Use of β-Blockers and Risk of Fractures

Abstract

Context Animal studies suggest that the ␤-blocker propranolol increases bone formation, but data on whether use of ␤-blockers (with or without concomitant use of thiazide diuretics) is associated with reduced fracture risk in humans are limited. Objective To determine whether use of ␤-blockers alone or in combination with thiazides is associated with a decreased risk of fracture in adults. Design, Setting, and Participants Case-control analysis using the UK General Practice Research Database (GPRD). The study included 30601 case patients aged 30 to 79 years with an incident fracture diagnosis between 1993 and 1999 and 120819 controls, matched to cases on age, sex, calendar time, and general practice attended. Main Outcome Measures Odds ratios (ORs) of having a fracture in association with use of ␤-blockers or a combination of ␤-blockers with thiazides. Results The most frequent fractures were of the hand/lower arm (n=12837 [42.0%]) and of the foot (n=4627 [15.1%]). Compared with patients who did not use either ␤-blockers or thiazide diuretics, the OR for current use of ␤-blockers only (Ն3 prescriptions) was 0.77 (95% confidence interval [CI], 0.72-0.83); for current use of thiazides only (Ն3 prescriptions), 0.80 (95% CI, 0.74-0.86); and for combined current use of ␤-blockers and thiazides, 0.71 (95% CI, 0.64-0.79). Data were adjusted for smoking; body mass index; number of practice visits; and use of calcium channel blockers, angiotensin-converting enzyme inhibitors, antipsychotics, antidepressants, statins, antiepileptics, benzodiazepines, corticosteroids, and estrogens. Conclusions Our data suggest that current use of ␤-blockers is associated with a reduced risk of fractures, taken alone as well as in combination with thiazide diuretics. Many elderly patients with hypertension who are at risk of developing osteoporosis may potentially benefit from combined therapy with ␤-blockers and thiazides.

Effects of propranolol on the development of glucocorticoid-induced osteoporosis in male rats

“…Although favorable associations between b-blocker use and bone mineral density or fracture risk were reported in the majority of the human studies [5,27,30,32], some studies found no effect or unfavorable associations [28,29]. It is possible that badrenergic receptor antagonists exert biphasic effects, favorable and deleterious, on the skeletal system not only in rats, but also in humans, depending on the dose or individual susceptibility.…”

Double disruption of α2A- and α2C -adrenoceptors results in sympathetic hyperactivity and high-bone-mass phenotype

“…On the other hand, the positive effects of beta blockers are not always detectable. In humans, a series of studies showed that beta blockers promote positive, (17)(18)(19)(20) negative, (21) or no effects (22)(23)(24) on bone mass.…”

Cilnidipine, but not amlodipine, ameliorates osteoporosis in ovariectomized hypertensive rats through inhibition of the N-type calcium channel

“…[1][2][3][4][5] Several antihypertensive drugs, including thiazides, b-blockers and angiotensin-converting enzyme inhibitors, decreased the risk of bone fractures and increased bone mineral density (BMD) clinically. [6][7][8][9][10] However, meta-analysis of observational studies on the effects of antihypertensive drugs on fracture outcomes demonstrated no significant association between fractures and calcium channel blockers (CCBs). [11][12][13] CCBs are divided into several subtypes, and non-dihydropyridinetype CCBs, but not dihydropyridine-type CCBs, are reported to reduce the risk of bone fractures through the inhibition of hyperparathyroidism-induced calcium uptake into osteoblasts and an elevation of intracellular calcium in osteoclasts.…”