Background A recently published meta-analysis of randomised, placebo-controlled trials of antiresorptive agents in postmenopausal women found a significant relationship between increases in bone mineral density (BMD) and reductions in risk of radiographic vertebral fractures, as well as a small risk reduction not explained by change in BMD.1 It is unknown, however, whether a similar relationship exists between increases in BMD and a reduction in risk of clinical nonvertebral fractures.
Objectives To examine the extent to which increases in BMD during antiresorptive therapy are associated with reductions in risk of nonvertebral fractures.
Methods We performed a meta-analysis of all randomised, placebo-controlled trials of antiresorptive agents conducted in postmenopausal women with osteoporosis with available relevant data. A total of 15 such trials with usable data were identified including a total of 1911 women with incident nonvertebral fractures over 54,952 women-years of follow up. Poisson regression was used to estimate the association between increase in BMD (change in the treatment group – change in placebo group) and relative risk (RR) of nonvertebral fractures across all trials; separate models were constructed for change in spine BMD and change in hip BMD.
Results Both models found a significant relationship between increases in BMD and reductions in nonvertebral fracture risk. For each 1 percent increase in bone mineral density at the lumbar spine, there was a 4.3 percent decrease in risk of nonvertebral fracture (P = 0.029); for each 1 percent increase in bone mineral density at the hip, there was a 8.8 percent decrease in risk of nonvertebral fracture (P = 0.016). In neither model was there a significant decrease in risk of nonvertebral fractures in the absence of increase in bone mineral density. Thus, an agent that increases spine BMD by 8% reduces nonvertebral fracture risk by about 40%, and an agent that increases hip BMD by 5% also reduces nonvertebral fracture risk by about 40%.
Conclusion These data demonstrate that larger increases in BMD at both the spine and hip are associated with greater reductions in risk of nonvertebral fractures. Antiresorptive agents which do not produce large increases in BMD do not appear to and would not be expected to decrease the risk of nonvertebral fractures.
J Clin Endocrinol Metab. 2000;85:231–6
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