Phytochemicals produced from plants have emerged as potential therapeutic candidates for regulating skeletal metabolism. This review presents a dualistic character of phytochemicals used in skeletal health, which can be a friend (beneficial) or a foe (harmful) of the bone mass. Anti-resorptive and osteoanabolic effects of bone-supportive phytochemicals (flavonoids, carotenoids, polyphenols, terpenoids, alkaloids, and polysaccharides) occur via multiple pathways, including the wingless-related integration site/ beta-catenin pathway, bone morphogenetic protein/SMAD (Sma and Mad related) protein pathway, and inhibition of receptor activator of nuclear factor kappa B ligand-mediated osteoclastogenesis, and regulation of oxidative stress and inflammation. The therapeutic efficacy of phytochemicals is supported by available preclinical and clinical data, specifically in postmenopausal osteoporosis. On the other hand, there are some phytochemicals that cause alteration in bone cell activity, which may block the availability of mineral and some may also result in decreased bone mass with long-term overconsumption. Nevertheless, to translate positive and negative outcomes into clinical practice is not yet an easy task because of poor standardization of botanical extracts, active compounds content variability, lack of bioavailability and pharmacokinetic information, and long-term safety assessment. In addition, the majority of clinical trials are based on surrogate endpoints, including bone turnover markers instead of the fractured outcome, and animal models are not always predictive of human reactions. Further characterization of phytochemicals into actual therapeutic and non-therapeutic nutrients will require standardization of phytochemicals, while studying their pharmacokinetic and toxicological profiles, after which doses can be optimized, on the basis of which structured trials with bone endpoints may help support the actual potential of the phytochemicals in bone health. This phytochemical dichotomy should be thoroughly understood in order to come up with safe and evidence-based, plant-based approaches to prevent osteoporosis and maintain bone health.
Mahadevia et al. (Thu,) studied this question.