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.

Treatment with beta-blockers, ACE inhibitors, and calcium-channel blockers is associated with a reduced fracture risk: a nationwide case–control study

“…In addition, by combining data from several national registers we were able to control for both health-related and socio-economic confounders. Our extensive confounder control may be the reason that our risk estimates of a 9% reduced risk of any fracture and hip fracture were smaller than the risk estimates observed in the British and Australian studies [6,8]. However, our findings of a reduced fracture risk are in contrast to previous studies from our group showing an increased fracture risk with no effect on bone mineral content (BMC) or BMD [7,28].…”

“…However, our findings of a reduced fracture risk are in contrast to previous studies from our group showing an increased fracture risk with no effect on bone mineral content (BMC) or BMD [7,28]. Importantly, whereas the two previous studies from our group were clinical studies, the present study, as well as the British [6] and Australian [8] studies, has used either registers [6] or questionnaires [8] to assess use of drugs and occurrence of fractures. Thus, different results have been obtained using different study designs.…”

“…To the best of our knowledge, our study is one of the first investigations on associations between use of ACE inhibitors and risk of fracture. In the British study on associations between use of beta-blockers and fracture risk, a sub-analysis showed results similar to ours, namely a reduced fracture risk (adjusted OR, 0.81; 95% CI, 0.73-0.89; P < 0.001) in longer-term users (> 20 prescriptions) of ACE inhibitors [6]. Findings from experimental studies support the notion of a possible effect of ACE inhibitors on bone.…”

Neuronal Regulation of Bone Remodeling

“…What has been established is that leptin is a negative independent predictor of bone mineral density (BMD) in adults [21] . Likewise, the majority of the available retrospective studies suggests a protective effect of beta-blockers on fracture risk, in agreement with the mouse and rat data [22][23][24][25][26] . Some reports, however, did not fi nd any signifi cant relationship between beta-blocker users and fracture risk [27,28] .…”

Pharmacoepidemiology – Assessing the Risks and Benefits of Drugs in the Postmarketing Phase

“…This we found indeed [10]. We also found significantly fewer fractures in patients taking beta-blockers in a large observation study which we conducted based on animal data and previous small observational studies in humans [11].…”