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The effect of femoral bone mineral density (BMD) and several parameters of femoral neck geometry (hip axis length, neck–shaft angle and mean femoral neck width) on hip fracture risk in a Spanish population was assessed in a cross-sectional study. All parameters were determined by dual-energy X-ray absorptiometry. There were 411 patients (116 men, 295 women; aged 60–90 years) with hip fractures in whom measurements were taken in the contralateral hip. Controls were 545 persons (235 men, 310 women; aged 60–90 years) who participated in a previous study on BMD in a healthy Spanish population. Femoral neck BMD was significantly lower, and neck–shaft angle and mean femoral neck width significantly higher, in fracture cases than in controls. The logistic regression analysis adjusted by age, height and weight showed that a decrease of 1 standard deviation (SD) in femoral neck BMD was associated with an odds ratio of hip fracture of 4.52 [95% confidence interval (CI) 2.93 to 6.96] in men and 4.45 (95% CI 3.11 to 6.36) in women; an increase of 1 SD in neck–shaft angle of 2.45 (95% CI 1.73 to 3.45) in men and 3.48 (95% CI 2.61 to 4.65) in women; and an increase of 1 SD in mean femoral neck width of 2.15 (95% CI 1.55 to 2.98) in men and 2.40 (95% CI 1.79 to 3.22) in women. The use of a combination of femoral BMD and geometric parameters of the femoral neck except for hip axis length may improve hip fracture risk prediction allowing a better therapeutic strategy for hip fracture prevention.

The aim of this study was to evaluate the risk of acute myocardial infarction in patients taking osteoporosis medication. Patients were taken from the SIDIAP or CPRD database and were matched using propensity scores. Patients with diabetes and chronic kidney disease taking SERMs were at an increased risk. The results favour the cardiovascular safety of alendronate as a first-line choice for osteoporosis treatment. This study aims to evaluate the comparative safety of anti-osteoporosis drugs based on the observed risk of acute myocardial infarction while on treatment in a primary care setting. This is a propensity-matched cohort study and meta-analysis. This study was conducted in two primary care record databases covering UK NHS (CPRD) and Catalan healthcare (SIDIAP) patients during 1995–2014 and 2006–2014, respectively. The outcome was acute myocardial infarction while on treatment. Users of alendronate (reference group) were compared to those of (1) other oral bisphosphonates (OBP), (2) strontium ranelate (SR), and (3) selective oestrogen receptor modulator (SERM), after matching on baseline characteristics (socio-demographics, fracture risk factors, comorbidities, and concomitant drug use) using propensity scores. Multiple imputation was used to handle missing data on confounders and competing risk modelling for the calculation of relative risk (sub-distribution hazard ratios (SHR)) according to therapy. Country-specific data were analysed individually and meta-analysed. A 10% increased risk of acute myocardial infarction was found in users of other bisphosphonates as compared to alendronate users within CPRD. The meta-analysis of CPRD and SIDIAP results showed a 9% increased risk in users of other bisphosphonate as compared to alendronate users. Sensitivity analysis showed SERMS users with diabetes and chronic kidney disease were at an elevated risk. This study provides additional data on the risk of acute myocardial infarction in patients receiving osteoporosis treatment. The results favour the cardiovascular safety of alendronate as a first-line choice for osteoporosis treatment.

There has been little published data on the effects of temperature on the performance of dual-energy X-ray absorptiometry (DXA) machines. We examined the effect of changes in ambient room temperature on the performance of three DXA scanners (DPXL, Expert-XL and Prodigy). The study involved repeat measurements of bone mineral density (BMD) using three different spine phantoms scanned at different ambient room temperatures, both before and after calibration procedures. The calibration or quality assurance (QA) scan calibrates the scanner, adjusting for the ambient room temperature at the time of calibration. There was a moderate correlation between change in temperature and change in BMD measured prior to recalibration for the Expert-XL (r=0.58) during normal clinical scanning conditions. There was no observed change in phantom BMD with change in temperature measured using the DXPL or Prodigy. After temperature change, without repeat calibration measurements, there was a strong correlation between temperature change and change in BMD measured using the Expert-XL (r=0.96, p<0.001). From the regression equation, a change of 2.5 °C could alter the calculated BMD result measured by the Expert-XL by 1.5%, which would significantly affect the precision of the DXA system. There was no significant correlation between temperature and BMD in the DXPL or Prodigy. The observed differences between the densitometers and the effect of temperature change are most likely due to the differing types of detector systems used. Operators must be made aware that solid state detectors of the sort used in the Expert-XL (charge-coupled devices, CCDs) are significantly affected by changes in ambient room temperature.

We demonstrate that glucocorticoids induce an osteoporotic phenotype in regenerating scales of zebrafish. Exposure to prednisolone results in altered mineral content, enhanced matrix breakdown, and an osteoporotic gene-expression profile in osteoblasts and osteoclasts. This highlights that the zebrafish scale provides a powerful tool for preclinical osteoporosis research. This study aims to evaluate whether glucocorticoid (prednisolone) treatment of zebrafish induces an osteoporotic phenotype in regenerating scales. Scales, a readily accessible dermal bone tissue, may provide a tool to study direct osteogenesis and its disturbance by glucocorticoids. In adult zebrafish, treated with 25 μM prednisolone phosphate via the water, scales were removed and allowed to regenerate. During regeneration scale morphology and the molar calcium/phosphorus ratio in scales were assessed and osteoblast and osteoclast activities were monitored by time profiling of cell-specific genes; mineralization was visualized by Von Kossa staining, osteoclast activity by tartrate-resistant acid phosphatase histochemistry. Prednisolone (compared to controls) enhances osteoclast activity and matrix resorption and slows down the build up of the calcium/phosphorus molar ratio indicative of altered crystal maturation. Prednisolone treatment further impedes regeneration through a shift in the time profiles of osteoblast and osteoclast genes that commensurates with an osteoporosis-like imbalance in bone formation. A glucocorticoid-induced osteoporosis phenotype as seen in mammals was induced in regenerating scalar bone of zebrafish treated with prednisolone. An unsurpassed convenience and low cost then make the zebrafish scale a superior model for preclinical studies in osteoporosis research.

We examined new users of osteoporosis drugs among seniors in Pennsylvania and found no evidence of healthy adherer bias on observed associations between adherence to treatment and non-vertebral fracture risk; we document fracture reduction with better adherence to bisphosphonates, yet no fracture reduction with better adherence to calcitonin or raloxifene. We examined the potential for “healthy adherer bias” when studying the effects of adherence to osteoporosis pharmacotherapy on fracture risk. Based on clinical trial evidence, bisphosphonates, calcitonin, and raloxifene reduce vertebral fracture risk; yet only bisphosphonates are documented to reduce non-vertebral fracture risk. This is a cohort study of older women in Pennsylvania who initiated osteoporosis drugs between 1995 and 2005. We included new users of bisphosphonates, calcitonin, and raloxifene. Adherence was categorized based on a measure of compliance as high [proportion of days covered (PDC) ≥ 80%], intermediate (50% < PDC < 80%), or low (PDC ≤ 50%) according to a 180-day ascertainment period. Non-vertebral fracture rates within 365 days after the ascertainment period were compared between adherence categories (reference = low) using Cox proportional hazard models and adjusting for fracture risk factors. Primary and secondary prevention cohorts were examined separately. Adherence to calcitonin and raloxifene were control analyses. We found little difference in fracture rates between levels of adherence to calcitonin, bisphosphonates for primary prevention, or raloxifene for secondary prevention. We document lower fracture rates among high versus low adherent bisphosphonate users for secondary prevention (HR = 0.53, 95%CI = 0.38–0.74) and higher fracture rates among high versus low adherent raloxifene users for primary prevention (HR = 2.01, 95%CI = 1.04–3.87). We document little evidence of healthy adherer bias when studying the association between better adherence to osteoporosis drugs and fracture risk reduction, with only better adherence to bisphosphonates reducing fracture risk. The higher fracture risk among highly adherent raloxifene users for primary prevention is likely due to residual confounding.

Treatment of vitamin D deficiency with vitamin D is a common procedure when taking care of elderly patients, calcium supplementation being added only when calcium dietary intake is insufficient. Here, we report the case of a 58-year-old female who was referred to our unit because of suspicion of Paget’s disease of the skull, based on elevated serum alkaline phosphatase and high skull methylene diphosphonate-technetium uptake. She had been prescribed cholecalciferol (100,000 IU/month) and calcium salts for the past 7 months after discovery of severe vitamin D deficiency by her primary care physician. No specific skull bone lesions were observed on both X-ray and computerized tomography. Serum calcium, phosphate and 25(OH) vitamin D levels were normal, while serum C-terminal cross-linked telopeptide, bone alkaline phosphatase and calcitriol were high and daily urinary calcium excretion was low. We found that she had not been compliant with the calcium prescription while vitamin D had been thoroughly taken. We suspected osteomalacia due to calcium deficiency. Both skull uptake and biological abnormalities normalised in few months after adding calcium supplementation to the vitamin D treatment, and spine bone mineral density increased by 9.5 % after 14 months of full treatment. The present case illustrates the necessity for adequate calcium intake during vitamin D repletion to normalise bone mineralisation and turnover and maintain the skeletal integrity.