Abstract
OBJECTIVE: Vascular calcification shares many features with skeletal mineralisation and shares an inverse relationship with osteoporosis (skeletal de-mineralisation). However, medications that reduce bone loss (anti-resorptives) have had inconsistent effects on extra-skeletal mineralisation (i.e. vascular and valvular calcification). As such, this paper aims to synthesise existing literature examining the effect of anti-resorptive treatments on extra-skeletal (vascular and valvular) calcification across populations. METHODS: Medline and Embase were searched (inception to October 2024) for studies that assessed the association between anti-resorptive medication use and vascular/valvular calcification. Pooled standardised mean differences (SMDs) with 95% confidence intervals (CI) were calculated for all outcomes, using random-effects model. Leave-one-out sensitivity analyses were performed for internal validity. RESULTS: Of 4071 articles screened, 33 were included in the review, and 15 (2344 participants) had data available for meta-analysis. Anti-resorptive use was associated with non-significant, small magnitude improvements in abdominal aortic calcification (decreased value), coronary artery calcification (decreased value) and ejection fraction (increased value) but significant small reduction in aortic valve area (representing less calcification on the valve) with standardised mean difference of - 0.45 (95% confidence interval (CI) - 0.99; 0.08, I(2) = 84%), - 1.19 (95% CI - 2.92; 0.55, I(2) = 91%), - 0.67 (95% CI - 1.72; 0.38, I(2) = 94%), 0.26 (95% CI - 0.14; 0.66, I(2) = 62%) and 0.56 (95% CI 0.07; 1.06, I(2) = 76%), respectively. CONCLUSION: The significance of small positive effect of anti-resorptives on aortic stenosis is clinically uncertain. Despite strong biological links between vascular calcification and skeletal mineralisation, anti-resorptives do not appear to have a strong favourable influence on extra-skeletal mineralisation. This suggests that mechanisms that link vascular calcification with osteoporosis may be acting in pathways not influenced by anti-resorptives. This systematic review and meta-analysis summarises the effect of anti-resorptives on vascular and valvular calcification. There is a small, positive effect of anti-resorptives on aortic stenosis, though this is of uncertain clinical importance.