Novel therapies in osteoporosis - Clinical update - 2025.

Rheumatological patients are at high risk of osteoporosis and fracture due to disease, treatments, comorbidity and physical and functional considerations. Treating osteoporosis optimally is paramount. Osteoporosis management is evolving rapidly beyond traditional therapies. This 2025 review examines available traditional therapies and novel pharmacological approaches developed. Key questions addressed include the mechanisms, efficacy, and safety of agents like the sclerostin inhibitor romosozumab, Parathyroid hormone targeted agents, cytokine inhibitors and the status of therapies targeting cathepsin K. We evaluate the growing importance of combined and sequential treatment strategies, particularly initiating potent anabolic or dual-action therapies followed by antiresorptives for high-risk patients. Furthermore, the review explores emerging therapeutic targets such as modulators of the Wnt pathway, inflammation, and bone cell metabolism, alongside advancements in drug delivery, gene therapy, and non-pharmacological interventions. Clinical implications for patient selection, monitoring, and navigating the expanding treatment landscape are discussed, highlighting future directions towards personalized osteoporosis care.