ArticlesRandomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures
Introduction
Osteoporosis is a common disorder that is a contributing factor in about 1·5 million fractures per year among women in the USA alone, with an estimated treatment cost of more than US$10 billion.1 On average, a 50-year-old white woman has a risk of hip fracture during her remaining lifetime of about 16%.2 About 1·7 million hip fractures occurred world wide in 1990.3
Randomised trials have shown increases in bone mass with several treatments, including oestrogen,4, 5 calcitonin,6 calcitriol,7 sodium fluoride,8, 9 and bisphosphonates.10, 11, 12 Trials of some of these drugs have also reported reductions in the incidence of vertebral fracture,4, 9, 11, 12 although some were small and of short duration, and in some the outcome was decrease in vertebral height. Only about a third of radiographically diagnosed vertebral fractures cause symptoms;13 the effect of these agents on clinically evident fractures is uncertain. A combination of calcium and vitamin D reduced the incidence of hip and non-spine fracture in very elderly women in nursing homes,14 and long-term use of oestrogen has been associated with reduced risk of hip fracture in observational studies.15 No randomised trial has shown, however, a reduction in risk of hip fracture in community-dwelling women.
Liberman and colleagues12 reported that the aminobisphosphonate alendronate sodium (alendronate) increases bone mineral density (BMD) at the spine and hip and in the whole body and reduces the risk of radiographically defined vertebral fracture in women with low BMD. Their study did not, however, have sufficient power to demonstrate a significant effect on non-vertebral fractures.
The Fracture Intervention Trial was designed to find out the effect of alendronate on the frequencies of vertebral and non-vertebral fractures in postmenopausal women with low bone mass.16 The investigation was carried out as two separate studies in women with and without vertebral fractures at baseline. We report here the results among women with at least one vertebral fracture at recruitment.
Section snippets
Methods
Participants were recruited from population-based listings in 11 metropolitan areas of the USA. All women in the Fracture Intervention Trial were aged between 55 and 81 years at baseline, had been postmenopausal for at least 2 years, and had femoral-neck BMD of 0·68 g/cm2 or less (QDR-2000 Hologic, Waltham, MA, USA), about 2·1 SDs below peak bone mass based on the manufacturer's normative data. Details of the study design and methods have been published previously.16 We excluded women with
Results
2027 women were recruited into the vertebral fracture arm of the Fracture Intervention Trial, 1022 to alendronate and 1005 to placebo (figure 1). Potential confounding variables were similarly distributed between the treatment groups (table 1). 97% of participants identified themselves as Caucasian, 1% as Asian, and 1% as African-American.
The average follow-up time was 2·9 years in both groups (range 0·7–3·5 alendronate, 0·3–3·5 placebo). Closeout information was obtained either in clinic or by
Discussion
We found that postmenopausal women with low bone mass and pre-existing vertebral fractures who received alendronate had a lower incidence of several types of fractures than women who received placebo. Our findings confirm those of Liberman and colleagues,12 and show in addition to the effect on radiographically defined vertebral fractures, effects on symptomatic vertebral fractures, hip fractures, and wrist fractures.
This randomised trial found a significant reduction in the risk of hip
References (30)
- et al.
Four-year study of intermittent cyclic etidronate treatment of postmenopausal osteoporosis: three years of blinded therapy followed by one year of open therapy
Am J Med
(1993) - et al.
The prevention and treatment of osteoporosis
N Engl J Med
(1992) - et al.
Lifetime risks of hip, Colles' or vertebral fracture and coronary heart disease among white postmenopausal women
Arch Intern Med
(1989) - et al.
Hip fractures in the elderly: a worldwide projection
Osteoporosis Int
(1992) - et al.
Treatment of postmenopausal osteoporosis with transdermal estrogen
Ann Intern Med
(1992) Long term effect of oestrogen replacement therapy on bone mass as measured by dual photon absorptiometry
BMJ
(1987)- et al.
Effect of calcitonin given intranasally on bone mass and fracture rates in established osteoporosis: a dose-response study
BMJ
(1992) - et al.
Treatment of postmenopausal osteoporosis with calcitriol or calcium
N Engl J Med
(1992) - et al.
Effect of the fluoride/calcium regimen on vertebral fracture occurrence in postmenopausal osteoporosis
N Engl J Med
(1982) - et al.
Treatment of postmenopausal osteoporosis with slow-release sodium fluoride: final report of a randomized controlled trial
Ann Intern Med
(1995)
Effect of intermittent cyclical etidronate therapy on bone mass and fracture rate in women with postmenopausal osteoporosis
N Engl J Med
Intermittent cyclical etidronate treatment of postmenopausal osteoporosis
N Engl J Med
Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis
N Engl J Med
Vertebral fractures: how large is the silent epidemic?
BMJ
Vitamin D3 and calcium to prevent hip fractures in elderly women
N Engl J Med
Cited by (3540)
Follow-up bone mineral density testing: 2023 official positions of the International Society for Clinical Densitometry
2024, Journal of Clinical DensitometryManagement of High-Risk Ankle Fractures
2024, Clinics in Podiatric Medicine and Surgery