Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
-
J. Bone Miner. Res. · Aug 2018
Randomized Controlled TrialA Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial Evaluating the Efficacy of Burosumab, an Anti-FGF23 Antibody, in Adults With X-Linked Hypophosphatemia: Week 24 Primary Analysis.
In X-linked hypophosphatemia (XLH), inherited loss-of-function mutations in the PHEX gene cause excess circulating levels of fibroblast growth factor 23 (FGF23), leading to lifelong renal phosphate wasting and hypophosphatemia. Adults with XLH present with chronic musculoskeletal pain and stiffness, short stature, lower limb deformities, fractures, and pseudofractures due to osteomalacia, accelerated osteoarthritis, dental abscesses, and enthesopathy. Burosumab, a fully human monoclonal antibody, binds and inhibits FGF23 to correct hypophosphatemia. ⋯ There were no treatment-related serious adverse events or meaningful changes from baseline in serum or urine calcium, intact parathyroid hormone, or nephrocalcinosis. These data support the conclusion that burosumab is a novel therapeutic addressing an important medical need in adults with XLH.© 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.
-
J. Bone Miner. Res. · Aug 2018
Differential Mortality and the Excess Rates of Hip Fracture Associated With Type 2 Diabetes: Accounting for Competing Risks in Fracture Prediction Matters.
Type 2 diabetes (T2DM) is associated with a reduced life expectancy. The latest published evidence suggests an increased risk of fractures among T2DM patients. We conducted a population-based cohort study to determine the impact of mortality as a competing risk in the study of the association between T2DM and hip fracture rates. ⋯ Accounting for death as a competing event (Fine-Gray models), the association between T2DM and hip fracture risk remained statistically significant (SHR 1.15; 95% CI, 1.09 to 1.21) and the probability of a hip fracture within 5 years was 2.3% for TD2M and 1.9% for non-TD2M patients compared to 2.6% and 2.1% respectively using Kaplan-Meier (KM) estimates. T2DM patients have a 50% increased mortality and, after adjusting for differential survival at 5 years, a 21% increased incidence of hip fracture when compared to matched non-T2DM. Failing to account for differential mortality leads to an overestimation of fracture risk. © 2018 American Society for Bone and Mineral Research.