Fracture risk in perimenopausal women treated with beta-blockers.
beta2-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 beta-adrenergic receptor antagonists (beta-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 beta-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 beta-blockers at baseline. Multiple regression- and logistic regression-analyses were performed. Treatment with beta-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 beta-blockers compared to untreated women (P < 0.001), whereas BMD at the lumbar spine and femoral neck did not differ between groups. beta-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.
Rejnmark
Lars
L
Dept. of Endocrinology and Metabolism C, Aarhus Amtssygehus, Aarhus University Hospital, Aarhus, Denmark. rejnmark@post6.tele.dk
Vestergaard
Peter
P
Kassem
Moustapha
M
Christoffersen
Bo Rud
BR
Kolthoff
Niels
N
Brixen
Kim
K
Mosekilde
Leif
L
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000886:Anthropometry; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D003404:Creatinine / Q000652:urine; D003430:Cross-Sectional Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005272:Femur Neck / Q000737:chemistry; D050723:Fractures, Bone / Q000453:epidemiology* / Q000517:prevention & control; D006801:Humans; D016015:Logistic Models; D008159:Lumbar Vertebrae / Q000737:chemistry / Q000000981:diagnostic imaging; D008875:Middle Aged; D016017:Odds Ratio; D015675:Osteocalcin / Q000097:blood; D011446:Prospective Studies; D011859:Radiography; D012044:Regression Analysis; D012307:Risk Factors; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D015675:Osteocalcin; D003404:Creatinine