Bone
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Sclerostin (Scl) is an osteocyte protein that decreases bone formation, and its inhibition by neutralizing antibodies (Scl-Ab) increases bone formation, mass and strength. We investigated the effects of Scl-Ab in mature ovariectomized (OVX) rats with a mechanistic focus on longer-term responses of osteoclasts, osteoblasts and osteocytes. Four-month-old Sprague-Dawley rats had OVX or sham surgery. ⋯ Tibial endocortical and periosteal BFR were increased at week 6 in the Scl-Ab group versus OVX-Veh controls, while at week 26 only endocortical BFR remained increased. The Scl-Ab group exhibited significant increments in skeletal mRNA expression of several osteocyte genes, with sost showing the greatest induction in both the tibia and vertebra. We propose that Scl-Ab administration, and/or the gains in bone volume that result, may have increased osteocytic expression of Scl as a possible means of regulating gains in bone mass.
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One quarter of osteoporotic fractures occur in men. TBS, a gray-level measurement derived from lumbar spine DXA image texture, is related to microarchitecture and fracture risk independently of BMD. Previous studies reported the ability of spine TBS to predict osteoporotic fractures in women. Our aim was to evaluate the ability of TBS to predict clinical osteoporotic fractures in men. ⋯ We observed that spine TBS predicted MOF and HF independently of the clinical FRAX score, HF independently of FRAX and BMD in men. Studies with more incident fractures are needed to confirm these findings.
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Atypical femoral fractures (AFFs) are stress-related fractures that are speculated to associate with long-term treatment with bisphosphonates for osteoporosis. A history of AFF is a high risk factor for the development of a subsequent AFF in the same location of the contralateral femur, suggesting that a patient's individual anatomical factor(s) are related to the fracture site of AFFs. In this study, we investigated the radiographs of fourteen AFFs (four bilateral fractures among ten patients) treated at six hospitals associated with our university between 2005 and 2010. ⋯ There was a positive correlation between the fracture site and the standing FTA in the patients with AFFs (r=0.82, 95% confidence interval; 0.49 to 0.94), indicating that the larger the standing FTA (varus alignment), the more distal the site of the fracture in the femur. The FTA of the patients with atypical diaphyseal femoral fracture were significantly larger compared to that of those with not only atypical subtrochanteric fractures but also TFFs. In conclusion, the fracture sites of AFFs are associated with the standing lower limb alignment, while those of TFFs are not.
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Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome characterized by renal phosphate wasting, hypophosphatemia and low calcitriol levels as well as clinical symptoms like diffuse bone and muscle pain, fatigue fractures or increased fracture risk. Conventional imaging methods, however, often fail to detect the small tumors. Lately, tumor localization clearly improved by somatostatin-receptor (SSTR) imaging, such as octreotide scintigraphy or octreotide SPECT/CT. ⋯ Follow-up DXA revealed an increase in BMD of up to 34.5% 1-year postoperative, indicating remineralization. No recurrence was observed. In conclusion our data indicates that 68Ga DOTA-TATE PET/CT is an effective and promising diagnostic tool in the diagnosis of TIO, even in patients in whom 111In-OCT prior failed to detect a tumor.
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Lack of physical activity (PA) is an important modifiable risk factor for bone mineral density (BMD). Time spent in sedentary behaviour (SB), or time spent in non-exercising seated and reclining postures, has recently emerged as a new public health risk, independent of the amount of time someone spends being active. As national surveys report that adults spend on average 8h per day being sedentary, rising to 10h a day in older age, it has been hypothesised that a repeated exposure to sitting in modern daily life, whether it is for travelling, working or leisure, might have a deleterious effect on bone health in a way that mirrors the results of studies into the effect of lengthy periods of bed-rest. The aim of this study was to investigate for the first time a) how time spent in SB is associated with bone mineral density (BMD), b) whether this association changes depending on the amount of time spent engaging in different intensity levels of PA, and c) if the pattern of accumulation of SB and long uninterrupted periods of SB are associated with BMD. ⋯ These results provide the first evidence that repeated exposure to sitting (SB), measured objectively in daily life, is deleteriously associated with BMD of the total femur and of all hip sub-regions in women, independent of the amount of time women engage in moderate and vigorous activity. This suggests that SB might be a risk factor for bone health in women independent of whether they engage in physical activity. In addition, the duration of SB bouts, rather than their frequency, appears to be deleteriously associated with BMD of the total femur and of all hip sub-regions. Future research should investigate the effect on bone health of interventions which set out to reduce SB and the duration of SB bouts in comparison, and as adjunct, to the promotion of PA. For men, SB is not significantly associated with BMD of the femur or spine and the results appear to confirm that moderate and vigorous activity has a protective effect.