A Thiazide a Day to Keep Fractures Away?

By Martina M. McGrath, MD
March 7, 2017

Observational data have indicated a reduction in fracture risk in patients treated for hypertension with thiazide diuretics.1 Thiazides reduce urinary calcium losses (hence their use in patients with calcium-based renal calculi) and have been postulated to have a stimulatory effect on osteoblasts, leading to improvements in bone density. However, there have been no randomized trials to demonstrate benefit of one antihypertensive class over another in protection against fractures. Patients with hypertension are at increased risk of falls and fractures, making this an important consideration, particularly in the elderly.

A recent post-hoc analysis of ALLHAT examined the risk of hip and pelvic fractures during the trial and follow-up period, according to treatment group.2 As a reminder, ALLHAT was a landmark blood pressure trial, examining the effect of chlorthalidone versus amlodipine, lisinopril, and doxazosin in preventing fatal coronary heart disease, nonfatal MI, and other cardiovascular (CV) events.3 The original trial showed that treatment with chlorthalidone was associated with lower rates of CV events compared with the other treatments. The doxazosin arm was stopped early due to a higher rate of heart failure and CV disease than the other arms.

This current analysis examined the incidence of hip and pelvic fractures in patients treated with chlorthalidone, lisinopril, or amlodipine during the five years of the study and through an additional five-year follow up period. The authors sought to see if thiazide use was associated with decreased risk of fractures and if so, was there was a persistent benefit observed during the follow-up period. Data regarding fractures was acquired through CMS Medicare billing data, and 22,180 patients were included in the analysis. Thirty-four patients had pelvic fractures and 307 patients had hip fractures during the trial period while 70 pelvic and 576 hip fracture occurred during follow-up. Participants treated with chlorthalidone had a 21% lower risk of hip or pelvic fracture during the trial, compared with those treated with either lisinopril or amlodipine.2 During the follow-up period, there continued to be a nonsignificant reduction in rates of fractures in patients enrolled in the thiazide arm compared with the other treatment arms.

How might this data influence prescribing practice? Thiazides are already recommended as first line antihypertensives due to their efficacy in preventing cardiovascular events. This paper describes an additional advantage to thiazides over other antihypertensives and suggests a benefit in switching to these agents in patients with decreased bone mineral density and elevated fracture risk.

References:

  1. Aung K, Htay T. Thiazide diuretics and the risk of hip fracture. The Cochrane database of systematic reviews 2011:CD005185.
  2. Puttnam R, Davis BR, Pressel SL, et al. Association of 3 Different Antihypertensive Medications With Hip and Pelvic Fracture Risk in Older Adults: Secondary Analysis of a Randomized Clinical Trial. JAMA internal medicine 2017;177:67-76.
  3. Officers A, Coordinators for the ACRGTA, Lipid-Lowering Treatment to Prevent Heart Attack T. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Jama 2002;288:2981-97.

Headshot of Dr. McGrathDr. Martina McGrath is an Instructor in Medicine at Harvard Medical School, and a member of the Renal Division, Department of Medicine, at Brigham and Women’s Hospital, both in Boston. Dr. McGrath is the Medical Editor for the Trends in Medicine blog.

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