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This systematic review evaluates how calcium channel blockers influence bone metabolism and fracture risk in older adults, suggesting implications for treatment.
Background Calcium channel blockers (CCBs) are widely prescribed for older adults at risk of osteoporotic fractures. Despite preclinical data suggesting CCB-mediated effects on bone remodelling, clinical findings on bone mineral density (BMD) & fractures are inconsistent. We systematically evaluated the relationship between CCB use, bone metabolism, & fracture outcomes. Methods PubMed, MEDLINE, & Embase were searched from inception to July 2025 for preclinical & clinical studies reporting fracture risk &/or parameters of bone metabolism. The primary outcome was fracture risk, with secondary outcomes including BMD, bone weight, biochemical markers of bone turnover (calcium, PTH, ALP, CTX, BMP-2, PINP), & biomechanical properties. Screening & data extraction followed PRISMA principles; risk of bias was assessed with appropriate tools (SYRCLE, RoB 2, ROBINS-I). A narrative synthesis was performed. Results 34 studies were included (17 preclinical; 17 clinical). Among clinical studies, 4/17 reported reduced BMD with CCBs; fracture risk increased in 4, decreased in 4, & was unchanged in 4; 1 study additionally reported a protective association with osteoporosis. Preclinical findings across 655 animals were mixed for BMD, calcium, PTH, ALP, & BMP-2. Notably, 5 studies reported lower CTX, 2 reported lower PINP, & 4 reported increased or unchanged bone strength with CCB exposure. Conclusions Evidence indicates CCBs may modulate bone physiology, yet clinical associations with BMD & fractures are heterogeneous. Discrepancies may reflect confounding factors like comorbidities & non-skeletal pathways affecting falls risk (for example CCB-induced orthostatic hypotension or sarcopenia); these mechanisms remain hypothesis-generating. Standardised preclinical endpoints & large, well-adjusted prospective cohorts stratified by dihydropyridine versus non-dihydropyridine agents, dose, & duration are needed to clarify skeletal effects.
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Kumar et al. (2026) studied this question.
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