Drs McCloskey and Kanis have served as consultants for and received research funding and speaker's fees from Schering. Drs Kayan, de Takats, Dey, and Ashford have received travel support to international bone meetings from Schering. Drs Brazier, Beneton, and Nicholl have received research funding from Schering. Drs Aropuu and Jalava are employees of Schering. All other authors state that they have no conflicts of interest.
Clodronate Reduces the Incidence of Fractures in Community-Dwelling Elderly Women Unselected for Osteoporosis: Results of a Double-Blind, Placebo-Controlled Randomized Study
Article first published online: 16 OCT 2006
Copyright © 2007 ASBMR
Journal of Bone and Mineral Research
Volume 22, Issue 1, pages 135–141, January 2007
How to Cite
McCloskey, E. V., Beneton, M., Charlesworth, D., Kayan, K., de Takats, D., Dey, A., Orgee, J., Ashford, R., Forster, M., Cliffe, J., Kersh, L., Brazier, J., Nichol, J., Aropuu, S., Jalava, T. and Kanis, J. A. (2007), Clodronate Reduces the Incidence of Fractures in Community-Dwelling Elderly Women Unselected for Osteoporosis: Results of a Double-Blind, Placebo-Controlled Randomized Study. J Bone Miner Res, 22: 135–141. doi: 10.1359/jbmr.061008
- Issue published online: 4 DEC 2009
- Article first published online: 16 OCT 2006
- Manuscript Accepted: 12 OCT 2006
- Manuscript Revised: 31 JUL 2006
- Manuscript Received: 2 FEB 2006
- clinical fractures;
A 3-year prospective, randomized, placebo-controlled trial of oral clodronate 800 mg showed that the incidence of clinical fractures was decreased by 20% in 5596 elderly women unselected for osteoporosis. The effect occurred in the absence of systematic calcium and vitamin D supplementation and was observed across a wide range of BMDs.
Introduction: To date, most studies with bisphosphonates have reported on their use in individuals selected to be at high risk for fracture usually by the presence of low BMD or a prior fragility fracture, usually of the spine. We wished to determine the effect of the bisphosphonate, clodronate, on the rate of fractures in women ⩾75 years of age living in the community.
Materials and Methods: Women ⩾75 years of age living in the general community in South Yorkshire and North Derbyshire, identified from general practice registers, were recruited by letter of invitation to a randomized, double-blind, controlled trial of 800 mg oral clodronate (Bonefos) or matching placebo daily over 3 years. The main outcomes were the incidences of hip and any clinical fracture.
Results: Of the 5579 elderly women included in the intention-to-treat analysis of efficacy, 114 had a new hip fracture during the 3-year treatment phase: 56 (2.0%) women in the clodronate group and 58 (2.1%) women in the placebo group (hazard ration [HR], 1.02; 95% CI, 0.71–1.47). Clodronate did, however, decrease the incidence of any clinical fracture by 20% (264 women [9.5%] versus 337 [12.1%] in the placebo group; HR, 0.80; 95% CI, 0.68–0.94). The incidence of osteoporosis-associated nonhip fractures was also significantly decreased by 29% (5.2% versus 7.4%; HR, 0.71; 95% CI, 0.57–0.87). The ability of clodronate to reduce the risk of osteoporotic fracture was independent of baseline BMD, but the number needed-to-treat was lower in the presence of osteoporosis.
Conclusions: Oral daily clodronate can prevent fractures without significant adverse effects in elderly women living in the general community. The effect on hip fracture risk is not significant, but an effect similar to that at other nonvertebral sites cannot be excluded. This study suggests that antiresorptive therapies can reduce fracture incidence in high-risk individuals even in the presence of a normal or osteopenic BMD.