Thiazide use associated with lower bone turnover, higher bone mineral density and lower hip fracture risk in older Irish adults

Abstract Background Thiazide diuretics are associated with higher bone mineral density (BMD) and reduced risk of hip fracture. The mechanisms underlying this association remain incompletely understood but are thought to include reduced urinary calcium excretion and potential direct skeletal effects. We aimed to explore the association between thiazide use and bone turnover markers (BTM), BMD, and hip fracture in older Irish adults. Methods: Participants aged >60 years from the TUDA cohort of Irish adults. The relationship between thiazide use and hip fracture was examined using multinomial regression, adjusting for age, sex, BMI, vitamin D, PTH, timed up and go, diabetes, lifestyle factors, eGFR, and steroid use. In a subsample excluding individuals on osteoporosis medications, thiazide use and BTM as well as densitometrically measured BMD at the hip and lumbar spine were explored, adjusting for similar covariates. BTMsmeasured were serum TRAP5b (tartrate-resistant acid phosphatase 5b) and bone-specific alkaline phosphatase (BAP). Results In the overall sample (n=4451; mean age 73.4±8.1 years; 66.9% female), 23.5% were thiazide users and 234 participants reported a previous hip fracture. Thiazide use was associated with lower risk of hip fracture before and after multivariate adjustment (OR 0.62, 95% CI:0.41–0.95, p=0.0286). In a subsample (n=1839), thiazide users had significantly lower serum TRAP5b (2.64 vs 2.81 U/L, p<0.001), lower BAP (15.4 vs 17.3 μg/L, p<0.001), and higher BMD at both the hip (1.007 vs 0.994 g/cm2, p=0.04) and lumbar spine (1.222 vs 1.203 g/cm2, p=0.04). Conclusion: These findings support a beneficial effect of thiazides on BMD and hip fracture risk, potentially mediated through bone turnover suppression. Experimental data suggest thiazides may directly affect osteoclast function, although few studies have specifically examined effects on BTMs While thiazides may have protective skeletal effects, their potential to increase fall risk in older adults must be carefully considered in clinical practice.