Hormonal remodeling and molecular mechanisms in postmenopausal osteoporosis: Pathogenesis and therapeutic implications (Review)

Postmenopausal osteoporosis (PMO) is a prevalent metabolic bone disorder characterized by accelerated bone loss, reduced bone mineral density, and increased fragility fracture risk.Although estrogen deficiency is considered a central driver of PMO, increasing evidence indicates that bone loss after menopause results from broader endocrine remodeling involving multiple hormones.Estrogen decline and the accompanying rise in follicle-stimulating hormone (FSH) are characteristic of the menopausal transition.Alterations in the parathyroid hormone (PTH)-vitamin d axis, oxytocin (OT) and calcitonin (CT) may also influence skeletal homeostasis, although their patterns and causal contributions are less consistently established in postmenopausal women.These pathways are discussed as interacting components of an endocrine framework with differing levels of supporting evidence.These coordinated hormonal alterations disrupt bone remodeling through several mechanisms, including impaired bone mechanical homeostasis, dysregulated osteoimmune interactions, altered calcium metabolism, and gut microbiota-bone axis imbalance.collectively, these changes promote osteoclast activation, suppress osteoblast function, and accelerate skeletal deterioration.current therapeutic approaches, such as hormone replacement therapy, bisphosphonates, selective estrogen receptor modulators, and PTH analogs, have improved the management of PMO but remain limited by safety concerns or restricted long-term efficacy.Emerging approaches, including FSH blockade, selected phytoestrogen-related interventions, modified CT delivery, and OT-related pathways have different levels of supporting evidence; most specific experimental strategies require human efficacy and safety validation before clinical application.An improved understanding of hormonal interactions and endocrine network remodeling may facilitate the development of more precise and individualized strategies for the prevention and treatment of PMO.