Anabolic first? The changing paradigm in osteoporosis

Abstract

Osteoporosis is a chronic skeletal disorder characterized by reduced bone mass and deterioration of bone microarchitecture, resulting in increased fragility fracture risk. Conventional antiresorptive therapies reduce bone resorption but have limited ability to restore lost bone. Thus, anabolic therapies have emerged as an important treatment option, particularly for patients at very high fracture risk. An anabolic-first followed by antiresorptive, sequential strategy offers an effective approach for patients at very high fracture risk, providing rapid and sustained improvement in bone strength and fracture prevention. Bone-forming/osteoanabolic agents, like Teriparatide, Abaloparatide, and Romosozumab, stimulate bone formation and produce rapid increases in bone mineral density (BMD) and reductions in vertebral and nonvertebral fracture risk. Romosozumab has demonstrated particularly substantial BMD gains and, when followed by antiresorptive therapy, significant reductions in vertebral, nonvertebral, and hip fractures. Evidence from comparative trials suggests that anabolic therapy can be superior to antiresorptive treatment in selected patients at very high fracture risk. Anabolic agents are therefore increasingly recommended as first-line treatment for patients with severe osteoporosis, multiple vertebral fractures, very low BMD, or fractures despite antiresorptive therapy. As the benefits of anabolic treatment are reversible after discontinuation, treatment should generally be followed by a potent antiresorptive agent to maintain BMD gains and fracture protection. Careful patient selection and monitoring are required, particularly regarding hypercalcemia with Teriparatide/ Abaloparatide and cardiovascular risk with Romosozumab. So, in conclusion, treatment should be individualized according to fracture risk, patient characteristics, safety considerations, availability, and cost.

[J Assoc Clin Endocrinol Diabetol Bangladesh, 2026;5(Suppl 1): S26]