Advances In Pharmacological and Alternative Therapies for Enhancing Fracture Repair in Postmenopausal Osteoporosis: a Narrative Review

Summary

This review summarizes therapeutic strategies for postmenopausal osteoporotic fracture healing, covering pathophysiology involving estrogen deficiency, oxidative stress, and ferroptosis. It evaluates conventional pharmacological agents and advocates for multi-target alternative therapies, including natural bioactive compounds and traditional medicines, to optimize bone regeneration through integrative sequential management.

Abstract

Postmenopausal osteoporosis (PMO) significantly increases the risk of fragility fractures. The profound estrogen deficiency, compounded by severe oxidative stress, ferroptosis, and an impaired osteoimmune microenvironment, disrupts the vital coupling of angiogenesis and osteogenesis. This disruption frequently leads to delayed fracture union and implant failure. This narrative review aims to consolidate the current literature regarding both conventional pharmacological interventions and specific alternative therapeutic strategies, providing a comprehensive conceptual framework for optimizing bone healing in PMO fractures. An extensive literature search of databases including the systematic-review and evidence-synthesis database, biomedical and pharmacological bibliographic database, multidisciplinary citation-indexing database, and public biomedical literature database was conducted for relevant studies published up to March 2026. While conventional antiresorptive and anabolic agents remain the gold standard for long-term secondary fracture prevention, their inherent limitations and "double-edged sword" effects during the acute fracture healing phase pose significant clinical challenges. Emerging evidence suggests that multi-target alternative therapies, particularly natural bioactive compounds and traditional Chinese medicine (TCM) formulas, offer a synergistic approach. By ameliorating systemic metabolic dysregulation and inhibiting lipid peroxidation-induced ferroptosis, these alternative therapies reshape localized immune-bone homeostasis. Addressing the delayed healing of postmenopausal fractures requires an evolution toward an integrative sequential management model. Although current supporting data predominantly derive from robust preclinical models, combining these alternative therapeutic strategies with conventional agents—and potentially utilizing advanced targeted biomaterial delivery systems—represents a highly promising frontier to optimize perioperative fracture management and enhance long-term skeletal integrity.

Introduction

PMO is characterized by low bone mass and microarchitectural deterioration, significantly increasing the risk of fragility fractures¹. The epidemiological and economic burdens are substantial; for instance, the extrapolated prevalence of clinically diagnosed vertebral fractures among U.S. postmenopausal women is approximately 9.3%². Furthermore, the accumulation of fragility fractures exponentially amplifies clinical and societal costs. Postmenopausal women sustaining three or more fractures experience a 2.2-fold higher mortality rate and incur 1.4 times higher annual healthcare costs compared to those without fractures<....