Introduction: Due to the estrogenic potential of soy isoflavones, their efficacy in modulating bone density remains inconsistent across different age groups. This study aimed to synthesize the available high-level evidence to evaluate the effects of isoflavone phytoestrogens on bone health indicators—specifically bone mineral density (BMD) and bone turnover markers (BTMs)—across pediatric, adolescent, and adult populations.

Methods: In this systematic overview, PubMed, Scopus, Web of Science, and the Cochrane Library were searched through March 2026. Following PRISMA guidelines, we included meta-analyses and randomized clinical trials assessing skeletal responses to isoflavones. Methodological quality was independently evaluated using the Jadad scale for primary trials and the AMSTAR checklist for meta-analyses. Owing to substantial heterogeneity in interventions, doses, and populations across eight studies, findings were synthesized narratively.

Results: Among postmenopausal women, isoflavone supplementation—particularly interventions exceeding 6 months—yielded significant, site-specific increases in BMD at the lumbar spine, femoral neck, and total hip, with genistein demonstrating the most pronounced efficacy. These densitometric improvements correlated with a distinct down-regulation of biochemical bone resorption markers, specifically urinary pyridinoline and serum C-telopeptide, predominantly at moderate daily doses below 90 mg. Conversely, stratifying findings by age and sex revealed that dietary or supplemental isoflavone exposure in infants and adolescent boys exerted no statistically significant impact on bone mineral content (BMC), bone area, or short-term anthropometric and skeletal growth indices.

Conclusion: Soy isoflavones effectively preserve bone mass in postmenopausal women, yet benefits remain unsupported in pediatric or male adolescent populations. This overview clarifies age-dependent skeletal responses and identifies critical research gaps regarding adolescent girls and premenopausal women, highlighting the need for targeted future clinical trials.