Aims: This meta-analysis and systematic review aimed to comprehensively investigate the effects of vitamin K supplementation on bone mineral density (BMD) at various sites and bone metabolism in middle-aged and older adults.Methods: The databases of PubMed, Web of Science, and Cochrane Library were thoroughly searched from inception to July 2023.Results: The results revealed that vitamin K supplementation increased BMD at the lumbar spine (p = 0.035). Moreover, the pooled effects demonstrated a notable increase in carboxylated osteocalcin (cOC) (p = 0.004), a decrease in uncarboxylated osteocalcin (ucOC) (p < 0.001), and no significant effect on total osteocalcin (tOC) (p = 0.076). Accordingly, the ratio of cOC to ucOC (p = 0.002) significantly increased, while the ratio of ucOC to tOC decreased (p = 0.043). However, there was no significant effect of vitamin K supplementation on other bone metabolism markers, such as cross-linked telopeptide of type 1 collagen (NTx), bone alkaline phosphatase (BAP), and procollagen I N-terminal propeptide (PINP). Subgroup analysis revealed that vitamin K notably enhanced bone health in females by increasing lumbar spine BMD (p = 0.028) and decreasing ucOC (p < 0.001). Vitamin K, especially vitamin K2, exhibited effects on maintaining or increasing lumbar spine BMD, and influencing the balance of cOC and ucOC.Conclusion: This review suggests that the beneficial effects of vitamin K supplementation on bone health primarily involve enhancing the carboxylation of OC rather than altering the total amount of OC.Cite this article: Bone Joint Res 2024;13(12):750–763.

Supplemental n-3 polyunsaturated fatty acids (PUFA) on bone metabolism have yielded inconsistent results. This study aimed to examine the effects of n-3 PUFA supplementation on bone metabolism markers and bone mineral density through a meta-analysis of randomized controlled trials. A systematic literature search was conducted using the PubMed, Web of Science, and EBSCO databases, updated to 1 March 2023. The intervention effects were measured as standard mean differences (SMD) and mean differences (MD). Additionally, n-3 PUFA with the untreated control, placebo control, or lower-dose n-3 PUFA supplements were compared, respectively. Further, 19 randomized controlled trials (RCTs) (22 comparisons, n = 2546) showed that n-3 PUFA supplementation significantly increased blood n-3 PUFA (SMD: 2.612; 95% CI: 1.649 to 3.575). However, no significant effects were found on BMD, CTx-1, NTx-1, BAP, serum calcium, 25(OH)D, PTH, CRP, and IL-6. Subgroup analyses showed significant increases in femoral neck BMD in females (0.01, 95% CI: 0.01 to 0.02), people aged 6 months (−0.19, 95% CI: −0.37 to −0.01). The present study demonstrated that n-3 PUFA supplementation might not have a significant effect on bone mineral density or bone metabolism markers, but have some potential benefits for younger postmenopausal subjects in the short term. Therefore, additional high-quality, long-term randomized controlled trials (RCTs) are warranted to fully elucidate the potential benefits of n-3 PUFA supplementation, as well as the combined supplementation of n-3 PUFA, on bone health.