P

Vitamin D supplementation has minor effects on parathyroid hormone and bone turnover markers in vitamin D-deficient bedridden older patients.

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Björkman, Mikko; Sorva, Antti; Risteli, Juha; Tilvis, Reijo

2008-01-01

to evaluate the effects of vitamin D supplementation on parathyroid function and bone turnover in aged, chronically immobile patients. a randomised double-blind controlled trial. two hundred and eighteen long-term inpatients aged over 65 years. the patients were randomised into treatment groups of I-III, each receiving 0 IU, 400 IU and 1200 IU cholecalciferol per day, respectively. In case of inadequate consumption of dairy products, patients received a daily calcium substitution of 500 mg. plasma concentrations of 25-hydroxyvitamin D (25-OHD), intact parathyroid hormone (PTH), amino-terminal propeptide of type I procollagen (PINP), a marker of bone formation, and carboxy-terminal telopeptide of type I collagen (ICTP), a marker of bone resorption, were measured at baseline and after 6 months. the patients (age 84.5 years) were chronically bedridden. The baseline 25-OHD was low (23 nmol/l), correlated inversely with PINP, and tended to associate inversely with PTH. The prevalence of vitamin D deficiency (VDD) (25-OHD < 50 nmol/l) was 98% and PTH was elevated in 23% of the patients. Vitamin D supplementation significantly increased 25-OHD concentrations (124% group II, 204% group III) and decreased PTH (-7% group II, -8% group III). PINP tended to decrease, but ICTP tended to increase, and only their ratio decreased significantly. The tendency of ICTP to increase was inconsistent. Changes in 25-OHD correlated inversely with those in PTH and PINP. vitamin D supplementation has minor effects on PTH and bone turnover in chronically immobilised aged patients with VDD. Further comparative studies and meta-analyses are warranted to elucidate the confounding effects of different mobility levels on the benefits of vitamin D supplementation in patients with differing baseline PTH levels.

Midlife women, bone health, vegetables, herbs and fruit study. The Scarborough Fair study protocol

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Gunn Caroline A

2013-01-01

Full Text Available Abstract Background Bone loss is accelerated in middle aged women but increased fruit/vegetable intake positively affects bone health by provision of micronutrients essential for bone formation, buffer precursors which reduce acid load and phytochemicals affecting inflammation and oxidative stress. Animal studies demonstrated bone resorption inhibiting properties of specific vegetables, fruit and herbs a decade ago. Objective: To increase fruit/vegetable intake in post menopausal women to 9 servings/day using a food specific approach to significantly reduce dietary acid load and include specific vegetables, fruit and herbs with bone resorbing inhibiting properties to assess effect on bone turnover, metabolic and inflammatory markers. Methods/Design The Scarborough Fair Study is a randomised active comparator controlled multi centre trial. It aimed to increase fruit and vegetable intake in 100 post menopausal women from ≤ 5 servings/day to ≥ 9 servings/day for 3 months. The women in the dietary intervention were randomly assigned to one of the two arms of the study. Both groups consumed ≥ 9 servings/day of fruit/vegetables and selected herbs but the diet of each group emphasised different fruit/vegetables/herbs with one group (B selecting from a range of vegetables, fruit and culinary herbs with bone resorbing inhibiting properties. 50 women formed a negative control group (Group C usual diet. Primary outcome variables were plasma bone markers assessed at baseline, 6 weeks and 12 weeks. Secondary outcome variables were plasma inflammation and metabolic markers and urinary electrolytes (calcium, magnesium, potassium and sodium assessed at baseline and 12 weeks. Dietary intake and urine pH change also were outcome variables. The dietary change was calculated with 3 day diet diaries and a 24 hour recall. Intervention participants kept a twice weekly record of fruit, vegetable and herb intake and urine pH. Discussion This study will provide

The Relevance of Osteoclastic and Osteoblastic Activity Markers Follow-Up in Patients on Antiresorptive Osteoporosis Treatment.

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Smilic, Tanja N; Novakovic, Tatjana R; Markovic-Jovanovic, Snezana R; Smilic, Ljiljana L J; Mitic, Javorka S; Radunovic, Miodrag L

2017-11-02

In general, markers of bone formation and markers of bone resorption are changing synergistically, so the monitoring of any osteoclastic and any osteoblastic marker should reflect the rate of bone transformation. The aim of the study is to monitor the bone metabolism markers in postmenopausal women with osteoporosis and osteopenia along with the variations caused by the effects of bisphosphonate therapy. The study involved 55 women of average age of 57.95 years, with osteopenia or osteoporosis. The patients with osteoporosis were treated with bisphosphonates (75 mg once a week); the laboratory tests were performed before the treatment and 6 months later. Patients with osteopenia were evaluated at the first assessment and 6 months later. The tests included bone densitometry, dual-energy X-ray absorptiometry, osteocalcin, alkaline phosphatase, collagen 1 N-terminal pro-peptide (P1NP), and beta C telopeptide of type I collagen (CTX). The mean T-score was -2.80 ± 0.63 before therapy and -2.64 ± 0.45 6 months later (p < 0.001). Women with osteoporosis had elevated levels of osteocalcin and P1NP at the first assessment, whereas the alkaline phosphatase level did not change with the treatment. After the introduction of antiresorptive therapy, the levels of osteocalcin and P1NP significantly decreased (p < 0.001). In the group with osteopenia, the biochemical markers activity were increased in both assessments. In patients with osteoporosis, Beta-CTX was increased in the first evaluation, and decreased after treatment (p = 0.001). The results indicate that the assessment of biochemical markers of bone metabolism show excellent results in the assessment of prognosis, monitoring the course and the response to various treatment regimens of osteoporosis and evince strong correlation with standard densitometry and dual-energy X-ray absorptiometry procedures. P1NP and CTX show better diagnostic applicability compared with osteocalcin and alkaline phosphatase

Effect of hormone replacement therapy on the bone mass and urinary excretion of pyridinium cross-links

OpenAIRE

Pardini,Dolores Perovano; Sabino,Anibal Tagliaferri; Meneses,Ana Maria; Kasamatsu,Teresa; Vieira,José Gilberto Henriques

2000-01-01

CONTEXT: The menopause accelerates bone loss and is associated with an increased bone turnover. Bone formation may be evaluated by several biochemical markers. However, the establishment of an accurate marker for bone resorption has been more difficult to achieve. OBJECTIVE: To study the effect of hormone replacement therapy (HRT) on bone mass and on the markers of bone resorption: urinary excretion of pyridinoline and deoxypyridinoline. DESIGN: Cohort correlational study. SETTING: Academic...

Effect of short-term upper-body resistance training on muscular strength, bone metabolic markers, and BMD in premenopausal women

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Liang MT

2012-11-01

Full Text Available Michael TC Liang,1 Lorena Quezada,1 WY Jamie Lau,1 Bulent Sokmen,2 Thomas W Spalding11Department of Kinesiology and Health Promotion, California State Polytechnic University, Pomona, CA, USA; 2Department of Kinesiology, Sonoma State University, Rohnert Park, CA, USAAbstract: To examine the effect of a 10-week upper-body resistance training program on bone turnover markers and site-specific bone mineral density (BMD in the wrist and distal half of the ulna and radius in untrained and healthy young premenopausal women.Methods: Twenty-two subjects (aged 22.1 ± 1.8 years were randomly assigned to a resistance training (n = 12 or no training control (n = 10 group. The following outcome variables were measured before and after 10 weeks of resistance training: (1 bone formation biomarker osteocalcin, and bone resorption biomarker tartrate-resistant acid phosphatase isoform 5b; (2 BMD in the wrist and distal half of the ulna and radius; (3 isokinetic strength of the elbow and knee extensors and flexors; (4 dynamic strength of the arm extensors and flexors; and (5 maximum number of push-ups.Results: The 10-week upper body resistance training intervention resulted in improved strength performance in push-ups (resistance training versus control: P < 0.05, chest presses (P < 0.05, and pulldowns (P < 0.05. However, there was no improvement in the BMD of the wrist (P > 0.05, BMD of the distal half of the ulna and radius (P > 0.05, and metabolic biomarkers osteocalcin (P > 0.05 and tartrate-resistant acid phosphatase isoform 5b (P > 0.05, except for the osteocalcin/tartrate-resistant acid phosphatase isoform 5b ratio. Also, no improvement in the resistance training group was observed for isokinetic strength of the knee and elbow flexion/extension.Conclusion: Upper-body muscular strength performance, but not bone metabolic markers and BMD of the wrist, can be improved with a 10-week upper body resistance training program of the nonweight-bearing limbs in

An evaluation of the effect of age and the peri-parturient period on bone metabolism in dairy cows as measured by serum bone-specific alkaline phosphatase activity and urinary deoxypyridinoline concentration.

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Sato, Reiichiro; Onda, Ken; Kato, Hajime; Ochiai, Hideharu; Kawai, Kazuhiro; Iriki, Tsunenori; Kaneko, Kazuyuki; Yamazaki, Yukio; Wada, Yasunori

2013-08-01

Various biochemical markers help to evaluate the state of bone turnover in humans and could be used during the peri-parturient period in dairy cows when calcium (Ca) metabolism changes dramatically. To investigate this, the peri-partum characteristics of serum bone-specific alkaline phosphatase (BAP) and urinary deoxypyridinoline (DPD) were investigated. Both serum BAP activity and urinary DPD concentrations were increased and demonstrated wide variability in younger animals, and these findings were consistent with other bone turnover markers. Around the time of parturition, serum Ca concentration and serum BAP activity in multiparous cows were significantly lower than in primiparous cows, but urinary DPD concentration was unchanged. The use of BAP as a bone formation marker appears to be valuable for evaluating bone remodelling status in cows, but the specificity of the test needs to be confirmed. The DPD/BAP ratio around parturition demonstrated a clear difference in bone turnover status between the two parity groups with multiparous cows demonstrating increased signs of bone resorption compared with primiparous cows, corresponding to the Ca requirement for milk production. In future studies, the applicability of the ratio of bone resorption marker to bone formation marker should be evaluated for bone turnover assessment. Copyright © 2013 Elsevier Ltd. All rights reserved.

A novel method for monitoring high-risk breast cancer with tumor markers

DEFF Research Database (Denmark)

Sölétormos, G; Nielsen, D; Schiøler, V

1993-01-01

cancer. METHODS: Ninety females with high-risk breast cancer were included in the study. Response evaluation was based upon clinical examination, x-rays or histology and elaborated marker criteria. RESULTS: During the marker monitoring period, metastases in four patients were confined to skin or lymph......BACKGROUND: An early and reliable diagnosis of metastatic spread has increased interest in serum tumor markers. This study investigated the ability of CA 15.3, CEA, and TPA to identify, predict, and exclude metastases in bone/viscera during adjuvant treatment and follow-up of high-risk breast...

Bone health measured using quantitative ultrasonography in adult males with muscular dystrophy

OpenAIRE

Morse, C.I.; Smith, J.; Denny, A.; Tweedale, J.; Searle, N.D.; Winwood, K.; Onambele-Pearson, G.L.

2016-01-01

Objectives: To compare muscle and bone health markers in adult males (aged 20-59 yrs) with and without muscular dystrophy (MD). Methods: Participants included 11 Fascioscapulohumeral (FSH), 11 Becker?s (Be), 9 limb girdle (LG), 11 Duchenne (DMD), and 14 non-dystrophic controls (CTRL). Physical activity was assessed using Bone (BPAQ) and disability specific (PASIPD) questionnaires. Bone QUS provided T- and Z scores from the Distal Radius (DR) and Mid-shaft tibia (MST). Tibialis anterior cross ...

Various effects of antidepressant drugs on bone microarchitectecture, mechanical properties and bone remodeling

International Nuclear Information System (INIS)

Bonnet, N.; Bernard, P.; Beaupied, H; Bizot, J.C.; Trovero, F.; Courteix, D.; Benhamou, C.L.

2007-01-01

The aim of this study was to evaluate the effects of various drugs which present antidepressant properties: selective serotonin-reuptake inhibitors (SSRIs, fluoxetine), serotonin and noradrenaline-reuptake inhibitors (Desipramine) and phosphodiesterase inhibitors (PDE, rolipram and tofisopam) on bone microarchitecture and biomechanical properties. Twelve female mice were studied per group starting at an age of 10 weeks. During 4 weeks, they received subcutaneously either placebo or 20 mg kg -1 day -1 of desipramine, fluoxetine or 10 mg kg -1 day -1 of rolipram or tofisopam. Serum Osteocalcin and CTx were evaluated by ELISA. Bone microarchitecture of the distal femur was characterized by X-ray microCT (Skyscan1072). Mechanical properties were assessed by three-point bending test (Instron 4501) and antidepressant efficacy by forced swimming and open field tests. Fluoxetine displayed lower TbTh (- 6.1%, p -1 , 6431 ± 1182 MPa) than in placebo (101 ± 9 N mm -1 , 8441 ± 1180 MPa). Bone markers indicated a significantly higher bone formation in tofisopam (+ 8.6%) and a lower in fluoxetine (- 56.1%) compared to placebo. These data suggest deleterious effects for SSRIs, both on trabecular and cortical bone and a positive effect of PDE inhibitors on trabecular bone. Furthermore tofisopam anabolic effect in terms of bone markers, suggests a potential therapeutic effect of the PDE inhibitors on bone

Secretory IgA, albumin, and bone-density level changes as markers of biostimulatory effects from laser radiation on the healing process after extraction of human molars on the lower jaw

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Kucerova, Hana; Dostalova, Tatjana; Himmlova, Lucia; Bartova, Jirina; Mazanek, Jiri

1999-05-01

The aim of study was to evaluate the effect of low-level laser radiation on the healing process after human lower molar extraction. Frequencies of 5 Hz, 292 Hz and 9000 Hz were used in this experiment. Monitoring the secretory IgA and albumin levels in saliva and changes in bone density were used as a marker of biostimulatory effect. Bone density after extraction and six month after surgical treatment was examined using the dental digital radiography. Wound closure was followed by healing of bone structure in extraction site. Changes of secretory IgA, albumin levels and bone density were compared in groups of patients with laser treatment and control group without any laser therapy. Differences in levels of the saliva markers were found to be significant comparing irradiated and non-irradiated groups, as well as comparing groups irradiated by various modulatory frequencies. Density of alveolar bone was examined on five slices acquired from every digital radiography image. Histogram were evaluated wit a computer program for microscopic image analysis. Density differences were verified in area of the whole slice. There were no significant differences found between bone density in irradiated and non irradiated groups perhaps due to our used therapeutical diagram.

The immunophenotype of bone marrow lymphocytes in children with immune thrombocytopenic purpura.

Science.gov (United States)

Alavi, Samin; Aryan, Zahra; Ghazizadeh, Farid; Arabi, Nahid; Nikougoftar, Mahin; Ebadi, Maryam

2014-09-01

Primary immune thrombocytopenic purpura (ITP), caused by immune system dysfunction, is recognized as the leading cause of thrombocytopenia in pediatric population. Nonetheless, inadequate studies have been performed on bone marrow immunophenotyping of children with ITP. In this study, we aimed to investigate the immunophenotype of bone marrow lymphocytes in these children. Between 2008 and 2012, 35 children with ITP and 26 age and sex matched healthy controls were recruited. All participants underwent bone marrow aspiration. Appropriate B-cell, T-cell, and myeloid lineage monoclonal antibodies were employed to determine the immunophenotype of these patients. CD10, CD19, and CD20, all indicative of premature B-cell markers, were significantly greater in children with ITP. CD22, mainly expressed on mature B cells was slightly, but not significantly reduced in the patients' group (P = .42). On the other hand, T cell markers including CD2, CD3, CD5, and CD7 were underexpressed. CD33, a specific marker for myeloid lineage, was underexpressed in the patients' group (5.6 ± 4.7 vs. 12.9 ± 7.3, P < .001). Noteworthy, the immunophenotype did not significantly differ between acute and persistent cases. Overall, a phenotype characterized by increased pre-B-cell markers along with decreased T cell immunophenotypic markers was observed in bone marrow lymphocytes of children with ITP in the present study. Further larger scale studies are recommended to confirm our findings, as precise mapping of the immunophenotype of lymphocytes in these patients would pave the road to improved diagnosis and treatment.

Skeletal development of mice lacking bone sialoprotein (BSP--impairment of long bone growth and progressive establishment of high trabecular bone mass.

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Wafa Bouleftour

Full Text Available Adult Ibsp-knockout mice (BSP-/- display shorter stature, lower bone turnover and higher trabecular bone mass than wild type, the latter resulting from impaired bone resorption. Unexpectedly, BSP knockout also affects reproductive behavior, as female mice do not construct a proper "nest" for their offsprings. Multiple crossing experiments nonetheless indicated that the shorter stature and lower weight of BSP-/- mice, since birth and throughout life, as well as their shorter femur and tibia bones are independent of the genotype of the mothers, and thus reflect genetic inheritance. In BSP-/- newborns, µCT analysis revealed a delay in membranous primary ossification, with wider cranial sutures, as well as thinner femoral cortical bone and lower tissue mineral density, reflected in lower expression of bone formation markers. However, trabecular bone volume and osteoclast parameters of long bones do not differ between genotypes. Three weeks after birth, osteoclast number and surface drop in the mutants, concomitant with trabecular bone accumulation. The growth plates present a thinner hypertrophic zone in newborns with lower whole bone expression of IGF-1 and higher IHH in 6 days old BSP-/- mice. At 3 weeks the proliferating zone is thinner and the hypertrophic zone thicker in BSP-/- than in BSP+/+ mice of either sex, maybe reflecting a combination of lower chondrocyte proliferation and impaired cartilage resorption. Six days old BSP-/- mice display lower osteoblast marker expression but higher MEPE and higher osteopontin(Opn/Runx2 ratio. Serum Opn is higher in mutants at day 6 and in adults. Thus, lack of BSP alters long bone growth and membranous/cortical primary bone formation and mineralization. Endochondral development is however normal in mutant mice and the accumulation of trabecular bone observed in adults develops progressively in the weeks following birth. Compensatory high Opn may allow normal endochondral development in BSP-/- mice

Serum bone alkaline phosphatase and calcaneus bone density predict fractures: a prospective study.

Science.gov (United States)

Ross, P D; Kress, B C; Parson, R E; Wasnich, R D; Armour, K A; Mizrahi, I A

2000-01-01

The aim of this study was to assess the ability of serum bone-specific alkaline phosphatase (bone ALP), creatinine-corrected urinary collagen crosslinks (CTx) and calcaneus bone mineral density (BMD) to identify postmenopausal women who have an increased risk of osteoporotic fractures. Calcaneus BMD and biochemical markers of bone turnover (serum bone ALP and urinary CTx) were measured in 512 community-dwelling postmenopausal women (mean age at baseline 69 years) participating in the Hawaii Osteoporosis Study. New spine and nonspine fractures subsequent to the BMD and biochemical bone markers measurements were recorded over an average of 2.7 years. Lateral spinal radiographs were used to identify spine fractures. Nonspine fractures were identified by self-report at the time of each examination. During the 2.7-year follow-up, at least one osteoporotic fracture occurred in 55 (10.7%) of the 512 women. Mean baseline serum bone ALP and urinary CTx were significantly higher among women who experienced an osteoporotic fracture compared with those women who did not fracture. In separate age-adjusted logistic regression models, serum bone ALP, urinary CTx and calcaneus BMD were each significantly associated with new fractures (odds ratios of 1.53, 1.54 and 1.61 per SD, respectively). Multiple variable logistic regression analysis identified BMD and serum bone ALP as significant predictors of fracture (p = 0.002 and 0.017, respectively). The results from this investigation indicate that increased bone turnover is significantly associated with an increased risk of osteoporotic fracture in postmenopausal women. This association is similar in magnitude and independent of that observed for BMD.

A population of serumdeprivation-induced bone marrow stem cells (SD-BMSC) expresses marker typical for embryonic and neural stem cells

International Nuclear Information System (INIS)

Sauerzweig, Steven; Munsch, Thomas; Lessmann, Volkmar; Reymann, Klaus G.; Braun, Holger

2009-01-01

The bone marrow represents an easy accessible source of adult stem cells suitable for various cell based therapies. Several studies in recent years suggested the existence of pluripotent stem cells within bone marrow stem cells (BMSC) expressing marker proteins of both embryonic and tissue committed stem cells. These subpopulations were referred to as MAPC, MIAMI and VSEL-cells. Here we describe SD-BMSC (serumdeprivation-induced BMSC) which are induced as a distinct subpopulation after complete serumdeprivation. SD-BMSC are generated from small-sized nestin-positive BMSC (S-BMSC) organized as round-shaped cells in the top layer of BMSC-cultures. The generation of SD-BMSC is caused by a selective proliferation of S-BMSC and accompanied by changes in both morphology and gene expression. SD-BMSC up-regulate not only markers typical for neural stem cells like nestin and GFAP, but also proteins characteristic for embryonic cells like Oct4 and SOX2. We hypothesize, that SD-BMSC like MAPC, MIAMI and VSEL-cells represent derivatives from a single pluripotent stem cell fraction within BMSC exhibiting characteristics of embryonic and tissue committed stem cells. The complete removal of serum might offer a simple way to specifically enrich this fraction of pluripotent embryonic like stem cells in BMSC cultures

Assessing the effect of dietary calcium intake and 25 OHD status on bone turnover in women in Pakistan.

Science.gov (United States)

Khan, Aysha Habib; Naureen, Ghazala; Iqbal, Romaina; Dar, Farhan Javed

2013-01-01

Bone health assessed in three towns of Karachi, Pakistan in females showed poor calcium intake, vitamin D deficiency, secondary hyperparathyroidism, and high bone turnover. Correlates of high bone turnover included females residing in Saddar Town, underweight females less than 30 years of age from low socio-economic status, and secondary hyperparathyroidism. To assess bone health and association of dietary calcium and 25 hydroxy vitamin D with bone turnover in the community-dwelling females of Karachi. Bone health was assessed in three randomly selected towns of Karachi, Pakistan. One premenopausal female fulfilling the inclusion criteria from each household was included in the study. Dietary calcium was assessed through a food frequency questionnaire and biochemical markers including calcium, phosphates, albumin, magnesium, creatinine, and SGPT, intact parathyroid hormone, 25 hydroxy vitamin D, and N-telopeptide of type I collagen were measured to assess the bone health. Three hundred and five females were included from three towns. Overall, 90.5% of females had vitamin D deficiency with 42.6 and 23.3% having secondary hyperparathyroidism and high bone turn over respectively. Prevalence of vitamin D deficiency, secondary hyperparathyroidism, and high bone turnover was significantly different among towns. Mean vitamin D levels were significantly low and iPTH levels significantly high in females with high bone turnover. Calcium intake was not significantly different among females with normal, high, and low bone turnover. Correlates of high bone turnover included females residing in Saddar Town, underweight females less than 30 years of age belonging to low socio-economic status, and secondary hyperparathyroidism. Compromised bone health is seen in community-dwelling females of Karachi. There is a need to perform large-scale community-based studies in all age groups to understand the interplay of markers in our population to understand the impact of these variables

The diagnostic and prognostic value of serum bone Gla protein (osteocalcin) in patients with recurrent breast cancer

DEFF Research Database (Denmark)

Kamby, C; Egsmose, C; Söletormos, G

1993-01-01

Serum bone Gla protein (S-BGP), a marker of bone metabolism, was measured in 60 patients included in a staging programme for recurrent breast cancer. Other diagnostic procedures comprised S-alkaline phosphatase (S-AP), bone scan (B-scan), bilateral iliac crest bone marrow biopsies, and radiological...... bone survey. The sites of recurrence were bone (61%), bone marrow (46%), soft tissue (52%), lung (13%), pleura (11%), liver (4%), and brain (2%). Radiology and bone biopsy served as key diagnoses as to the presence or absence of bone metastases. The diagnostic efficiency of B-scan and S-AP was greater...

Dairy products, yogurts, and bone health.

Science.gov (United States)

Rizzoli, René

2014-05-01

Fracture risk is determined by bone mass, geometry, and microstructure, which result from peak bone mass (the amount attained at the end of pubertal growth) and from the amount of bone lost subsequently. Nutritional intakes are an important environmental factor that influence both bone mass accumulation during childhood and adolescence and bone loss that occurs in later life. Bone growth is influenced by dietary intake, particularly of calcium and protein. Adequate dietary calcium and protein are essential to achieve optimal peak bone mass during skeletal growth and to prevent bone loss in the elderly. Dairy products are rich in nutrients that are essential for good bone health, including calcium, protein, vitamin D, potassium, phosphorus, and other micronutrients and macronutrients. Studies supporting the beneficial effects of milk or dairy products on bone health show a significant inverse association between dairy food intake and bone turnover markers and a positive association with bone mineral content. Fortified dairy products induce more favorable changes in biochemical indexes of bone metabolism than does calcium supplementation alone. The associations between the consumption of dairy products and the risk of hip fracture are less well established, although yogurt intake shows a weakly positive protective trend for hip fracture. By consuming 3 servings of dairy products per day, the recommended daily intakes of nutrients essential for good bone health may be readily achieved. Dairy products could therefore improve bone health and reduce the risk of fractures in later life.

Synergistic Effects of Aerobic Exercise after Bone Marrow Stem Cell Transplantation on Recovery of Dopaminergic Neurons and Angiogenesis Markers of Parkinsonian Rats

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Seyed Abdollah Hashemvarzi

2016-03-01

Full Text Available Abstract: Parkinson is a progressive neurodegenerative disease in central nervous system. Non-pharmacologic treatment methods such as stem cell transplantation and exercise have been considered as a treatment. The purpose of this study was to evaluate the synergistic effects of aerobic exercise after bone marrow stem cells transplantation on recovery of dopaminergic neurons and promotion of angiogenesis markers in the striatum of parkinsonian rats. 42 rats were divided into six groups: Normal (N, Sham (S, Parkinson’s (P, Stem cells transplanted Parkinson’s (SP, Exercised Parkinson’s (EP and Stem cells transplanted+Exercised Parkinson’s (SEP. To create a model of Parkinson's, the striatum was destroyed by injection of 6-hydroxy-dopamine into the striatum through stereotaxic apparatus. Stem cells were derived from the bone marrow of femur and tibia of male rats aged 6-8 weeks. After cultivation, approximately 5×105 cells were injected into the striatum of rats through the channel. Aerobic exercise was included 8 weeks of running on treadmill with a speed of 15 meters per minute. At the end of the study, all subjects were decapitated and striatum tissues were separately isolated for measurement of vascular endothelial growth factor (VEGF, dopamine (DA and tyrosine hydroxylase (TH levels. VEGF, DA and TH levels in the striatum of parkinsonian rats significantly increased in treatment groups (SP, EP and SEP, especially in SEP group compared to P group after treatment (P<0.05. The BMSCs transplantation in combination with exercise would have synergistic effects leading to functional recovery, dopaminergic neurons recovery and promotion of angiogenesis marker in the striatum of parkinsonian rats. Keywords: Stem cells, Aerobic exercise, Neurotrophic factors, Parkinson

Enhancement of Bone Marrow-Derived Mesenchymal Stem Cell Osteogenesis and New Bone Formation in Rats by Obtusilactone A

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Yi-Hsiung Lin

2017-11-01

Full Text Available The natural pure compound obtusilactone A (OA was identified in Cinnamomum kotoense Kanehira & Sasaki, and shows effective anti-cancer activity. We studied the effect of OA on osteogenesis of bone marrow-derived mesenchymal stem cells (BMSCs. OA possesses biocompatibility, stimulates Alkaline Phosphatase (ALP activity and facilitates mineralization of BMSCs. Expression of osteogenesis markers BMP2, Runx2, Collagen I, and Osteocalcin was enhanced in OA-treated BMSCs. An in vivo rat model with local administration of OA via needle implantation to bone marrow-residing BMSCs revealed that OA increased the new bone formation and trabecular bone volume in tibias. Micro-CT images and H&E staining showed more trabecular bone at the needle-implanted site in the OA group than the normal saline group. Thus, OA confers an osteoinductive effect on BMSCs via induction of osteogenic marker gene expression, such as BMP2 and Runx2 expression and subsequently elevates ALP activity and mineralization, followed by enhanced trabecular bone formation in rat tibias. Therefore, OA is a potential osteoinductive drug to stimulate new bone formation by BMSCs.

Relationship between bone turnover markers and the heel stiffness index measured by quantitative ultrasound in middle-aged and elderly Japanese men

Science.gov (United States)

Nishimura, Takayuki; Arima, Kazuhiko; Abe, Yasuyo; Kanagae, Mitsuo; Mizukami, Satoshi; Okabe, Takuhiro; Tomita, Yoshihito; Goto, Hisashi; Horiguchi, Itsuko; Aoyagi, Kiyoshi

2018-01-01

Abstract The aim of the present study was to investigate the age-related patterns and the relationships between serum levels of tartrate-resistant acid phosphatase-5b (TRACP-5b) or bone-specific alkaline phosphatase (BAP), and the heel stiffness index measured by quantitative ultrasound (QUS) in 429 Japanese men, with special emphasis on 2 age groups (40–59 years and 60 years or over). The heel stiffness index (bone mass) was measured by QUS. Serum samples were collected, and TRACP-5b and BAP levels were measured. The stiffness index was significantly decreased with age. Log (TRACP-5b) was significantly increased with age, but Log (BAP) was stable. Generalized linear models showed that higher levels of Log (TRACP-5b) and Log (BAP) were correlated with a lower stiffness index after adjusting for covariates in men aged 60 years or over, but not in men aged 40 to 59 years. In conclusion, higher rates of bone turnover markers were associated with a lower stiffness index only in elderly men. These results may indicate a different mechanism of low bone mass among different age groups of men. PMID:29465590

Significance of bone specific alkaline phosphatase as a tumor marker in malignant bone tumor

International Nuclear Information System (INIS)

Kim, Sug Jun; Jeon, Dae Geun; Huh, Kwang

1998-01-01

The relationship between total alkaline phosphatase activity and bone forming lesion is a well known fact. But alkaline phosphatase consist mainly of two portion (liver, bone). To clarify the exact activity of bone forming tissue, quantitative measurement of BALP is essential. Two finds of tests were performed for their feasibility as a laboratory test (wheat germ lectin vs electrophoresis). We analyzed 40 bony lesion and got 58 samples. Lectin method was simple, economic, with reliable resproducability. Owing to the small number of test sample, we could not identify the relationship between the disease activity and measured BALP level. Further collection of clinical sample and analysis the pattern of BALP on each clinical settings. (author). 8 refs

Effect of a Particulate and a Putty-Like Tricalcium Phosphate-Based Bone-grafting Material on Bone Formation, Volume Stability and Osteogenic Marker Expression after Bilateral Sinus Floor Augmentation in Humans

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Christine Knabe

2017-07-01

Full Text Available This study examines the effect of a hyaluronic acid (HyAc containing tricalcium phosphate putty scaffold material (TCP-P and of a particulate tricalcium phosphate (TCP-G graft on bone formation, volume stability and osteogenic marker expression in biopsies sampled 6 months after bilateral sinus floor augmentation (SFA in 7 patients applying a split-mouth design. 10% autogenous bone chips were added to the grafting material during surgery. The grain size of the TCP granules was 700 to 1400 µm for TCP-G and 125 to 250 µm and 500 to 700 µm (ratio 1:1 for TCP-P. Biopsies were processed for immunohistochemical analysis of resin-embedded sections. Sections were stained for collagen type I (Col I, alkaline phosphatase (ALP, osteocalcin (OC and bone sialoprotein (BSP. Furthermore, the bone area and biomaterial area fraction were determined histomorphometrically. Cone-beam CT data recorded after SFA and 6 months later were used for calculating the graft volume at these two time points. TCP-P displayed more advantageous surgical handling properties and a significantly greater bone area fraction and smaller biomaterial area fraction. This was accompanied by significantly greater expression of Col I and BSP and in osteoblasts and osteoid and a less pronounced reduction in grafting volume with TCP-P. SFA using both types of materials resulted in formation of sufficient bone volume for facilitating stable dental implant placement with all dental implants having been in function without any complications for 6 years. Since TCP-P displayed superior surgical handling properties and greater bone formation than TCP-G, without the HyAc hydrogel matrix having any adverse effect on bone formation or graft volume stability, TCP-P can be regarded as excellent grafting material for SFA in a clinical setting. The greater bone formation observed with TCP-P may be related to the difference in grain size of the TCP granules and/or the addition of the HyAc.

Possible Role of Garlic Oil and Parsley Extract in Ameliorating Radiation-Induced Bone Loss in Female Rats

International Nuclear Information System (INIS)

Ramadan, L.; El-Sabbagh, W.; Kenawy, S.

2011-01-01

To Investigate the possible protective effect of garlic oil and parsley extract against bone loss resulted in female virgin rats exposed to fractionated doses of gamma-radiation (1 Gy 3 times weekly for 5 weeks). Urinary calcium (U Ca), calcium to creatinine ratio (Ca/Cr), hydroxyproline and serum phosphorus were measured as bone resorption bio markers, while serum osteocalcine (OST) and serum alkaline phosphatase (ALP) were measured as bone formation bio markers. Furthermore, nitric oxide (NO) which represents the balance in bone remodeling was measured. Malondiadehyde level (MDA) as well as superoxide dismutase activity (SOD) was measured as oxidative stress bio markers. Female irradiated rats in the present study had significant increases in both bone resorption and bone formation bio markers after 6 weeks from the last exposure to gamma-radiation. Irradiated rats also had significant decreases in plasma NO indicating imbalance in bone remodeling as well as significant increase in oxidative stress bio markers. Daily treatment with garlic oil extracted in olive oil improved all measured parameters except OST level, while the vehicle used for garlic oil (extra virgin olive oil) significantly decreased bone resorption bio markers. Parsley extract induced normalization to all bone resorption and formation parameters measured in irradiated rats. Daily administration of garlic oil and parsley extract protected the bone from degeneration induced by exposure to fractionated doses of gamma radiation.

Preeclampsia - a risk factor for osteoporosis? Analysis of maternal Sclerostin levels and markers of bone turnover in patients with pre-eclampsia.

Science.gov (United States)

Wild, Julia; Pateisky, Petra; Küssel, Lorenz; Huf, Wolfgang; Ott, Johannes; Haslinger, Peter; Knöfler, Martin; Zeisler, Harald

2014-08-01

The role of preeclampsia (PE) in affecting bone metabolism could not be clarified in the past years. Recently Sclerostin, a new marker of bone metabolism which is known to have an inhibitory effect on bone formation causing osteoporosis, was discovered. To investigate serum levels of Sclerostin and markers of bone turnover in women with normotensive pregnancies and pregnancies complicated by PE. In this prospective study we enrolled 22 women with PE and 22 healthy pregnant women to observe serum levels of carboxyterminal propeptide of type I collagen (PICP), cross-linked carboxyl terminal telopeptide of the type I collagen (ICTP), calcium, phosphate, 25-hydroxyvitamin D and parathyroid hormone. In 16 preeclamptic and 16 healthy pregnant women, serum Sclerostin levels were analyzed. Serum levels of Sclerostin (mean ± standard deviation: healthy 10.5 ± 8.1 pmol/l versus PE 11.5 ± 9.4 pmol/l, p = 0.768), ICTP (healthy 0.3 ± 0.2 ng/ml versus PE 0.4 ± 0.1 ng/ml, p = 0.462), PICP (healthy 59.9 ± 49.9 ng/ml versus PE 89.0 ± 62.0 ng/ml, p = 0.094), phosphate (healthy 1.1 ± 0.2 mmol/l versus PE 1.2 ± 0.4 mmol/l, p = 0.162) and parathyroid hormone (healthy 26.9 ± 14 pg/ml versus PE 35.3 ± 17.6 pg/ml, p = 0.08) showed no significant differences between the groups. Significantly lower serum calcium (healthy 2.3 ± 0.1 mmol/l versus PE 2.2 ± 0.2 mmol/l, p < 0.005) and serum 25-Hydroxyvitamin D (healthy 39.3 ± 16.7 nmol/l versus PE 23.9 ± 16.9 nmol/l, p < 0.005) were observed in preeclamptic women. Pregnancies complicated by PE show no signs of high bone turnover and may not lead to a higher risk of osteoporosis in later life.

MECHANISMS IN ENDOCRINOLOGY: Diabetes mellitus, a state of low bone turnover - a systematic review and meta-analysis.

Science.gov (United States)

Hygum, Katrine; Starup-Linde, Jakob; Harsløf, Torben; Vestergaard, Peter; Langdahl, Bente L

2017-03-01

To investigate the differences in bone turnover between diabetic patients and controls. A systematic review and meta-analysis. A literature search was conducted using the databases Medline at PubMed and EMBASE. The free text search terms 'diabetes mellitus' and 'bone turnover', 'sclerostin', 'RANKL', 'osteoprotegerin', 'tartrate-resistant acid' and 'TRAP' were used. Studies were eligible if they investigated bone turnover markers in patients with diabetes compared with controls. Data were extracted by two reviewers. A total of 2881 papers were identified of which 66 studies were included. Serum levels of the bone resorption marker C-terminal cross-linked telopeptide (-0.10 ng/mL (-0.12, -0.08)) and the bone formation markers osteocalcin (-2.51 ng/mL (-3.01, -2.01)) and procollagen type 1 amino terminal propeptide (-10.80 ng/mL (-12.83, -8.77)) were all lower in patients with diabetes compared with controls. Furthermore, s-tartrate-resistant acid phosphatase was decreased in patients with type 2 diabetes (-0.31 U/L (-0.56, -0.05)) compared with controls. S-sclerostin was significantly higher in patients with type 2 diabetes (14.92 pmol/L (3.12, 26.72)) and patients with type 1 diabetes (3.24 pmol/L (1.52, 4.96)) compared with controls. Also, s-osteoprotegerin was increased among patients with diabetes compared with controls (2.67 pmol/L (0.21, 5.14)). Markers of both bone formation and bone resorption are decreased in patients with diabetes. This suggests that diabetes mellitus is a state of low bone turnover, which in turn may lead to more fragile bone. Altered levels of sclerostin and osteoprotegerin may be responsible for this. © 2017 European Society of Endocrinology.

Low bone turnover phenotype in Rett syndrome

DEFF Research Database (Denmark)

Roende, Gitte; Petersen, Janne; Ravn, Kirstine

2014-01-01

Background:Patients with Rett syndrome (RTT) are at risk of having low bone mass and low-energy fractures.Methods:We characterised bone metabolism by both bone formation and resorption markers in blood in a RTT population of 61 girls and women and 122 well-matched healthy controls. Levels of N-te...

Normal tempo of bone formation in Turner syndrome despite signs of accelerated bone resorption

DEFF Research Database (Denmark)

Cleemann, Line Hartvig; Holm, Kirsten Bagge; Kobbernagel, Hanne

2011-01-01

Aims: To evaluate area bone mineral density (aBMD) and volumetric BMD (vBMD) by dual-energy X-ray absorptiometry, and relations to bone markers and hormones in adolescent women with Turner syndrome (TS). Methods: Cross-sectional study in TS patients (n = 37, 16.7 ± 3.4 years) and control group (n...

Normal Tempo of Bone Formation in Turner Syndrome despite Signs of Accelerated Bone Resorption

DEFF Research Database (Denmark)

Cleemann, Line; Holm, Kirsten; Kobbernagel, Hanne

2011-01-01

Aims: To evaluate area bone mineral density (aBMD) and volumetric BMD (vBMD) by dual-energy X-ray absorptiometry, and relations to bone markers and hormones in adolescent women with Turner syndrome (TS). Methods: Cross-sectional study in TS patients (n = 37, 16.7 ± 3.4 years) and control group (n...

The globoseries glycosphingolipid SSEA-4 is a marker of bone marrow-derived clonal multipotent stromal cells in vitro and in vivo.

Science.gov (United States)

Rosu-Myles, Michael; McCully, Jennifer; Fair, Joel; Mehic, Jelica; Menendez, Pablo; Rodriguez, Rene; Westwood, Carole

2013-05-01

The therapeutic potential of multipotent stromal cells (MSC) may be enhanced by the identification of markers that allow their discrimination and enumeration both in vivo and in vitro. Here, we investigated the ability of embryonic stem cell-associated glycosphingolipids to isolate human MSC from both whole-bone-marrow (BM) and stromal cell cultures. Only SSEA-4 was consistently expressed on cells within the CD45loCD105hi marrow fraction and could be used to isolate cells with the capacity to give rise to stromal cultures containing MSC. Human stromal cultures, generated in either the presence or absence of serum, contained heterogeneous cell populations discriminated by the quantity of SSEA-4 epitopes detected on their surface. A low level of surface SSEA-4 (SSEA-4lo) correlated with undetectable levels of the α2,3-sialyltransferase-II enzyme required to synthesize SSEA-4; a reduced proliferative potential; and the loss of fat-, bone-, and cartilage-forming cells during long-term culture. In vitro, single cells with the capacity to generate multipotent stromal cultures were detected exclusively in the SSEA-4hi fraction. Our data demonstrate that a high level of surface epitopes for SSEA-4 provides a definitive marker of MSC from human BM.

Vitamin D status in relation to obesity, bone mineral density, bone turnover markers and vitamin D receptor genotypes in healthy Saudi pre- and postmenopausal women.

Science.gov (United States)

Ardawi, M-S M; Qari, M H; Rouzi, A A; Maimani, A A; Raddadi, R M

2011-02-01

The various factors that may contribute to vitamin D deficiency or insufficiency were examined among healthy Saudi pre- and postmenopausal women. Vitamin D deficiency was highly prevalent among studied Saudi women with obesity, poor sunlight exposure, poor dietary vitamin D supplementation and age as the main risk factors. The various factors that may contribute to vitamin D deficiency or insufficiency in relation to bone health among Saudi women are not known. The main objectives of the present study were to determine the factors influencing vitamin D status in relation to serum 25-hydroxyvitamin D (25(OH)D), intact parathyroid hormone (PTH), bone turnover markers (BTMs), bone mineral density (BMD), and vitamin D receptor genotype (VDR) in healthy Saudi pre- and postmenopausal women. A total number of 1,172 healthy Saudi women living in the Jeddah area were randomly selected and studied. Anthropometric parameters, socioeconomic status, sun exposure index together with serum levels of 25(OH)D, calcitriol, intact PTH, Ca, PO4, Mg, creatinine, albumin, and biochemical BTMs were measured. BMD was measured by a dual energy X-ray absorptiometry and VDR genotypes were also determined. About 80.0% of Saudi women studied exhibited vitamin D deficiency (serum 25(OH)D75 nmol/L). Secondary hyperparathyroidism was evident in 18.5% and 24.6% in pre- and postmenopausal women with 25(OH)Dobesity, poor exposure to sunlight, poor dietary vitamin D supplementation, and age.

Calcium intake in winter pregnancy attenuates impact of vitamin D inadequacy on urine NTX, a marker of bone resorption.

Science.gov (United States)

O'Brien, Eileen C; Kilbane, Mark T; McKenna, Malachi J; Segurado, Ricardo; Geraghty, Aisling A; McAuliffe, Fionnuala M

2018-04-01

Pregnancy is characterised by increased bone turnover, but high bone turnover with resorption exceeding formation may lead to negative maternal bone remodelling. Recent studies are conflicting regarding the effect of calcium on skeletal health in pregnancy. The aim of this study was to examine the seasonal effect of serum 25-hydroxyvitamin D (25OHD) and dietary calcium on a marker of bone resorption. This was prospective study of 205 pregnant women [two cohorts; early pregnancy at 13 weeks (n = 96), and late pregnancy at 28 weeks (n = 109)]. Serum 25OHD and urine cross-linked N-telopeptides of type I collagen (uNTX) were measured at both time points. Intakes of vitamin D and calcium were recorded using 3-day food diaries at each trimester. Compared to summer pregnancies, winter pregnancies had significantly lower 25OHD and significantly higher uNTX. Higher calcium intakes were negatively correlated with uNTX in winter, but not summer. In late pregnancy, compared to those reporting calcium intakes ≥1000 mg/day, intakes of <1000 mg/day were associated with a greater increase in uNTX in winter pregnancies than in summer (41.8 vs. 0.9%). Increasing calcium intake in winter by 200 mg/day predicted a 13.3% reduction in late pregnancy uNTX. In late pregnancy, during winter months when 25OHD is inadequate, intakes of dietary calcium <1000 mg/day were associated with significantly increased bone resorption (uNTX). Additional dietary calcium is associated with reduced bone resorption in late pregnancy, with greater effect observed in winter. Further research regarding optimal dietary calcium and 25OHD in pregnancy is required, particularly for women gestating through winter.

Determination of processed animal proteins, including meat and bone meal, in animal feed

NARCIS (Netherlands)

Gizzi, G.; Holst, von C.; Baeten, V.; Berben, G.; Raamsdonk, van L.W.D.

2004-01-01

The presence of processed animal proteins (PAP), including meat and bone meal (MBM) from various species, in animal feed was investigated. It was demonstrated that microscopy is the most reliable method for enforcing the current total MBM ban in the European Uion (EU). It was shown that near

The effects of low environmental cadmium exposure on bone density

Energy Technology Data Exchange (ETDEWEB)

Trzcinka-Ochocka, M., E-mail: ochocka@imp.lodz.pl [Department of Chemical Hazards, Laboratory of Biomonitoring, Nofer Institute of Occupational Medicine, Lodz (Poland); Jakubowski, M. [Department of Chemical Hazards, Laboratory of Biomonitoring, Nofer Institute of Occupational Medicine, Lodz (Poland); Szymczak, W. [Department of Environmental Epidemiology, Nofer Institute of Occupational Medicine, Lodz (Poland); Insitute of Psychology, University of Lodz (Poland); Janasik, B.; Brodzka, R. [Department of Chemical Hazards, Laboratory of Biomonitoring, Nofer Institute of Occupational Medicine, Lodz (Poland)

2010-04-15

Recent epidemiological data indicate that low environmental exposure to cadmium, as shown by cadmium body burden (Cd-U), is associated with renal dysfunction as well as an increased risk of cadmium-induced bone disorders. The present study was designed to assess the effects of low environmental cadmium exposure, at the level sufficient to induce kidney damage, on bone metabolism and mineral density (BMD). The project was conducted in the area contaminated with cadmium, nearby a zinc smelter located in the region of Poland where heavy industry prevails. The study population comprised 170 women (mean age=39.7; 18-70 years) and 100 men (mean age=31.9; 18-76 years). Urinary and blood cadmium and the markers of renal tubular dysfunction ({beta}{sub 2}M-U RBP, NAG), glomerular dysfunction (Alb-U and {beta}{sub 2}M-S) and bone metabolism markers (BAP-S, CTX-S) as well as forearm BMD, were measured. The results of this study based on simple dose-effect analysis showed the relationship between increasing cadmium concentrations and an increased excretion of renal dysfunction markers and decreasing bone density. However, the results of the multivariate analysis did not indicate the association between exposure to cadmium and decrease in bone density. They showed that the most important factors that have impact on bone density are body weight and age in the female subjects and body weight and calcium excretion in males. Our investigation revealed that the excretion of low molecular weight proteins occurred at a lower level of cadmium exposure than the possible loss of bone mass. It seems that renal tubular markers are the most sensitive and significant indicators of early health effects of cadmium intoxication in the general population. The correlation of urinary cadmium concentration with markers of kidney dysfunction was observed in the absence of significant correlations with bone effects. Our findings did not indicate any effects of environmental cadmium exposure on bone

Rapamycin inhibits BMP-7-induced osteogenic and lipogenic marker expressions in fetal rat calvarial cells.

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Yeh, Lee-Chuan C; Ma, Xiuye; Ford, Jeffery J; Adamo, Martin L; Lee, John C

2013-08-01

Bone morphogenetic proteins (BMPs) promote osteoblast differentiation and bone formation in vitro and in vivo. BMPs canonically signal through Smad transcription factors, but BMPs may activate signaling pathways traditionally stimulated by growth factor tyrosine kinase receptors. Of these, the mTOR pathway has received considerable attention because BMPs activate P70S6K, a downstream effector of mTOR, suggesting that BMP-induced osteogenesis is mediated by mTOR activation. However, contradictory effects of the mTOR inhibitor rapamycin (RAPA) on bone formation have been reported. Since bone formation is thought to be inversely related to lipid accumulation and mTOR is also important for lipid synthesis, we postulated that BMP-7 may stimulate lipogenic enzyme expression in a RAPA-sensitive mechanism. To test this hypothesis, we determined the effects of RAPA on BMP-7-stimulated expression of osteogenic and lipogenic markers in cultured fetal rat calvarial cells. Our study showed that BMP-7 promoted the expression of osteogenic and lipogenic markers. The effect of BMP-7 on osteogenic markers was greater in magnitude than on lipogenic markers and was temporally more sustained. RAPA inhibited basal and BMP-7-stimulated osteogenic and lipogenic marker expression and bone nodule mineralization. The acetyl CoA carboxylase inhibitor TOFA stimulated the expression of osteoblast differentiation markers, whereas palmitate suppressed their expression. We speculate that the BMP-7-stimulated adipogenesis is part of the normal anabolic response to BMPs, but that inappropriate activation of the lipid biosynthetic pathway by mTOR could have deleterious effects on bone formation and could explain paradoxical effects of RAPA to promote bone formation. Copyright © 2013 Wiley Periodicals, Inc.

Short-term variability in biomarkers of bone metabolism in sheep.

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Sousa, Cristina P; de Azevedo, Jorge T; Reis, Rui L; Gomes, Manuela E; Dias, Isabel R

2014-01-01

Changes in bone remodeling during pathological states and during their treatment can be assessed noninvasively by measuring biomarkers of bone metabolism. Their application is limited, however, by the potential biological variability in the levels of these biomarkers over time. To determine the short-term variability in biomarkers of bone metabolism in adult sheep, the authors measured serum levels of alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP), osteocalcin (OC), N-terminal propeptide of type-III procollagen (PIIINP), deoxypyridinoline (DPD), tartrate-resistant acid phosphatase (TRAP), calcium and phosphorus intermittently over a 12-week period. There were significant differences in mean ALP activity and in phosphorus concentrations over time, but all other biomarkers showed no significant short-term variability. The results suggest that biomarkers of bone metabolism in sheep, especially the bone resorption marker DPD and the bone formation marker BALP, can be used reliably to detect changes in bone cellular activity.

Alteration In Bones Metabolism In Active Rheumatoid Arthritis

International Nuclear Information System (INIS)

Salem, E.S.

2013-01-01

The strength and integrity of the human skeleton depends on a delicate equilibrium between bone resorption and bone formation. Osteocalcin (OC) is synthesized by osteoblasts and is considered to be a marker of bone formation and helps in corporating calcium into bone tissue. Rheumatoid arthritis (RA) is an autoimmune inflammatory joint disease characterized by bone complication including bone pain, erosion and osteoporosis. The aim of the present study is to evaluate some factors responsible in bone metabolism termed OC, vitamin D (vit. D), oncostatin M (OSM), ionized calcium and alkaline phosphatase. Fifty pre-menopausal female patients with active RA and twenty healthy controls of the same age were included in the present study. Radioimmunoassay (RIA) was used to estimate serum OC and active vitamin D. The quantitative determination of ionized calcium and alkaline phosphatase were carried out colorimetrically. OSM was measured by ELISA and serum levels of OC and active vitamin D were significantly decreased in RA patients as compared to those of the control group. On the other hand, the levels of serum OSM, ionized calcium and alkaline phosphatase were significantly increased in the RA patients as compared to their healthy control subjects. The results of this study indicated that early investigation and therapy of disturbances of bone metabolism in active RA are necessary for better prognosis and exhibited the importance of OC as a diagnostic tool of alterations of bone metabolism in RA patients.

Osteoblast recruitment routes in human cancellous bone remodeling

DEFF Research Database (Denmark)

Kristensen, Helene Bjørg; Andersen, Thomas Levin; Marcussen, Niels

2014-01-01

It is commonly proposed that bone forming osteoblasts recruited during bone remodeling originate from bone marrow perivascular cells, bone remodeling compartment canopy cells, or bone lining cells. However, an assessment of osteoblast recruitment during adult human cancellous bone remodeling...... is lacking. We addressed this question by quantifying cell densities, cell proliferation, osteoblast differentiation markers, and capillaries in human iliac crest biopsy specimens. We found that recruitment occurs on both reversal and bone-forming surfaces, as shown by the cell density and osterix levels...

Assessing bone status in patients awaiting liver transplantation.

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Wibaux, Cécile; Legroux-Gerot, Isabelle; Dharancy, Sébastien; Boleslawski, Emmanuel; Declerck, Nicole; Canva, Valérie; Mathurin, Philippe; Pruvot, François-René; Cortet, Bernard

2011-07-01

Osteoporosis is common in liver transplant recipients as a result of both iatrogenic factors and preexisting hepatic osteodystrophy. To assess the prevalences of osteoporosis and fractures and to identify risk factors for these two abnormalities in patients awaiting liver transplantation for end-stage liver disease. Between January 2006 and December 2007, patients on a liver transplant waiting list underwent a routine evaluation comprising the identification of risk factors for osteoporosis, radiographs of the spine, bone mineral density measurements (BMD), and laboratory tests (phosphate and calcium levels, hormone assays, liver function tests, and bone turnover markers). We studied 99 patients (70 males and 20 females; mean age, 55 ± 8 years) including 75% with alcohol-induced cirrhosis with or without hepatocarcinoma. Among them, 36% had radiographic vertebral fractures, 38% had osteoporosis, 35% had osteopenia, and 88% had vitamin D insufficiency or deficiency (25(OH)vitamin D3bone resorption markers correlated negatively with BMD at the spine and hip. The Model for End-Stage Liver Disease score correlated negatively with hip BMD. Our findings suggest high prevalences of low BMD values and vertebral fractures among patients awaiting liver transplantation. Bone status should be evaluated routinely in candidates to liver transplantation. Copyright © 2011 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Growth hormone (GH) effects on bone and collagen turnover in healthy adults and its potential as a marker of GH abuse in sports: a double blind, placebo-controlled study. The GH-2000 Study Group.

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Longobardi, S; Keay, N; Ehrnborg, C; Cittadini, A; Rosén, T; Dall, R; Boroujerdi, M A; Bassett, E E; Healy, M L; Pentecost, C; Wallace, J D; Powrie, J; Jørgensen, J O; Saccà, L

2000-04-01

The effects of GH on bone remodeling in healthy adults have not been systematically investigated. An analysis of these effects might provide insights into GH physiology and might yield data useful for the detection of GH doping in sports. The aim of this study was to evaluate the effects of GH administration on biochemical markers of bone and collagen turnover in healthy volunteers. Ninety-nine healthy volunteers of both sexes were enrolled in a multicenter, randomized, double blind, placebo-controlled study and assigned to receive either placebo (40 subjects) or recombinant human GH (0.1 IU/kg day in 29 subjects and 0.2 IU/kg x day in 30 subjects). The treatment duration was 28 days, followed by a 56-day wash-out period. The biochemical markers evaluated were the bone formation markers osteocalcin and C-terminal propeptide of type I procollagen, the resorption marker type I collagen telopeptide, and the soft tissue marker procollagen type III. All variables increased on days 21 and 28 in the two active treatment groups vs. levels in both the baseline (P < 0.01) and placebo (P < 0.01) groups. The increment was more pronounced in the 0.2 IU/kg-day group and remained significant on day 84 for procollagen type III (from 0.53 +/- 0.13 to 0.61 +/- 0.14 kU/L; P < 0.02) and osteocalcin (from 12.2 + 2.9 to 14.6 +/- 3.6 UG/L; P < 0.02), whereas levels of C-terminal propeptide of type I procollagen and type I collagen telopeptide declined after day 42 and were no longer significantly above baseline on day 84 (from 3.9 +/- 1.2 to 5.1 +/-1.5 microg/L and from 174 +/- 60 to 173 +/- 53 microg/L, respectively). Gender-related differences were observed in the study; females were less responsive than males to GH administration with respect to procollagen type III and type I collagen telopeptide (P < 0.001). In conclusion, exogenous GH administration affects the biochemical parameters of bone and collagen turnover in a dose- and gender-dependent manner. As GH-induced modifications

Bone mass and turnover in fibromyalgia

DEFF Research Database (Denmark)

Jacobsen, Søren; Gam, A; Egsmose, C

1993-01-01

Physical inactivity accelerates bone loss. Since patients with fibromyalgia are relatively physically inactive, bone mass and markers of bone metabolism were determined in 12 premenopausal women with fibromyalgia and in healthy age matched female control subjects. No differences were found in lum.......01. This was linked to lower urinary creatinine excretion (p = 0.02) probably reflecting lower physical activity in the patients with fibromyalgia. We conclude that bone mass and turnover are generally not affected in premenopausal women with fibromyalgia....

Bones and Crohn's: Estradiol deficiency in men with Crohn's disease is not associated with reduced bone mineral density

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Boehm BO

2008-10-01

Full Text Available Abstract Background Reduced bone mineral density (BMD and osteoporosis are frequent in Crohn's disease (CD, but the underlying mechanisms are still not fully understood. Deficiency of sex steroids, especially estradiol (E2, is an established risk factor in postmenopausal osteoporosis. Aim To assess if hormonal deficiencies in male CD patients are frequent we investigated both, sex steroids, bone density and bone metabolism markers. Methods 111 male CD patients underwent osteodensitometry (DXA of the spine (L1–L4. Disease related data were recorded. Disease activity was estimated using Crohn's disease activity index (CDAI. Testosterone (T, dihydrotestosterone (DHT, estradiol (E2, sex hormone binding globulin (SHBG, Osteocalcin and carboxyterminal cross-linked telopeptids (ICTP were measured in 111 patients and 99 age-matched controls. Results Patients had lower T, E2 and SHBG serum levels (p 10 g had lower BMD. 32 (28.8% patients showed osteoporosis, 55 (49.5% osteopenia and 24 (21.6% had normal BMD. Patients with normal or decreased BMD showed no significant difference in their hormonal status. No correlation between markers of bone turnover and sex steroids could be found. ICTP was increased in CD patients (p Conclusion We found an altered hormonal status – i.e. E2 and, to a lesser extent T deficiency – in male CD patients but failed to show an association to bone density or markers of bone turnover. The role of E2 in the negative skeletal balance in males with CD, analogous to E2 deficiency in postmenopausal females, deserves further attention.

Pathophysiologic basics and diagnostic limits of conventional bone scanning

International Nuclear Information System (INIS)

Schuemichen, C.; Dunkelmann, S.

2006-01-01

Normal bone scan demonstrates the physiological regional bone formation rate, which is related to bone remodeling and maintenance of calcium homeostasis. Osteotrope radiopharmaceuticals can be used as a perfusion marker as well as a marker of regional bone formation rate. Local hyperperfusion without increased bone formation is seen in disuse atrophy and reflex sympathic dystrophy, which are difficult to discriminate, local hypoperfusion is responsible for false negative results in osteomyelitis. A local increased bone formation rate is the substrate of a positive finding in bone fracture, inflammation, tumors, metastases and other lesions. In direct comparison with other imaging modalities (MRT, scintigraphy with non-osteotrope radiopharmaceutical and PET, but not CT and multislice-CT), planar bone scintigraphy shows an unexpected deficiency in sensitivity, which can be almost or completely overcome by using SPECT or even better 18 F-fluoride PET. These techniques will also improve specificity, which still is a weak point of bone scanning, despite improved imaging performance and a huge experience in this field. The introduction of SPECT/CT und PET/CT in bone scanning will be even more desirable for this reason. (orig.)

Bone lesions in Chinese POEMS syndrome patients: imaging characteristics and clinical implications.

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Wang, Fengdan; Huang, Xufei; Zhang, Yan; Li, Jian; Zhou, Daobin; Jin, Zhengyu

2016-01-01

Objective. Bone lesion is crucial for diagnosing and management of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin change (POEMS) syndrome, a rare plasma cell disorder. This study is to compare the effectiveness of X-ray skeletal survey (SS) and computed tomography (CT) for detecting bone lesions in Chinese POEMS syndrome patients, and to investigate the relationship between bone lesion features and serum markers. Methods. SS and chest/abdomen/pelvic CT images of 38 Chinese patients (26 males, 12 females, aged 21-70 years) with POEMS syndrome recruited at our medical center between January 2013 and January 2015 were retrospectively analyzed. Bone lesions identified by CT were further categorized according to the size (10 mm) and appearance (osteosclerotic, lytic, mixed). The percentage of plasma cells in bone marrow smears, type of immunoglobulin, platelet (Plt), and levels of serum bone metabolic markers and inflammatory factors including alkaline phosphatase (ALP), calcium, phosphate, parathyroid hormone (PTH), beta-isomerized C-telopeptide (β-CTx), vascular endothelial growth factor (VEGF), and interleukin (IL)-6 levels were also recorded. Results. Of the 38 POEMS syndrome patients, the immunoglobulin heavy chain isotypes were IgA in 25 patients (65.8%; 25/38) and IgG in 13 patients (34.2%; 13/38), and the light chain isotypes were λ in 35 patients (92.1%; 35/38) and κ in 3 patients (7.9%; 3/38). There were 23 patients with thrombocytosis. More patients with bone lesions were detected by CT than by SS (97.4% vs. 86.8%). The most commonly affected location was the pelvis (89.5%), followed by the spine, clavicle/scapula/sternum/ribs, skull, and long bones. Of the 38 POEMS syndrome patients, 35 (94.6%) had osteosclerotic and 32 (86.5%) had mixed lesions. Osteosclerotic lesions were typically scattered, variable in size, and plaque-like, whereas mixed lesions were pouch-shaped or soup bubble-like with a clear sclerotic margin and were

Short-Term Effects of Kefir-Fermented Milk Consumption on Bone Mineral Density and Bone Metabolism in a Randomized Clinical Trial of Osteoporotic Patients.

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Tu, Min-Yu; Chen, Hsiao-Ling; Tung, Yu-Tang; Kao, Chao-Chih; Hu, Fu-Chang; Chen, Chuan-Mu

2015-01-01

Milk products are good sources of calcium that may reduce bone resorption and help prevent bone loss as well as promote bone remodeling and increase bone formation. Kefir is a product made by kefir grains that degrade milk proteins into various peptides with health-promoting effects, including antithrombotic, antimicrobial and calcium-absorption enhancing bioactivities. In a controlled, parallel, double-blind intervention study over 6 months, we investigated the effects of kefir-fermented milk (1,600 mg) supplemented with calcium bicarbonate (CaCO3, 1,500 mg) and bone metabolism in 40 osteoporosis patients, and compared them with CaCO3 alone without kefir supplements. Bone turnover markers were measured in fasting blood samples collected before therapy and at 1, 3, and 6 months. Bone mineral density (BMD) values at the spine, total hip, and hip femoral neck were assessed by dual-energy x-ray absorptiometry (DXA) at baseline and at 6 months. Among patients treated with kefir-fermented milk, the relationships between baseline turnover and 6 months changes in DXA-determined BMD were significantly improved. The serum β C-terminal telopeptide of type I collagen (β-CTX) in those with T-scores > -1 patients significantly decreased after three months treatment. The formation marker serum osteocalcin (OC) turned from negative to positive after 6 months, representing the effect of kefir treatment. Serum parathyroid hormone (PTH) increased significantly after treatment with kefir, but decreased significantly in the control group. PTH may promote bone remodeling after treatment with kefir for 6 months. In this pilot study, we concluded that kefir-fermented milk therapy was associated with short-term changes in turnover and greater 6-month increases in hip BMD among osteoporotic patients. ClinicalTrials.gov NCT02361372.

Short-Term Effects of Kefir-Fermented Milk Consumption on Bone Mineral Density and Bone Metabolism in a Randomized Clinical Trial of Osteoporotic Patients.

Directory of Open Access Journals (Sweden)

Min-Yu Tu

Full Text Available Milk products are good sources of calcium that may reduce bone resorption and help prevent bone loss as well as promote bone remodeling and increase bone formation. Kefir is a product made by kefir grains that degrade milk proteins into various peptides with health-promoting effects, including antithrombotic, antimicrobial and calcium-absorption enhancing bioactivities. In a controlled, parallel, double-blind intervention study over 6 months, we investigated the effects of kefir-fermented milk (1,600 mg supplemented with calcium bicarbonate (CaCO3, 1,500 mg and bone metabolism in 40 osteoporosis patients, and compared them with CaCO3 alone without kefir supplements. Bone turnover markers were measured in fasting blood samples collected before therapy and at 1, 3, and 6 months. Bone mineral density (BMD values at the spine, total hip, and hip femoral neck were assessed by dual-energy x-ray absorptiometry (DXA at baseline and at 6 months. Among patients treated with kefir-fermented milk, the relationships between baseline turnover and 6 months changes in DXA-determined BMD were significantly improved. The serum β C-terminal telopeptide of type I collagen (β-CTX in those with T-scores > -1 patients significantly decreased after three months treatment. The formation marker serum osteocalcin (OC turned from negative to positive after 6 months, representing the effect of kefir treatment. Serum parathyroid hormone (PTH increased significantly after treatment with kefir, but decreased significantly in the control group. PTH may promote bone remodeling after treatment with kefir for 6 months. In this pilot study, we concluded that kefir-fermented milk therapy was associated with short-term changes in turnover and greater 6-month increases in hip BMD among osteoporotic patients.ClinicalTrials.gov NCT02361372.

Growth on poly(L-lactic acid) porous scaffold preserves CD73 and CD90 immunophenotype markers of rat bone marrow mesenchymal stromal cells.

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Zamparelli, Alessandra; Zini, Nicoletta; Cattini, Luca; Spaletta, Giulia; Dallatana, Davide; Bassi, Elena; Barbaro, Fulvio; Iafisco, Michele; Mosca, Salvatore; Parrilli, Annapaola; Fini, Milena; Giardino, Roberto; Sandri, Monica; Sprio, Simone; Tampieri, Anna; Maraldi, Nadir M; Toni, Roberto

2014-10-01

Few data are available on the effect of biomaterials on surface antigens of mammalian bone marrow-derived, adult mesenchymal stromal cells (MSCs). Since poly(L-lactic acid) or PLLA is largely used in tissue engineering of human bones, and we are developing a reverse engineering program to prototype with biomaterials the vascular architecture of bones for their bioartificial reconstruction, both in humans and animal models, we have studied the effect of porous, flat and smooth PLLA scaffolds on the immunophenotype of in vitro grown, rat MSCs in the absence of any coating, co-polymeric enrichment, and differentiation stimuli. Similar to controls on plastic, we show that our PLLA scaffold does not modify the distribution of some surface markers in rat MSCs. In particular, the maintained expression of CD73 and CD90 on two different subpopulations (small and large cells) is consistent with their adhesion to the PLLA scaffold through specialized appendages, and to their prominent content in actin. In addition, our PLLA scaffold favours retention of the intermediate filament desmin, believed a putative marker of undifferentiated state. Finally, it preserves all rat MSCs morphotypes, and allows for their survival, adhesion to the substrate, and replication. Remarkably, a subpopulation of rat MSCs grown on our PLLA scaffold exhibited formation of membrane protrusions of uncertain significance, although in a size range and morphology compatible with either motility blebs or shedding vesicles. In summary, our PLLA scaffold has no detrimental effect on a number of features of rat MSCs, primarily the expression of CD73 and CD90.

Triple bone labeling of canine mandibles

DEFF Research Database (Denmark)

Pinholt, E M; Kwon, P H

1990-01-01

Fluorescence microscopy was used for evaluation of new bone formation in 16 canine mandibles augmented with hydroxylapatite (HA) granules. Three fluorochromes were injected at different time intervals during therapeutic radiation treatment. Oxytetracycline, DCAF, and alizarin-complexone were given...... intravenously to mark the bone level at these times, respectively. Oxytetracycline, which defined the baseline of bone at implantation of HA, was detectable in 42% of animals that were irradiated and in no animal of the nonirradiated control group. The marker DCAF, designating levels of bone at the start...

Hemopoietic stem cell niches, recovery from radiation and bone marrow transfusions

International Nuclear Information System (INIS)

Cronkite, E.P.; Carsten, A.L.; Brecher, G.; Feinendegen, L.

1979-01-01

Studies were conducted on the appearance of cells in recipient bone marrow with chromosome markers after bone marrow transfusion to recipients that had different treatments. Investigators tried to replete the bone marrow CFV spleen at various times after recovery from maximal sublethal doses of x radiation or during continuous exposure to tritiated water. Studies were made on the effect of diverse treatments on the acceptance of bone marrow transfusions as shown by chromosomal markers. Results showed that the bone marrow of animals rescued by transfusion of 4 x 10 6 bone marrow cells will accept from 0 to 25% of the second transfusion of bone marrow cells given one to 4 months after the first transfusion and examined 2 to 3 weeks after the second transfusion. This may be due to the second transfusion filling up empty niches

Short communication: Effect of commercial or depurinized milk diet on plasma advanced oxidation protein products, cardiovascular markers, and bone marrow CD34+ stem cell potential in rat experimental hyperuricemia.

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Kocic, Gordana; Sokolovic, Dusan; Jevtovic, Tatjana; Cvetkovic, Tatjana; Veljkovic, Andrej; Kocic, Hristina; Stojanovic, Svetlana; Jovanovic, Aneta; Jovanovic, Jelena; Zivkovic, Petar

2014-11-01

Cardiovascular repair and myocardial contractility may be improved by migration of bone marrow stem cells (BMSC) and their delivery to the site of injury, a process known as BMSC homing. The aim of our study was to examine the dietary effect of a newly patented depurinized milk (DP) that is almost free of uric acid and purine and pyrimidine compounds compared with a standard commercial 1.5% fat UHT milk diet or allopurinol therapy in rat experimental hyperuricemia. Bone marrow stem cell potential (BMCD34(+), CD34-postive bone marrow cells), plasma oxidative stress parameters [advanced oxidation protein products, AOPP) and thiobarbituric acid reactive substances (TBARS)], myocardial damage markers [creatine phosphokinase (CPK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH)], plasma cholesterol, and high-density lipoprotein cholesterol were investigated. The DP milk diet significantly increased the number of BMCD34(+) stem cells compared with commercial UHT milk. Allopurinol given alone also increased the number of BMCD34(+). Hyperuricemia caused a significant increase in all plasma enzyme markers for myocardial damage (CPK, LDH, and AST). A cardioprotective effect was achieved with allopurinol but almost equally with DP milk and more than with commercial milk. Regarding plasma AOPP, TBARS, and cholesterol levels, the most effective treatment was DP milk. In conclusion, the protective role of a milk diet on cardiovascular function may be enhanced through the new depurinized milk diet, which may improve cardiovascular system function via increased bone marrow stem cell regenerative potential, decreased plasma oxidative stress parameters, and decreased levels of myocardial damage markers and cholesterol. New dairy technology strategies focused on eliminating harmful milk compounds should be completely nontoxic. Novel milk products should be tested for their ability to improve tissue repair and function. Copyright © 2014 American Dairy Science

Comparison of the buccolingual inclination in alveolar bone and tooth using dental CBCT

International Nuclear Information System (INIS)

Kim, Sung Eun; Kim, Jin Soo; Kim, Jae Duk

2008-01-01

It is important to determine the bucco-lingual inclination of implants on radiographs before the implant surgery. The purpose of this study was to compare the buccolingual inclination in alveolar bone and the tooth with dental cone beam CT and to prepare the standard for the buccolingual inclination of implant. Axial, panoramic, and buccolingually sectioned images of 80 implant cases with stent including straight marker using CB Mercuray TM (Hitachi, Japan) were evaluated. The comparison of the buccolingual inclination of remained alveolar bone with the tooth and the marker on buccolingually sectioned views was performed statistically. The average buccolingual inclination of remained alveolar bone and tooth was 82.8 ± 4.6 .deg. C and 85.8 ± 4.7 .deg. C (p 0.05, r=0.12) at the 2nd premolar area in upper jaw. The average buccolingual inclination of remained alveolar bone and tooth was 81.3 ± 8.3 .deg. C and 87.5 ± 6.3 .deg. C (p>0.05, r=0.85) at the lower 2nd premolar area and 94.3 ± 6.6 .deg. C and 93.3 ± 7.2 .deg. C respectively (p>0.05, r=0.91) at the 1st molar area in lower jaw. The inclinations of markers were very different from those of remained bone at the most of areas except the upper 2nd premolar area (r=0.79). We recommend dental CBCT analysis for determining the buccolingual inclination of dental implant, because of significant difference, in average, between the buccolingual inclination of remained alveolar bone and tooth.

Bone marrow-derived and peritoneal macrophages have different inflammatory response to oxLDL and M1/M2 marker expression

DEFF Research Database (Denmark)

Bisgaard, Line S; Mogensen, Christina K; Rosendahl, Alexander

2016-01-01

Macrophages are heterogeneous and can polarize into specific subsets, e.g. pro-inflammatory M1-like and re-modelling M2-like macrophages. To determine if peritoneal macrophages (PEMs) or bone marrow derived macrophages (BMDMs) resembled aortic macrophages from ApoE-/- mice, their M1/M2 phenotype,......, ACSL1, SRB1, DGAT1, and cpt1a) was decreased in advanced versus early lesions. In conclusion, PEMs and BMDMs are phenotypically distinct and differ from macrophages in lesions with respect to expression of M1/M2 markers and lipid metabolism genes....

Identification of differentiation-stage specific molecular markers for the osteoblastic phenotype

DEFF Research Database (Denmark)

Twine, Natalie; Chen, Li; Wilkins, Marc

to age-matched control (n=4). Using RNA-seq and cluster analysis, we identified a set of stage-specific molecular markers that define the progression of OB phenotype during ex vivo culture of hMSC, predict in vivo bone formation capacity of hMSC and can be employed to study the mechanisms of impaired......The phenotype of osteoblastic (OB) cells in culture is currently defined using a limited number of markers of low sensitivity and specificity which belong mostly to extracellular matrix proteins. Also, for clinical use of human skeletal (mesenchymal) stem cells (hMSC) in bone regeneration......, there is a need to identify predictive markers for in vivo bone forming capacity. Thus, we employed Illumina RNA sequencing (RNASeq) to examine changes in gene expression across 8 time points between 0-12 days of ex vivo OB differentiation of hMSC. We identified a subset of expressed genes as potentially...

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

International Nuclear Information System (INIS)

Bahk, Yong-Whee

2013-01-01

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.

Bone metabolism in cow milk allergic children.

Science.gov (United States)

Jakusova, Lubica; Jesenak, Milos; Schudichova, Jela; Banovcin, Peter

2013-07-01

Children with cow milk allergy are suspected to develop calcium metabolism disturbances. We observed increased markers of bone turnover in these children. Children with cow milk allergy are more prone to develop the disturbances of the bone mineralization even in the first year of life.

The effect of infection and lag screw fixation on revascularization and new bone deposition in membranous bone grafts in a rabbit model.

Science.gov (United States)

Fialkov, J A; Phillips, J H; Walmsley, S L; Morava-Protzner, I

1996-08-01

We have suggested that rigid fixation of membranous bone grafts in the presence of infection may improve graft-recipient bone union by facilitating graft revascularzation. To test this hypothesis, we grafted autogenous membranous bone grafts to the mandibles of 94 New Zealand White rabbits. Lag screw fixation was applied in half the animals. The wounds were inoculated with a range of Staphylococcus aureus doses. Infected and noninfected rabbits were injected weekly over a 5-week course with fluorescein bone markers and with a marker of vascular endothelium (procion red) just prior to sacrifice. Revascularization and new bone deposition in the grafts were then quantified histologically for the 75 rabbits available for data collection. Infection decreased the amount of graft revascularized and the amount of new bone deposited for both rigidly fixated and nonfixated grafts. Grafts fixated with a lag screw showed a greater amount of revascularization and new bone deposition in the presence and absence of infection when compared with nonfixated grafts, supporting the hypothesis that rigid fixation of membranous bone grafts in the presence of infection may promote graft survival and union by improving revascularization and osteogenesis within the graft.

Effect of Daily Exposure to an Isolated Soy Protein Supplement on Body Composition, Energy and Macronutrient Intake, Bone Formation Markers, and Lipid Profile in Children in Colombia.

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Mejía, Wilson; Córdoba, Diana; Durán, Paola; Chacón, Yersson; Rosselli, Diego

2018-01-16

A soy protein-based supplement may optimize bone health, support physical growth, and stimulate bone formation. This study aimed to assess the effect of a daily soy protein supplement (SPS) on nutritional status, bone formation markers, lipid profile, and daily energy and macronutrient intake in children. One hundred seven participants (62 girls), ages 2 to 9, started the study and were randomly assigned to lunch fruit juice with (n = 57, intervention group) or without (n = 50, control group) addition of 45 g (230 Kcal) of a commercial SPS during 12 months; 84 children (51 girls, 33 boys) completed the study (45 and 39 intervention and control, respectively). Nutritional assessment included anthropometry and nutrient intakes; initial and final blood samples were taken; insulin-like growth factor-I (IGF-I), osteocalcin, bone specific alkaline phosphatase (BAP), insulin-like growth factor binding protein-3 (IGFBP-3), cholesterol, triglycerides, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were analyzed. Statistically significant changes (p < .05) in body mass index and weight for age Z scores were observed between groups while changes in body composition were not. Changes in energy, total protein, and carbohydrate intakes were significantly higher in the intervention group (p < .01). Calorie intake changes were statistically significant between groups (p < .001), and BAP decreased in both groups, with values within normal ranges. Osteocalcin, IGFBP-3, and lipid profile were not different between groups. IGF-I levels and IGF/IGFBP-3 ratio increased significantly in both groups. In conclusion, changes in macronutrient and energy intake and nutritional status in the intervention group compared to control group may ensure harmonious and adequate bone health and development.

LAG-3 Represents a Marker of CD4+ T Cells with Regulatory Activity in Patients with Bone Fracture.

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Wang, Jun; Ti, Yunfan; Wang, Yicun; Guo, Guodong; Jiang, Hui; Chang, Menghan; Qian, Hongbo; Zhao, Jianning; Sun, Guojing

2018-04-19

The lymphocyte activation gene 3 (LAG-3) is a CD4 homolog with binding affinity to MHC class II molecules. It is thought that LAG-3 exerts a bimodal function, such that co-ligation of LAG-3 and CD3 could deliver an inhibitory signal in conventional T cells, whereas, on regulatory T cells, LAG-3 expression could promote their inhibitory function. In this study, we investigated the role of LAG-3 expression on CD4 + T cells in patients with long bone fracture. We found that LAG-3 + cells represented approximately 13% of peripheral blood CD4 + T cells on average. Compared to LAG-3 - CD4 + T cells, LAG-3 + CD4 + T cells presented significantly higher Foxp3 and CTLA-4 expression. Directly ex vivo or with TCR stimulation, LAG-3 + CD4 + T cells expressed significantly higher levels of IL-10 and TGF-β than LAG-3 - CD4 + T cells. Interestingly, blocking the LAG-3-MHC class II interaction actually increased the IL-10 expression by LAG-3 + CD4 + T cells. The frequency of LAG-3 + CD4 + T cell was positively correlated with restoration of healthy bone function in long bone fracture patients. These results together suggested that LAG-3 is a marker of CD4 + T cells with regulatory function; at the same time, LAG-3 might have limited the full suppressive potential of Treg cells.

Bone Structural Changes and Estimated Strength After Gastric Bypass Surgery Evaluated by HR-pQCT

DEFF Research Database (Denmark)

Frederiksen, Katrine Diemer; Hanson, Stine; Hansen, Stinus

2016-01-01

Roux-en-Y gastric bypass surgery (RYGB) is an effective treatment of morbid obesity, with positive effects on obesity-related complications. The treatment is associated with bone loss, which in turn might increase fracture risk. The aim of this study was to evaluate changes in bone mineral density...... (BMD) and bone architecture assessed using dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT), 6 and 12 months after RYGB, and correlate them to changes in selected biochemical markers. A prospective cohort study included 25 morbidly obese...

The relationship between bone turnover and insulin sensitivity and secretion

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Frost, Morten; Balkau, Beverley; Hatunic, Mensud

2018-01-01

Bone metabolism appears to influence insulin secretion and sensitivity, and insulin promotes bone formation in animals, but similar evidence in humans is limited. The objectives of this study are to explore if bone turnover markers were associated with insulin secretion and sensitivity and to det...

Reduction of nocturnal rise in bone resorption by subcutaneous GLP-2

DEFF Research Database (Denmark)

Henriksen, Dennis B; Alexandersen, Peter; Byrjalsen, Inger

2004-01-01

-CTX), a marker of bone resorption. In contrast, GLP-2 was found to have a neutral effect on bone formation, as assessed by serum osteocalcin. Since increased s-CTX levels are normally observed at night, we conducted bedtime studies in healthy postmenopausal women. The objective was to study the effect of GLP-2...... injection on bone turnover given at bedtime. A total of 81 postmenopausal women were included in two randomised placebo-controlled studies. In conclusion, we found a dose-related reduction of s-CTX after injection of GLP-2 (P ....07) by the treatment, suggestive of a stimulative effect on bone formation. An area under the curve (AUC0-10 h) analysis for s-CTX after GLP-2 injection confirmed the dose-related decrease as compared to placebo (P

RANKL/Osteoprotegerin System and Bone Turnover in Hashimoto Thyroiditis.

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Konca Degertekin, Ceyla; Turhan Iyidir, Ozlem; Aktas Yılmaz, Banu; Elbeg, Sehri; Pasaoglu, Ozge Tugce; Pasaoglu, Hatice; Cakır, Nuri; Arslan, Metin

2016-10-01

Hypothyroidism is associated with changes in bone metabolism. The impact of hypothyroidism and the associated autoimmunity on the mediators of bone turnover in Hashimoto's thyroiditis (HT) is not known. In this study, we assessed the levels of OPG, RANKL, and IL-6 along with markers of bone formation as osteocalcin (OC) and markers of bone resorption as type 1 collagen C telopeptide (CTX) and tartrate-resistant acid phosphatase isoform 5b (TRAcP 5b) in 30 hypothyroid and 30 euthyroid premenopausal HT patients and 20 healthy premenopausal controls. We found that TRAcP 5b (p = 0.006), CTX (p = 0.01), OC (p = 0.017), and IL-6 (p Thyroid autoimmunity might have a unique impact on OPG/RANKL levels apart from the resultant hypothyroidism.

Multilineage differentiation of porcine bone marrow stromal cells associated with specific gene expression pattern

DEFF Research Database (Denmark)

Zou, Lijin; Zou, Xuenong; Chen, Li

2007-01-01

There are increasing reports regarding differentiation of bone marrow stromal cells (BMSC) from human and various species of animals including pigs. The phenotype and function of BMSC along a mesenchymal lineage differentiation are well characterized by specific transcription factors and marker g...

Reproductive performance and bone status markers of gilts and lactating sows supplemented with two different forms of vitamin D¹

DEFF Research Database (Denmark)

Lauridsen, Charlotte; Halekoh, U; Larsen, Torben

2010-01-01

was not influenced by dietary vitamin D treatments, except for a lower number of still born piglets (P = 0.03, SE = 0.40) with the high doses of vitamin D (1,400 and 2,000 IU vitamin D, giving 1.17 and 1.13 still born piglets per litter, respectively) compared with the low doses of vitamin D (200 and 800 IU vitamin...... D, giving 1.98 and 1.99 still born piglets per litter, respectively). In the gilt trial, the ultimate strength of the bones (P = 0.01) and their content of ash (P = 0.02) were higher when D3 was supplemented in doses larger than 800 IU compared to the same level of Hy•D supplementation. In the sow...... experiment, lactation day (P piglets affected their plasma bone health markers. In conclusion, above...

In vitro bone formation using muscle-derived cells: a new paradigm for bone tissue engineering using polymer-bone morphogenetic protein matrices.

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Lu, Helen H; Kofron, Michelle D; El-Amin, Saadiq F; Attawia, Mohammed A; Laurencin, Cato T

2003-06-13

Over 800,000 bone grafting procedures are performed in the United States annually, creating a demand for viable alternatives to autogenous bone, the grafting standard in osseous repair. The objective of this study was to examine the efficacy of a BMP-polymer matrix in inducing the expression of the osteoblastic phenotype and in vitro bone formation by muscle-derived cells. Specifically, we evaluated the ability of bone morphogenetic protein-7 (BMP-7), delivered from a poly(lactide-co-glycolide) (PLAGA) matrix, to induce the differentiation of cells derived from rabbit skeletal muscle into osteoblast-like cells and subsequently form mineralized tissue. Results confirmed that muscle-derived cells attached and proliferated on the PLAGA substrates. BMP-7 released from PLAGA induced the muscle-derived cells to increase bone marker expression and form mineralized cultures. These results demonstrate the efficacy of a BMP-polymer matrix in inducing the expression of the osteoblastic phenotype by muscle-derived cells and present a new paradigm for bone tissue engineering.

Effects of Nrf2 Deficiency on Bone Microarchitecture in an Experimental Model of Osteoporosis

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Lidia Ibáñez

2014-01-01

Full Text Available Objective. Redox imbalance contributes to bone fragility. We have evaluated the in vivo role of nuclear factor erythroid derived 2-related factor-2 (Nrf2, an important regulator of cellular responses to oxidative stress, in bone metabolism using a model of postmenopausal osteoporosis. Methods. Ovariectomy was performed in both wild-type and mice deficient in Nrf2 (Nrf2−/−. Bone microarchitecture was analyzed by μCT. Serum markers of bone metabolism were also measured. Reactive oxygen species production was determined using dihydrorhodamine 123. Results. Sham-operated or ovariectomized Nrf2−/− mice exhibit a loss in trabecular bone mineral density in femur, accompanied by a reduction in cortical area in vertebrae. Nrf2 deficiency tended to increase osteoblastic markers and significantly enhanced osteoclastic markers in sham-operated animals indicating an increased bone turnover with a main effect on bone resorption. We have also shown an increased production of oxidative stress in bone marrow-derived cells from sham-operated or ovariectomized Nrf2−/− mice and a higher responsiveness of bone marrow-derived cells to osteoclastogenic stimuli in vitro. Conclusion. We have demonstrated in vivo a key role of Nrf2 in the maintenance of bone microarchitecture.

Molecular changes in articular cartilage and subchondral bone in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis.

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Pickarski, Maureen; Hayami, Tadashi; Zhuo, Ya; Duong, Le T

2011-08-24

Osteoarthritis (OA) is a debilitating, progressive joint disease. Similar to the disease progression in humans, sequential events of early cartilage degradation, subchondral osteopenia followed by sclerosis, and late osteophyte formation were demonstrated in the anterior cruciate ligament transection (ACLT) or ACLT with partial medial meniscectomy (ACLT + MMx) rat OA models. We describe a reliable and consistent method to examine the time dependent changes in the gene expression profiles in articular cartilage and subchondral bone. Local regulation of matrix degradation markers was demonstrated by a significant increase in mRNA levels of aggrecanase-1 and MMP-13 as early as the first week post-surgery, and expression remained elevated throughout the 10 week study. Immunohistochemistry confirmed MMP-13 expression in differentiated chondrocytes and synovial fibroblasts at week-2 and cells within osteophytes at week-10 in the surgically-modified-joints. Concomitant increases in chondrocyte differentiation markers, Col IIA and Sox 9, and vascular invasion markers, VEGF and CD31, peaked around week-2 to -4, and returned to Sham levels at later time points in both models. Indeed, VEGF-positive cells were found in the deep articular chondrocytes adjacent to subchondral bone. Osteoclastic bone resorption markers, cathepsin K and TRAP, were also elevated at week-2. Confirming bone resorption is an early local event in OA progression, cathepsin K positive osteoclasts were found invading the articular cartilage from the subchondral region at week 2. This was followed by late disease events, including subchondral sclerosis and osteophyte formation, as demonstrated by the upregulation of the osteoanabolic markers runx2 and osterix, toward week-4 to 6 post-surgery. In summary, this study demonstrated the temporal and cohesive gene expression changes in articular cartilage and subchondral bone using known markers of OA progression. The findings here support genome-wide profiling

Bone mass and turnover in fibromyalgia

DEFF Research Database (Denmark)

Jacobsen, Søren; Gam, A; Egsmose, C

1993-01-01

Physical inactivity accelerates bone loss. Since patients with fibromyalgia are relatively physically inactive, bone mass and markers of bone metabolism were determined in 12 premenopausal women with fibromyalgia and in healthy age matched female control subjects. No differences were found...... in lumbar bone mineral density, femoral neck bone mineral density, serum levels of alkaline phosphatase, osteocalcin, ionized calcium and phosphate. The urinary excretion of both hydroxyproline and calcium relative to urinary creatinine excretion was significantly higher in patients with fibromyalgia, p = 0.......01. This was linked to lower urinary creatinine excretion (p = 0.02) probably reflecting lower physical activity in the patients with fibromyalgia. We conclude that bone mass and turnover are generally not affected in premenopausal women with fibromyalgia....

Bone lesions in Chinese POEMS syndrome patients: imaging characteristics and clinical implications

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Fengdan Wang

2016-08-01

Full Text Available Objective. Bone lesion is crucial for diagnosing and management of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin change (POEMS syndrome, a rare plasma cell disorder. This study is to compare the effectiveness of X-ray skeletal survey (SS and computed tomography (CT for detecting bone lesions in Chinese POEMS syndrome patients, and to investigate the relationship between bone lesion features and serum markers. Methods. SS and chest/abdomen/pelvic CT images of 38 Chinese patients (26 males, 12 females, aged 21–70 years with POEMS syndrome recruited at our medical center between January 2013 and January 2015 were retrospectively analyzed. Bone lesions identified by CT were further categorized according to the size (10 mm and appearance (osteosclerotic, lytic, mixed. The percentage of plasma cells in bone marrow smears, type of immunoglobulin, platelet (Plt, and levels of serum bone metabolic markers and inflammatory factors including alkaline phosphatase (ALP, calcium, phosphate, parathyroid hormone (PTH, beta-isomerized C-telopeptide (β-CTx, vascular endothelial growth factor (VEGF, and interleukin (IL-6 levels were also recorded. Results. Of the 38 POEMS syndrome patients, the immunoglobulin heavy chain isotypes were IgA in 25 patients (65.8%; 25/38 and IgG in 13 patients (34.2%; 13/38, and the light chain isotypes were λ in 35 patients (92.1%; 35/38 and κ in 3 patients (7.9%; 3/38. There were 23 patients with thrombocytosis. More patients with bone lesions were detected by CT than by SS (97.4% vs. 86.8%. The most commonly affected location was the pelvis (89.5%, followed by the spine, clavicle/scapula/sternum/ribs, skull, and long bones. Of the 38 POEMS syndrome patients, 35 (94.6% had osteosclerotic and 32 (86.5% had mixed lesions. Osteosclerotic lesions were typically scattered, variable in size, and plaque-like, whereas mixed lesions were pouch-shaped or soup bubble-like with a clear sclerotic margin and were

Paget's disease of bone resembling bone metastasis from gastric cancer.

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Shimoyama, Yasuyuki; Kusano, Motoyasu; Shimoda, Yoko; Ishihara, Shingo; Toyomasu, Yoshitaka; Ohno, Tetsuro; Mochiki, Erito; Sano, Takaaki; Hirato, Junko; Mori, Masatomo

2011-08-01

A 74-year-old man had an endoscopic type 0'-IIc tumor in the upper gastric body on the greater curvature and biopsy showed the tumor to be a well-differentiated adenocarcinoma (Group 5). He was referred to us for endoscopic submucosal dissection (ESD). Endoscopy revealed fold convergency, fold swelling, and fusion of the fold, indicating tumor invasion into the submucosa, which was outside the indications for ESD. In addition, there was an increase of serum bone-type alkaline phosphatase (ALP-III and ALP-IV) and urinary cross-linked N-terminal telopeptide of type I collagen (a bone metabolism marker), while (18)F-fluorodeoxyglucose positron emission tomography showed increased uptake in the left pelvis and Th10, suggesting bone metastases. We first diagnosed gastric cancer with bone metastases; however, the symptoms suggested pathological bone fracture and no bone pain. Therefore, a computed tomography-guided aspiration bone biopsy was performed to exclude the possibility of Paget's disease of bone. Biopsy specimens revealed no tumor and a mosaic pattern. No increased uptake of (18)F-FAMT (L-[3-(18)F] α-methyltyrosine) supported a diagnosis of no bone metastases from gastric cancer. We finally diagnosed gastric cancer accompanied by Paget's disease of bone and performed a laparoscopy-assisted proximal gastrectomy. The pathological diagnosis was U less 0-IIb, and U post 0-IIc ypT1a (M) N0H0P0M0 yp stage IA. In gastric cancer patients with suspected bone metastasis, we also need to consider Paget's disease of bone.

Bone biology in the elderly: clinical importance for fracture treatment

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Rolvien Tim

2016-12-01

Full Text Available Age-related bone impairment often leads to fragility fractures in the elderly. Although excellent surgical care is widely provided, diagnosis and treatment of the underlying bone disorder are often not kept in mind. The interplay of the three major bone cells – osteoblasts, osteoclasts, and osteocytes – is normally well regulated via the secretion of messengers to control bone remodeling. Possible imbalances that might occur in the elderly are partly due to age, genetic risk factors, and adverse lifestyle factors but importantly also due to imbalances in calcium homeostasis (mostly due to vitamin D deficiency or hypochlorhydria, which have to be eliminated. Therefore, the cooperation between the trauma surgeon and the osteologist is of major importance to diagnose and treat the respective patients at risk. We propose that any patient suffering from fragility fractures is rigorously screened for osteoporosis and metabolic bone diseases. This includes bone density measurement by dual-energy X-ray absorptiometry, laboratory tests for calcium, phosphate, vitamin D, and bone turnover markers, as well as additional diagnostic modalities if needed. Thereby, most risk factors, including vitamin D deficiency, can be identified and treated while patients who meet the criteria for a specific therapy (i.e. antiresorptive and osteoanabolic receive such. If local health systems succeed to manage this process of secondary fracture prevention, morbidity and mortality of fragility fractures will decline to a minimum level.

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 ....... The increased levels of markers of type I collagen metabolism (s-ICTP, Pyr) and s-AlbCorrCa2+ in patients with active disease and patients treated with GC may be a result of increased degradation in synovium, cartilage and bone due to the inflammatory process.......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...... 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...

Bone Loss During Spaceflight: Available Models and Counter-Measures

Science.gov (United States)

Morris, Jonathan; Bach, David; Geller, David

2015-01-01

There is ongoing concern for human health during spaceflights. Of particular interest is the uncoupling of bone remodeling and its resultant effect on calcium metabolism and bone loss. The calculated average loss of bone mineral density (BMD) is approximately 1-1.5% per month of spaceflight. The effect of decreased BMD on associated fractures in astronauts is not known. Currently on the International Space Station (ISS), bone loss is managed through dietary supplements and modifications and resistance exercise regimen. As the duration of space flights increases, a review of the current methods available for the prevention of bone loss is warranted. The goal of this project is to review and summarize recent studies that have focused on maintaining BMD during exposure to microgravity. Interventions were divided into physical (Table 1), nutritional (Table 2), or pharmacologic (Table 3) categories. Physical modalities included resistance exercise, low level vibration, and low intensity pulsed ultrasound. Nutritional interventions included altering protein, salt, and fat intake; and vitamin D supplementation. Pharmacologic interventions included the use of bisphosphonates and beta blockers. Studies reported outcomes based on bone density determined by DXA bone scan, micro-architecture of histology and microCT, and serum and urine markers of bone turnover. The ground analog models utilized to approximate osseous physiology in microgravity included human patients previously paralyzed or subjects confined to bedrest. Ground analog animal models include paralysis, immobilization and ovariectomies. As a result of the extensive research performed there is a multi-modality approach available for the management of BMD during spaceflight that includes resistance training, nutrition and dietary supplements. However, there is a paucity of literature describing a formalized tiered protocol to guide investigators through the progression from animal models to human patient ground

Olives and Bone: A Green Osteoporosis Prevention Option

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Kok-Yong Chin

2016-07-01

Full Text Available Skeletal degeneration due to aging, also known as osteoporosis, is a major health problem worldwide. Certain dietary components confer protection to our skeletal system against osteoporosis. Consumption of olives, olive oil and olive polyphenols has been shown to improve bone health. This review aims to summarize the current evidence from cellular, animal and human studies on the skeletal protective effects of olives, olive oil and olive polyphenols. Animal studies showed that supplementation of olives, olive oil or olive polyphenols could improve skeletal health assessed via bone mineral density, bone biomechanical strength and bone turnover markers in ovariectomized rats, especially those with inflammation. The beneficial effects of olive oil and olive polyphenols could be attributed to their ability to reduce oxidative stress and inflammation. However, variations in the bone protective, antioxidant and anti-inflammatory effects between studies were noted. Cellular studies demonstrated that olive polyphenols enhanced proliferation of pre-osteoblasts, differentiation of osteoblasts and decreased the formation of osteoclast-like cells. However, the exact molecular pathways for its bone health promoting effects are yet to be clearly elucidated. Human studies revealed that daily consumption of olive oil could prevent the decline in bone mineral density and improve bone turnover markers. As a conclusion, olives, olive oil and its polyphenols are potential dietary interventions to prevent osteoporosis among the elderly.

Effects of Fermented Milk Products on Bone.

Science.gov (United States)

Rizzoli, René; Biver, Emmanuel

2018-04-01

Fermented milk products like yogurt or soft cheese provide calcium, phosphorus, and protein. All these nutrients influence bone growth and bone loss. In addition, fermented milk products may contain prebiotics like inulin which may be added to yogurt, and provide probiotics which are capable of modifying intestinal calcium absorption and/or bone metabolism. On the other hand, yogurt consumption may ensure a more regular ingestion of milk products and higher compliance, because of various flavors and sweetness. Bone mass accrual, bone homeostasis, and attenuation of sex hormone deficiency-induced bone loss seem to benefit from calcium, protein, pre-, or probiotics ingestion, which may modify gut microbiota composition and metabolism. Fermented milk products might also represent a marker of lifestyle promoting healthy bone health.

Adenoviral Mediated Expression of BMP2 by Bone Marrow Stromal Cells Cultured in 3D Copolymer Scaffolds Enhances Bone Formation.

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Sharma, Sunita; Sapkota, Dipak; Xue, Ying; Sun, Yang; Finne-Wistrand, Anna; Bruland, Ove; Mustafa, Kamal

2016-01-01

Selection of appropriate osteoinductive growth factors, suitable delivery method and proper supportive scaffold are critical for a successful outcome in bone tissue engineering using bone marrow stromal cells (BMSC). This study examined the molecular and functional effect of a combination of adenoviral mediated expression of bone morphogenetic protein-2 (BMP2) in BMSC and recently developed and characterized, biodegradable Poly(L-lactide-co-є-caprolactone){poly(LLA-co-CL)}scaffolds in osteogenic molecular changes and ectopic bone formation by using in vitro and in vivo approaches. Pathway-focused custom PCR array, validation using TaqMan based quantitative RT-PCR (qRT-PCR) and ALP staining showed significant up-regulation of several osteogenic and angiogenic molecules, including ALPL and RUNX2 in ad-BMP2 BMSC group grown in poly(LLA-co-CL) scaffolds both at 3 and 14 days. Micro CT and histological analyses of the subcutaneously implanted scaffolds in NOD/SCID mice revealed significantly increased radiopaque areas, percentage bone volume and formation of vital bone in ad-BMP2 scaffolds as compared to the control groups both at 2 and 8 weeks. The increased bone formation in the ad-BMP2 group in vivo was paralleled at the molecular level with concomitant over-expression of a number of osteogenic and angiogenic genes including ALPL, RUNX2, SPP1, ANGPT1. The increased bone formation in ad-BMP2 explants was not found to be associated with enhanced endochondral activity as evidenced by qRT-PCR (SOX9 and FGF2) and Safranin O staining. Taken together, combination of adenoviral mediated BMP-2 expression in BMSC grown in the newly developed poly(LLA-co-CL) scaffolds induced expression of osteogenic markers and enhanced bone formation in vivo.

Serum tumor markers in pediatric osteosarcoma: a summary review

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Savitskaya Yulia A

2012-03-01

Full Text Available Abstract Osteosarcoma is the most common primary high-grade bone tumor in both adolescents and children. Early tumor detection is key to ensuring effective treatment. Serum marker discovery and validation for pediatric osteosarcoma has accelerated in recent years, coincident with an evolving understanding of molecules and their complex interactions, and the compelling need for improved pediatric osteosarcoma outcome measures in clinical trials. This review gives a short overview of serological markers for pediatric osteosarcoma, and highlights advances in pediatric osteosarcoma-related marker research within the past year. Studies in the past year involving serum markers in patients with pediatric osteosarcoma can be assigned to one of four categories, i.e., new approaches and new markers, exploratory studies in specialized disease subsets, large cross-sectional validation studies, and longitudinal studies, with and without an intervention. Most of the studies have examined the association of a serum marker with some aspect of the natural history of pediatric osteosarcoma. As illustrated by the many studies reviewed, several serum markers are emerging that show a credible association with disease modification. The expanding pool of informative osteosarcoma-related markers is expected to impact development of therapeutics for pediatric osteosarcoma positively and, it is hoped, ultimately clinical care. Combinations of serum markers of natural immunity, thyroid hormone homeostasis, and bone tumorigenesis may be undertaken together in patients with pediatric osteosarcoma. These serum markers in combination may do better. The potential effect of an intrinsic dynamic balance of tumor angiogenesis residing within a single hormone (tri-iodothyronine is an attractive concept for regulation of vascularization in pediatric osteosarcoma.

GLP-1 receptor agonist treatment increases bone formation and prevents bone loss in weight-reduced obese women

DEFF Research Database (Denmark)

Iepsen, Eva Pers Winning; Lundgren, Julie Rehné; Hartmann, Bolette

2015-01-01

with or without administration of the GLP-1 RA liraglutide (1.2mg/day) for 52 weeks. In case of weight gain, up to two meals per day could be substituted with a low-calorie diet product in order to maintain the weight loss. MAIN OUTCOME MEASURES: Total, pelvic and arm-leg bone mineral content (BMC) and bone...... markers (CTX-1 and P1NP) were investigated before, after weight loss and after 52 weeks weight maintenance. Primary end points: Change in BMC and bone markers after 52 weeks weight maintenance with or without GLP-1 RA treatment. RESULTS: Total, pelvic and arm-leg BMC decreased during weight maintenance...... in the control group (ptotal and arm-leg BMC loss was 4 times greater in the control group compared to the liraglutide group (estimated difference 27g (95% CI 5-48), p=0.01), although the 12% weight loss was maintained in both groups...

The Effect of Long-Term Exercise on the Production of Osteoclastogenic and Antiosteoclastogenic Cytokines by Peripheral Blood Mononuclear Cells and on Serum Markers of Bone Metabolism

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J. Kelly Smith

2016-01-01

Full Text Available Although it is recognized that the mechanical stresses associated with physical activity augment bone mineral density and improve bone quality, our understanding of how exercise modulates bone homeostasis at the molecular level is lacking. In a before and after trial involving 43 healthy adults, we measured the effect of six months of supervised exercise training on the spontaneous and phytohemagglutinin-induced production of osteoclastogenic cytokines (interleukin-1α, tumor necrosis factor-α, antiosteoclastogenic cytokines (transforming growth factor-β1 and interleukins 4 and 10, pleiotropic cytokines with variable effects on osteoclastogenesis (interferon-γ, interleukin-6, and T cell growth and differentiation factors (interleukins 2 and 12 by peripheral blood mononuclear cells. We also measured lymphocyte phenotypes and serum markers of bone formation (osteocalcin, bone resorption (C-terminal telopeptides of Type I collagen, and bone homeostasis (25 (OH vitamin D, estradiol, testosterone, parathyroid hormone, and insulin-like growth factor 1. A combination of aerobic, resistance, and flexibility exercises done on average of 2.5 hours a week attenuated the production of osteoclastogenic cytokines and enhanced the production of antiosteoclastogenic cytokines. These changes were accompanied by a 16% reduction in collagen degradation products and a 9.8% increase in osteocalcin levels. We conclude that long-term moderate intensity exercise exerts a favorable effect on bone resorption by changing the balance between blood mononuclear cells producing osteoclastogenic cytokines and those producing antiosteoclastogenic cytokines. This trial is registered with Clinical Trials.gov Identifier: NCT02765945.

Vitamin D and estrogen receptor-alpha genotype and indices of bone mass and bone turnover in Danish girls

DEFF Research Database (Denmark)

Cusack, S.; Mølgaard, C.; Michaelsen, K. F.

2006-01-01

(VDR) (FokI, TaqI) and estrogen receptor-alpha (ER alpha) (PvuII, XbaI), and bone mineral density (BMD), bone mineral content (BMC), and markers of bone turnover in 224 Danish girls aged 11-12 years. BMD and BMC were measured by dual-energy X-ray absorptiometry. Serum osteocalcin, 25(OH......Peak bone mass is a major determinant of osteoporosis risk in later life. It is under strong genetic control; however, little is known about the identity of the genes involved. In the present study, we investigated the relationship between polymorphisms in the genes encoding the vitamin D receptor...

New insights to the role of aryl hydrocarbon receptor in bone phenotype and in dioxin-induced modulation of bone microarchitecture and material properties

International Nuclear Information System (INIS)

Herlin, Maria; Finnilä, Mikko A.J.; Zioupos, Peter; Aula, Antti; Risteli, Juha; Miettinen, Hanna M.; Jämsä, Timo; Tuukkanen, Juha; Korkalainen, Merja; Håkansson, Helen; Viluksela, Matti

2013-01-01

Bone is a target for high affinity aryl hydrocarbon receptor (AHR) ligands, such as dioxins. Although bone morphology, mineral density and strength are sensitive endpoints of dioxin toxicity, less is known about effects on bone microarchitecture and material properties. This study characterizes TCDD-induced modulations of bone tissue, and the role of AHR in dioxin-induced bone toxicity and for normal bone phenotype. Six AHR-knockout (Ahr −/− ) and wild-type (Ahr +/+ ) mice of both genders were exposed to TCDD weekly for 10 weeks, at a total dose of 200 μg/kg bw. Bones were examined with micro-computed tomography, nanoindentation and biomechanical testing. Serum levels of bone remodeling markers were analyzed, and the expression of genes related to osteogenic differentiation was profiled using PCR array. In Ahr +/+ mice, TCDD-exposure resulted in harder bone matrix, thinner and more porous cortical bone, and a more compact trabecular bone compartment. Bone remodeling markers and altered expression of a number of osteogenesis related genes indicated imbalanced bone remodeling. Untreated Ahr −/− mice displayed a slightly modified bone phenotype as compared with untreated Ahr +/+ mice, while TCDD exposure caused only a few changes in bones of Ahr −/− mice. Part of the effects of both TCDD-exposure and AHR-deficiency were gender dependent. In conclusion, exposure of adult mice to TCDD resulted in harder bone matrix, thinner cortical bone, mechanically weaker bones and most notably, increased trabecular bone volume fraction in Ahr +/+ mice. AHR is involved in bone development of a normal bone phenotype, and is crucial for manifestation of TCDD-induced bone alterations. - Highlights: • TCDD disrupts bone remodeling resulting in altered cortical and trabecular bone. • In trabecular bone an anabolic effect is observed. • Cortical bone is thinner, more porous, harder, stiffer and mechanically weaker. • AHR ablation results in increased trabecular bone

New insights to the role of aryl hydrocarbon receptor in bone phenotype and in dioxin-induced modulation of bone microarchitecture and material properties

Energy Technology Data Exchange (ETDEWEB)

Herlin, Maria, E-mail: maria.herlin@ki.se [Institute of Environmental Medicine, Karolinska Institutet, Stockholm (Sweden); Finnilä, Mikko A.J., E-mail: mikko.finnila@oulu.fi [Department of Medical Technology, Institute of Biomedicine, University of Oulu, Oulu (Finland); Department of Anatomy and Cell Biology, Institute of Biomedicine, University of Oulu, Oulu (Finland); Zioupos, Peter, E-mail: p.zioupos@cranfield.ac.uk [Biomechanics Laboratories, Department of Engineering and Applied Science, Cranfield University, Shrivenham SN6 8LA (United Kingdom); Aula, Antti, E-mail: antti.aula@gmail.com [Department of Medical Physics, Imaging Centre, Tampere University Hospital, Tampere (Finland); Department of Biomedical Engineering, Tampere University of Technology, Tampere (Finland); Risteli, Juha, E-mail: juha.risteli@ppshp.fi [Department of Clinical Chemistry, Oulu University Hospital, Oulu (Finland); Miettinen, Hanna M., E-mail: hanna.miettinen@crl.com [Department of Environmental Health, National Institute for Health and Welfare, Kuopio (Finland); Jämsä, Timo, E-mail: timo.jamsa@oulu.fi [Department of Medical Technology, Institute of Biomedicine, University of Oulu, Oulu (Finland); Department of Diagnostic Radiology, Oulu University Hospital, Oulu (Finland); Tuukkanen, Juha, E-mail: juha.tuukkanen@oulu.fi [Department of Anatomy and Cell Biology, Institute of Biomedicine, University of Oulu, Oulu (Finland); Korkalainen, Merja, E-mail: merja.korkalainen@thl.fi [Department of Environmental Health, National Institute for Health and Welfare, Kuopio (Finland); Håkansson, Helen, E-mail: Helen.Hakansson@ki.se [Institute of Environmental Medicine, Karolinska Institutet, Stockholm (Sweden); Viluksela, Matti, E-mail: matti.viluksela@thl.fi [Department of Environmental Health, National Institute for Health and Welfare, Kuopio (Finland); Department of Environmental Science, University of Eastern Finland, Kuopio (Finland)

2013-11-15

Bone is a target for high affinity aryl hydrocarbon receptor (AHR) ligands, such as dioxins. Although bone morphology, mineral density and strength are sensitive endpoints of dioxin toxicity, less is known about effects on bone microarchitecture and material properties. This study characterizes TCDD-induced modulations of bone tissue, and the role of AHR in dioxin-induced bone toxicity and for normal bone phenotype. Six AHR-knockout (Ahr{sup −/−}) and wild-type (Ahr{sup +/+}) mice of both genders were exposed to TCDD weekly for 10 weeks, at a total dose of 200 μg/kg bw. Bones were examined with micro-computed tomography, nanoindentation and biomechanical testing. Serum levels of bone remodeling markers were analyzed, and the expression of genes related to osteogenic differentiation was profiled using PCR array. In Ahr{sup +/+} mice, TCDD-exposure resulted in harder bone matrix, thinner and more porous cortical bone, and a more compact trabecular bone compartment. Bone remodeling markers and altered expression of a number of osteogenesis related genes indicated imbalanced bone remodeling. Untreated Ahr{sup −/−} mice displayed a slightly modified bone phenotype as compared with untreated Ahr{sup +/+} mice, while TCDD exposure caused only a few changes in bones of Ahr{sup −/−} mice. Part of the effects of both TCDD-exposure and AHR-deficiency were gender dependent. In conclusion, exposure of adult mice to TCDD resulted in harder bone matrix, thinner cortical bone, mechanically weaker bones and most notably, increased trabecular bone volume fraction in Ahr{sup +/+} mice. AHR is involved in bone development of a normal bone phenotype, and is crucial for manifestation of TCDD-induced bone alterations. - Highlights: • TCDD disrupts bone remodeling resulting in altered cortical and trabecular bone. • In trabecular bone an anabolic effect is observed. • Cortical bone is thinner, more porous, harder, stiffer and mechanically weaker. • AHR ablation

[CHARACTERISTICS OF OSTEOCYTE CELL LINES FROM BONES FORMED AS A RESULT OF MEMBRANOUS (SKULL BONES) AND CHONDRAL (LONG BONES) OSSIFICATION].

Science.gov (United States)

Avrunin, A S; Doktorov, A A

2016-01-01

The aim of this work was to analyze the literature data and the results of authors' own research, to answer the question--if the osteocytes of bone tissues resulting from membranous and chondral ossification, belong to one or to different cell lines. The differences between the cells of osteocyte lines derived from bones resulting from membranous and chondral ossification were established in: 1) the magnitude of the mechanical signal, initiating the development of the process of mechanotransduction; 2) the nature of the relationship between the magnitude of the mechanical signal that initiates the reorganization of the architecture of bone structures and the resource of their strength; in membranous bones significantly lower mechanical signal caused a substantially greater increment of bone strength resource; 3) the biological activity of bone structures, bone fragments formed from membranous tissue were more optimal for transplantation; 4) the characteristics of expression of functional markers of bone cells at different stages of their differentiation; 5) the nature of the reaction of bone cells to mechanical stress; 6) the sensitivity of bone cells to one of the factors controlling the process of mechanotransduction (PGI2); 7) the functioning of osteocytes during lactation. These differences reflect the functional requirements to the bones of the skeleton--the supporting function in the bones of the limbs and the shaping and protection in the bones of the cranial vault. These data suggest that the results of research conducted on the bones of the skull, should not be transferred to the entire skeleton as a whole.

Hypovitaminosis D and hyperparathyroidism: effects on bone turnover and bone mineral density among perinatally HIV-infected adolescents.

Science.gov (United States)

Sudjaritruk, Tavitiya; Bunupuradah, Torsak; Aurpibul, Linda; Kosalaraksa, Pope; Kurniati, Nia; Prasitsuebsai, Wasana; Sophonphan, Jiratchaya; Ananworanich, Jintanat; Puthanakit, Thanyawee

2016-04-24

The impact of hypovitaminosis D and secondary hyperparathyroidism on bone mineral density (BMD) in the setting of pediatric HIV infection remains unclear. This study aimed to determine the prevalence of hypovitaminosis D and hyperparathyroidism and their effects on bone turnover and BMD among HIV-infected adolescents in Southeast Asia. A multicenter, cross-sectional study evaluating bone health and vitamin D metabolism in HIV-infected adolescents in Thailand and Indonesia. Perinatally HIV-infected adolescents aged 10-18 years on antiretroviral therapy with virologic suppression were enrolled. Serum 25-hydroxyvitamin D, intact parathyroid hormone, and bone turnover markers (C-terminal cross-linked telopeptide of type I collagen and procollagen type I amino-terminal propeptide) were assessed; serum 25-hydroxyvitamin D less than 20 ng/ml and intact parathyroid hormone more than 65 pg/ml were defined as hypovitaminosis D and hyperparathyroidism, respectively. Lumbar spine (L2-L4) BMD Z-score -2 or less was defined as low BMD. Of 394 adolescents, 57% were women. The median age [interquartile range (IQR)] was 15.0 (13.3-16.9) years. The prevalence of hypovitaminosis D, hyperparathyroidism, and both conditions were 21% [95% confidence interval (CI): 17-25%], 17% (95% CI: 13-20%), and 5% (95% CI: 3-7%), respectively. Adolescents with hypovitaminosis D and secondary hyperparathyroidism had the highest median bone resorption (C-terminal cross-linked telopeptide of type I collagen: 1610 vs. 1270 ng/l; P = 0.04) and bone formation (procollagen type I amino-terminal propeptide: 572 vs. 330 μg/l; P = 0.02) markers, and the greatest proportion of low BMD (42 vs. 15%; P = 0.01) compared with the rest of the cohort. Hypovitaminosis D complicated with secondary hyperparathyroidism was associated with increased bone turnover and bone loss. Early treatment of hypovitaminosis D before hyperparathyroidism occurs may be important to prevent bone mass deterioration.

Automatic analysis of trabecular bone structure from knee MRI

DEFF Research Database (Denmark)

Marques, Joselene; Granlund, Rabia; Lillholm, Martin

2012-01-01

We investigated the feasibility of quantifying osteoarthritis (OA) by analysis of the trabecular bone structure in low-field knee MRI. Generic texture features were extracted from the images and subsequently selected by sequential floating forward selection (SFFS), following a fully automatic......, uncommitted machine-learning based framework. Six different classifiers were evaluated in cross-validation schemes and the results showed that the presence of OA can be quantified by a bone structure marker. The performance of the developed marker reached a generalization area-under-the-ROC (AUC) of 0...

Lower bone turnover markers in metabolic syndrome and diabetes: the population-based Study of Health in Pomerania.

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Lerchbaum, E; Schwetz, V; Nauck, M; Völzke, H; Wallaschofski, H; Hannemann, A

2015-05-01

Accumulating evidence demonstrates an important interaction between bone and energy metabolism. We aimed to study the associations of three bone turnover markers (BTM: osteocalcin, beta-crosslaps, procollagen type 1 N-terminal propeptide) as well as of 25-hydroxyvitamin D and parathyroid hormone with metabolic syndrome (MetS) or type 2 diabetes mellitus (T2DM) in a large population-based cohort. This cross-sectional study comprised 2671 adult men and women participating in the first follow-up of the population-based Study of Health in Pomerania (SHIP-1). Multivariable logistic regression analyses were performed to assess sex-specific associations between the BTMs, 25-hydroxyvitamin D or parathyroid hormone and metabolic disease. All models were adjusted for age, body mass index, smoking status, physical activity, estimated glomerular filtration rate and month of blood sampling. The models for women were further adjusted for menopausal status. Higher BTM or 25-hydroxyvitamin D concentrations were associated with significantly lower odds for metabolic disease, while there was no association between parathyroid hormone and MetS or T2DM. Our results contribute to the accumulating evidence of a cross-sectional association between high BTM or 25-hydroxyvitamin D concentrations and a lower prevalence of MetS or T2DM. Further research is necessary to evaluate the mechanisms underlying these results. Copyright © 2015 Elsevier B.V. All rights reserved.

High calcium concentration in bones promotes bone metastasis in renal cell carcinomas expressing calcium-sensing receptor.

Science.gov (United States)

Joeckel, Elke; Haber, Tobias; Prawitt, Dirk; Junker, Kerstin; Hampel, Christian; Thüroff, Joachim W; Roos, Frederik C; Brenner, Walburgis

2014-02-28

The prognosis for renal cell carcinoma (RCC) is related to a high rate of metastasis, including 30% of bone metastasis. Characteristic for bone tissue is a high concentration of calcium ions. In this study, we show a promoting effect of an enhanced extracellular calcium concentration on mechanisms of bone metastasis via the calcium-sensing receptor (CaSR) and its downstream signaling molecules. Our analyses were performed using 33 (11/category) matched specimens of normal and tumor tissue and 9 (3/category) primary cells derived from RCC patients of the 3 categories: non-metastasized, metastasized into the lung and metastasized into bones during a five-year period after nephrectomy. Expression of CaSR was determined by RT-PCR, Western blot analyses and flow cytometry, respectively. Cells were treated by calcium and the CaSR inhibitor NPS 2143. Cell migration was measured in a Boyden chamber with calcium (10 μM) as chemotaxin and proliferation by BrdU incorporation. The activity of intracellular signaling mediators was quantified by a phospho-kinase array and Western blot. The expression of CaSR was highest in specimens and cells of patients with bone metastases. Calcium treatment induced an increased migration (19-fold) and proliferation (2.3-fold) exclusively in RCC cells from patients with bone metastases. The CaSR inhibitor NPS 2143 elucidated the role of CaSR on the calcium-dependent effects. After treatment with calcium, the activity of AKT, PLCγ-1, p38α and JNK was clearly enhanced and PTEN expression was almost completely abolished in bone metastasizing RCC cells. Our results indicate a promoting effect of extracellular calcium on cell migration and proliferation of bone metastasizing RCC cells via highly expressed CaSR and its downstream signaling pathways. Consequently, CaSR may be regarded as a new prognostic marker predicting RCC bone metastasis.

The circulating concentration and ratio of total and high molecular weight adiponectin in post-menopausal women with and without osteoporosis and its association with body mass index and biochemical markers of bone metabolism.

Science.gov (United States)

Sodi, R; Hazell, M J; Durham, B H; Rees, C; Ranganath, L R; Fraser, W D

2009-09-01

There is increasing evidence suggesting that adiponectin plays a role in the regulation of bone metabolism. This was a cross-sectional study of 34 post-menopausal women with and 37 without osteoporosis. All subjects had body mass index (BMI), bone mineral density (BMD), total-, high molecular weight (HMW)-adiponectin and their ratio, osteoprotegerin (OPG), a marker of bone resorption (betaCTX) and formation (P1NP) measured. We observed a positive correlation between BMI and BMD (r=0.44, plean subjects but there was no difference between those with or without osteoporosis. There were significant negative correlations between HMW/total-adiponectin ratio and BMI (r=-0.27, p=0.030) and with OPG (r=-0.44, pproduction of OPG thereby affecting osteoclasts mediated bone resorption.

Bone mineral density and metabolic indices in hyperthyroidism.

Science.gov (United States)

Al-Nuaim, A; El-Desouki, M; Sulimani, R; Mohammadiah, M

1991-09-01

Hyperthyroidism can alter bone metabolism by increasing both bone resorption and formation. The increase in bone resorption predominates, leading to a decrease in bone mass. To assess the effect of hyperthyroidism on bone and mineral metabolism, we measured bone density using single photon absorptiometry in 30 untreated hyperthyroid patients. Patients were categorized into three groups based on sex and alkaline phosphatase levels: 44 sex- and age-matched subjects were used as controls. Bone densities were significanlty lower in all patient groups compared with controls. Alkaline phosphatase was found to be a useful marker for assessing severity of bone disease in hyperthyroid patients as there is significant bone density among patients with higher alkaline phosphatase value. Hyperthyroidism should be considered in the differential diagnosis of unexplained alkaline phophatase activity.

Therapeutic Effect of Cistanoside A on Bone Metabolism of Ovariectomized Mice

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Xiaoxue Xu

2017-01-01

Full Text Available Cistanoside A (Cis A, an active phenylethanoid glycoside isolated from Cistanche deserticola Y. C. Ma, has received our attention because of its possible role in the treatment of osteoporosis. In the present study, we evaluated the effects of Cis A on an ovariectomized (OVX mice model and investigated its underlying molecular mechanisms of action. After 12 weeks of orally-administrated intervention, Cis A (20, 40 and 80 mg/kg body weight/day exhibited significant antiosteoporotic effects on OVX mice, evidenced by enhanced bone strength, bone mineral density and improved trabecular bone microarchitecture. Meanwhile, the activities of bone resorption markers, including tartrate-resistant acid phosphatase (TRAP, deoxypyridinoline (DPD and cathepsin K, were decreased, and the bioactivity of bone formation marker alkaline phosphatase (ALP was increased. Mechanistically, Cis A inhibited the expression of TNF-receptor associated factor 6 (TRAF6, an upstream molecule that is shared by both nuclear factor kappa-light chain enhancer of activated B cells (NF-κB and phosphatidylinositol 3-kinase (PI3K/Akt pathways and subsequently suppressed the levels of receptor activators of nuclear factor kappaB ligand (RANKL, downregulated the expression of NF-κB and upregulated osteoprotegerin (OPG, PI3K and Akt, which means Cis A possessed antiosteoporotic activity in ovariectomized mice via TRAF6-mediated NF-kappaB inactivation and PI3K/Akt activation. Put together, we present novel findings that Cis A, by downregulating TRAF6, coordinates the inhibition of NF-κB and stimulation of PI3K/Akt pathways to promote bone formation and prevent bone resorption. These data demonstrated the potential of Cis A as a promising agent for the treatment of osteoporosis disease.

Effects of a Combination Therapy of Sclerostin Antibody III and Raloxifene on Bone Formation Markers in Ovariectomized Rats

International Nuclear Information System (INIS)

Allam, H. I. G.

2016-01-01

Objective: To determine the systemic effect of sclerostin monoclonal antibody (Scl-AbIII) administration on markers of bone formation and compare it with a combination of sclerostin antibody and raloxifene. Study Design: Experimental study. Place and Duration of Study: Medical College Animal House at King Khaled University Hospital, Riyadh, Saudi Arabia, from January to November 2014. Methodology: Forty-five female rats were divided into 5 groups equally; 1 control group and 4 groups of ovariectomized (OVX) rats: control OVX rats and OVX rats treated by Scl-AbIII, raloxifene or Scl-AbIII+raloxifene one month after ovariectomy, continued for 4 weeks. At the end of treatment, serum levels of Bone Specific Alkaline Phosphatase (BSAP), alkaline phosphatase, osteocalcin, Insulin-like Growth Factor-1 (IGF-1), Parathyroid Hormone (PTH), Ca/sup 2+/ and phosphorus were measured. Uterus was weighed and body weight change was calculated. Results: Scl-AbIII or raloxifene treatment produced significant increase of serum BSAP, osteocalcin, IGF-1, PTH and Ca/sup 2+/ levels. Raloxifene, either alone or combined with Scl-AbIII attenuated the decrease in uterus wet weight, and the increase in body weight seen in OVX rats. Combination therapy of Scl-AbIII, and raloxifene produced significant increase of serum alkaline phosphatase, osteocalcin and IGF-1 levels than treatment with either Scl-AbIII or raloxifene alone. Conclusion: Combination therapy of Scl-AbIII and raloxifene is an attractive strategy to enhance bone formation and can offer better gain over treatment with either one of them alone. Confirmation of these preliminary observations must await careful long-term studies. (author)

Handheld FRET-Aptamer Sensor for Bone Markers, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — Astronauts lose approximately 1-1.5% of their bone mass per month during space travel due to a lack of physical stress in the microgravity environment. Although, no...

Bone Density Development of the Temporal Bone Assessed by Computed Tomography.

Science.gov (United States)

Takahashi, Kuniyuki; Morita, Yuka; Ohshima, Shinsuke; Izumi, Shuji; Kubota, Yamato; Horii, Arata

2017-12-01

The temporal bone shows regional differences in bone development. The spreading pattern of acute mastoiditis shows age-related differences. In infants, it spreads laterally and causes retroauricular swelling, whereas in older children, it tends to spread medially and causes intracranial complications. We hypothesized that bone maturation may influence the spreading pattern of acute mastoiditis. Eighty participants with normal hearing, aged 3 months to 42 years, participated in this study. Computed tomography (CT) values (Hounsfield unit [HU]) in various regions of the temporal bone, such as the otic capsule (OC), lateral surface of the mastoid cavity (LS), posterior cranial fossa (PCF), and middle cranial fossa (MCF), were measured as markers of bone density. Bone density development curves, wherein CT values were plotted against age, were created for each region. The age at which the CT value exceeded 1000 HU, which is used as an indicator of bone maturation, was calculated from the development curves and compared between the regions. The OC showed mature bone at birth, whereas the LS, PCF, and MCF showed rapid maturation in early childhood. However, there were significant regional differences in the ages of maturation: 1.7, 3.9, and 10.8 years for the LS, PCF, and MCF, respectively. To our knowledge, this is the first report to show regional differences in the maturation of temporal bone, which could partly account for the differences in the spreading pattern of acute mastoiditis in individuals of different ages.

A study of changes in bone metabolism in cases of gender identity disorder.

Science.gov (United States)

Miyajima, Tsuyoshi; Kim, Yoon Taek; Oda, Hiromi

2012-07-01

The aim of this study was to determine the effect of increasing estrogen and decreasing androgen in males and increasing androgen and decreasing estrogen in females on bone metabolism in patients with gender identity disorder (GID). We measured and examined bone mineral density (BMD) and bone metabolism markers retrospectively in GID patients who were treated in our hospital. In addition, we studied the effects of treatment on those who had osteoporosis. Patients who underwent a change from male to female (MtF) showed inhibition of bone resorption and increased L2-4 BMD whereas those who underwent a change from female to male (FtM) had increased bone resorption and decreased L2-4 BMD. Six months after administration of risedronate to FtM patients with osteoporosis, L2-4 BMD increased and bone resorption markers decreased. These results indicate that estrogen is an important element with regard to bone metabolism in males.

Evaluation of a Topical Herbal Agent for the Promotion of Bone Healing

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Wing-Sum Siu

2015-01-01

Full Text Available A topically used Chinese herbal paste, namely, CDNR, was designed to facilitate fracture healing which is usually not addressed in general hospital care. From our in vitro studies, CDNR significantly inhibited the release of nitric oxide from RAW264.7 cells by 51 to 77%. This indicated its anti-inflammatory effect. CDNR also promoted the growth of bone cells by stimulating the proliferation of UMR106 cells up to 18%. It also increased the biomechanical strength of the healing bone in a drill-hole defect rat model by 16.5% significantly. This result revealed its in vivo efficacy on facilitation of bone healing. Furthermore, the detection of the chemical markers of CDNR in the skin and muscle of the treatment area demonstrated its transdermal properties. However, CDNR did not affect the bone turnover markers in serum of the rats. With its anti-inflammatory and bone formation properties, CDNR is found effective in promoting bone healing.

Biochemical markers of mineral bone disorder in South African ...

African Journals Online (AJOL)

/L) suggestive of high turnover bone disease, was present in 47.3 % of the study population. In multiple-logistic regression analysis, the odds ratio for developing hyperparathyroidism with hypocalcaemia and hyperphosphataemia were 5.32 ...

Molecular changes in articular cartilage and subchondral bone in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis

Directory of Open Access Journals (Sweden)

Zhuo Ya

2011-08-01

Full Text Available Abstract Background Osteoarthritis (OA is a debilitating, progressive joint disease. Methods Similar to the disease progression in humans, sequential events of early cartilage degradation, subchondral osteopenia followed by sclerosis, and late osteophyte formation were demonstrated in the anterior cruciate ligament transection (ACLT or ACLT with partial medial meniscectomy (ACLT + MMx rat OA models. We describe a reliable and consistent method to examine the time dependent changes in the gene expression profiles in articular cartilage and subchondral bone. Results Local regulation of matrix degradation markers was demonstrated by a significant increase in mRNA levels of aggrecanase-1 and MMP-13 as early as the first week post-surgery, and expression remained elevated throughout the 10 week study. Immunohistochemistry confirmed MMP-13 expression in differentiated chondrocytes and synovial fibroblasts at week-2 and cells within osteophytes at week-10 in the surgically-modified-joints. Concomitant increases in chondrocyte differentiation markers, Col IIA and Sox 9, and vascular invasion markers, VEGF and CD31, peaked around week-2 to -4, and returned to Sham levels at later time points in both models. Indeed, VEGF-positive cells were found in the deep articular chondrocytes adjacent to subchondral bone. Osteoclastic bone resorption markers, cathepsin K and TRAP, were also elevated at week-2. Confirming bone resorption is an early local event in OA progression, cathepsin K positive osteoclasts were found invading the articular cartilage from the subchondral region at week 2. This was followed by late disease events, including subchondral sclerosis and osteophyte formation, as demonstrated by the upregulation of the osteoanabolic markers runx2 and osterix, toward week-4 to 6 post-surgery. Conclusions In summary, this study demonstrated the temporal and cohesive gene expression changes in articular cartilage and subchondral bone using known markers of

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 ...

Rat bone marrow progenitor cells transduced in situ by rSV40 vectors differentiate into multiple central nervous system cell lineages.

Science.gov (United States)

Louboutin, Jean-Pierre; Liu, Bianling; Reyes, Beverly A S; Van Bockstaele, Elisabeth J; Strayer, David S

2006-12-01

Using bone marrow-directed gene transfer, we tested whether bone marrow-derived cells may function as progenitors of central nervous system (CNS) cells in adult animals. SV40-derived gene delivery vectors were injected directly into femoral bone marrow, and we examined transgene expression in blood and brain for 0-16 months thereafter by immunostaining for FLAG epitope marker. An average of 5% of peripheral blood cells and 25% of femoral marrow cells were FLAG(+) throughout the study. CNS FLAG-expressing cells were mainly detected in the dentate gyrus (DG) and periventricular subependymal zone (PSZ). Although absent before 1 month and rare at 4 months, DG and PSZ FLAG(+) cells were abundant 16 months after bone marrow injection. Approximately 5% of DG cells expressed FLAG, including neurons (48.6%) and microglia (49.7%), and occasional astrocytes (1.6%), as determined by double immunostaining for FLAG and lineage markers. These data suggest that one or more populations of cells resident within adult bone marrow can migrate to the brain and differentiate into CNS-specific cells.

Facial profile markers in second- and third-trimester fetuses with trisomy 18

NARCIS (Netherlands)

Vos, F. I.; De Jong-Pleij, E. A P; Bakker, M.; Tromp, E.; Manten, G. T R; Bilardo, C. M.

2015-01-01

Objectives To evaluate nasal bone length (NBL), maxilla-nasion-mandible (MNM) angle, fetal profile (FP) line, prenasal thickness (PT), prenasal thickness to nasal bone length (PT:NBL) ratio and prefrontal space ratio (PFSR) as markers of trisomy 18 in the second and third trimesters of pregnancy.

Gingival crevicular fluid bone turnover biomarkers: How postmenopausal women respond to orthodontic activation.

Science.gov (United States)

Smuthkochorn, Sorapan; Palomo, J Martin; Hans, Mark G; Jones, Corey S; Palomo, Leena

2017-07-01

Bone turnover associated with orthodontic tooth movement is evidenced by increased bone turnover markers in gingival crevicular fluid (GCF). Postmenopausal women have an increased concentration of serum bone turnover markers. The filtrate of this serum makes up GCF, but little is known of the bone turnover around teeth in this cohort. The objective of this investigation was to compare the GCF bone turnover markers in premenopausal vs postmenopausal women receiving orthodontic treatment at baseline and at orthodontic activation. Twenty-eight women were enrolled in the study and separated into 2 groups: premenopausal (16) and postmenopausal (12). Bone turnover was evaluated by GCF at baseline and 24 hours after orthodontic appliance activation. GCF concentrations of RANKL and OPN were measured using ELISA. Baseline and change in concentrations were compared between groups. Baseline RANKL and OPN were significantly different between the premenopausal and postmenopausal groups (P orthodontic appliance activation in both groups (P orthodontic activation was not significantly different between groups. Although postmenopausal women have a different bone turnover profile at baseline than do their premenopausal counterparts, there is no difference in their response to orthodontic activation. This confers a level of security associated with orthodontic activation. Future studies are warranted to construct biomarker curves throughout orthodontic therapy. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

An informative constitutional cytogenetic marker found in a patient post bone marrow transplantation

Energy Technology Data Exchange (ETDEWEB)

Zaslav, A.L.; Graziano, J.; Ebert, R. [Albert Einstein College of Medicine, New Hyde Park, NY (United States)] [and others

1994-09-01

It is cytogenetically difficult to distinguish between host and donor cells in allogeneic bone marrow transplantation (BMT) individuals of the same sex. Here we describe a patient with a cytogenetic marker found after BMT. A 7-month-old male presented with leukemia which was CD7+, CD33+, HLADR+, and CD4-, CD8-, indicating a diagnosis of acute stem cell leukemia (ASCL). Cytogenetic analysis revealed an abnormal clone in all of the cells analyzed: 46,XY,t(2;8)(p11.2;q24),inv(9)(p13p24). This translocation is associated with B-cell acute lymphoblastic leukemia (ALL); thus, it was possible for this patient to develop B-cell ALL. The abnormal clone persisted along with normal 46,XY cells, and evolved in several of seven additional analyses. The patient was treated with two courses of chemotherapy and failed to attain cytogenetic remission. While in relapse, the patient received a BMT from his 3-year-old brother. Two weeks later, a different translocation was seen in all cells: 46,XY,t(3;12)(p21;q21). This result could be interpreted in two ways: (1) the structural abnormality was indicative of a newly evolved clone related to the patient`s disease; or (2) the donor was a balanced translocation carrier. Cytogenetic analysis of peripheral blood from the donor revealed the same translocation seen in the patient. Parental blood chromosomes were normal indicating that the donor carried a de novo balanced translocation. Subsequent chromosome analysis of both peripheral blood and BM from the patient revealed the presence of the translocation in all cells. De novo balanced translocations are rare and occur with a frequency of 1/2,000 live borns. The family received genetic counseling and was informed of the possible reproductive risks to translocation carriers. This unusual finding will serve as a useful cytogenetic marker to assist in monitoring the patient`s clinical course, i.e., chimerism and remission status.

Bone Resorption Increases as Early as the Second Day in Head- Down Bed Rest

Science.gov (United States)

Heer, M.; Kamps, N.; Mika, C.; Boese, A.; Gerzer, R.

Long-term bed rest and space mission studies have shown that immobilization as well as microgravity induce increased bone resorption while bone formation tends to decrease. In order to analyze the kinetics of short-term changes in bone turnover we studied in a randomized, strictly controlled crossover design the effects of 6 days 6° head-down tilt bed rest (HDT) in 8 male healthy subjects (mean body weight (BW): 70.1 +/- 1.88 kg; mean age: 25.5 +/- 1.04 years) in our metabolic ward. Two days before arriving in the metabolic ward the subjects started with a diet consisting of an energy content of 10 MJ/d, 2000 mg Calcium/d, 400 i.U. Vitamin D, 200 mEq Na+ and 50 ml water/kg BW/d. The diet was continued in the metabolic ward. The metabolic ward period (11days) was divided into 3 parts: 4 ambulatory days, 6 days either HDT or control and 1 recovery day. Continuous urine collection started on the first day in the metabolic ward to analyze calcium excretion and bone resorption markers, namely C-telopeptide (CTX) and N-telopeptide (NTX). On the 2nd ambulatory day in the metabolic ward and on the 5th day in HDT or control blood was drawn to analyze serum calcium, parathyroid hormone, and bone formation markers (bone Alkaline Phosphatase (bAP), Procollagen-I-Propeptide (P-I-CP). Both study phases were identical with respect to environmental conditions, study protocol and diet. Urinary calcium excretion was as early as the first day in immobilization increased (pcontrol. But, already on the 2nd day of immobilization both bone resorption markers significantly increased. NTX-excretion was increased by 28.7 +/- 14.0% (pcontrol. In contrast to the bone resorption markers, the formation marker P-I-CP tended to decrease as early as the fifth day of immobilization (phormone-, as well as bAP concentrations were unchanged. We conclude from these results of a pronounced rise of bone resorption markers that already 24 hours of immobilization induce a significant rise in osteoclast

Age-related differences in hormonal and nutritional impact on lean anorexia nervosa bone turnover uncoupling.

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Galusca, B; Bossu, C; Germain, N; Kadem, M; Frere, D; Lafage-Proust, M H; Lang, F; Estour, B

2006-01-01

In anorexia nervosa (AN) patients osteoporosis occurs within a framework of multiple hormonal abnormalities as a result of bone turnover uncoupling, with decreased bone formation and increased bone resorption. The aim of study was to evaluate the hormonal and nutritional relationships with both of these bone remodeling compartments and their eventual modifications with age. In a cohort of 115 AN patients (mean BMI:14.6 kg/m2) that included 60 mature adolescents (age: 15.5-20 years) and 55 adult women (age: 20-37 years) and in 28 age-matched controls (12 mature adolescents and 16 adults) we assessed: bone markers [serum osteocalcin, skeletal alkaline phosphatase (sALP), C-telopeptide of type I collagen (sCTX) and tartrate-resistant acid phosphatase type 5b (TRAP 5b)], nutritional markers [ body mass index (BMI, fat and lean mass), hormones (free tri-iodothyronine (T3), free T4, thyroid stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH), 17 beta estradiol, free testosterone index (FTI), dehydroepiandrosterone (DHEAS), insulin-like growth factor 1 (IGF-1), growth hormone (GH) and cortisol], plasma methoxyamines (metanephrine and normetanephrine) and calcium metabolism parameters [parathyroid hormone (PTH), Ca, vitamin D3]. Osteocalcin reached similar low levels in both AN age subgroups. sCTX levels were found to be elevated in all AN subjects and higher in mature adolescents than in adult AN (11,567+/-895 vs. 8976+/-805 pmol/l, psALP was significantly lower only in mature adolescent AN patients, while there were no significant differences in the levels of TRAP 5b between AN patients and age-matched control groups. Osteocalcin correlated with sCTX in the control subjects (r=0.65) but not in the AN patients, suggesting the independent regulation of these markers in AN patients. Osteocalcin levels strongly correlated with freeT3, IGF-I, 17 beta estradiol and cortisol, while sCTX correlated with IGF-I, GH and cortisol in both age

Biochemical markers of mineral bone disorder in South African ...

African Journals Online (AJOL)

In multiple-logistic regression analysis, the odds ratio for developing hyperpara- thyroidism with ... Materials and methods ... 2009 to April 2016) at two dialysis centers in Johannes- ... gestive of high turnover bone disease, was present in 47.3.

Vitamin D supplementation, bone turnover, and inflammation in HIV-infected patients.

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Benguella, L; Arbault, A; Fillion, A; Blot, M; Piroth, C; Denimal, D; Duvillard, L; Ornetti, P; Chavanet, P; Maillefert, J-F; Piroth, L

2018-04-13

To assess whether vitamin D supplementation could be associated with a modification of inflammatory markers and bone turnover in HIV-1-infected patients. Patients who participated in an initial survey in 2010 and who were followed in the same department were included in a new study in 2012. Between 2010 and 2012, vitamin D supplementation was offered to patients presenting with hypovitaminosis D as per appropriate guidelines. Clinical examinations were performed, and fasting blood samples were taken for inflammation and bone marker evaluations. Of the 263 patients who participated in the 2010 study, 198 were included in the 2012 study. Hypovitaminosis D was observed in 47% (36/77) of participants supplemented as per appropriate guidelines, in 78% (75/97) of transiently or incompletely supplemented participants, and in 71% (17/24) of non-supplemented participants (mainly because vitamin D levels in 2010 were normal). No significant correlation between vitamin D supplementation and the 2-year inflammation outcome (IL-6 and hsCRP) or C-terminal telopeptide levels was observed. However, a decrease in IL6 levels over the 2 years significantly correlated with reaching a normal vitamin D level (OR=0.89 per+1pg/mL IL6 increase, 95% CI=0.81-0.97, P=0.015). Vitamin D supplementation decreases the risk of hypovitaminosis D but does not decrease the risk of inflammation nor bone turnover, unless normal 25-OH vitamin D levels are reached. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Identification of Novel Equine (Equus caballus Tendon Markers Using RNA Sequencing

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Jan M. Kuemmerle

2016-11-01

Full Text Available Although several tendon-selective genes exist, they are also expressed in other musculoskeletal tissues. As cell and tissue engineering is reliant on specific molecular markers to discriminate between cell types, tendon-specific genes need to be identified. In order to accomplish this, we have used RNA sequencing (RNA-seq to compare gene expression between tendon, bone, cartilage and ligament from horses. We identified several tendon-selective gene markers, and established eyes absent homolog 2 (EYA2 and a G-protein regulated inducer of neurite outgrowth 3 (GPRIN3 as specific tendon markers using RT-qPCR. Equine tendon cells cultured as three-dimensional spheroids expressed significantly greater levels of EYA2 than GPRIN3, and stained positively for EYA2 using immunohistochemistry. EYA2 was also found in fibroblast-like cells within the tendon tissue matrix and in cells localized to the vascular endothelium. In summary, we have identified EYA2 and GPRIN3 as specific molecular markers of equine tendon as compared to bone, cartilage and ligament, and provide evidence for the use of EYA2 as an additional marker for tendon cells in vitro.

Daily online bony correction is required for prostate patients without fiducial markers or soft-tissue imaging.

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Johnston, M L; Vial, P; Wiltshire, K L; Bell, L J; Blome, S; Kerestes, Z; Morgan, G W; O'Driscoll, D; Shakespeare, T P; Eade, T N

2011-09-01

To compare online position verification strategies with offline correction protocols for patients undergoing definitive prostate radiotherapy. We analysed 50 patients with implanted fiducial markers undergoing curative prostate radiation treatment, all of whom underwent daily kilovoltage imaging using an on-board imager. For each treatment, patients were set-up initially with skin tattoos and in-room lasers. Orthogonal on-board imager images were acquired and the couch shift to match both bony anatomy and the fiducial markers recorded. The set-up error using skin tattoos and offline bone correction was compared with online bone correction. The fiducial markers were used as the reference. Data from 1923 fractions were analysed. The systematic error was ≤1 mm for all protocols. The average random error was 2-3mm for online bony correction and 3-5mm for skin tattoos or offline-bone. Online-bone showed a significant improvement compared with offline-bone in the number of patients with >5mm set-up errors for >10% (P20% (Pmarkers or daily soft-tissue imaging. Copyright © 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Meninges harbor cells expressing neural precursor markers during development and adulthood.

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Bifari, Francesco; Berton, Valeria; Pino, Annachiara; Kusalo, Marijana; Malpeli, Giorgio; Di Chio, Marzia; Bersan, Emanuela; Amato, Eliana; Scarpa, Aldo; Krampera, Mauro; Fumagalli, Guido; Decimo, Ilaria

2015-01-01

Brain and skull developments are tightly synchronized, allowing the cranial bones to dynamically adapt to the brain shape. At the brain-skull interface, meninges produce the trophic signals necessary for normal corticogenesis and bone development. Meninges harbor different cell populations, including cells forming the endosteum of the cranial vault. Recently, we and other groups have described the presence in meninges of a cell population endowed with neural differentiation potential in vitro and, after transplantation, in vivo. However, whether meninges may be a niche for neural progenitor cells during embryonic development and in adulthood remains to be determined. In this work we provide the first description of the distribution of neural precursor markers in rat meninges during development up to adulthood. We conclude that meninges share common properties with the classical neural stem cell niche, as they: (i) are a highly proliferating tissue; (ii) host cells expressing neural precursor markers such as nestin, vimentin, Sox2 and doublecortin; and (iii) are enriched in extracellular matrix components (e.g., fractones) known to bind and concentrate growth factors. This study underlines the importance of meninges as a potential niche for endogenous precursor cells during development and in adulthood.

Rate of Clinical Complete Response for 1 Year or More in Bone-Metastatic Breast Cancer after Comprehensive Treatments including Autologous Formalin-Fixed Tumor Vaccine.

Science.gov (United States)

Kuranishi, Fumito; Imaoka, Yuki; Sumi, Yuusuke; Uemae, Yoji; Yasuda-Kurihara, Hiroko; Ishihara, Takeshi; Miyazaki, Tsubasa; Ohno, Tadao

2018-01-01

No effective treatment has been developed for bone-metastatic breast cancer. We found 3 cases with clinical complete response (cCR) of the bone metastasis and longer overall survival of the retrospectively examined cohort treated comprehensively including autologous formalin-fixed tumor vaccine (AFTV). AFTV was prepared individually for each patient from their own formalin-fixed and paraffin-embedded breast cancer tissues. Three patients maintained cCR status of the bone metastasis for 17 months or more. Rate of cCR for 1 year or more appeared to be 15% (3/20) after comprehensive treatments including AFTV. The median overall survival time (60.0 months) and the 3- to 8-year survival rates after diagnosis of bone metastasis were greater than those of historical control cohorts in Japan (1988-2002) and in the nationwide population-based cohort study of Denmark (1999-2007). Bone-metastatic breast cancer may be curable after comprehensive treatments including AFTV, although larger scale clinical trial is required.

Mechanism of Action of Bortezomib and the New Proteasome Inhibitors on Myeloma Cells and the Bone Microenvironment: Impact on Myeloma-Induced Alterations of Bone Remodeling

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Fabrizio Accardi

2015-01-01

Full Text Available Multiple myeloma (MM is characterized by a high capacity to induce alterations in the bone remodeling process. The increase in osteoclastogenesis and the suppression of osteoblast formation are both involved in the pathophysiology of the bone lesions in MM. The proteasome inhibitor (PI bortezomib is the first drug designed and approved for the treatment of MM patients by targeting the proteasome. However, recently novel PIs have been developed to overcome bortezomib resistance. Interestingly, several preclinical data indicate that the proteasome complex is involved in both osteoclast and osteoblast formation. It is also evident that bortezomib either inhibits osteoclast differentiation induced by the receptor activator of nuclear factor kappa B (NF-κB ligand (RANKL or stimulates the osteoblast differentiation. Similarly, the new PIs including carfilzomib and ixazomib can inhibit bone resorption and stimulate the osteoblast differentiation. In a clinical setting, PIs restore the abnormal bone remodeling by normalizing the levels of bone turnover markers. In addition, a bone anabolic effect was described in responding MM patients treated with PIs, as demonstrated by the increase in the osteoblast number. This review summarizes the preclinical and clinical evidence on the effects of bortezomib and other new PIs on myeloma bone disease.

Comparison between skin-mounted fiducials and bone-implanted fiducials for image-guided neurosurgery

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Rost, Jennifer; Harris, Steven S.; Stefansic, James D.; Sillay, Karl; Galloway, Robert L., Jr.

2004-05-01

Point-based registration for image-guided neurosurgery has become the industry standard. While the use of intrinsic points is appealing because of its retrospective nature, affixing extrinsic objects to the head prior to scanning has been demonstrated to provide much more accurate registrations. Points of reference between image space and physical space are called fiducials. The extrinsic objects which generate those points are fiducial markers. The markers can be broken down into two classifications: skin-mounted and bone-implanted. Each has distinct advantages and disadvantages. Skin-mounted fiducials require simply sticking them on the patient in locations suggested by the manufacturer, however, they can move with tractions placed on the skin, fall off and perhaps the most dangerous problem, they can be replaced by the patient. Bone implanted markers being rigidly affixed to the skull do not present such problems. However, a minor surgical intervention (analogous to dental work) must be performed to implant the markers prior to surgery. Therefore marker type and use has become a decision point for image-guided surgery. We have performed a series of experiments in an attempt to better quantify aspects of the two types of markers so that better informed decisions can be made. We have created a phantom composed of a full-size plastic skull [Wards Scientific Supply] with a 500 ml bag of saline placed in the brain cavity. The skull was then sealed. A skin mimicking material, DragonSkinTM [SmoothOn Company] was painted onto the surface and allowed to dry. Skin mounted fiducials [Medtronic-SNT] and bone-implanted markers [Z-Kat]were placed on the phantom. In addition, three additional bone-implanted markers were placed (two on the base of the skull and one in the eye socket for use as targets). The markers were imaged in CT and 4 MRI sequences (T1-weighted, T2 weighted, SPGR, and a functional series.) The markers were also located in physical space using an Optotrak

Bone metabolism in renal transplant patients treated with cyclosporine or sirolimus.

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Campistol, Josep M; Holt, David W; Epstein, Solomon; Gioud-Paquet, Martine; Rutault, Karine; Burke, James T

2005-09-01

Sirolimus is a new immunosuppressive agent used as treatment to prevent acute renal allograft rejection. One of the complications of renal transplantation and subsequent long-term immunosuppression is bone loss associated with osteoporosis and consequent fracture. Two open-label, randomized, phase 2 studies comparing sirolimus versus cyclosporine (CsA) included indices of bone metabolism as secondary end-points. Markers of bone turnover, serum osteocalcin and urinary N-telopeptides, were measured over a 1-year period in 115 patients receiving either CsA or sirolimus as a primary therapy in combination with azathioprine and glucocorticoids (study A) or mycophenolate mofetil (MMF) and glucocorticoids (study B). Urinary excretion of N-telopeptides and the concentrations of serum osteocalcin were consistently higher in the CsA-treated patients and significantly different at week 24 for N-telopeptides and at weeks 12, 24, and 52 for osteocalcin. In conclusion, future trials are warranted to test whether a sirolimus-based regimen conserves bone mineral density compared with a CsA-based regimen.

Description and assessment of a registration-based approach to include bones for attenuation correction of whole-body PET/MRI.

Science.gov (United States)

Marshall, Harry R; Patrick, John; Laidley, David; Prato, Frank S; Butler, John; Théberge, Jean; Thompson, R Terry; Stodilka, Robert Z

2013-08-01

Attenuation correction for whole-body PET/MRI is challenging. Most commercial systems compute the attenuation map from MRI using a four-tissue segmentation approach. Bones, the most electron-dense tissue, are neglected because they are difficult to segment. In this work, the authors build on this segmentation approach by adding bones using a registration technique and assessing its performance on human PET images. Twelve oncology patients were imaged with FDG PET/CT and MRI using a Turbo-FLASH pulse sequence. A database of 121 attenuation correction quality CT scans was also collected. Each patient MRI was compared to the CT database via weighted heuristic measures to find the "most similar" CT in terms of body geometry. The similar CT was aligned to the MRI with a deformable registration method. Two MRI-based attenuation maps were computed. One was a standard four-tissue segmentation (air, lung, fat, and lean tissue) using basic image processing techniques. The other was identical, except the bones from the aligned CT were added. The PET data were reconstructed with the patient's CT-based attenuation map (the silver standard) and both MRI-based attenuation maps. The relative errors of the MRI-based attenuation corrections were computed in 14 standardized volumes of interest, in lesions, and over whole tissues. The squared Pearson correlation coefficient was also calculated over whole tissues. Statistical testing was done with ANOVAs and paired t-tests. The MRI-based attenuation correction ignoring bone had relative errors ranging from -37% to -8% in volumes of interest containing bone. By including bone, the magnitude of the relative error was reduced in all cases (pbone was improved from a mean of -7.5% to 2% (pbone reduced the magnitude of relative error in three cases (pbone slightly increased relative error in lung from 7.7% to 8.0% (p=0.002), in fat from 8.5% to 9.2% (pbone from -14.6% to 1.3% (pbone was included or not. The approach to include bones in MRI

Clinical Usefulness of Implanted Fiducial Markers for Hypofractionated Radiotherapy of Prostate Cancer

International Nuclear Information System (INIS)

Choi, Young Min; Ahn, Sung Hwan; Lee, Hyung Hwan; Lee, Hyung Sik; Hur, Woo Joo; Yoon, Jin Han; Kim, Tae Hyo; Kim, Soo Dong; Yun, Seong Guk

2011-01-01

To assess the usefulness of implanted fiducial markers in the setup of hypofractionated radiotherapy for prostate cancer patients by comparing a fiducial marker matched setup with a pelvic bone match. Four prostate cancer patients treated with definitive hypofractionated radiotherapy between September 2009 and August 2010 were enrolled in this study. Three gold fiducial markers were implanted into the prostate and through the rectum under ultrasound guidance around a week before radiotherapy. Glycerin enemas were given prior to each radiotherapy planning CT and every radiotherapy session. Hypofractionated radiotherapy was planned for a total dose of 59.5 Gy in daily 3.5 Gy with using the Novalis system. Orthogonal kV X-rays were taken before radiotherapy. Treatment positions were adjusted according to the results from the fusion of the fiducial markers on digitally reconstructed radiographs of a radiotherapy plan with those on orthogonal kV X-rays. When the difference in the coordinates from the fiducial marker fusion was less than 1 mm, the patient position was approved for radiotherapy. A virtual bone matching was carried out at the fiducial marker matched position, and then a setup difference between the fiducial marker matching and bone matching was evaluated. Three patients received a planned 17-fractionated radiotherapy and the rest underwent 16 fractionations. The setup error of the fiducial marker matching was 0.94±0.62 mm (range, 0.09 to 3.01 mm; median, 0.81 mm), and the means of the lateral, craniocaudal, and anteroposterior errors were 0.39±0.34 mm, 0.46±0.34 mm, and 0.57±0.59 mm, respectively. The setup error of the pelvic bony matching was 3.15±2.03 mm (range, 0.25 to 8.23 mm; median, 2.95 mm), and the error of craniocaudal direction (2.29±1.95 mm) was significantly larger than those of anteroposterior (1.73±1.31 mm) and lateral directions (0.45±0.37 mm), respectively (p< 0.05). Incidences of over 3 mm and 5 mm in setup difference among the

3H-tetracycline as a proxy for 41Ca for measuring dietary perturbations of bone resorption

International Nuclear Information System (INIS)

Weaver, Connie; Cheong, Jennifer; Jackson, George; Elmore, David; McCabe, George; Martin, Berdine

2007-01-01

Our group is interested in evaluating early effects of dietary interventions on bone loss. Postmenopausal women lose bone following reduction in estrogen which leads to increased risk of fracture. Traditional means of monitoring bone loss and effectiveness of treatments include changes in bone density, which takes 6 months to years to observe effects, and changes in biochemical markers of bone turnover, which are highly variable and lack specificity. Prelabeling bone with 41 Ca and measuring urinary 41 Ca excretion with accelerator mass spectrometry provides a sensitive, specific, and rapid approach to evaluating effectiveness of treatment. To better understand 41 Ca technology as a tool for measuring effective treatments on reducing bone resorption, we perturbed bone resorption by manipulating dietary calcium in rats. We used 3 H-tetracycline ( 3 H-TC) as a proxy for 41 Ca and found that a single dose is feasible to study bone resorption. Suppression of bone resorption, as measured by urinary 3 H-TC, by dietary calcium was observed in rats stabilized after ovariectomy, but not in recently ovariectomized rats

Neural differentiation potential of human bone marrow-derived mesenchymal stromal cells: misleading marker gene expression

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Montzka Katrin

2009-03-01

Full Text Available Abstract Background In contrast to pluripotent embryonic stem cells, adult stem cells have been considered to be multipotent, being somewhat more restricted in their differentiation capacity and only giving rise to cell types related to their tissue of origin. Several studies, however, have reported that bone marrow-derived mesenchymal stromal cells (MSCs are capable of transdifferentiating to neural cell types, effectively crossing normal lineage restriction boundaries. Such reports have been based on the detection of neural-related proteins by the differentiated MSCs. In order to assess the potential of human adult MSCs to undergo true differentiation to a neural lineage and to determine the degree of homogeneity between donor samples, we have used RT-PCR and immunocytochemistry to investigate the basal expression of a range of neural related mRNAs and proteins in populations of non-differentiated MSCs obtained from 4 donors. Results The expression analysis revealed that several of the commonly used marker genes from other studies like nestin, Enolase2 and microtubule associated protein 1b (MAP1b are already expressed by undifferentiated human MSCs. Furthermore, mRNA for some of the neural-related transcription factors, e.g. Engrailed-1 and Nurr1 were also strongly expressed. However, several other neural-related mRNAs (e.g. DRD2, enolase2, NFL and MBP could be identified, but not in all donor samples. Similarly, synaptic vesicle-related mRNA, STX1A could only be detected in 2 of the 4 undifferentiated donor hMSC samples. More significantly, each donor sample revealed a unique expression pattern, demonstrating a significant variation of marker expression. Conclusion The present study highlights the existence of an inter-donor variability of expression of neural-related markers in human MSC samples that has not previously been described. This donor-related heterogeneity might influence the reproducibility of transdifferentiation protocols as

Relationships between serum Omentin-1 levels and bone mineral density in older men with osteoporosis

Institute of Scientific and Technical Information of China (English)

Li Yang; Xin-Lan Zhao; Bin Liao; Ai-Ping Qin

2016-01-01

Objective: To investigate the correlation between serum Omentin-1 levels and the presence of osteoporosis in older men. Methods: Serum Omentin-1, bone turnover biochemical markers, and bone mineral density (BMD) were determined in 45 older men with osteoporosis or 45 older men without osteoporosis (65e70 years old). Results: Omentin-1 levels were increased in older men with osteoporosis, and the differences remained significant after con-trolling for fat mass. Omentin-1 was negatively correlated with BMD. In a multiple linear stepwise regression analysis, Omentin-1, lean mass, but not fat mass, were independent predictors of BMD for the combined group. Significant negative correlations between Omentin-1 and bone-specific alkaline phosphatase (BAP) and bone cross-linked N-telopeptides of typeⅠcollagen (NTX) were found. Omentin-1 was also independently associated with BMD and bone turnover markers in older men with osteoporosis and control groups that were considered separately. Conclusions: Omentin-1 is an independent predictor of BMD in older men with osteoporosis, and it is negatively correlated with bone turnover biochemical markers. It is suggested that Omentin-1 may exert a negative effect on bone mass through the regulation of the osteoblast differentiation in the older men with osteoporosis.

Rhus javanica Gall Extract Inhibits the Differentiation of Bone Marrow-Derived Osteoclasts and Ovariectomy-Induced Bone Loss

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Tae-Ho Kim

2016-01-01

Full Text Available Inhibition of osteoclast differentiation and bone resorption is a therapeutic strategy for the management of postmenopausal bone loss. This study investigated the effects of Rhus javanica (R. javanica extracts on bone marrow cultures to develop agents from natural sources that may prevent osteoclastogenesis. Extracts of R. javanica (eGr cocoons spun by Rhus javanica (Bell. Baker inhibited the osteoclast differentiation and bone resorption. The effects of aqueous extract (aeGr or 100% ethanolic extract (eeGr on ovariectomy- (OVX- induced bone loss were investigated by various biochemical assays. Furthermore, microcomputed tomography (µCT was performed to study bone remodeling. Oral administration of eGr (30 mg or 100 mg/kg/day for 6 weeks augmented the inhibition of femoral bone mineral density (BMD, bone mineral content (BMC, and other factors involved in bone remodeling when compared to OVX controls. Additionally, eGr slightly decreased bone turnover markers that were increased by OVX. Therefore, it may be suggested that the protective effects of eGr could have originated from the suppression of OVX-induced increase in bone turnover. Collectively, the findings of this study indicate that eGr has potential to activate bone remodeling by inhibiting osteoclast differentiation and bone loss.

[Bone ultrasonography in kidney disease: applications and limitations].

Science.gov (United States)

Aucella, Filippo; Gesuete, Antonio; Cicchella, Antonio; Granata, Antonio; Fiorini, Fulvio; Guglielmi, Giuseppe

2012-01-01

Quantitative ultrasound (QUS) of the bone is a technique that is generating great interest among bone structure researchers because of its intrinsic features. Its safety and low cost make it an ideal technique for repeated measurements over time such as in chronic disease or when it is necessary to monitor the effects of prescribed therapies. The method was developed for the study of osteoporosis and the sites of measurement are all peripheral, including the distal diaphyses and metaphyses of the phalanges, calcaneus, radius and tibia. QUS parameters, however, cannot be used directly for the diagnosis of osteoporosis according to the WHO criteria, although many authors have shown that ultrasound parameters, particularly those of calcaneal QUS, can predict the risk of osteoporotic fractures independently of MBD. Very promising results with the use of QUS have been obtained in corticosteroid-induced osteoporosis, rheumatoid arthritis, Cushing's syndrome, cystic fibrosis, osteomalacia, thalassemia and osteopenia related to parenteral nutrition. QUS can also monitor the effectiveness of therapy in various pathological conditions. In nephrology the combined use of phalangeal QUS and biochemical markers of bone turnover allows adequate follow-up of patients on dialysis and renal transplant recipients with alterations or disorders of the bone.

Dietary patterns in men and women are simultaneously determinants of altered glucose metabolism and bone metabolism.

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Langsetmo, Lisa; Barr, Susan I; Dasgupta, Kaberi; Berger, Claudie; Kovacs, Christopher S; Josse, Robert G; Adachi, Jonathan D; Hanley, David A; Prior, Jerilynn C; Brown, Jacques P; Morin, Suzanne N; Davison, Kenneth S; Goltzman, David; Kreiger, Nancy

2016-04-01

We hypothesized that diet would have direct effects on glucose metabolism with direct and indirect effects on bone metabolism in a cohort of Canadian adults. We assessed dietary patterns (Prudent [fruit, vegetables, whole grains, fish, and legumes] and Western [soft drinks, potato chips, French fries, meats, and desserts]) from a semiquantitative food frequency questionnaire. We used fasting blood samples to measure glucose, insulin, homeostatic model assessment insulin resistance (HOMA-IR), 25-hydroxyvitamin D (25OHD), parathyroid hormone, bone-specific alkaline phosphatase (a bone formation marker), and serum C-terminal telopeptide (CTX; a bone resorption marker). We used multivariate regression models adjusted for confounders and including/excluding body mass index. In a secondary analysis, we examined relationships through structural equations models. The Prudent diet was associated with favorable effects on glucose metabolism (lower insulin and HOMA-IR) and bone metabolism (lower CTX in women; higher 25OHD and lower parathyroid hormone in men). The Western diet was associated with deleterious effects on glucose metabolism (higher glucose, insulin, and HOMA-IR) and bone metabolism (higher bone-specific alkaline phosphatase and lower 25OHD in women; higher CTX in men). Body mass index adjustment moved point estimates toward the null, indicating partial mediation. The structural equation model confirmed the hypothesized linkage with strong effects of Prudent and Western diet on metabolic risk, and both direct and indirect effects of a Prudent diet on bone turnover. In summary, a Prudent diet was associated with lower metabolic risk with both primary and mediated effects on bone turnover, suggesting that it is a potential target for reducing fracture risk. Copyright © 2016 Elsevier Inc. All rights reserved.

Bone tumors

International Nuclear Information System (INIS)

Unni, K.K.

1988-01-01

This book contains the proceedings on bone tumors. Topics covered include: Bone tumor imaging: Contribution of CT and MRI, staging of bone tumors, perind cell tumors of bone, and metastatic bone disease

Anti-osteoporotic activity of harpagide by regulation of bone formation in osteoblast cell culture and ovariectomy-induced bone loss mouse models.

Science.gov (United States)

Chung, Hwa-Jin; Kyung Kim, Won; Joo Park, Hyen; Cho, Lan; Kim, Me-Riong; Kim, Min Jeong; Shin, Joon-Shik; Ho Lee, Jin; Ha, In-Hyuk; Kook Lee, Sang

2016-02-17

Harpagide, an iridoid glucoside, is a constituent of the root of Harpagophytum procumbens var. sublobatum (Engl.) Stapf, Devil's claw which has been used in patients with osteoarthritis (OA). In the present study, we investigated the anti-osteoporotic potential of harpagide and its underlying mechanism of action in in vitro cell culture and in vivo bone loss animal models. Harpagide was obtained from the alkalic hydrolysis of harpagoside, a major constituent of H. procumbens var. sublobatum Analysis of biomarkers for bone formation in osteoblastic MC3T3-E1 cells and bone resorption in osteoclast cells derived from mouse bone marrow cells was performed to evaluate the mechanism of action. The protective activity of harpagide against bone loss was also evaluated in ovariectomized (OVX) mouse model. Harpagide improved bone properties by stimulating the process of differentiation and maturation of osteoblast cells and suppressing the process of RANKL-induced differentiation of osteoclast cells. In OVX-induced bone loss mouse model, oral administration of harpagide significantly improved recovery of bone mineral density, trabecular bone volume, and trabecular number in the femur. Harpagide also prevented increase of trabecular separation and structure model index induced by OVX. Harpagide effectively inhibited the serum levels of biochemical markers of bone loss, including alkaline phosphatase, osteocalcin, C-terminal telopeptide, and tartrate-resistant acid phosphatase. Taken together, the present study demonstrates that harpagide has a potential for prevention of bone loss in OVX mice by regulating the stimulation of osteoblast differentiation and the suppression of osteoclast formation. Therefore, these findings suggest that harpagide might serve as a bioactive compound derived from H. procumbens var. sublobatum for improvement of age-dependent bone destruction disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Bone Mineral Density in Patients with Growth Hormone Deficiency - Does a Gender Difference Exist?

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Hitz, Mette; Jensen, Jens-Erik Beck; Eskildsen, PC

2006-01-01

OBJECTIVE: The aim of the study was to clarify whether a gender difference exists with respect to bone mineral density (BMD) and bone mineral content (BMC) in adult patients with growth hormone deficiency (GHD). DESIGN: A case-control design. METHODS: Blood sampling for measurements of calcium......, phosphate, creatinine, PTH, vitamin D, IGF-1, markers of bone formation and bone resorption, and dual energy X-ray absorptiometry (DEXA), to determine BMD and BMC of the lumbar spine, hip, distal arm and total body, were performed in 34 patients with GHD (19 females) and 34 sex-, age- and weight...... identical BMD values at all regions. This gender difference was even more obvious when BMD values were expressed as Z-scores or as three-dimensional BMD of the total body. The bone formation and bone resorption markers, as well as calcium and vitamin D, were all at the same levels in GH...

Bone mineral density in patients with growth hormone deficiency: does a gender difference exist?

DEFF Research Database (Denmark)

Hitz, Mette Friberg; Jensen, Jens-Erik Beck; Eskildsen, Peter C

2006-01-01

OBJECTIVE: The aim of the study was to clarify whether a gender difference exists with respect to bone mineral density (BMD) and bone mineral content (BMC) in adult patients with growth hormone deficiency (GHD). DESIGN: A case-control design. METHODS: Blood sampling for measurements of calcium......, phosphate, creatinine, PTH, vitamin D, IGF-1, markers of bone formation and bone resorption, and dual energy X-ray absorptiometry (DEXA), to determine BMD and BMC of the lumbar spine, hip, distal arm and total body, were performed in 34 patients with GHD (19 females) and 34 sex-, age- and weight...... identical BMD values at all regions. This gender difference was even more obvious when BMD values were expressed as Z-scores or as three-dimensional BMD of the total body. The bone formation and bone resorption markers, as well as calcium and vitamin D, were all at the same levels in GH...

Effect of antitumour necrosis factor-alpha therapy on bone turnover in patients with active Crohn's disease: a prospective study.

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Ryan, B M; Russel, M G V M; Schurgers, L; Wichers, M; Sijbrandij, J; Stockbrugger, R W; Schoon, E

2004-10-15

Patients with Crohn's disease are at increased risk of osteoporosis. Disease activity and circulating proinflammatory cytokines are thought to play a role in this process. Infliximab, a chimaeric antitumour necrosis factor-alpha antibody is effective in the treatment of Crohn's disease. The aim of this study was to investigate the impact of treatment with infliximab on bone turnover in Crohn's disease patients. This was a prospective trial. Twenty-four patients with active Crohn's disease were treated with infliximab (5 mg/kg). Bone markers were assayed pre- and post-treatment. Bone formation was measured using serum bone-specific alkaline phosphatase and total osteocalcin and bone resorption using serum N-telopeptide cross-linked type 1 collagen. Infliximab therapy caused a significant increase in both markers of bone formation in patients with active Crohn's disease. No significant change in the bone resorption marker serum N-telopeptide cross-linked type 1 was found. Infliximab therapy had a significant beneficial effect on bone metabolism in patients with active Crohn's disease. These findings further support the theory that active ongoing inflammation and high levels of circulating cytokines play a pivotal role in the pathogenesis of bone loss in patients with Crohn's disease.

Targeting sphingosine-1-phosphate lyase as an anabolic therapy for bone loss.

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Weske, Sarah; Vaidya, Mithila; Reese, Alina; von Wnuck Lipinski, Karin; Keul, Petra; Bayer, Julia K; Fischer, Jens W; Flögel, Ulrich; Nelsen, Jens; Epple, Matthias; Scatena, Marta; Schwedhelm, Edzard; Dörr, Marcus; Völzke, Henry; Moritz, Eileen; Hannemann, Anke; Rauch, Bernhard H; Gräler, Markus H; Heusch, Gerd; Levkau, Bodo

2018-05-01

Sphingosine-1-phosphate (S1P) signaling influences bone metabolism, but its therapeutic potential in bone disorders has remained unexplored. We show that raising S1P levels in adult mice through conditionally deleting or pharmacologically inhibiting S1P lyase, the sole enzyme responsible for irreversibly degrading S1P, markedly increased bone formation, mass and strength and substantially decreased white adipose tissue. S1P signaling through S1P 2 potently stimulated osteoblastogenesis at the expense of adipogenesis by inversely regulating osterix and PPAR-γ, and it simultaneously inhibited osteoclastogenesis by inducing osteoprotegerin through newly discovered p38-GSK3β-β-catenin and WNT5A-LRP5 pathways. Accordingly, S1P 2 -deficient mice were osteopenic and obese. In ovariectomy-induced osteopenia, S1P lyase inhibition was as effective as intermittent parathyroid hormone (iPTH) treatment in increasing bone mass and was superior to iPTH in enhancing bone strength. Furthermore, lyase inhibition in mice successfully corrected severe genetic osteoporosis caused by osteoprotegerin deficiency. Human data from 4,091 participants of the SHIP-Trend population-based study revealed a positive association between serum levels of S1P and bone formation markers, but not resorption markers. Furthermore, serum S1P levels were positively associated with serum calcium , negatively with PTH , and curvilinearly with body mass index. Bone stiffness, as determined through quantitative ultrasound, was inversely related to levels of both S1P and the bone formation marker PINP, suggesting that S1P stimulates osteoanabolic activity to counteract decreasing bone quality. S1P-based drugs should be considered as a promising therapeutic avenue for the treatment of osteoporotic diseases.

Development of a molecular test of Paget's disease of bone.

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Guay-Bélanger, Sabrina; Simonyan, David; Bureau, Alexandre; Gagnon, Edith; Albert, Caroline; Morissette, Jean; Siris, Ethel S; Orcel, Philippe; Brown, Jacques P; Michou, Laëtitia

2016-03-01

Depending on populations, 15 to 40% of patients have a familial form of Paget's disease of bone (PDB), which is transmitted in an autosomal-dominant mode of inheritance with incomplete penetrance. To date, only SQSTM1 gene mutations have been linked to the disease. Several single nucleotide polymorphisms (SNPs) have been associated with PDB in patient non-carriers of SQSTM1 mutations, but they have minor size effects. The current clinical practice guidelines still recommend to measure total serum alkaline phosphatase (sALP) for PDB screening. However, genetic or bone biomarkers alone may lack sensitivity to detect PDB. Thus, the objective of this study was to develop a molecular test of PDB, combining genetic and bone biomarkers, in order to detect PDB, which is frequently asymptomatic. We genotyped 35 SNPs previously associated with PDB in 305 patients, and 292 healthy controls. In addition, serum levels of 14 bone biomarkers were assayed in 51 patients and 151 healthy controls. Bivariate and multivariate logistic regression models with adjustment for age and sex were fitted to search for a combination of SNPs and/or bone biomarkers that could best detect PDB in patient non-carriers of SQSTM1 mutations. First, a combination of five genetic markers gave rise to the highest area under the ROC curve (AUC) with 95% confidence interval [95% CI] of 0.731 [0.688; 0.773], which allowed us to detect 81.5% of patients with PDB. Second, a combination of two bone biomarkers had an AUC of 0.822 [0.726; 0.918], and was present in 81.5% of patients with PDB. Then, the combination of the five genetic markers and the two bone biomarkers increased the AUC up to 0.892 [0.833; 0.951], and detected 88.5% of patients with PDB. These results suggested that an algorithm integrating first a screen for SQSTM1 gene mutations, followed by either a genetic markers combination or a combined genetic and biochemical markers test in patients non-carrier of any SQSTM1 mutation, may detect the PDB

Epithelial architectural destruction is necessary for bone marrow derived cell contribution to regenerating prostate epithelium.

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Palapattu, Ganesh S; Meeker, Alan; Harris, Timothy; Collector, Michael I; Sharkis, Saul J; DeMarzo, Angelo M; Warlick, Christopher; Drake, Charles G; Nelson, William G

2006-08-01

Using various nonphysiological tissue injury/repair models numerous studies have demonstrated the capacity of bone marrow derived cells to contribute to the repopulation of epithelial tissues following damage. To investigate whether this phenomenon might also occur during periods of physiological tissue degeneration/regeneration we compared the ability of bone marrow derived cells to rejuvenate the prostate gland in mice that were castrated and then later treated with dihydrotestosterone vs mice with prostate epithelium that had been damaged by lytic virus infection. Using allogenic bone marrow grafts from female donor transgenic mice expressing green fluorescent protein transplanted into lethally irradiated males we were able to assess the contributions of bone marrow derived cells to recovery of the prostatic epithelium in 2 distinct systems, including 1) surgical castration followed 1 week later by dihydrotestosterone replacement and 2) intraprostatic viral injection. Eight to 10-week-old male C57/Bl6 mice were distributed among bone marrow donor-->recipient/prostate injury groups, including 5 with C57/Bl6-->C57/Bl6/no injury, 3 with green fluorescent protein-->C57/Bl6/no injury, 3 with green fluorescent protein-->C57/Bl6/vehicle injection, 4 with green fluorescent protein-->C57/Bl6/virus injection and 3 each with green fluorescent protein-->C57/Bl6/castration without and with dihydrotestosterone, respectively. Prostate tissues were harvested 3 weeks after dihydrotestosterone replacement or 14 days following intraprostatic viral injection. Prostate tissue immunofluorescence was performed with antibodies against the epithelial marker cytokeratin 5/8, the hematopoietic marker CD45 and green fluorescent protein. Mice that sustained prostate injury from vaccinia virus infection with concomitant severe inflammation and glandular disruption showed evidence of bone marrow derived cell reconstitution of prostate epithelium, that is approximately 4% of all green

Rate of Clinical Complete Response for 1 Year or More in Bone-Metastatic Breast Cancer after Comprehensive Treatments including Autologous Formalin-Fixed Tumor Vaccine

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Fumito Kuranishi

2018-01-01

Full Text Available Introduction. No effective treatment has been developed for bone-metastatic breast cancer. We found 3 cases with clinical complete response (cCR of the bone metastasis and longer overall survival of the retrospectively examined cohort treated comprehensively including autologous formalin-fixed tumor vaccine (AFTV. Patients and Methods. AFTV was prepared individually for each patient from their own formalin-fixed and paraffin-embedded breast cancer tissues. Results. Three patients maintained cCR status of the bone metastasis for 17 months or more. Rate of cCR for 1 year or more appeared to be 15% (3/20 after comprehensive treatments including AFTV. The median overall survival time (60.0 months and the 3- to 8-year survival rates after diagnosis of bone metastasis were greater than those of historical control cohorts in Japan (1988–2002 and in the nationwide population-based cohort study of Denmark (1999–2007. Conclusion. Bone-metastatic breast cancer may be curable after comprehensive treatments including AFTV, although larger scale clinical trial is required.

Bone loss in women with type 1 diabetes

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tanderup joergensen, maj-britt; christensen, jesper olund; Svendsen, Ole Lander

2015-01-01

Background: Although osteoporosis has been investigated and debated in the diabetic population over the past decades, very little is known about the spontaneous changes in bone mineral density (BMD) and biochemical markers of bone turnover in pre- and postmenopausal type 1 diabetic (T1DM) women...... over time. Aim: To measure spontaneous changes in BMD and biochemical markers of bone turnover in pre- and postmenopausal T1DM women. Subjects: 53 T1DM women (31 premenopausal and 22 postmenopausal) from the outpatient clinic were enrolled in the study in 1993 and 35 (22 premenopausal, 13...... postmenopausal) were reexamined in 1997. Method: BMD was measured at femoral neck (f.n.), spine (L2 - L4), total body and forearm with DXA or SXA in 53 T1DM women. 4 years later a re-scan was carried out on 35 T1DM. Results: In premenopausal subjects a yearly decrease less than 1% at f.n., spine, forearm...

Bone conditioned media (BCM) improves osteoblast adhesion and differentiation on collagen barrier membranes.

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Fujioka-Kobayashi, Masako; Caballé-Serrano, Jordi; Bosshardt, Dieter D; Gruber, Reinhard; Buser, Daniel; Miron, Richard J

2016-07-04

The use of autogenous bone chips during guided bone regeneration procedures has remained the gold standard for bone grafting due to its excellent combination of osteoconduction, osteoinduction and osteogenesis. Recent protocols established by our group have characterized specific growth factors and cytokines released from autogenous bone that have the potential to be harvested and isolated into bone conditioned media (BCM). Due to the advantageous osteo-promotive properties of BCM, the aims of the present study was to pre-coat collagen barrier membranes with BCM and investigate its effect on osteoblast adhesion, proliferation and differentiation for possible future clinical use. Scanning electron microscopy (SEM) was first used to qualitative assess BCM protein accumulation on the surface of collagen membranes. Thereafter, undifferentiated mouse ST2 stromal bone marrow cells were seeded onto BioGide porcine derived collagen barrier membranes (control) or barrier membranes pre-coated with BCM (test group). Control and BCM samples were compared for cell adhesion at 8 h, cell proliferation at 1, 3 and 5 days and real-time PCR at 5 days for osteoblast differentiation markers including Runx2, alkaline phosphatase (ALP), osteocalcin (OCN) and bone sialoprotein (BSP). Mineralization was further assessed with alizarin red staining at 14 days post seeding. SEM images demonstrated evidence of accumulated proteins found on the surface of collagen membranes following coating with BCM. Analysis of total cell numbers revealed that the additional pre-coating with BCM markedly increased cell attachment over 4 fold when compared to cells seeded on barrier membranes alone. No significant difference could be observed for cell proliferation at all time points. BCM significantly increased mRNA levels of osteoblast differentiation markers including ALP, OCN and BSP at 5 days post seeding. Furthermore, barrier membranes pre-coated with BCM demonstrated a 5-fold increase in alizarin

The value of combined examination of serum CYFRA21-1 levels and bone scan in the diagnosis of bone metastasis in lung cancer

International Nuclear Information System (INIS)

Yu Jing; Wang Junhong; Zhengping

2007-01-01

Objective: To explore the value of combined examination of serum tumor markers CYFRA21-1 and bone scan in the diagnosis of bone metastasis in lung cancer. Methods: Bone scan and serum CYFRA21-1 levels (with CLIA) determination were performed in 138 patients with lung cancer and 56 patients with benign lung diseases. Results: The serum level of CYFRA21-1 were significantly higher in patients with bone metastasis than those in patients without bone metastasis. The levels were also higher in patients without bone metastasis than those in controls. Most patients with bone metastasis had positive results in bone scan (97.4%), only 2 of the 78 had negative bone scan but positive with CT or MRI. A few patients without bone metastasis and controls had positive bone scan results, caused by previous operation or injury. Conclusion: The combined detection of CYFRA21-1 and bone scan were valuable in the diagnosis of bone metastasis of lung cancer. (authors)

Pomegranate Peel Extract Prevents Bone Loss in a Preclinical Model of Osteoporosis and Stimulates Osteoblastic Differentiation in Vitro

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Mélanie Spilmont

2015-11-01

Full Text Available The nutritional benefits of pomegranate have attracted great scientific interest. The pomegranate, including the pomegranate peel, has been used worldwide for many years as a fruit with medicinal activity, mostly antioxidant properties. Among chronic diseases, osteoporosis, which is associated with bone remodelling impairment leading to progressive bone loss, could eventually benefit from antioxidant compounds because of the involvement of oxidative stress in the pathogenesis of osteopenia. In this study, with in vivo and ex vivo experiments, we investigated whether the consumption of pomegranate peel extract (PGPE could limit the process of osteopenia. We demonstrated that in ovariectomized (OVX C57BL/6J mice, PGPE consumption was able to significantly prevent the decrease in bone mineral density (−31.9%; p < 0.001 vs. OVX mice and bone microarchitecture impairment. Moreover, the exposure of RAW264.7 cells to serum harvested from mice that had been given a PGPE-enriched diet elicited reduced osteoclast differentiation and bone resorption, as shown by the inhibition of the major osteoclast markers. In addition, PGPE appeared to substantially stimulate osteoblastic MC3T3-E1 alkaline phosphatase (ALP activity at day 7, mineralization at day 21 and the transcription level of osteogenic markers. PGPE may be effective in preventing the bone loss associated with ovariectomy in mice, and offers a promising alternative for the nutritional management of this disease.

Pomegranate Peel Extract Prevents Bone Loss in a Preclinical Model of Osteoporosis and Stimulates Osteoblastic Differentiation in Vitro.

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Spilmont, Mélanie; Léotoing, Laurent; Davicco, Marie-Jeanne; Lebecque, Patrice; Miot-Noirault, Elisabeth; Pilet, Paul; Rios, Laurent; Wittrant, Yohann; Coxam, Véronique

2015-11-11

The nutritional benefits of pomegranate have attracted great scientific interest. The pomegranate, including the pomegranate peel, has been used worldwide for many years as a fruit with medicinal activity, mostly antioxidant properties. Among chronic diseases, osteoporosis, which is associated with bone remodelling impairment leading to progressive bone loss, could eventually benefit from antioxidant compounds because of the involvement of oxidative stress in the pathogenesis of osteopenia. In this study, with in vivo and ex vivo experiments, we investigated whether the consumption of pomegranate peel extract (PGPE) could limit the process of osteopenia. We demonstrated that in ovariectomized (OVX) C57BL/6J mice, PGPE consumption was able to significantly prevent the decrease in bone mineral density (-31.9%; p < 0.001 vs. OVX mice) and bone microarchitecture impairment. Moreover, the exposure of RAW264.7 cells to serum harvested from mice that had been given a PGPE-enriched diet elicited reduced osteoclast differentiation and bone resorption, as shown by the inhibition of the major osteoclast markers. In addition, PGPE appeared to substantially stimulate osteoblastic MC3T3-E1 alkaline phosphatase (ALP) activity at day 7, mineralization at day 21 and the transcription level of osteogenic markers. PGPE may be effective in preventing the bone loss associated with ovariectomy in mice, and offers a promising alternative for the nutritional management of this disease.

CD146/MCAM defines functionality of human bone marrow stromal stem cell populations

DEFF Research Database (Denmark)

Harkness, Linda; Zaher, Walid; Ditzel, Nicholas

2016-01-01

BACKGROUND: Identification of surface markers for prospective isolation of functionally homogenous populations of human skeletal (stromal, mesenchymal) stem cells (hMSCs) is highly relevant for cell therapy protocols. Thus, we examined the possible use of CD146 to subtype a heterogeneous hMSC...... population. METHODS: Using flow cytometry and cell sorting, we isolated two distinct hMSC-CD146(+) and hMSC-CD146(-) cell populations from the telomerized human bone marrow-derived stromal cell line (hMSC-TERT). Cells were examined for differences in their size, shape and texture by using high...... and adipocytes on the basis of gene expression and protein production of lineage-specific markers. In vivo, hMSC-CD146(+) and hMSC-CD146(-) cells formed bone and bone marrow organ when implanted subcutaneously in immune-deficient mice. Bone was enriched in hMSC-CD146(-) cells (12.6 % versus 8.1 %) and bone...

Bone health measured using quantitative ultrasonography in adult males with muscular dystrophy.

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Morse, C I; Smith, J; Denny, A; Tweedale, J; Searle, N D; Winwood, K; Onambele-Pearson, G L

2016-12-14

To compare muscle and bone health markers in adult males (aged 20-59 yrs) with and without muscular dystrophy (MD). Participants included 11 Fascioscapulohumeral (FSH), 11 Becker's (Be), 9 limb girdle (LG), 11 Duchenne (DMD), and 14 non-dystrophic controls (CTRL). Physical activity was assessed using Bone (BPAQ) and disability specific (PASIPD) questionnaires. Bone QUS provided T- and Z scores from the Distal Radius (DR) and Mid-shaft tibia (MST). Tibialis anterior cross sectional area (TA ACSA ) was measured using B-mode ultrasound. Grip strength was measured in all but DMD. Physical activity was lower in DMD, FSH and BeMD than CTRL (PPASIPD correlated with grip strength (r=0.65, P<0.01) and TA ACSA (r=0.46, P<0.01). Muscle size, strength, and bone health was lower in adult males with MD compared to adult males without MD, the extent of this is partially determined by physical activity.

Challenges of Estimating Fracture Risk with DXA: Changing Concepts About Bone Strength and Bone Density.

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Licata, Angelo A

2015-07-01

Bone loss due to weightlessness is a significant concern for astronauts' mission safety and health upon return to Earth. This problem is monitored with bone densitometry (DXA), the clinical tool used to assess skeletal strength. DXA has served clinicians well in assessing fracture risk and has been particularly useful in diagnosing osteoporosis in the elderly postmenopausal population for which it was originally developed. Over the past 1-2 decades, however, paradoxical and contradictory findings have emerged when this technology was widely employed in caring for diverse populations unlike those for which it was developed. Although DXA was originally considered the surrogate marker for bone strength, it is now considered one part of a constellation of factors-described collectively as bone quality-that makes bone strong and resists fracturing, independent of bone density. These characteristics are beyond the capability of routine DXA to identify, and as a result, DXA can be a poor prognosticator of bone health in many clinical scenarios. New clinical tools are emerging to make measurement of bone strength more accurate. This article reviews the historical timeline of bone density measurement (dual X-ray absorptiometry), expands upon the clinical observations that modified the relationship of DXA and bone strength, discusses some of the new clinical tools to predict fracture risk, and highlights the challenges DXA poses in the assessment of fracture risk in astronauts.

Inactivity-induced bone loss is not exacerbated by moderate energy restriction

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Heer, M.; Boese, A.; Baecker, N.; Zittermann, A.; Smith, S. M.

Severe energy restriction leads to decreased bone mineral density (BMD) in postmenopausal women, adolescent females, and in male athletes. Astronauts in space also lose bone mass, and most of them have reduced energy intake (about 25 % below requirements). The aim of our study was to examine if bone loss in space is partly induced by moderate energy restriction. Physiological changes of space flight were simulated by 6 head-down tilt bed rest (HDBR). Nine healthy male subjects (age: 23.6 ± 3.0 years; BMI: 23.0 ± 2.9 kg/m2, mean ± SD) finished four study phases, two of normocaloric nutrition, either ambulatory or HDBR, and two of hypocaloric nutrition, either ambulatory or HDBR. Urine samples (24 h) were analyzed for calcium excretion (UCaV) and bone resorption markers (C-Telopeptide, CTX, and N-Telopeptide, NTX). Serum calcium, parathyroid hormone (PTH) and bone formation markers (Procollagen-I-C-terminal-Peptide, PICP, Procollagen-I-N-terminal-Peptide, PINP, and bone-specific alkaline phosphatase, bAP) were analyzed. No significant changes in serum calcium or PTH were noted either during HDBR or during hypocaloric nutrition. PICP, but not PINP or bAP, decreased significantly during HDBR (normocaloric: prestriction did not exaggerate bone resorption during HDBR.

Expression of RANKL/OPG during bone remodeling in vivo

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Tanaka, H., E-mail: tnk@ymghp.jp [Department of Orthopedic Surgery, Yamaguchi Grand Medical Center, 77 Ohsaki, Hofu, Yamaguchi 747-8511 (Japan); Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224 (United States); Mine, T. [Department of Orthopedic Surgery, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505 (Japan); Ogasa, H. [Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224 (United States); Department of Orthopedic Surgery, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505 (Japan); Taguchi, T. [Department of Orthopedic Surgery, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505 (Japan); Liang, C.T. [Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224 (United States); National Health Research Institutes, Taipei 115, Taiwan (China)

2011-08-12

Highlights: {yields} This is the first study to determine the relationship between osteogenic differentiation and RANKL/OPG expression during bone remodeling in vivo. {yields} The OPG expression peak occurred during the bone formation phase, whereas the marked elevation of RANKL expression was observed during the bone resorption phase. {yields} Histological analysis showed that RANKL/OPG immunoreactivity was predominantly associated with bone marrow cells in the marrow cavity. {yields} The present study confirmed that RANKL/OPG are key factors linking bone formation to resorption during the bone remodeling process. -- Abstract: The interaction between receptor activator of nuclear factor {kappa}B ligand (RANKL) and osteoprotegerin (OPG) plays a dominant role in osteoclastogenesis. As both proteins are produced by osteoblast lineage cells, they are considered to represent a key link between bone formation and resorption. In this study, we investigated the expression of RANKL and OPG during bone remodeling in vivo to determine the relationship between osteoclastogenic stimulation and osteoblastic differentiation. Total RNA was prepared from rat femurs after marrow ablation on days 0, 3, 6, and 9. The temporal activation patterns of osteoblast-related genes (procollagen {alpha}1 (I), alkaline phosphatase, osteopontin, and osteocalcin) were examined by Northern blot analysis. An appreciable increase in the expression of these osteoblast markers was observed on day 3. The peak increase in gene expression was observed on day 6 followed by a slight reduction by day 9. Real-time PCR analysis showed that the OPG mRNA expression was markedly upregulated on day 6 and slightly decreased on day 9. In contrast, RANKL mRNA expression was increased by more than 20-fold on day 9. The RANKL/OPG ratio, an index of osteoclastogenic stimulation, peaked on day 9. Histological analysis showed that RANKL and OPG immunoreactivity were predominantly associated with bone marrow cells. The

Expression of RANKL/OPG during bone remodeling in vivo

International Nuclear Information System (INIS)

Tanaka, H.; Mine, T.; Ogasa, H.; Taguchi, T.; Liang, C.T.

2011-01-01

Highlights: → This is the first study to determine the relationship between osteogenic differentiation and RANKL/OPG expression during bone remodeling in vivo. → The OPG expression peak occurred during the bone formation phase, whereas the marked elevation of RANKL expression was observed during the bone resorption phase. → Histological analysis showed that RANKL/OPG immunoreactivity was predominantly associated with bone marrow cells in the marrow cavity. → The present study confirmed that RANKL/OPG are key factors linking bone formation to resorption during the bone remodeling process. -- Abstract: The interaction between receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG) plays a dominant role in osteoclastogenesis. As both proteins are produced by osteoblast lineage cells, they are considered to represent a key link between bone formation and resorption. In this study, we investigated the expression of RANKL and OPG during bone remodeling in vivo to determine the relationship between osteoclastogenic stimulation and osteoblastic differentiation. Total RNA was prepared from rat femurs after marrow ablation on days 0, 3, 6, and 9. The temporal activation patterns of osteoblast-related genes (procollagen α1 (I), alkaline phosphatase, osteopontin, and osteocalcin) were examined by Northern blot analysis. An appreciable increase in the expression of these osteoblast markers was observed on day 3. The peak increase in gene expression was observed on day 6 followed by a slight reduction by day 9. Real-time PCR analysis showed that the OPG mRNA expression was markedly upregulated on day 6 and slightly decreased on day 9. In contrast, RANKL mRNA expression was increased by more than 20-fold on day 9. The RANKL/OPG ratio, an index of osteoclastogenic stimulation, peaked on day 9. Histological analysis showed that RANKL and OPG immunoreactivity were predominantly associated with bone marrow cells. The expression of bone formation

Effect of hormone replacement therapy on the bone mass and urinary excretion of pyridinium cross-links.

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Pardini, D P; Sabino, A T; Meneses, A M; Kasamatsu, T; Vieira, J G

2000-01-06

The menopause accelerates bone loss and is associated with an increased bone turnover. Bone formation may be evaluated by several biochemical markers. However, the establishment of an accurate marker for bone resorption has been more difficult to achieve. To study the effect of hormone replacement therapy (HRT) on bone mass and on the markers of bone resorption: urinary excretion of pyridinoline and deoxypyridinoline. Cohort correlational study. Academic referral center. 53 post-menopausal women, aged 48-58 years. Urinary pyr and d-pyr were measured in fasting urine samples by spectrofluorometry after high performance liquid chromatography and corrected for creatinine excretion measured before treatment and after 1, 2, 4 and 12 months. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry (DEXA) before treatment and after 12 months of HRT. The BMD after HRT was about 4.7% (P < 0.0004); 2% (P < 0.002); and 3% (P < 0. 01) higher than the basal values in lumbar spine, neck and trochanter respectively. There were no significant correlations between pyridinium cross-links and age, weight, menopause duration and BMD. The decrease in pyr and d-pyr was progressive after HRT, reaching 28.9% (P < 0.0002), and 42% (P < 0.0002) respectively after 1 year. Urinary pyridinoline and deoxypyridinoline excretion decreases early in hormone replacement therapy, reflecting a decrease in the bone resorption rate, and no correlation was observed with the bone mass evaluated by densitometry.

Analysing the effect of multiple sclerosis on vitamin D related biochemical markers of bone remodelling.

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McKenna, Malachi J; Murray, Barbara; Lonergan, Roisin; Segurado, Ricardo; Tubridy, Niall; Kilbane, Mark T

2018-03-01

The Irish population is at risk of vitamin D deficiency during the winter months, but the secular trend over the past 40 years is for marked improvement. Multiple sclerosis (MS) is common in Ireland with a latitudinal pattern favouring highest incidence in northern regions; MS is linked strongly with vitamin D status as a causal factor. We sought firstly to study the relationship between vitamin D status and vitamin D-related bone biochemistry, and secondly to evaluate if MS had an independent effect on vitamin D related markers of bone remodelling. Using a case-control design of 165 pairs (MS patient and matched control) residing in three different geographic regions during winter months, we measured serum 25-hydroxyvitamin D (25OHD), parathyroid hormone (PTH), C-terminal telopeptide of type I collagen (CTX) and total procollagen type I amino-terminal propeptide (PINP). Given the paired case-control design, associations were explored using mixed-effects linear regression analysis with the patient-control pair as a random effect and after log transformation of 25OHD. A two-way interaction effect was tested for vitamin D status (25OHD <30nmol/L) and the presence of MS on PTH, CTX, and PINP. In the total group, just over one-third (34.5%) had 25OHD <30nmol/L. PTH was elevated in 7.6%. CTX was not elevated in any case, and PINP was elevated in 4.5%. On mixed-effects linear regression analysis after adjusting for confounders (age, sex, renal function, and serum albumin), we demonstrated the principal determinant of 25OHD was geographical location (p<0.001), of PTH was 25OHD (p<0.001), of CTX was PTH (p<0.001), and of PINP was PTH (p<0.001). MS did not have an independent effect on PTH (p=0.921), CTX (p=0.912), or PINP (p=0.495). As regards an interaction effect, the presence of MS and 25OHD <30nmol/L was not significant but tended towards having lower PTH (p=0.207). In conclusion, in Ireland in winter only a minority had any abnormality in the secondary indices of

Natural calcium isotonic composition of urine as a marker of bone mineral balance

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Skulan, J.; Bullen, T.; Anbar, A.D.; Puzas, J.E.; Shackelford, L.; LeBlanc, A.; Smith, S.M.

2007-01-01

Background: We investigated whether changes in the natural isotopic composition of calcium in human urine track changes in net bone mineral balance, as predicted by a model of calcium isotopic behavior in vertebrates. If so, isotopic analysis of natural urine or blood calcium could be used to monitor short-term changes in bone mineral balance that cannot be detected with other techniques. Methods: Calcium isotopic compositions are expressed as ??44Ca, or the difference in parts per thousand between the 44Ca/40Ca of a sample and the 44Ca/ 40Ca of a standard reference material. ??44Ca was measured in urine samples from 10 persons who participated in a study of the effectiveness of countermeasures to bone loss in spaceflight, in which 17 weeks of bed rest was used to induce bone loss. Study participants were assigned to 1 of 3 treatment groups: controls received no treatment, one treatment group received alendronate, and another group performed resistive exercise. Measurements were made on urine samples collected before, at 2 or 3 points during, and after bed rest. Results: Urine ??44Ca values during bed rest were lower in controls than in individuals treated with alendronate (P bone mineral density data. Conclusion: Results confirm the predicted relationship between bone mineral balance and calcium isotopes, suggesting that calcium isotopic analysis of urine might be refined into a clinical and research tool. ?? 2007 American Association for Clinical Chemistry.

Bone status and adipokine levels in children on vegetarian and omnivorous diets.

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Ambroszkiewicz, Jadwiga; Chełchowska, Magdalena; Szamotulska, Katarzyna; Rowicka, Grażyna; Klemarczyk, Witold; Strucińska, Małgorzata; Gajewska, Joanna

2018-03-23

Measurements of bone mineral density (BMD) reflect bone status but not the dynamics of bone turnover. Biochemical markers, which show global skeletal activity, were validated for the assessment of bone formation and resorption processes. Adipokines also play a significant role in the regulation of bone metabolism. To assess body composition, bone mineral density, bone turnover markers and adipokine levels in relation to vegetarian and omnivorous diets. The study included 53 vegetarian and 53 omnivorous prepubertal healthy children matched for age and sex (median age 7.0 years). Body composition and BMD were assessed by dual-energy X-ray absorptiometry. 25-hydroxyvitamin D and parathormone levels were measured by chemiluminescence method. Serum carboxy-terminal propeptide of type I collagen (CICP), total osteocalcin (OC) and its forms carboxylated (c-OC) and undercarboxylated (uc-OC), C-terminal cross-linking telopeptide of collagen type I (CTX), leptin and adiponectin levels were determined using immunoenzymatic assays. Both groups of children were comparable in terms of body composition, except for the percentage of fat mass, which was lower (19.24 vs. 21.77%, p = 0.018) in vegetarians. Mean values of total BMD z-score and lumbar spine BMD z-score were lower (-0.583 vs. -0.194, p = 0.009 and -0.877 vs. -0.496, p = 0.019, respectively) in vegetarians compared with omnivores. Serum leptin level was about 2-fold lower (1.39 vs. 2.94 ng/mL, p vegetarians, however, adiponectin concentration was similar in both groups. Vegetarians had similar concentration of 25-hydroxyvitamin D, but higher parathormone (40.8 vs. 32.1 pg/mL, p = 0.015) and CTX (1.94 vs. 1.76 ng/mL, p = 0.077) levels than omnivores. Total osteocalcin and CICP concentrations were comparable in both groups, however, c-OC/uc-OC ratio was higher (1.43 vs. 1.04 ng/mL, p vegetarians. We found positive correlation between c-OC and nutritional parameters adjusted for total energy intake (plant

Alendronate has a residual effect on bone mass in postmenopausal Danish women up to 7 years after treatment withdrawal

DEFF Research Database (Denmark)

Bagger, Yu Z; Tankó, László B; Alexandersen, Peter

2003-01-01

for 7, 5, or 3 yr, respectively. Bone mineral density of the lumbar spine, hip, and forearm was measured by dual-energy x-ray absorptiometry. Biochemical markers of bone turnover were induced serum C-terminal telopeptides of type I collagen (CTX) and osteocalcin. Women who received alendronate (2...... was found in women treated with alendronate 20 mg per day for 2 yr (9.7%, P=0.01 vs. placebo). The rate of bone loss after alendronate withdrawal was comparable to the bone loss observed in the placebo group. Bone markers tended to reverse back to normal levels, but were still affected even several years...

Protective Effects of Vildagliptin against Pioglitazone-Induced Bone Loss in Type 2 Diabetic Rats.

Science.gov (United States)

Eom, Young Sil; Gwon, A-Ryeong; Kwak, Kyung Min; Kim, Ju-Young; Yu, Seung Hee; Lee, Sihoon; Kim, Yeun Sun; Park, Ie Byung; Kim, Kwang-Won; Lee, Kiyoung; Kim, Byung-Joon

2016-01-01

Long-term use of thiazolidinediones (TZDs) is associated with bone loss and an increased risk of fracture in patients with type 2 diabetes (T2DM). Incretin-based drugs (glucagon-like peptide-1 (GLP-1) agonists and dipeptidylpeptidase-4 (DPP-4) inhibitors) have several benefits in many systems in addition to glycemic control. In a previous study, we reported that exendin-4 might increase bone mineral density (BMD) by decreasing the expression of SOST/sclerostin in osteocytes in a T2DM animal model. In this study, we investigated the effects of a DPP-4 inhibitor on TZD-induced bone loss in a T2DM animal model. We randomly divided 12-week-old male Zucker Diabetic Fatty (ZDF) rats into four groups; control, vildagliptin, pioglitazone, and vildagliptin and pioglitazone combination. Animals in each group received the respective treatments for 5 weeks. We performed an intraperitoneal glucose tolerance test (IPGTT) before and after treatment. BMD and the trabecular micro-architecture were measured by DEXA and micro CT, respectively, at the end of the treatment. The circulating levels of active GLP-1, bone turnover markers, and sclerostin were assayed. Vildagliptin treatment significantly increased BMD and trabecular bone volume. The combination therapy restored BMD, trabecular bone volume, and trabecular bone thickness that were decreased by pioglitazone. The levels of the bone formation marker, osteocalcin, decreased and that of the bone resorption marker, tartrate-resistant acid phosphatase (TRAP) 5b increased in the pioglitazone group. These biomarkers were ameliorated and the pioglitazone-induced increase in sclerostin level was lowered to control values by the addition of vildagliptin. In conclusion, our results indicate that orally administered vildagliptin demonstrated a protective effect on pioglitazone-induced bone loss in a type 2 diabetic rat model.

Bone health in Down syndrome.

Science.gov (United States)

García-Hoyos, Marta; Riancho, José Antonio; Valero, Carmen

2017-07-21

Patients with Down syndrome have a number of risk factors that theoretically could predispose them to osteoporosis, such as early aging, development disorders, reduced physical activity, limited sun exposure, frequent comorbidities and use of drug therapies which could affect bone metabolism. In addition, the bone mass of these people may be affected by their anthropometric and body composition peculiarities. In general terms, studies in adults with Down syndrome reported that these people have lower areal bone mineral density (g/cm 2 ) than the general population. However, most of them have not taken the smaller bone size of people with Down syndrome into account. In fact, when body mineral density is adjusted by bone size and we obtain volumetric body mineral density (g/cm 3 ), the difference between both populations disappears. On the other hand, although people with Down syndrome have risk factor of hypovitaminosis D, the results of studies regarding 25(OH)D in this population are not clear. Likewise, the studies about biochemical bone markers or the prevalence of fractures are not conclusive. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

The modified Glasgow prognostic score in patients undergoing surgery for bone and soft tissue sarcoma.

Science.gov (United States)

Morhij, Rossel; Mahendra, Ashish; Jane, Mike; McMillan, Donald C

2017-05-01

The prognostic significance of markers of the systemic inflammatory response in patients with soft tissue and bone sarcomas remains unclear. Therefore, the present study aimed to compare the prognostic value of markers of the systemic inflammatory response in patients undergoing surgery for primary soft tissue and bone sarcoma. Patients who underwent resection of primary soft tissue/bone sarcoma between 2008 and 2012 and had pre-operative measurements of the systemic inflammatory response [C-reactive protein, albumin, white cell, neutrophil, lymphocyte and platelet counts, and the combination of C-reactive protein and albumin (mGPS)] were included in the study (n = 111). The majority of the patients were ≤50 years old (84%), were female (63%), had soft tissue sarcoma (62%), and had tumours >10 cm (52%), mostly of high grade (85%). The median follow-up of survivors was 50 months (range 34-78); 24 (21%) developed local recurrence, 35 (31%) developed distant metastases and 30 (30%) died of their cancer. On univariate analysis, tumour size (P sarcoma. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Long term effect of thiazides on bone mass in women with hypercalciuric nephrolithiasis

OpenAIRE

Spivacow, Francisco R; Negri, Armando L; del Valle, Elisa E

2013-01-01

Background: Decreased bone mineral density and increased prevalence of bone fractures have been found in patients with idiopathic hypercalciuria. It is not yet clear if thiazide treatment prevent these events. Methods: We retrospectively evaluated bone mass and biochemical markers of bone turnover in response to thiazide therapy in 52 consecutive female patients with idiopathic hypercalciuria and nephrolithiasis. Patients were divided in two subgroups according to their menopausal status: 25 ...

Bone loss in rheumatoid arthritis

International Nuclear Information System (INIS)

Gotfredsen, A.; Als, O.S.; Hassager, C.; Christiansen, C.

1986-01-01

The authors studied 159 patients with rheumatoid arthritis (RA) treated with a variety of drugs. Stratification of the patients was done according to treatment, sex, menopausal state, duration of the disease, and functional impairment. Forearm bone mineral content (BMC) and total body bone mineral (TBBM) were measured by single and dual photon absorptiometry. Bone turnover was estimated by biochemical markers. All patients had significantly decreased BMC and TBBM compared to normals. Comparing glucocorticoid and penicillamine treatment in premenopausal patients, they found significantly lower BMC and TBBM values in the glucocorticoid treated group. However, no differences in BMC and TBBM values were found in the corresponding postmenopausal groups. In the premenopausal glucocorticoid group with the duration of treatment and cumulated dose correlated with BMC, whereas no such correlations were found in the postmenopausal women. In the patients who did not receive glucocorticoids they found significant relationships between BMC and functional impairment as well as duration of the disease. Indices of bone turnover rose with increasing functional, impairment, particularly those of bone resorption

Large artery stiffness and carotid intima-media thickness in relation to markers of calcium and bone mineral metabolism in African women older than 46 years.

Science.gov (United States)

Gafane, L F; Schutte, R; Kruger, I M; Schutte, A E

2015-03-01

Vascular calcification and cardiovascular diseases have been associated with altered bone metabolism. We explored the relationships of arterial pressures and carotid intima-media thickness (CIMT) with parathyroid hormone, 25-hydroxycholecalciferol and their ratio (PTH:25(OH)D3) as well as a marker of bone resorption (CTX) in lean and overweight/obese African women. A population of 434 African women older than 46 years was divided into lean and overweight/obese groups. We assessed brachial blood pressure, central pulse pressure (cPP) and CIMT, and determined PTH, 25(OH)D3 and CTX concentrations. Overweight/obese women had elevated PTH and PTH:25(OH)D3 compared with lean women (both Pwomen had higher CTX (Pwomen CIMT was independently associated with PTH:25(OH)D3 (R(2)=0.22; β=0.26; P=0.003), whereas in obese women cPP was associated with both PTH:25(OH)D3 (R2=0.20; β=0.17; P=0.017) and CTX (R2=0.20; β=0.17; P=0.025). In conclusion, we found that in African women with increased adiposity, cPP (as a surrogate measure of arterial stiffness), was positively associated with alterations in bone metabolism and calciotropic hormones, whereas CIMT of lean women was positively associated with PTH:25(OH)D3. Our results suggest that alterations in bone and calcium metabolism may contribute to arterial calcification in older African women.

Toxicity of uranium and lead on osteoblastic bone cells

International Nuclear Information System (INIS)

Milgram, S.; Thiebault, C.; Carriere, M.; Gouget, B.; Malaval, L.

2007-01-01

Bone is one of the main retention organs affected by uranium (U) and lead (Pb). Intoxications have been documented to inhibit bone formation and impair bone modeling and remodeling. However, only few studies dealt with cellular and molecular mechanisms of their toxicity. The purpose of this study was to investigate the acute cytotoxicity of U and Pb and their phenotypic effects on ROS17/2.8 osteoblastic cells. The most likely forms of the toxics in contact with cells after blood contamination were selected for cell exposure. Results show that whatever their speciation, bone cells are always more sensitive to Pb than to U. Moreover, Pb is toxic when it is left free in the exposure medium or when it is complexed with bicarbonate, cysteine or citrate, but not with albumin or phosphate. U is more cytotoxic when it is complexed with transferrin than with bicarbonate. A direct correlation between toxicity and cellular accumulation could be observed. Beside, exposure of U or Pb to bone cells induces a speciation-dependant variation of RNA expression of two markers of bone formation and mineralization: osteocalcin (OCN) and bone sialoprotein (BSP). OCN and BSP-expression could be activated in sub-toxic condition, respectively, by Pb-albumin (1.6-fold) and U-bicarbonate (2.3-fold). In the meantime, U-transferrin and Pb-citrate lead to an inhibition of the two markers. This study shows a complex mechanism of toxicity of two heavy metals with a significant phenotypic impact on osteoblastic cells highly dependant on metal speciation which controls cell accumulation. (authors)

CD34 defines an osteoprogenitor cell population in mouse bone marrow stromal cells

DEFF Research Database (Denmark)

Abdallah, Basem M; Al-Shammary, Asma; Skagen, Peter

2015-01-01

Bone marrow stromal cells (BMSCs, also known as bone marrow-derived mesenchymal stem cells) and their progenitors have been identified based on retrospective functional criteria. CD markers are employed to define cell populations with distinct functional characteristics. However, defining and pro...

Identifying A Molecular Phenotype for Bone Marrow Stromal Cells With In Vivo Bone Forming Capacity

DEFF Research Database (Denmark)

Larsen, Kenneth H; Frederiksen, Casper M; Burns, Jorge S

2009-01-01

(17% versus 5%) and a larger percentage of genes with predicted SP3 transcription factor binding sites in their promoter region (21% versus 8%). On the other hand, hBMSC-TERT(-Bone) cells expressed a larger number of immune-response related genes (26% versus 8%). In order to test for the predictive...... value of these markers, we studied the correlation between their expression levels in 6 different hBMSC-derived clones and the ability to form bone in vivo. We found a significant correlation for, decorin, lysyl oxidase-like 4, natriuretic peptide receptor C, and tetranectin. No significant positive...

Effect of hormone replacement therapy on the bone mass and urinary excretion of pyridinium cross-links

Directory of Open Access Journals (Sweden)

Dolores Perovano Pardini

2000-01-01

Full Text Available CONTEXT: The menopause accelerates bone loss and is associated with an increased bone turnover. Bone formation may be evaluated by several biochemical markers. However, the establishment of an accurate marker for bone resorption has been more difficult to achieve. OBJECTIVE: To study the effect of hormone replacement therapy (HRT on bone mass and on the markers of bone resorption: urinary excretion of pyridinoline and deoxypyridinoline. DESIGN: Cohort correlational study. SETTING: Academic referral center. SAMPLE: 53 post-menopausal women, aged 48-58 years. MAIN MEASUREMENTS: Urinary pyr and d-pyr were measured in fasting urine samples by spectrofluorometry after high performance liquid chromatography and corrected for creatinine excretion measured before treatment and after 1, 2, 4 and 12 months. Bone mineral density (BMD was measured by dual energy X-ray absorptiometry (DEXA before treatment and after 12 months of HRT. RESULTS: The BMD after HRT was about 4.7% (P < 0.0004; 2% (P < 0.002; and 3% (P < 0.01 higher than the basal values in lumbar spine, neck and trochanter respectively. There were no significant correlations between pyridinium cross-links and age, weight, menopause duration and BMD. The decrease in pyr and d-pyr was progressive after HRT, reaching 28.9% (P < 0.0002, and 42% (P < 0.0002 respectively after 1 year. CONCLUSIONS: Urinary pyridinoline and deoxypyridinoline excretion decreases early in hormone replacement therapy, reflecting a decrease in the bone resorption rate, and no correlation was observed with the bone mass evaluated by densitometry.

Relationship between markers of body fat and calcaneal bone stiffness differs between preschool and primary school children: results from the IDEFICS baseline survey.

Science.gov (United States)

Sioen, Isabelle; Mouratidou, Theodora; Herrmann, Diana; De Henauw, Stefaan; Kaufman, Jean-Marc; Molnár, Dénes; Moreno, Luis A; Marild, Staffan; Barba, Gianvincenzo; Siani, Alfonso; Gianfagna, Francesco; Tornaritis, Michael; Veidebaum, Toomas; Ahrens, Wolfgang

2012-10-01

The aim of this study was to investigate the relationship between markers of body fat and bone status assessed as calcaneal bone stiffness in a large sample of European healthy pre- and primary school children. Participants were 7,447 children from the IDEFICS study (spread over eight different European countries), age 6.1 ± 1.8 years (range 2.1-9.9), 50.5 % boys. Anthropometric measurements (weight, height, bioelectrical impedance, waist and hip circumference, and tricipital and subscapular skinfold thickness) as well as quantitative ultrasonographic measurements to determine calcaneal stiffness index (SI) were performed. Partial correlation analysis, linear regression analysis, and ANCOVA were stratified by sex and age group: preschool boys (n = 1,699) and girls (n = 1,599) and primary school boys (n = 2,062) and girls (n = 2,087). In the overall study population, the average calcaneal SI was equal to 80.2 ± 14.0, ranging 42.4-153. The results showed that preschool children with higher body fat had lower calcaneal SI (significant correlation coefficients between -0.05 and -0.20), while primary school children with higher body fat had higher calcaneal SI (significant correlation coefficients between 0.05 and 0.13). After adjusting for fat-free mass, both preschool and primary school children showed an inverse relationship between body fat and calcaneal stiffness. To conclude, body fat is negatively associated with calcaneal bone stiffness in children after adjustment for fat-free mass. Fat-free mass may confound the association in primary school children but not in preschool children. Muscle mass may therefore be an important determinant of bone stiffness.

Microscopic Gold Particle-Based Fiducial Markers for Proton Therapy of Prostate Cancer

International Nuclear Information System (INIS)

Lim, Young Kyung; Kwak, Jungwon; Kim, Dong Wook; Shin, Dongho; Yoon, Myonggeun; Park, Soah; Kim, Jin Sung; Ahn, Sung Hwan; Shin, Jungwook; Lee, Se Byeong; Park, Sung Yong; Pyo, Hong Ryeol; Kim, Dae Yong M.D.; Cho, Kwan Ho

2009-01-01

Purpose: We examined the feasibility of using fiducial markers composed of microscopic gold particles and human-compatible polymers as a means to overcome current problems with conventional macroscopic gold fiducial markers, such as dose reduction and artifact generation, in proton therapy for prostate cancer. Methods and Materials: We examined two types of gold particle fiducial marker interactions: that with diagnostic X-rays and with a therapeutic proton beam. That is, we qualitatively and quantitatively compared the radiographic visibility of conventional gold and gold particle fiducial markers and the CT artifacts and dose reduction associated with their use. Results: The gold particle fiducials could be easily distinguished from high-density structures, such as the pelvic bone, in diagnostic X-rays but were nearly transparent to a proton beam. The proton dose distribution was distorted <5% by the gold particle fiducials with a 4.9% normalized gold density; this was the case even in the worst configuration (i.e., parallel alignment with a single-direction proton beam). In addition, CT artifacts were dramatically reduced for the gold particle mixture. Conclusion: Mixtures of microscopic gold particles and human-compatible polymers have excellent potential as fiducial markers for proton therapy for prostate cancer. These include good radiographic visibility, low distortion of the depth-dose distribution, and few CT artifacts.

Cadmium-induced bone effect is not mediated via low serum 1,25-dihydroxy vitamin D

International Nuclear Information System (INIS)

Engstroem, Annette; Skerving, Staffan; Lidfeldt, Jonas; Burgaz, Ann; Lundh, Thomas; Samsioe, Goeran; Vahter, Marie; Akesson, Agneta

2009-01-01

Cadmium is a widespread environmental pollutant, which is associated with increased risk of osteoporosis. It has been proposed that cadmium's toxic effect on bone is exerted via impaired activation of vitamin D, secondary to the kidney effects. To test this, we assessed the association of cadmium-induced bone and kidney effects with serum 1,25-dihydroxyvitamin D (1,25(OH) 2 D); measured by enzyme immunoassay. For the assessment, we selected 85 postmenopausal women, based on low (0.14-0.39 μg/L) or high (0.66-2.1 μg/L) urinary cadmium, within a cross-sectional population-based women's health survey in Southern Sweden. We also measured 25-hydroxy vitamin D, cadmium in blood, bone mineral density and several markers of bone remodeling and kidney effects. Although there were clear differences in both kidney and bone effect markers between women with low and high cadmium exposure, the 1,25(OH) 2 D concentrations were not significantly different (median, 111 pmol/L (5-95th percentile, 67-170 pmol/L) in low- and 125 pmol/L (66-200 pmol/L) in high-cadmium groups; p=0.08). Also, there was no association between 1,25(OH) 2 D and markers of bone or kidney effects. It is concluded that the low levels of cadmium exposure present in the studied women, although high enough to be associated with lower bone mineral density and increased bone resorption, were not associated with lower serum concentrations of 1,25(OH) 2 D. Hence, decreased circulating levels of 1,25(OH) 2 D are unlikely to be the proposed link between cadmium-induced effects on kidney and bone

Effects of a triphasic combination oral contraceptive containing norgestimate/ethinyl estradiol on biochemical markers of bone metabolism in young women with osteopenia secondary to hypothalamic amenorrhea.

Science.gov (United States)

Grinspoon, S K; Friedman, A J; Miller, K K; Lippman, J; Olson, W H; Warren, M P

2003-08-01

This multicenter, double-blind, placebo-controlled, randomized study of 45 patients evaluated the short-term effects of an oral contraceptive [Ortho Tri-Cyclen, 180-250 micro g of norgestimate (NGM) and 35 microg of ethinyl estradiol (EE)] on biochemical markers of bone resorption, formation, and osteoprotegerin in young women (mean age +/- SD, 26.5 +/- 6.3 yr) with hypothalamic amenorrhea and osteopenia. Body fat, endocrine, and cognitive function were evaluated as secondary endpoints. Biomarkers of bone metabolism were measured at baseline and after three cycles of NGM/EE or placebo. There were significant decreases in mean values of N-telopeptide [mean (SD), -13.4 (13.4) vs. 1.2 (23.8) nmol bone collagen equivalents (BCE)/mmol creatinine (Cr); P = 0.001] and deoxypyridinoline [-1.2 (2.9) vs. -0.5 (1.5) nmol deoxypyridinoline/mmol Cr; P = 0.021] as well as significant decreases in bone specific alkaline phosphatase [-5.1 (3.5) vs. 0.4 (3.1) ng/ml; P < 0.001], osteocalcin [-5.9 (3.6) vs. -2.9 (3.7); P = 0.016], and procollagen of type I propeptide [-35.2 (44.6) vs. -0.2 (30.0) ng/ml; P = 0.025], but not osteoprotegerin [0.39 (1.46) vs. -0.2 (0.49) pmol/liter; P = 0.397] in the NGM/EE vs. placebo group. There were no significant differences between groups with respect to changes in cognitive function, mood, body weight, body mass index, body fat, percentage of body fat, and all endocrine levels except FSH, [-3.7 (3.8) vs. -0.6 (2.1) IU/liter; P < 0.001, NGM/EE vs. placebo]. No serious adverse events were reported in either group. These results suggest that NGM/EE decreases bone turnover in osteopenic premenopausal women with hypothalamic amenorrhea. Further studies are needed to determine whether estrogen will increase bone density in this population.

Bone histomorphometry in de novo renal transplant recipients indicates a further decline in bone resorption 1 year posttransplantation.

Science.gov (United States)

Evenepoel, Pieter; Behets, Geert J; Viaene, Liesbeth; D'Haese, Patrick C

2017-02-01

Renal transplantation is believed to have a major impact on bone health. The present prospective observational bone biopsy study aimed to define the natural history of bone histomorphometry parameters in contemporaneous de novo renal transplant recipients. Paired bone biopsies were performed at the time of transplantation and at one-year posttransplantation in an unselected cohort of 36 patients referred for deceased kidney replacement. Parameters of mineral metabolism and circulating bone turnover markers were monitored as well. Static parameters of bone formation and especially bone resorption being already low-normal in the majority of patients at the time of renal transplantation, further declined during the first posttransplant year. However, interindividual variation was substantial, and significance was reached only for bone resorption parameters. Bone mineralization and trabecular bone volume were within the normal range at the time of transplantation (83.3% and 91.7% of graft recipients, respectively) and showed little change one-year posttransplantation. Changes in osteoclast number were paralleled by changes in circulating tartrate-resistant acid phosphatase 5b levels. Finally, cumulative glucocorticoid dose, but not the posttransplantation parathyroid hormone level, associated with trabecular bone loss. Thus, the impact of renal transplantation on bone histomorphometry is limited with only bone resorption, being already low at the time of transplantation, showing a further decline. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Effect of angiotensin II receptor blocker, olmesartan, on turnover of bone metabolism in bedridden elderly hypertensive women with disuse syndrome.

Science.gov (United States)

Aoki, Motokuni; Kawahata, Hirohisa; Sotobayashi, Daisuke; Yu, Hisahiro; Moriguchi, Atsushi; Nakagami, Hironori; Ogihara, Toshio; Morishita, Ryuichi

2015-08-01

Although recent studies suggest that several antihypertensive drugs could reduce the risk of bone fracture, it is still unclear how these drugs act on bone remodeling, especially in elderly women with severe osteoporosis with disuse syndrome. In the present study, we investigated the effects of a calcium channel blocker (CCB) and an angiotensin II receptor blocker (ARB) on bone metabolism in elderly bedridden women with hypertension and disuse syndrome. Elderly bedridden women (aged >75 years) receiving antihypertensive therapy treated with CCB were recruited in the present study. The participants were divided into two groups--CCB group and ARB group--and followed up to 12 months. Markers of bone resorption were markedly increased, suggesting accelerated bone resorption in the participants of the present study. In the follow-up period, the patients treated with a CCB showed a significant decrease in bone mineral density in a time-dependent manner, accompanied by a significant increase in bone resorption markers, whereas treatment with olmesartan inhibited bone loss, associated with attenuation of increased bone resorption markers. Bone mineral density of femoral neck in the CCB group was significantly lower than that in the ARB group at 6 months. The present study showed inhibitory effects of an ARB on bone resorption in hypertensive patients with accelerated bone resorption, such as elderly bedridden women, and indicated an important role of the renin-angiotensin system in bone metabolism. In elderly hypertensive patients, ARB might be expected to have additional beneficial potential to maintain bone health in bedridden patients. © 2014 Japan Geriatrics Society.

Effect of epimedium pubescen flavonoid on bone mineral status and bone turnover in male rats chronically exposed to cigarette smoke.

Science.gov (United States)

Gao, Shu-guang; Cheng, Ling; Li, Kang-hua; Liu, Wen-He; Xu, Mai; Jiang, Wei; Wei, Li-Cheng; Zhang, Fang-jie; Xiao, Wen-feng; Xiong, Yi-lin; Tian, Jian; Zeng, Chao; Sun, Jin-peng; Xie, Qiang; Lei, Guang-hua

2012-06-19

Epimedii herba is one of the most frequently used herbs in formulas that are prescribed for the treatment of osteoporosis in China and its main constituent is Epimedium pubescen flavonoid (EPF). However, it is unclear whether EPF during chronic exposure to cigarette smoke may have a protective influence on the skeleton. The present study investigated the effect of EPF on bone mineral status and bone turnover in a rat model of human relatively high exposure to cigarette smoke. Fifty male Wistar rats were randomized into five groups: controls, passive smoking groups and passive smoking rats administered EPF at three dosage levels (75, 150 or 300 mg/kg/day) in drinking water for 4 months. A rat model of passive smoking was prepared by breeding male rats in a cigarette-smoking box. Bone mineral content (BMC), bone mineral density (BMD), bone turnover markers, bone histomorphometric parameters and biomechanical properties were examined. Smoke exposure decreased BMC and BMD, increased bone turnover (inhibited bone formation and stimulated its resorption), affected bone histomorphometry (increased trabecular separation and osteoclast surface per bone surface; decreased trabecular bone volume, trabecular thickness, trabecular number, cortical thickness, bone formation rate and osteoblast surface per bone surface), and reduced mechanical properties. EPF supplementation during cigarette smoke exposure prevented smoke-induced changes in bone mineral status and bone turnover. The results suggest that EPF can prevent the adverse effects of smoke exposure on bone by stimulating bone formation and inhibiting bone turnover and bone resorption.

Biochemical markers of bone metabolism reflect osteoclastic and osteoblastic activity in multiple myeloma

DEFF Research Database (Denmark)

Abildgaard, N; Glerup, H; Rungby, Jørgen

2000-01-01

In order to evaluate the use of recently developed assays of bone metabolism in multiple myeloma we performed a histomorphometric study of bone biopsies in 16 myeloma patients. Furthermore, we measured the levels of interleukin-6 (IL-6), soluble IL-6 receptor (IL-6sR), IL-1beta, tumour necrosis f...

Dioscin inhibits osteoclast differentiation and bone resorption though down-regulating the Akt signaling cascades

International Nuclear Information System (INIS)

Qu, Xinhua; Zhai, Zanjing; Liu, Xuqiang; Li, Haowei; Ouyang, Zhengxiao; Wu, Chuanlong; Liu, Guangwang; Fan, Qiming; Tang, Tingting; Qin, An; Dai, Kerong

2014-01-01

Highlights: •A natural-derived compound, dioscin, suppresses osteoclast formation and bone resorption. •Dioscin inhibits osteolytic bone loss in vivo. •Dioscin impairs the Akt signaling cascades pathways during osteoclastogenesis. •Dioscin have therapeutic value in treating osteoclast-related diseases. -- Abstract: Bone resorption is the unique function of osteoclasts (OCs) and is critical for both bone homeostasis and pathologic bone diseases including osteoporosis, rheumatoid arthritis and tumor bone metastasis. Thus, searching for natural compounds that may suppress osteoclast formation and/or function is promising for the treatment of osteoclast-related diseases. In this study, we for the first time demonstrated that dioscin suppressed RANKL-mediated osteoclast differentiation and bone resorption in vitro in a dose-dependent manner. The suppressive effect of dioscin is supported by the reduced expression of osteoclast-specific markers. Further molecular analysis revealed that dioscin abrogated AKT phosphorylation, which subsequently impaired RANKL-induced nuclear factor-kappaB (NF-κB) signaling pathway and inhibited NFATc1 transcriptional activity. Moreover, in vivo studies further verified the bone protection activity of dioscin in osteolytic animal model. Together our data demonstrate that dioscin suppressed RANKL-induced osteoclast formation and function through Akt signaling cascades. Therefore, dioscin is a potential natural agent for the treatment of osteoclast-related diseases

Dioscin inhibits osteoclast differentiation and bone resorption though down-regulating the Akt signaling cascades

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Qu, Xinhua; Zhai, Zanjing; Liu, Xuqiang; Li, Haowei [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Ouyang, Zhengxiao [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Department of Orthopaedics, Hunan Provincial Tumor Hospital and Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha (China); Wu, Chuanlong [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Liu, Guangwang [Department of Orthopaedic Surgery, The Central Hospital of Xuzhou, Affiliated Hospital of Medical Collage of Southeast University, Xuzhou (China); Fan, Qiming; Tang, Tingting [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Qin, An, E-mail: dr.qinan@gmail.com [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Dai, Kerong, E-mail: krdai@163.com [Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China)

2014-01-10

Highlights: •A natural-derived compound, dioscin, suppresses osteoclast formation and bone resorption. •Dioscin inhibits osteolytic bone loss in vivo. •Dioscin impairs the Akt signaling cascades pathways during osteoclastogenesis. •Dioscin have therapeutic value in treating osteoclast-related diseases. -- Abstract: Bone resorption is the unique function of osteoclasts (OCs) and is critical for both bone homeostasis and pathologic bone diseases including osteoporosis, rheumatoid arthritis and tumor bone metastasis. Thus, searching for natural compounds that may suppress osteoclast formation and/or function is promising for the treatment of osteoclast-related diseases. In this study, we for the first time demonstrated that dioscin suppressed RANKL-mediated osteoclast differentiation and bone resorption in vitro in a dose-dependent manner. The suppressive effect of dioscin is supported by the reduced expression of osteoclast-specific markers. Further molecular analysis revealed that dioscin abrogated AKT phosphorylation, which subsequently impaired RANKL-induced nuclear factor-kappaB (NF-κB) signaling pathway and inhibited NFATc1 transcriptional activity. Moreover, in vivo studies further verified the bone protection activity of dioscin in osteolytic animal model. Together our data demonstrate that dioscin suppressed RANKL-induced osteoclast formation and function through Akt signaling cascades. Therefore, dioscin is a potential natural agent for the treatment of osteoclast-related diseases.

Early Subchondral Bone Loss at Arthritis Onset Predicted Late Arthritis Severity in a Rat Arthritis Model.

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Courbon, Guillaume; Cleret, Damien; Linossier, Marie-Thérèse; Vico, Laurence; Marotte, Hubert

2017-06-01

Synovitis is usually observed before loss of articular function in rheumatoid arthritis (RA). In addition to the synovium and according to the "Inside-Outside" theory, bone compartment is also involved in RA pathogenesis. Then, we investigated time dependent articular bone loss and prediction of early bone loss to late arthritis severity on the rat adjuvant-induced arthritis (AIA) model. Lewis female rats were longitudinally monitored from arthritis induction (day 0), with early (day 10) and late (day 17) steps. Trabecular and cortical microarchitecture parameters of four ankle bones were assessed by microcomputed tomography. Gene expression was determined at sacrifice. Arthritis occurred at day 10 in AIA rats. At this time, bone erosions were detected on four ankle bones, with cortical porosity increase (+67%) and trabecular alterations including bone volume fraction (BV/TV: -13%), and trabecular thickness decrease. Navicular bone assessment was the most reproducible and sensitive. Furthermore, strong correlations were observed between bone alterations at day 10 and arthritis severity or bone loss at day 17, including predictability of day 10 BV/TV to day 17 articular index (R 2  = 0.76). Finally, gene expression at day 17 confirmed massive osteoclast activation and interestingly provided insights on strong activation of bone formation inhibitor markers at the joint level. In rat AIA, bone loss was already observed at synovitis onset and was predicted late arthritis severity. Our results reinforced the key role of subchondral bone in arthritis pathogenesis, in favour to the "Inside-Outside" theory. Mechanisms of bone loss in rat AIA involved resorption activation and formation inhibition changes. J. Cell. Physiol. 232: 1318-1325, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

High frequency of vertebral fracture and low bone quality in patients with rheumatoid arthritis-Results from TOMORROW study.

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Okano, Tadashi; Inui, Kentaro; Tada, Masahiro; Sugioka, Yuko; Mamoto, Kenji; Wakitani, Shigeyuki; Koike, Tatsuya; Nakamura, Hiroaki

2017-05-01

Osteoporosis is one of the complications in patients with rheumatoid arthritis (RA). In this study, we researched the morbidity of existing vertebral fractures and the risk factors for vertebral fractures in patients with RA. This study included 413 participants, 208 patients with RA, and 205 age- and sex-matched controls without RA. Clinical data, radiographic assessment of vertebral fracture from T4 to L4 in thoracic and lumber spine, bone mineral density (BMD), and bone metabolic markers (BMM) were analyzed. Vertebral fractures were observed more frequently, severe and multiple in patients with RA. In the logistic regression analysis, age (adjusted odds ratios (OR): 1.07, 95% confidence interval (CI): 1.04-1.09) and RA (adjusted OR: 1.72, 95% CI: 1.04-2.83) were risk factors for existing vertebral fracture. Moreover, two bone matrix-related markers, undercarboxylated osteocalcin (ucOC) (adjusted OR: 1.68, 95% CI: 1.02-2.78), and urinary pentocidine (adjusted OR: 2.51, 95% CI: 1.48-4.24) were associated with existing vertebral fracture. High frequent, multiple, and severe vertebral fractures were found in patients with RA compared to the controls. Low bone quality might be the cause of the frequent prevalence of vertebral fracture in patients with RA.

Bone mineral density and bone scintigraphy in adult Saudi female patients with Osteomalacia

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El-Desouki, Mahmoud I.; Othman, Saleh M.; Fouda, Mona A.

2004-01-01

This prospective study was conducted to demonstrate the role of bone mineral density (BMD) and bone scan in the management of adult Saudi female patients with established diagnosis of osteomalacia. Bone scan using Tc99m methylene diphosphate (MDP) and BMD of the lumbar spine and femoral neck using dual x-ray absorptiometry (DXA) were performed at the time of diagnosis 6 months and one year after therapy in 96 Saudi female patients attending the metabolic bone disease clinic at King Khalid University Hospital, King Saud University, Riyadh, Kingdom of Saudi Arabia, between January 1997 through to June 1999, aged between 20 and 73 years (mean 42 years). Alkaline phosphates, calcium and inorganic phosphorus were measured for all patients before and after treatment. 25 Hydroxy vitamin D was only measured with the first BMD measurements. A bone profile showed typical biochemical abnormalities of osteomalacia.The bone scan showed features of superscan in all patients and pseudofractures in 43 patients. BMD measures were compared with that of normal Saudi subjects matched for age and sex. The BMD was low at diagnosis and showed significant improvement after therapy. The improvement of bone density in response to therapy was more evident in lumbar spine than in femoral neck bone.Our results showed that BMD in adult Saudi female patients with osteomalacia was markedly affected probably due to specific constitutional and environmental factors ( inadeqate exercise, lack of sun exposure and lack of intake of milk and dairy products). In addition, lumbar BMD and serum calcium appeared to be better markers to monitor therapy.Bone scan helped in demonstrating disease activity, the presence of pseudofractures. (author)

Current role of bone scan with phosphonates in the follow-up of breast cancer

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Maffioli, Lorenzo; Florimonte, Luigia; Pagani, Luca; Butti, Ivana; Roca, Isabel

2004-01-01

A number of studies have demonstrated that bone scintigraphy has high sensitivity and efficacy in the early detection of bone metastases from several tumours, including breast cancer. Bone scintigraphy is the most definitive tool for diagnosing and monitoring metastatic spread of breast cancer. However, in the past decade there has been a wide debate on its impact on survival time, morbidity and quality of life. Worldwide economic restrictions and these studies have led to the adoption of an almost minimalist policy for breast cancer follow-up using evidence-based guidelines. The recommended breast cancer surveillance testing includes only a few procedures (history, physical and breast self-examination, patient education on symptoms, pelvic examination). The routine use of additional tests, such as blood cell count, tumour markers, liver ultrasonography, bone scan and chest X-rays, is not recommended. Accordingly, scintigraphy should be reserved for a limited number of patients. On the other hand, early diagnosis of bone involvement may reduce the risk of skeletal related events, thus leading to a significant improvement in quality of life. Furthermore, new drugs (e.g. bisphosphonates) can now delay the onset of bone metastasis and reduce the number of patients who experience skeletal complications. In conclusion, the evidence of the clinical usefulness of bone scintigraphy (to allow early planning of new treatments in advanced disease) has to be re-evaluated, possibly by large randomised prospective trials. (orig.)

[Efficacy of zoledronic acid combined with chemotherapy in treatment of skeletal metastases of non-small cell lung cancer and the bone metabolic markers].

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Hu, Xiao-ye; Zou, Qing-feng; Jin, Chuan; Li, Wei-dong; Chen, Wen-sheng; Ma, Lei

2010-06-01

To evaluate the clinical efficacy of zoledronic acid combined with chemotherapy in the management of skeletal metastasis of non-small cell lung cancer (NSCLC) and investigate the value in urine amino-terminal telopeptide of type I collagen (uNTX) and serum bone specific alkaline phosphatase (sBALP) in monitoring skeletal metastasis of NSCLC. From February, 2007 to January, 2009, 32 NSCLC patients with bone metastases received treatment with zoledronic acid at the dose of 4 mg given every 3 weeks and platinum-based chemotherapy (each cycle lasting for 3 weeks). Before and during the treatments, uNTX and sBALP were measured in these patients using ELISA and precipitation with wheat germ lectin, respectively. The patients were followed up for skeletal-related events (SREs) and status of survival. A significant decrease occurred in the pain scores and analgesic use in the patients after the therapy. SREs were not observed during the treatment. Serum creatinine and calcium levels underwent no significant variation during the treatment. Eleven patients reported 14 possible zoledronic acid-related adverse events. The concentration of uNTX and sBALP in patients with bone metastases was above the upper limit of the normal range. A positive correlation was observed between the levels of the markers and the extent of bone metastases. At the third month, uNTX and sBALP were significantly lowered, but radionuclide whole-body bone imaging showed no obvious changes. Of the 32 patients, 24 had elevated uNTX values, which became normal after the treatment in 15 patients and remained elevated in the other 9 patients. SREs occurred in these two subgroups at the rates of 53% and 89% (P=0.039), respectively. Twenty-six patients had elevated sBALP level, and 16 of them exhibited normal sBALP level after the treatment. The incidences of SREs in the patients with elevated and normal sBALP level were 50% and 90% (P=0.038), respectively. The levels of uNTX/Cr and sBALP were not correlated

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

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

2007-01-01

 Introduction. The secreted glycoprotein YKL-40 (CHI3L1, HC gp-39) is a potential player in the tumor-host interactions affecting several aspects of multiple myeloma (MM) including bone destruction. Previous studies support a role for YKL-40 in remodelling of the extracellular matrix, in angiogen...... Introduction. The secreted glycoprotein YKL-40 (CHI3L1, HC gp-39) is a potential player in the tumor-host interactions affecting several aspects of multiple myeloma (MM) including bone destruction. Previous studies support a role for YKL-40 in remodelling of the extracellular matrix...... and followed for up to 30 months. Skeletal related events (SRE) were registered and subdivided in vertebral fractures and osteolytic events including non-vertebral fractures. Results. 57% of the patients had a S-YKL-40 elevated above the upper limit in an age specific 90 per cent reference range for healthy...... adults. Patients with elevated S-YKL-40 had a higher total X-ray score (p=0.005) and higher levels of S-CTX-MMP (p=0.003), U-PYD (p=0.004) and U-DPD (p=0.002), while U-NTX-1 and the markers of bone formation did not differ from the levels seen in patients with normal S-YKL-40. During follow-up 21...

Bone morphogenetic protein-2 functions as a negative regulator in the differentiation of myoblasts, but not as an inducer for the formations of cartilage and bone in mouse embryonic tongue

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Suzuki Erika

2011-07-01

Full Text Available Abstract Background In vitro studies using the myogenic cell line C2C12 demonstrate that bone morphogenetic protein-2 (BMP-2 converts the developmental pathway of C2C12 from a myogenic cell lineage to an osteoblastic cell lineage. Further, in vivo studies using null mutation mice demonstrate that BMPs inhibit the specification of the developmental fate of myogenic progenitor cells. However, the roles of BMPs in the phases of differentiation and maturation in skeletal muscles have yet to be determined. The present study attempts to define the function of BMP-2 in the final stage of differentiation of mouse tongue myoblast. Results Recombinant BMP-2 inhibited the expressions of markers for the differentiation of skeletal muscle cells, such as myogenin, muscle creatine kinase (MCK, and fast myosin heavy chain (fMyHC, whereas BMP-2 siRNA stimulated such markers. Neither the recombinant BMP-2 nor BMP-2 siRNA altered the expressions of markers for the formation of cartilage and bone, such as osteocalcin, alkaline phosphatase (ALP, collagen II, and collagen X. Further, no formation of cartilage and bone was observed in the recombinant BMP-2-treated tongues based on Alizarin red and Alcian blue stainings. Neither recombinant BMP-2 nor BMP-2 siRNA affected the expression of inhibitor of DNA binding/differentiation 1 (Id1. The ratios of chondrogenic and osteogenic markers relative to glyceraldehyde-3-phosphate dehydrogenase (GAPDH, a house keeping gene were approximately 1000-fold lower than those of myogenic markers in the cultured tongue. Conclusions BMP-2 functions as a negative regulator for the final differentiation of tongue myoblasts, but not as an inducer for the formation of cartilage and bone in cultured tongue, probably because the genes related to myogenesis are in an activation mode, while the genes related to chondrogenesis and osteogenesis are in a silencing mode.