Unlocking the mechanistic insights of clinically proven natural products against osteoporosis

Osteoporosis is marked by reduced bone mass and structural deterioration, increasing fracture risk, especially in older adults and postmenopausal women. Current osteoporosis treatments target bone remodeling, including bisphosphonates, SERMs, and monoclonal antibodies like denosumab. However, their shortcomings necessitate safer and more potent alternatives, such as natural compounds from plants and marine sources, due to their estrogenic, anti-inflammatory, and antioxidant properties. A thorough literature search was conducted using databases such as Web of Science, Scopus, and PubMed, employing various keywords including osteoporosis, natural products for osteoporosis, and clinically proven natural products for osteoporosis. After screening and filtering for relevance, 179 articles were selected for evaluation. Natural compounds like oligopin, olive extract, Cissus quadrangularis, green tea, omega-3 polyunsaturated fatty acids, garlic, curcumin, Asparagus racemosus (Shatavari), Acanthopanax senticosus, resveratrol, soy isoflavones, S-equol, a combination of rho iso-alpha acid, berberine, vitamin D3, and vitamin K1, red clover, a combination of Polygonum odoratum and Morus alba, Epimedium brevicornum Maxim, and Opuntia ficus-indica demonstrated efficacy in bone metabolism regulation. By altering critical pathways like RANK/RANKL/OPG, Wnt/β-catenin, and nuclear factor kappa-B (NF-κB), these substances promoted osteoblast differentiation and suppressed osteoclastogenesis. This study suggests that the mentioned natural products are effective in treating osteoporosis without causing notable adverse reactions.