Summary This study was to determine if antibody against sclerostin (Scl-Ab) could prevent glucocorticoid (GC)-induced osteoporosis in mice. We found that Scl-Ab prevented GC-induced reduction in bone mass and bone strength and that the anabolic effects of Scl-Ab might be partially achieved through the preservation of osteoblast activity through autophagy. Introduction Glucocorticoids (GCs) inhibit bone formation by altering osteoblast and osteocyte cell activity and lifespan. A monoclonal antibody against sclerostin, Scl-Ab, increased bone mass in both preclinical animal and clinical studies in subjects with low bone mass. The objectives of this study were to determine if treatment with the Scl-Ab could prevent loss of bone mass and strength in a mouse model of GC excess and to elucidate if Scl-Ab modulated bone cell activity through autophagy. Methods We generated reporter mice that globally expressed dsRed fused to LC3, a protein marker for autophagosomes, and evaluated the dose-dependent effects of GCs (0, 0.8, 2.8, and 4 mg/kg/day) and Scl-Ab on autophagic osteoblasts, bone mass, and bone strength. Results GC treatment at 2.8 and 4 mg/kg/day of methylprednisolone significantly lowered trabecular bone volume (Tb-BV/TV) at the lumbar vertebrae and distal femurs, cortical bone mass at the mid-shaft femur (FS), and cortical bone strength compared to placebo (PL). In mice treated with GC and Scl-Ab, Tb-BV/TV increased by 60–125 %, apparent bone strength of the lumbar vertebrae by 30–70 %, FS-BV by 10–18 %, and FS-apparent strength by 13–15 %, as compared to GC vehicle-treated mice. GC treatment at 4 mg/kg/ day reduced the number of autophagic osteoblasts by 70 % on the vertebral trabecular bone surface compared to the placebo group (PL, GC 0 mg), and GC + Scl-Ab treatment. Conclusions Treatment with Scl-Ab prevented GC-induced reduction in both trabecular and cortical bone mass and strength and appeared to maintain osteoblast activity through autophagy.

SummaryPatient characteristics contributing to imminent risk for fracture, defined as risk of near-term fracture within the next 12 to 24 months, have not been well defined. In patients without recent fracture, we identified factors predicting imminent risk for vertebral/nonvertebral fracture, including falls, age, comorbidities, and other potential fall risk factors.PurposeSeveral factors contribute to long-term fracture risk in patients with osteoporosis, including age, bone mineral density, and fracture history. Some patients may be at imminent risk for fracture, defined here as a risk of near-term fracture within 12–24 months. Many patient characteristics contributing to imminent risk for fracture have not been well defined. This case-control study used US commercial and Medicare supplemental insured data for women and men without recent fracture to identify factors associated with imminent risk for fracture.MethodsPatients included were aged ≥50 with osteoporosis, had a vertebral or nonvertebral fracture claim (index date; fracture group) or no fracture claim (control group) from January 1, 2006, to September 30, 2012, continuously enrolled and without fracture in the 24 months before index. Potential risk factors during the period before fracture were assessed.ResultsUsing data from 12 months before fracture, factors significantly associated with imminent risk for fracture were previous falls, older age, poorer health status, specific comorbidities (psychosis, Alzheimer’s disease, central nervous system disease), and other fall risk factors (wheelchair use, psychoactive medication use, mobility impairment). Similar findings were observed with data from 24 months before fracture.ConclusionsIn patients with osteoporosis and no recent fracture, falls, older age, poorer health status, comorbidities, and other potential fall risk factors were predictive of imminent risk for fracture. Identification of factors associated with imminent risk for vertebral/nonvertebral fracture may help identify and risk stratify those patients most in need of immediate and appropriate treatment to decrease fracture risk.Electronic supplementary materialThe online version of this article (doi:10.1007/s11657-016-0280-5) contains supplementary material, which is available to authorized users.

Our findings demonstrate that SOST KO mice were protected from the major sublesional bone loss that invariably follows SCI. The evidence indicates that sclerostin is an important mediator of the marked sublesional bone loss after SCI, and that pharmacological inhibition of sclerostin may represent a promising novel approach to this challenging clinical problem.

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A 1 -A 2 9 8 the clinical trial and assumed equal in the models. Costs and outcomes beyond first year were discounted at a 5% annual rate. RESULTS: Denosumab was associated with lower frequency of SRE due to clinical superiority versus ZA, and with higher costs. The incremental cost per SRE avoided was estimated at $78,844. Although a formal threshold for this outcome is not available in Mexico, the ICER obtained is 40% below the commonly accepted threshold in Mexico (based on the GDP per capita). The ICER remained below the local accepted threshold in all univariate sensitivity analyses. In the probabilistic sensitivity analysis, denosumab became the most preferred option from a willingness to pay of approximately 100 000 Mexican pesos. CONCLUSIONS: These results suggest denosumab represents good value for money in the prevention of SRE in prostate cancer patients with BM in Mexico. OBJECTIVES:To evaluate the most cost-effective strategy of staging non-small cell lung cancer with hybrid PET/CT to avoid unnecessary surgeries. METHODS: A decision tree model was developed with four work-up approaches: CT alone, PET/CT for all, PET/CT when negative CT, and CT plus PET/CT for all. Mediastinoscopy was included in all alternatives to confirm positive CT or PET/CT. Surgery was considered unnecessary when the work-up drives to resectable stage but the model predicts loco regional or distant metastasis. The model incorporated evidence-based data from the literature and associated costs were evaluated from the Brazilian public health care system perspective. The costs of PET/CT in Brazil were estimated in previous study by microcosts technique. The impact of uncertainties on the model was verified by deterministic and probabilistic sensitivity analyses (PSA).