Low bone mineral density (BMD) is an important and modifiable risk factor for fracture in postmenopausal women with osteoporosis. Denosumab (DMAb) shows a stronger relationship between BMD increases and antifracture efficacy than oral bisphosphonate (BP) therapies. Subjects who remain at higher risk of fracture despite current BP therapy need treatment. In two studies, DMAb significantly increased BMD and decreased bone turnover markers vs a BP (ibandronate (IBN) or risedronate (RIS)) in subjects previously treated with, but suboptimally adherent to, a BP. We evaluated the effects of DMAb vs a BP (IBN and RIS) to increase BMD in a subset of subjects at higher risk of fracture. Both studies had multicentre, randomized, open-label, parallel-group designs in which postmenopausal women ≥55 years were randomized 1:1 to DMAb 60 mg S.C. Q6M or a BP 150 mg P.O. QM for 12 months. In this combined post-hoc analysis, higher-risk subjects were identified by meeting ≥1 risk criterion (baseline age ≥75 years, total hip (TH) or femoral neck (FN) BMD T-score ≤−2.5, TH or FN BMD T-score ≤−1.0+ prior osteoporotic fracture, sCTX-1 >0.9 ng/ml and TH or FN BMD T-score ≤−2.0) and % BMD change from baseline at TH, FN and lumbar spine (LS) at month 12 was calculated. Subjects (852 DMAb and 851 BP) had a mean (S.D.) age 67 (7.4) years and mean (S.D.) TH, FN and LS T-score of −1.7 (0.8), −2.0 (0.7), and −2.4 (1.0) respectively. For subjects at higher risk of fracture (475 DMAb and 469 BP), compared with BP (IBN and RIS), at 12 months DMAb significantly increased TH (2.2 vs 0.8%), FN (1.8 vs 0.3%) and LS BMD (3.7 vs 1.4%; P<0.0001 for all). These results are consistent with the overall study population and lower risk subgroup (treatment-by-risk subgroup interaction, P>0.05). In general, adverse events and serious adverse events were similar between DMAb and the comparator BP groups. In conclusion, for subjects who were previously suboptimally treated with a BP and remained at higher risk of fracture, transitioning to DMAb led to significantly greater increases in BMD at 12 months than cycling to another BP. These results in higher-risk subjects are consistent with those obtained in the overall population and support DMAb as an alternative therapeutic option for women at higher risk of fracture.
17 May 2014 - 20 May 2014