Bone-sparing effects of Pueraria mirifica extract on bone loss in androgen-deficient cynomolgus macaques (Macaca fascicularis)

Background: Synthetic estrogens provide remarkable benefits for bone health in men; however, they also present several drawbacks after long-term use. Pueraria mirifica, a phytoestrogen-rich herb, has garnered attention due to its positive effects and minimal adverse side effects on bone in females. Most research on bone health has been conducted on rodents; however, bone architecture and remodeling in rodents differ from those in humans, making it challenging to apply the results to clinical trials. Objectives: Thus, this study assessed the bonesparing effects of P. mirifica extract (PME) in androgen-deficient male cynomolgus macaques. Materials and Methods: Adult male macaques were divided into three groups: Sham-operated, orchidectomized, and orchidectomized treated with PME, consisting of 5, 5, and 4 animals per group, respectively. After surgery, animals were kept for 2 months to induce bone loss and were fed either a standard diet or a diet mixed with PME for 10 months. Bone mineral content (BMC) and geometry (bone area, cortical thickness, periosteal, and endosteal circumferences) of the radius and tibia at both metaphysis and diaphysis, as well as serum alkaline phosphatase (ALP) levels, were measured every 2 months. Results: Androgen deficiency induced bone loss in BMC and bone geometry, particularly in the cortical compartment of both radius and tibia at metaphysis, through the enlargement of the endosteal circumference, which aligned with increased serum ALP. PME mitigated bone loss, particularly in the cortical compartment of the radius and tibia at diaphysis, and marginally reduced serum ALP levels. Conclusion: Our study demonstrated that the effects of androgen deficiency and phytoestrogen supplementation on bone differ depending on the bone compartment, site, and type, indicating that osteoporotic treatment in humans should consider each bone compartment, site, and type rather than treating the body as a whole. In addition, PME may provide an alternative approach to maintaining bone health in men.