| dc.description.abstract | Introduction and Aim
Bone mineral density (BMD) is one of the strongest predictors of future fracture risk. As the population ages, understanding the effects of commonly prescribed medications on BMD is increasingly important. This study aimed to describe the relationship between commonly prescribed cardiovascular and other medication classes and BMD. Secondary hyperparathyroidism (SHPT) frequently results from vitamin D deficiency (<30 nmol/l), a common issue among older adults, particularly in northern latitudes like Ireland. A further aim was to evaluate the prevalence and predictors of SHPT and its relationship with BMD and bone turnover markers (BTMs).
Methodology
Data were analyzed from the Trinity-Ulster-Department of Agriculture (TUDA) study of Irish adults aged 60 and over. Participants on bisphosphonates, denosumab, or other osteoporosis therapies were excluded from the medication and BMD analysis. BMD was measured at the femoral neck, total hip, and lumbar spine using densitometry. Univariate and multivariate analyses were used to examine associations between medications and BMD, adjusting for age, sex, body mass index (BMI), physical frailty, vitamin D, parathyroid hormone (PTH), estimated glomerular filtration rate (eGFR), lifestyle factors, comorbidities, and other medications.
Multivariate logistic regression was used to identify predictors of SHPT. A subset analysis assessed the relationship between SHPT and BMD and BTMs: bone-specific alkaline phosphatase (BAP) and tartrate-resistant acid phosphatase 5b (TRAP5b). Participants with eGFR <30 ml/min or calcium >=2.5 mmol/l were excluded.
Results
In the medication and BMD analysis (n=2,218; mean age 69.3 years; 58.3 percent female), multivariate analysis showed that statin use was associated with higher BMD at the femoral neck (p=0.045) and total hip (p=0.013), but not the spine. Thiazide diuretics were associated with higher BMD at all sites (p<0.001), while loop diuretics were associated with lower BMD at the total hip (p=0.036), but not at the femoral neck or spine. Beta-blocker use was associated with higher BMD at the femoral neck (p=0.017) and lumbar spine (p=0.015). Angiotensin receptor blockers (ARBs) were associated with higher BMD at all sites: femoral neck (p=0.014), total hip (p=0.004), and lumbar spine (p<0.001). NSAID use was associated with higher spine BMD (p=0.009), but not with BMD at other sites. No significant associations were found between BMD and ACE inhibitors, dihydropyridine calcium channel blockers (DCCBs), SSRIs, TCAs, or PPIs.
In the SHPT analysis (n=4,139; mean age 73.6 +/- 7.9 years; 65.1 percent female), 19.4 percent were vitamin D deficient. Among participants not using calcium supplements, predictors of SHPT included vitamin D deficiency (p<0.001), eGFR 30-44 ml/min (p<0.001), loop diuretic use (p<0.001), BMI (p=0.001), eGFR 45-59 ml/min (p<0.001), and 25(OH)D levels of 30-49 nmol/l (p=0.002). In those taking calcium supplements, similar predictors were observed, with PPI use (p=0.018) also associated with SHPT, while 25(OH)D 30-49 nmol/l was not.
SHPT was associated with higher BTMs (BAP p=0.013, TRAP5b p=0.013) and lower BMD at the femoral neck (p=0.033) and total hip (p=0.017), but not at the spine.
Conclusion
Statins, thiazide diuretics, ARBs, NSAIDs, and beta-blockers were associated with higher BMD, while loop diuretics were associated with lower BMD at the hip. While the positive effect of thiazides is well established, the associations with other drugs such as ARBs are less well described. Despite the large and well-characterized cohort, the cross-sectional design limits causal inference, and longitudinal studies and randomized controlled trials are needed to guide clinical decision-making. Although BMD is central to fracture risk, other pathways such as fall risk and bone quality may also be influenced by these medications and require further investigation.
Approximately one in six older Irish adults had SHPT in this cohort, which was associated with lower hip BMD and elevated BTMs. Vitamin D deficiency and 25(OH)D levels between 30 and 49 nmol/l were significant predictors. These findings underscore the importance of maintaining adequate vitamin D status in older adults. The association of loop diuretics and PPIs with SHPT suggests that these drugs should be prescribed with caution in this population. | en |
