Beta-Blockers Alone or in Comb
By Yael Waknine
Medscape Medical News
Sept. 14, 2004 — Beta-blocker therapy is associated with a significantly reduced risk of fractures when prescribed alone or in combination with thiazide diuretics, according to the results of a large, retrospective, population-based study published in the Sept. 15 issue of JAMA.
"Animal studies suggest that the β-blocker propanolol increases bone formation, but data on whether use of β-blockers (with or without concomitant use of thiazide diuretics) is associated with reduced fracture risk in humans are limited," writes Raymond G. Schlienger, PhD, MPH, from the University Hospital Basel in Switzerland, and colleagues, noting that thiazide diuretics are thought to protect against bone loss by reducing urinary calcium excretion.
Using the U.K. General Practice Research Database (GPRD), investigators identified the records of 30,601 patients aged 30 to 79 years with an incident fracture diagnosis between 1993 and 1999. Control subjects (n = 120,819) had not sustained a fracture and matched the case patients with respect to age, sex, calendar time, and general practice attended.
Current users of beta-blockers, thiazides, or thiazide-like diuretics were defined as those having received a prescription within 60 days prior to the date of fracture. Long-term users were defined as those having received at least 20 prescriptions, each representing one to three months of therapy.
Fractures of the hand/lower arm (42.0%) and foot (15.1%) were most common. Data analysis correlating fracture incidence with drug therapy included adjustments 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.
Results showed that current beta-blocker users had a significantly reduced risk of fracture (odds ratio [OR], 0.77; 95% confidence interval [CI], 0.72 - 0.83), as did current users of thiazides (OR, 0.80; 95% CI, 0.74 - 0.86) compared with nonusers of beta-blockers or thiazides. Current users of both beta-blockers and thiazides had the lowest relative risk of fracture (OR, 0.71; 95% CI, 0.64 - 0.79) compared with nonusers.
Long-term use of beta-blockers had a stronger protective effect against fractures in men (OR, 0.69) than in women (OR, 0.92) after adjustments for number of practice visits (indicative of health status), medical attention, and number of drugs used. "[T]he differences in drug use between men and women may not explain the differences in effect size with longer-term β-blocker use," the authors comment. "This difference should be explored in future studies.
"[T]he present large case-control analysis provides evidence that use of β-blockers — alone or in combination with thiazide diuretics — is associated with a significantly decreased fracture risk," the authors write, noting that additional observational studies and controlled trials are needed to confirm these findings.
"Many elderly patients with hypertension who are at risk of developing osteoporosis may potentially benefit from combined therapy with [relatively inexpensive] β-blockers and thiazides," the authors conclude.
One of the authors is the recipient of a grant from the Swiss National Science Foundation.
JAMA. 2004;292:1326-1332
Reviewed by Gary D. Vogin, MD
