Antihypertensive drugs demonstrate varying levels of hip fracture risk: A systematic review and meta-analysis

• Published in: Injury Vol. 53; no. 3; pp. 1098 - 1107
• Main Authors: Langerhuizen, David W.G., Verweij, Lukas P.E., van der Wouden, Johannes C., Kerkhoffs, Gino M.M.J., Janssen, Stein J.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.03.2022
• Subjects: Adolescent; Adult; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Antihypertensive Agents - therapeutic use; Antihypertensives drugs; Calcium Channel Blockers - adverse effects; Hip fractures; Hip Fractures - drug therapy; Hip Fractures - epidemiology; Hip Fractures - prevention & control; Humans; Hypertension - drug therapy; Systematic review; Antihypertensives drugs; Systematic review; Hip fractures
• ISSN: 0020-1383; 1879-0267
• DOI: 10.1016/j.injury.2021.09.036

•Very low certainty of evidence was found that thiazides and beta-blockers were associated with a reduced hip fracture risk.•One study, reporting on angiotensin receptor blockers, suggested a protective effect for hip fractures. Conflicting findings were found in four studies for calcium-channel blockers and in two studies for ACE inhibitors. By aggregating the literature, we evaluated the association between use of specific antihypertensive drugs and the risk of hip fractures compared with nonuse. We systematically searched the Pubmed, Embase, and Cochrane databases from inception of each database until July 30, 2020 to identify articles including patients 18 years of age or older reporting on the association between antihypertensive drugs and the risk of hip fracture. Antihypertensive drugs were restricted to thiazides; beta-blockers; calcium-channel blockers; angiotensin-converting enzyme (ACE) inhibitors; and angiotensin receptor blockers. Nonusers encompass all patients that are not using the specific antihypertensive drug that has been reported. Unadjusted odds ratios with 95% confidence intervals (CIs) of the association between antihypertensive drug use and hip fractures were reported. Meta-analysis was performed when a minimum of five studies were identified for each antihypertensive drug class. Quality assessment was done using ROBINS-I tool. The GRADE approach was used to evaluate the certainty of the evidence. Of 962 citations, 22 observational studies were included; 9 studies had a cohort design and 13 studies were case-control studies. No randomized controlled trials were identified. We found very low certainty of evidence that both thiazides (pooled odds ratio: 0.85, 95% CI 0.73 to 0.99, p = 0.04) as well as beta-blockers (pooled odds ratio: 0.88, 95% CI 0.79 to 0.98, p = 0.02) were associated with a reduced hip fracture risk as compared to specific nonuse. One study, reporting on angiotensin receptor blockers, also suggested a protective effect for hip fractures, whereas we found conflicting findings in four studies for calcium-channel blockers and in two studies for ACE inhibitors. Among 22 observational studies, we found very low certainty of evidence that, compared to specific nonuse of antihypertensive drugs, use of thiazides, beta-blockers, and angiotensin receptor blockers were associated with a reduced protective hip fracture risk, while conflicting findings for calcium-channel blockers and ACE inhibitors were found. Given the low quality of included studies, further research –randomized controlled trials– are needed to definitively assess the causal relationship between specific antihypertensive drug classes and (relatively infrequent) hip fractures.