Impact of denosumab on the peripheral skeleton of postmenopausal women with osteoporosis: bone density, mass, and strength of the radius, and wrist fracture.

Abstract

OBJECTIVE:

The aim of this study was to report the effects of denosumab on radius cortical and trabecular bone density, mass, and strength, and wrist fracture incidence in the FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months) study.

METHODS:

In the FREEDOM study, postmenopausal women with osteoporosis (N = 7,808) received placebo or 60 mg of denosumab every 6 months for 36 months. Radius bone mineral density (BMD), bone mineral content, and strength (polar moment of inertia) were evaluated in two prespecified substudies using dual-energy x-ray absorptiometry (placebo, n = 209; denosumab, n = 232) or quantitative CT (placebo, n = 48; denosumab, n = 62). Prespecified analysis assessed wrist fracture incidence in all FREEDOM participants (placebo, N = 3,906; denosumab, N = 3,902), and post hoc subgroup analyses evaluated those with higher fracture risk (baseline femoral neck T-score ≤-2.5; placebo, N = 1,406; denosumab, N = 1,384).

RESULTS:

Denosumab significantly increased areal BMD (assessed by dual-energy x-ray absorptiometry) and volumetric BMD, bone mineral content, and polar moment of inertia (assessed by quantitative CT), compared with placebo, in radius cortical and trabecular bone at all time points evaluated (all P < 0.05). Wrist fracture incidence was 2.9% for placebo and 2.5% for denosumab (relative risk reduction, 16%; P = 0.21) on month 36. Participants with a femoral neck T-score of -2.5 or lower were at increased risk for wrist fracture, and denosumab significantly reduced wrist fracture incidence compared with placebo (placebo, 4.0%; denosumab, 2.4%; relative risk reduction, 40%; absolute risk reduction, 1.6%; P = 0.03).

CONCLUSIONS:

Denosumab significantly improves radius bone density, mass, and strength compared with placebo. In higher-risk women, denosumab significantly reduces wrist fracture risk.

• Authors: James A Simon, Christopher Recknor, Alfred H Moffett Jr, Jonathan D Adachi, Edward Franek, E Michael Lewiecki, Michael R McClung, Carlos A Mautalen, Sergio Ragi-Eis, Geoffrey C Nicholson, Christian Muschitz, Ranuccio Nuti, Ove Törring, Andrea Wang, Cesar Libanati
• Journal: Menopause (New York, N.Y.) (Menopause) Vol. 20 Issue 2 Pg. 130-7 (Feb 2013) ISSN: 1530-0374 [Electronic] United States
• PMID: 23010883 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• Bone Density Conservation Agents
• Placebos
• RANK Ligand
• Denosumab

Topics

• Absorptiometry, Photon
• Aged
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Bone Density (drug effects)
• Bone Density Conservation Agents (therapeutic use)
• Bone and Bones (drug effects, physiopathology)
• Denosumab
• Double-Blind Method
• Female
• Humans
• Middle Aged
• Osteoporosis, Postmenopausal (drug therapy, physiopathology)
• Placebos
• RANK Ligand (antagonists & inhibitors)
• Radius (diagnostic imaging, physiopathology)
• Radius Fractures (epidemiology, prevention & control)
• Risk
• Tomography, X-Ray Computed
• Ulna Fractures (epidemiology)