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The Impact of Antihypertensive Medications on Bone Mineral Density and Fracture Risk
Joshua I Barzilay1, Barry R Davis2, Sara L Pressel2
1Division of Endocrinology, Kaiser Permanente of Georgia, 3650 Steve Reynolds Blvd, Duluth, Atlanta, GA, 30096, USA. Joshua.barzilay@kp.org.
Insights
Thiazide diuretics significantly lower fracture risk in older adults with hypertension compared to other blood pressure medications. This bone-protective effect of thiazide diuretics appears to be long-lasting.
Area of Science:
- Gerontology
- Pharmacology
- Orthopedics
Background:
- Hypertension is a common condition in older adults, increasing their risk of fractures.
- Antihypertensive medications, including thiazide diuretics, calcium channel blockers (CCBs), and angiotensin-converting enzyme inhibitors (ACEi), are widely used.
- The impact of these medications on fracture risk requires further investigation.
Purpose of the Study:
- To evaluate the effect of thiazide diuretics on fracture risk in older hypertensive individuals.
- To compare the fracture risk associated with thiazide diuretics versus CCBs and ACEi.
Main Methods:
- Post hoc analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.
- Inclusion of 22,180 participants during the in-trial period (4.9-year follow-up) and 16,622 during the post-trial period (7.8-year total follow-up).
- Comparison of fracture risk (hip and pelvic) between participants randomized to thiazide diuretics, CCBs, and ACEi.
Main Results:
- During the trial, thiazide diuretics were associated with a lower risk of fracture compared to CCBs or ACEi (HR 0.79; p=0.04).
- Fracture risk was significantly lower with thiazide diuretics versus ACEi (HR 0.75; p=0.04) but not significantly different versus CCB (HR 0.87; p=0.17).
- Over the entire follow-up, fracture incidence was non-significantly lower with thiazide diuretics versus ACEi or CCB (HR 0.87; p=0.10).
Conclusions:
- Thiazide diuretic treatment demonstrates a benefit in preventing fractures compared to other antihypertensive medications.
- The bone-protective effects of thiazide diuretics are suggested to be long-lasting.
- These findings support the use of thiazide diuretics for fracture risk reduction in hypertensive older adults.
Purpose Of Review:
This review summarizes the impact of thiazide diuretics on fracture risk in older hypertensive individuals.
Recent Findings:
We performed a post hoc evaluation of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, a randomized, prospective, double blind hypertension study comparing a thiazide-like diuretic, a calcium channel blocker (CCB), and an angiotensin converting enzyme inhibitor (ACEi). We examined the risk of hip and pelvic fractures during the in-trial period (n = 22,180 participants; mean 4.9-year follow-up) and during the post-trial period using national data bases (n = 16,622 participants) (mean total follow-up 7.8 years). During the trial, participants randomized to the thiazide diuretic versus the CCB or the ACEi had a lower risk of fracture on adjusted analyses (HR 0.79 [95% CI, 0.63, 0.98], p = 0.04). Risk of fracture was significantly lower in participants randomized to the diuretic as compared to those randomized to the ACEi (HR 0.75 [95% CI, 0.58, 0.98]; p = 0.04), but not significantly different compared to the CCB (HR 0.87 [95% CI, 0.71, 1.09]; p = 0.17). Over the entire trial and post-trial period of follow-up, the cumulative incidence of fractures was non-significantly lower in participants assigned to the diuretic vs assignment to the ACEi or the CCB (HR 0.87 [0.74-1.03], p = 0.10) and versus each medication separately. These findings establish a benefit for thiazide diuretic treatment for the prevention of fractures versus other commonly used antihypertensive medications using prospective, randomized data. The effects of the thiazide diuretic on bone appear to be long lasting.
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