J H Krege1, X Wan. 1. Lilly USA, LLC, Lilly Corporate Center, Indianapolis, IN 46285, USA. kregejh@lilly.com
Abstract
PURPOSE: In the Fracture Prevention Trial, the risks of any nonvertebral fracture (relative risk [RR] 0.65, P=0.04) and any fragility nonvertebral fracture (RR 0.47, P=0.02) were significantly reduced in the teriparatide 20 μg/day (teriparatide) versus placebo group. The purpose of this analysis was to examine the efficacy of teriparatide versus placebo on a variety of other nonvertebral fracture outcomes. MATERIALS AND METHODS: The Fracture Prevention Trial was a double-blind trial of postmenopausal women with osteoporosis and vertebral fractures randomly assigned to teriparatide (N=541) or placebo (N=544) administered by daily self-injection for a median of 19 months and a median follow-up of 21 months. All patients received calcium and vitamin D supplementation. Reports of nonvertebral fractures were collected from patients at each visit and confirmed by review of a radiograph or written radiology report. Nonvertebral fractures were recorded for the following sites: distal radius/wrist, humerus, rib/clavicle, hip, ankle, distal foot, pelvis, or other. Pathological fractures and fractures of the face, skull, metacarpals, fingers and toes were excluded. Fractures were classified by investigators as fragility or traumatic fractures. The three endpoints considered were six nonvertebral sites (nonvert-6), a set of common nonvertebral fractures described in a Food and Drug Administration Guidance document for the treatment and prevention of postmenopausal osteoporosis (FDA), and a European Union major set (major) of nonvertebral fractures. RESULTS: For teriparatide versus placebo, the point estimates for the RR of nonvert-6 (RR 0.54, P=0.06; fragility RR 0.32, P=0.014), FDA (RR 0.60, P=0.15; fragility RR 0.38, P=0.05), and major (RR 0.52, P=0.02; fragility RR 0.38, P=0.02) nonvertebral fracture endpoints were smaller than for the all nonvertebral fracture endpoint. Lower RRs were observed when the outcomes were limited to fragility fractures, and significant reductions in traumatic nonvertebral fractures were not observed. CONCLUSION: In the Fracture Prevention Trial, the risk reduction for nonvertebral fracture in patients treated with teriparatide versus placebo depended on the set of nonvertebral fractures included in the analysis; lower RRs were observed for nonvertebral fractures most likely to be of osteoporotic origin. No significant reductions in traumatic nonvertebral fractures were observed.
RCT Entities:
PURPOSE: In the Fracture Prevention Trial, the risks of any nonvertebral fracture (relative risk [RR] 0.65, P=0.04) and any fragility nonvertebral fracture (RR 0.47, P=0.02) were significantly reduced in the teriparatide 20 μg/day (teriparatide) versus placebo group. The purpose of this analysis was to examine the efficacy of teriparatide versus placebo on a variety of other nonvertebral fracture outcomes. MATERIALS AND METHODS: The Fracture Prevention Trial was a double-blind trial of postmenopausal women with osteoporosis and vertebral fractures randomly assigned to teriparatide (N=541) or placebo (N=544) administered by daily self-injection for a median of 19 months and a median follow-up of 21 months. All patients received calcium and vitamin D supplementation. Reports of nonvertebral fractures were collected from patients at each visit and confirmed by review of a radiograph or written radiology report. Nonvertebral fractures were recorded for the following sites: distal radius/wrist, humerus, rib/clavicle, hip, ankle, distal foot, pelvis, or other. Pathological fractures and fractures of the face, skull, metacarpals, fingers and toes were excluded. Fractures were classified by investigators as fragility or traumatic fractures. The three endpoints considered were six nonvertebral sites (nonvert-6), a set of common nonvertebral fractures described in a Food and Drug Administration Guidance document for the treatment and prevention of postmenopausal osteoporosis (FDA), and a European Union major set (major) of nonvertebral fractures. RESULTS: For teriparatide versus placebo, the point estimates for the RR of nonvert-6 (RR 0.54, P=0.06; fragility RR 0.32, P=0.014), FDA (RR 0.60, P=0.15; fragility RR 0.38, P=0.05), and major (RR 0.52, P=0.02; fragility RR 0.38, P=0.02) nonvertebral fracture endpoints were smaller than for the all nonvertebral fracture endpoint. Lower RRs were observed when the outcomes were limited to fragility fractures, and significant reductions in traumatic nonvertebral fractures were not observed. CONCLUSION: In the Fracture Prevention Trial, the risk reduction for nonvertebral fracture in patients treated with teriparatide versus placebo depended on the set of nonvertebral fractures included in the analysis; lower RRs were observed for nonvertebral fractures most likely to be of osteoporotic origin. No significant reductions in traumatic nonvertebral fractures were observed.