Future directions of osteoanabolic therapies in osteoporosis: Integrating current anabolic agents and emerging senescence-targeted strategies.

Abstract

Osteoporosis therapeutics have advanced from antiresorptive drugs that slow bone loss to osteoanabolic and dual-action agents that can rapidly rebuild skeletal integrity and reduce fracture risk. Yet the current anabolic era leaves important clinical questions unresolved: why responses vary among older adults, why gains are transient, how best to sequence therapy, and how to sustain skeletal resilience in the biologically aged bone microenvironment. Cellular senescence has emerged as a plausible mechanistic bridge linking skeletal aging, chronic inflammation, impaired osteoblastogenesis, increased osteoclastogenesis, marrow adiposity, diabetes-associated fragility, and delayed repair. Preclinical studies show that senescent-cell clearance can prevent or partially reverse age-related bone loss, while early human senolytic data suggest that skeletal response may depend on baseline senescent-cell burden. This review discusses current anabolic therapies, the rationale for senescence-targeted approaches, and future biomarker-informed strategies to integrate anabolic induction, antiresorptive consolidation, and experimental modulation of skeletal aging biology.