Search

The risk of osteoporotic fracture is inversely related to bone mineral density (BMD), but how spatial BMD pattern influences fracture risk remains incompletely understood. This study used a pixel-level spatiotemporal atlas of proximal femoral BMD in 13,338 white European women (age 20–97 years) to quantitate age-related texture variation in BMD maps and generate a “reference” map of bone aging. We introduce a new index, called Densitometric Bone Age (DBA), as the age at which an individual site-specific BMD map (the proximal femur is studied here) best matches the median aging trajectory at that site in terms of the root mean squared error (RMSE). The ability of DBA to predict incident hip fracture and hip fracture pattern over 5 years following baseline BMD was compared against conventional region-based BMD analysis in a subset of 11,899 women (age 45–97 years), for which follow-up fracture records exist. There were 208 subsequent incident hip fractures in the study populations (138 femoral necks [FNs], 52 trochanteric [TR], 18 sites unspecified). DBA had modestly better performance compared to the conventional FN-BMD, TR-BMD, and total hip (TOT)-BMD in identifying hip fractures measured as the area under the curve (AUC) using receiver operating characteristics (ROC) curve analysis by 2% (95% confidence interval [CI], −0.5% to 3.5%), 3% (95% CI, 1.0% to 4.0%), and 1% (95% CI, 0.4% to 1.6%), respectively. Compared to FN-BMD T-score, DBA improved the ROC-AUC for predicting TR fractures by ~5% (95% CI, 1.1% to 9.8%) with similar performance in identifying FN fractures. Compared to TR-BMD T-score, DBA improved the ROC-AUC for the prediction of FN fractures by ~3% (95% CI, 1.1% to 4.9%), with similar performance in identifying TR fractures. Our findings suggest that DBA may provide a spatially sensitive measure of proximal femoral fragility that is not captured by FN-BMD or TR-BMD alone.

In the Maternal Vitamin D Osteoporosis Study (MAVIDOS) randomized trial, vitamin D supplementation in pregnancy did not lead to greater neonatal bone mass across the trial as a whole, but, in a prespecified secondary analysis by season of birth, led to greater neonatal bone mass among winter-born babies. Demonstrating persistence of this effect into childhood would increase confidence in a long-term benefit of this intervention. We investigated whether antenatal vitamin D supplementation increases offspring bone mineralization in early childhood in a prespecified, single-center follow-up of a double-blinded, multicenter, randomized controlled clinical trial based in the UK (MAVIDOS). A total of 1123 women in early pregnancy with a baseline 25-hydroxyvitamin D level 25–100 nmol/L from three research centers (2008–2014) were randomized to 1000 IU/d cholecalciferol or matched placebo from 14 weeks of gestation to delivery. Offspring born at the Southampton, UK research center were assessed at age 4 years (2013–2018). Anthropometry and dual-energy X-ray absorptiometry (DXA) were performed (yielding whole body less head [WBLH] bone mineral content [BMC], areal bone mineral density [aBMD], bone area [BA], and body composition). Of 723 children, 564 (78.0%) children attended the 4-year visit, 452 of whom had a useable DXA. Maternal vitamin D supplementation led to greater WBLH aBMD in the children compared with placebo (mean [95% confidence interval {CI}]: supplemented group: 0.477 (95% CI, 0.472–0.481) g/cm2; placebo group: 0.470 (95% CI, 0.466–0.475) g/cm2, p = 0.048). Associations were consistent for BMC and lean mass, and in age- and sex-adjusted models. Effects were observed across the whole cohort irrespective of season of birth. Maternal-child interactions were observed, with a greater effect size among children with low milk intake and low levels of physical activity. Child weight, height, and body mass index (BMI) were similar by maternal randomization group. These findings suggest a sustained beneficial effect of maternal vitamin D supplementation in pregnancy on offspring aBMD at age 4 years, but will require replication in other trials.

Randomized control trials (RCTs) have shown that certain intravenous iron preparations can induce high levels of fibroblast growth factor 23 (FGF-23) and persistent hypophosphatemia. Repeated iron infusions may lead to prolonged hypophosphatemia and osteomalacia events not captured by RCTs. Several previous case reports have described skeletal adverse effects after repeated iron infusions. To characterize these effects, we conducted a systematic review of case reports. MEDLINE, Embase, Web of Science, and Cochrane databases were searched in March 2021. We selected case reports of patients ≥16 years old. Study quality was assessed using the tool from Murad and colleagues. We report the results in a narrative summary. We identified 28 case reports, reporting 30 cases. Ages ranged from 28 to 80 years (median 50 years). Most patients (n = 18) received ferric carboxymaltose (FCM), whereas 8 received saccharated ferric oxide (SFO) and 3 received iron polymaltose (IPM). All but 2 cases had more than five infusions (range 2 to 198, median 17). The lowest phosphate levels ranged from 0.16 to 0.77 mmol/L (median 0.36 mmol/L). Intact FGF-23 (iFGF-23) was high when measured. Serum 25OH vitamin D was low in 10 of 21 cases measured and 1,25(OH)2 vitamin D in 12 of 18. Alkaline phosphatase was high in 18 of 22 cases. Bone or muscle pain was reported in 28 of the 30 cases. Twenty patients had pseudofractures, 9 had fractures, and 6 patients had both. All 15 available bone scans showed focal isotope uptake. Case reports tend to report severe cases, so potential reporting bias should be considered. Osteomalacia is a potential complication of repeated iron infusion, especially in patients with gastrointestinal disorders receiving prolonged therapy. Pain and fractures or pseudofractures are common clinical findings, associated with low phosphate, high iFGF-23, high alkaline phosphatase, and abnormal isotope bone scan. Discontinuing or switching the iron formulation was an effective intervention in most cases.

Osteoporosis in men is a common but often overlooked disorder by clinicians. The criterion for osteoporosis diagnosis in men is similar to that in women—namely, a bone mineral density (BMD) that is 2·5 standard deviations or more below the mean for the young adult population (aged 20–29 years; T-score –2·5 or lower), measured at the hip or lumbar spine. Sex steroids are important for bone health in men and, as in women, oestrogens have a key role. Most men generally have bigger and stronger bones than women and typically have less bone loss during their lifetime. Men typically fracture less often than women, although they have a higher mortality rate after a fracture. Secondary osteoporosis is more common in men than in women. Lifestyle changes, adequate calcium, vitamin D intake, and exercise programmes are recommended for the management of osteoporosis in men. Bisphosphonates, denosumab, and teriparatide have been shown to increase BMD and are used for pharmacological treatment. In this Review, we report an updated overview of osteoporosis in men, describe new treatments and concepts, and discuss persistent controversies in the area.

Context\ud \ud Parathyroid hormone (PTH) replacement is a promising approach in the management of hypoparathyroidism but long-acting analogues need to be developed. To date, animal models for testing PTH required parathyroidectomy by surgery. We have developed a nonsurgical rodent hypoparathyroid model and tested a delayed-clearance PTH molecule (DC-PTH).\ud \ud \ud \ud Objective\ud \ud The aim of this study was to use cinacalcet to suppress calcium levels in normal rats and to reverse these effects with the administration of PTH or PTH analogues\ud \ud \ud \ud Methods\ud \ud Male Wistar rats were gavaged with either 30 mg/kg cinacalcet-HCl (cinacalcet) or vehicle only. Animals were then dosed with either single or repeated subcutaneous doses of PTH 1-34 or a DC-PTH at 20 nmol/kg. Control animals received vehicle only. Serum samples were analyzed for ionized calcium (iCa), phosphate, PTH, and DC-PTH. A pharmacokinetic-pharmacodynamic (PK-PD) model was built for cinacalcet, PTH 1-34, and DC-PTH using Phoenix64.\ud \ud \ud \ud Results\ud \ud Cinacalcet reduced iCa levels between 2 and 24 hours, returning to baseline by 72 hours post dose with nadir at 8 hours (analysis of variance P