Fracture Risk in Perimenopausal Women Treated with Beta-Blockers

β2-adrenergic receptors have been identified on human osteoblastic and osteoclastic cells, raising the question of a sympathetic regulation of bone metabolism. We investigated effects of treatment with β-adrenergic receptor antagonists (β-blockers) on bone turnover, bone mineral density (BMD), and fracture risk. Within the Danish Osteoporosis Prevention Study (DOPS) a population based, comprehensive cohort study of 2016 perimenopausal women, associations between treatment with β-blockers and bone turnover and BMD were assessed in a cross-sectional design at the start of study. Moreover, in a nested case-control design, fracture risk during the subsequent 5 years was assessed in relation to treatment with β-blockers at baseline. Multiple regression- and logistic regression-analyses were performed. Treatment with β-blockers was associated with a threefold increased fracture risk (OR_adj 3.3; 95% CI: 1.1–9.4). Analyses on duration of treatment showed that women who had been treated for more than 8 years had a higher fracture risk (OR_adj 5.3; 95% CI: 1.1–26.3) than those treated for less than 8 years (OR_adj 2.4; 95% CI: 0.6–9.5). In addition, cross-sectional data showed 20% lower serum osteocalcin levels (an osteoblastic marker of bone formation) in women treated with β-blockers compared to untreated women (P < 0.001), whereas BMD at the lumbar spine and femoral neck did not differ between groups. β-blockers may decrease the activity of bone-forming cells and thereby increase fracture risk. However, confirmative studies and studies exploring mechanisms of action are needed.