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Alendronate and fractures

One of the options for trying to prevent fractures in postmenopausal women is the use of bisphosphonates. A new, large, randomised trial shows who is likely to benefit with alendronate, and the extent of that benefit [1].

Study


From over one million women contacted by mail, 2214 were eventually randomised to alendronate and 2218 to placebo in 11 centres. The blinded treatments were alendronate 5 mg per day for the first two years, increased to 10 mg per day at the second annual visit because other trials suggested this dose had greater effects on bone mineral density. Women had to be 50 to 85 years old, postmenopausal for at least two years and have a femoral neck bone mineral density about two standard deviations below the mean of normal young adult white women. There were exclusions for various medical problems and consumption of exogenous oestrogens.

There were frequent visits over four years for bone mineral density measurements and a spine X-ray at the end of the study. The primary outcomes were clinical fractures (non-spine fractures of hip, arm, wrist etc) and radiological vertebral fractures.

Results


The groups were comparable at baseline. There was a significant effect of alendronate on bone mineral density - data for the femoral neck over four years is shown in the Figure.



There was no significant effect of alendronate on the risk of all clinical fractures, though the number of fractures at sites other than the hip, wrist or spine (70% of the total clinical fractures) was reduced by alendronate (relative risk 0.79, 95% CI 0.65 to 0.96). The number needed to treat (Table) with alendronate over four years to prevent a fracture other than at the hip spine or wrist was 50 (27 to 321).
NNTs with alendronate in postmenopausal women
Type of fracture Alendronate number/total Placebo number/total NNT (95% CI)
All patients
Clinical fractures except spine, hip and wrist 182/2214 227/2218 50 (27 to 321)
Vertebral fractures 43/2214 78/2218 64 (39 to 162)
Patients with lowest bone mineral density
Clinical fractures (all) 107/819 159/812 15 (10 to 34)
Vertebral fractures 22/819 44/812 37 (22 to 122)

Alendronate also reduced the number of women with at least one radiological vertebral fracture (relative risk 0.56, 95%CI 0.39 to 0.80). The number needed to treat with alendronate over four years to prevent at least one radiological fracture of the spine was 64 (39 to 162).

A planned subgroup analysis examined the effect of alendronate according to the bone mineral density at the femoral neck. Significant effects of alendronate were found in women whose bone mineral density was more than 2.5 standard deviations below that of young white women, a definition which covered about 37% of women in the study.

Clinical fractures (all sites) were significantly reduced in this group by alendronate, with a relative risk of 0.64 (0.50 to 0.82) and a number needed to treat over four years of 15 (10 to 34) to prevent any clinical fracture. For radiological vertebral fractures the relative risk was 0.50 (0.31 to 0.82) and the number needed to treat was 37 (22 to 122).

Comment


This was a large trial directed towards women most at risk of fracture because of their low bone mineral density. Perhaps its most significant feature was that it further identified those women with the lowest femoral neck bone density who would benefit most from alendronate treatment, and who could be identified using an increasingly available diagnostic test. This combination of test and treatment efficacy should simplify guidance and maximise quality and value for money.

Reference:

  1. SR Cummings et al. Effect of alendronate on risk fracture in women with low bone density but without vertebral fractures. JAMA 1998 280: 2077-2082.



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