The relationship between treatment-related changes in total hip bone mineral density measured after 12, 18 and 24 months and fracture risk reduction in osteoporosis clinical trials: the FNIH-ASBMR-SABRE Project.

There is a strong association between total hip bone mineral density (THBMD) changes after 24 months of treatment and reduced fracture risk. We examined whether changes in THBMD after 12- and 18 months of treatment are also associated with fracture risk reduction. We used individual patient data (n = 122 235 participants) from 22 randomised, placebo-controlled, double-blind trials of osteoporosis medications. We calculated the difference in mean percent change in THBMD (active-placebo) at 12, 18, and 24 months using data available for each trial. We determined the treatment-related fracture reductions for the entire follow-up period, using logistic regression for radiologic vertebral fractures and Cox regression for hip, non-vertebral, "all" (combination of non-vertebral, clinical vertebral, and radiologic vertebral) fractures, and all clinical fractures (combination of non-vertebral and clinical vertebral). We performed meta-regression to estimate the study-level association (r2 and 95% confidence interval) between treatment-related differences in THBMD changes for each BMD measurement interval and fracture risk reduction. The meta-regression revealed that for vertebral fractures, the r2 (95% confidence interval) was 0.59 (0.19, 0.75), 0.69 (0.32, 0.82), and 0.73 (0.33, 0.84) for 12, 18 and 24 months, respectively. Similar patterns were observed for hip: r2 = 0.27 (0.00, 0.54), 0.39 (0.02, 0.63), and 0.41 (0.02, 0.65); non-vertebral: r2 = 0.27 (0.01, 0.52), 0.49 (0.10, 0.69), and 0.53 (0.11, 0.72); all fractures: r2 = 0.44 (0.10, 0.64), 0.63 (0.24, 0.77), and 0.66 (0.25, 0.80); and all clinical fractures: r2 = 0.46 (0.11, 0.65), 0.64 (0.26, 0.78), and 0.71 (0.32, 0.83), for 12-, 18- and 24-month changes in THBMD, respectively. These findings demonstrate that treatment-related THBMD changes at 12, 18 and 24 months are associated with fracture risk reductions across trials. We conclude that BMD measurement intervals as short as 12 months could be used to assess fracture efficacy, but the association is stronger with longer BMD measurement intervals.