# Postmenopausal Osteoporosis: From Molecular Pathways to Therapeutic Targets—A Mechanism-to-Practice Framework Integrating Pharmacotherapy, Fall Prevention, and Adherence into Patient-Centered Care

## TL;DR

This review proposes a unified care model for postmenopausal osteoporosis that integrates drug mechanisms, fall prevention, and adherence to improve fracture prevention.

## Contribution

A mechanism-to-practice framework that maps drugs to molecular pathways and integrates clinical priorities into patient-centered care.

## Key findings

- Antiresorptives are suitable for moderate-risk patients, while anabolic-first treatment is better for those at very high fracture risk.
- Fall prevention and medication adherence are critical for improving outcomes, as fewer than 20% of post-fracture patients receive therapy.
- Controversies include T-score vs. FRAX thresholds, limitations of trabecular bone score, and cost-effectiveness of anabolic-first strategies.

## Abstract

The next frontier in postmenopausal osteoporosis management lies not in novel pharmacological agents, but in the systematic integration of mechanism-guided drug selection, fall prevention, and long-term adherence strategies into a unified patient-centered care model. This review is intended for clinicians and clinical researchers involved in the diagnosis, treatment, and long-term management of postmenopausal osteoporosis. We provide a mechanism-to-practice framework that explicitly maps each therapeutic class to the specific molecular pathway it targets: bisphosphonates inhibit osteoclast function downstream of RANKL activation; denosumab blocks RANKL directly at the cytokine level; romosozumab inhibits sclerostin to restore Wnt-mediated bone formation. This mechanistic foundation supports a risk-stratified treatment paradigm in which antiresorptives address accelerated remodeling in moderate-risk patients, while patients at very high fracture risk—characterized by severe bone deficit or recent fragility fractures—benefit from an anabolic-first approach followed by consolidation. Beyond drug selection, we examine the persistent treatment gap in which fewer than 20% of post-fracture patients receive therapy, arguing that fall prevention—responsible for >90% of hip fractures—and medication adherence deserve equal priority in clinical practice. We further analyze key controversies, including T-score- versus FRAX-based intervention thresholds, limitations of the trabecular bone score, cost-effectiveness constraints on anabolic-first sequencing, and evidence gaps in post-denosumab transition strategies. By synthesizing mechanistic insights, guideline recommendations, and critical appraisal of current limitations, this review offers not only an overview of existing knowledge but a coherent decision-support model aimed at improving fracture prevention through comprehensive, individualized care.