Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

Do Thiazide Diuretics Protect Against Fracture Risk?

JAMA; 2017 Jan; Puttnam, Davis, et al

Compared with other hypertensive medications, the use of thiazide-type diuretic therapy was beneficial in reducing hip and pelvic fracture risk in older adults, a recent study found. This study examined hip and pelvic fracture hospitalizations in Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants randomized to first-step therapy with a thiazide-type diuretic (chlorthalidone), a calcium channel blocker (amlodipine besylate), or an angiotensin-converting enzyme inhibitor (lisinopril). Recruitment was from February 1994 to January 1998; in-trial follow-up ended in March 2002. The mean follow-up was 4.9 years. Researchers found:

  • The study included 22,180 participants, followed for up to 8 years during masked therapy.
  • Use of the thiazide-like diuretic chlorthalidone was associated with a 21% significantly lower risk of hip and pelvic fractures compared with either lisinopril or amlodipine, and a significantly lower risk compared with lisinopril alone during approximately 4.9 years of follow-up.
  • Fracture risk continued to be lower in users of chlorthalidone compared with lisinopril or amlodipine together or alone, during 5 additional years of follow-up.


Puttnam R, Davis BR, Pressel SL, for the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Collaborative Research Group. Association of 3 different antihypertensive medications with hip and pelvic fracture risk in older adults. Secondary analysis of a randomized clinical trial. JAMA Intern Med. 2017;177(1):67-76. doi:10.1001/jamainternmed.2016.6821.


The Eighth Joint National Committee (JNC 8) recommends initial treatment with an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, calcium channel blocker, or thiazide-type diuretic in the nonblack hypertensive population, and in the black hypertensive population a calcium channel blocker or thiazide-type diuretic.1 In the ALLHAT trial, the largest randomized trial on antihypertensive treatment ever conducted, chlorthalidone was superior to amlodipine and lisinopril in preventing heart failure, and to lisinopril (blacks only) in preventing stroke.2 Demonstrating a 21% decreased risk of hip and pelvic fractures, this current study is consistent with a previous meta-analysis of 21 case-control and cohort studies that showed a 24% decrease in risk of hip fracture compared with other antihypertensive agents.3 The consistency of these observational and randomized trial results (decreased incidence of osteoporotic fractures with thiazide-like diuretics and the demonstrated superiority of thiazides on cardiovascular endpoints) provides strong rationale to choose this inexpensive, effective class of mediations as our first-line antihypertensive agent of choice. —Neil Skolnik, MD

  1. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults. Report from the panel members appointed to the Eighth Joint National Committee (JNC 8).JAMA. 2014;311(5):507-520. doi:10.1001/jama.2013.284427.
  2. ALLHAT officers and coordinators for the ALLHAT Collaborative Research Group. 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(23):2981-2997.
  3. Aung K, Htay T. Thiazide diuretics and the risk of hip fracture. Cochrane Database Syst Rev. 2011;(10): CD005185. doi:10.1002/14651858.