Bone
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Randomized Controlled Trial
Treatment of early stage osteonecrosis of the femoral head with autologous implantation of bone marrow-derived and cultured mesenchymal stem cells.
Treatment of early-stage osteonecrosis of the femoral head (ONFH) with autologous implantation of iliac crest bone marrow-derived mononuclear cells, which contain tens of thousands of bone marrow mesenchymal stem cells (BMMSCs), recently achieved a promising outcome. ⋯ Ex vivo expansion of autologous BMMSCs can reliably provide a greater number of BMMSCs for FH implantation. This intervention is safe and effective in delaying or avoiding FH collapse, which may necessitate total hip replacement.
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Sclerostin, the Wnt signaling antagonist encoded by the Sost gene, is secreted by osteocytes and inhibits bone formation by osteoblasts. Mechanical stimulation reduces sclerostin expression, suggesting that osteocytes might coordinate the osteogenic response to mechanical force by locally unleashing Wnt signaling. To investigate whether sclerostin downregulation is a pre-requisite for load-induced bone formation, we conducted experiments in transgenic mice (TG) engineered to maintain high levels of SOST expression during mechanical loading. ⋯ In contrast, load-induced bone formation was reduced by 70-85% in TG mice, due to lower MS/BS and complete inhibition of MAR. Moreover, Wnt target gene expression induced by loading in WT mice was absent in TG mice. Thus, downregulation of Sost/sclerostin in osteocytes is an obligatory step in the mechanotransduction cascade that activates Wnt signaling and directs osteogenesis to where bone is structurally needed.
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To gain insight into the clinical effect of teriparatide and alendronate on the hip, we performed non-linear finite element analysis of quantitative computed tomography (QCT) scans from 48 women who had participated in a randomized, double-blind clinical trial comparing the effects of 18-month treatment of teriparatide 20 μg/d or alendronate 10mg/d. The QCT scans, obtained at baseline, 6, and 18 months, were analyzed for volumetric bone mineral density (BMD) of trabecular bone, the peripheral bone (defined as all the cortical bone plus any endosteal trabecular bone within 3 mm of the periosteal surface), and the integral bone (both trabecular and peripheral), and for overall femoral strength in response to a simulated sideways fall. At 18 months, we found in the women treated with teriparatide that trabecular volumetric BMD increased versus baseline (+4.6%, p<0.001), peripheral volumetric BMD decreased (-1.1%, p<0.05), integral volumetric BMD (+1.0%, p=0.38) and femoral strength (+5.4%, p=0.06) did not change significantly, but the ratio of strength to integral volumetric BMD ratio increased (+4.0%, p=0.04). ⋯ For the women treated with alendronate, there were small (<1.0%) but non-significant changes compared to baseline in all these parameters. The only significant between-treatment difference was in the change in trabecular volumetric BMD (p<0.005); related, we also found that, for a given change in peripheral volumetric BMD, femoral strength increased more for teriparatide than for alendronate (p=0.02). We conclude that, despite different compartmental volumetric BMD responses for these two treatments, we could not detect any overall difference in change in femoral strength between the two treatments, although femoral strength increased more than integral volumetric BMD after treatment with teriparatide.
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Yerba Mate (Ilex paraguariensis) tea consumption is higher in Argentina and other South American countries than those of coffee or tea (Camellia sinensis). The effects of Yerba Mate on bone health have not previously been explored. From a program for osteoporosis prevention and treatment, postmenopausal women who drank at least 1 L of Yerba Mate tea daily during 4 or more years (n=146) were identified, and matched by age and time since menopause with an equal number of women who did not drink Yerba Mate tea. ⋯ Yerba Mate drinkers had a 9.7% higher lumbar spine BMD (0.952 g/cm(2) versus 0.858 g/cm(2): p<0.0001) and a 6.2% higher femoral neck BMD (0.817 g/cm(2) versus 0.776 g/cm(2); p=0.0002). In multiple regression analysis, Yerba Mate drinking was the only factor, other than body mass index, which showed a positive correlation with BMD at both the lumbar spine (p<0.0001) and the femoral neck (p=0.0028). Results suggest a protective effect of chronic Yerba Mate consumption on bone.