Citrus polyphenols for bone health: A systematic review of experimental and human studies

Citrus fruits are rich in flavanones hesperidin, naringenin, neohesperidin, and neoeriocitrin with emerging osteoprotective potential. This PRISMA-compliant systematic review integrated evidence from in vitro, in vivo, and human studies identified across PubMed, Scopus, and Google Scholar (2014–2025). Fifteen studies met eligibility (8 in vitro, 6 in vivo, 1 randomized human trial). Preclinical findings indicate enhanced osteoblastogenesis via ERK/Smad and Wnt/β-catenin signalling and suppression of osteoclastogenesis through RANKL–NF-κB/NFATc1, alongside reduced oxidative and inflammatory stress. Animal models demonstrated improved trabecular microarchitecture and accelerated fracture healing. In the only human trial found, hesperidin plus calcium improved calcium retention by ∼5.5% versus calcium alone. Overall citrus flavanones seem to exhibit convergent anabolic and anti-resorptive effects; however, long-duration, well-powered clinical trials with standardized formulations are required to establish efficacy for osteoporosis prevention.