Strontium Ranelate

This narrative review explores the therapeutic potential of repurposing medications originally developed or approved for osteoporosis to treat non-osteoporotic conditions. Given their pharmacologic profiles and safety data, these agents offer promising therapeutic alternatives in both rare and common diseases with unmet clinical needs.

Evidence from preclinical models, observational data, and randomised trials supports the repositioning of several osteoporosis drugs. Cyclic etidronate has shown efficacy in halting arterial calcification progression in pseudoxanthoma elasticum. Pamidronate has demonstrated symptom improvement in adult chronic nonbacterial osteitis. Neridronate is approved only in Italy for complex regional pain syndrome type I. Denosumab has shown therapeutic effects in Langerhans cell histiocytosis and has structural benefits in erosive hand osteoarthritis and rheumatoid arthritis. Parathyroid hormone analogues (rhPTH [1-84] and teriparatide) improve calcium-phosphate homeostasis in chronic and genetic hypoparathyroidism. Calcilytics, though originally discontinued for osteoporosis, show emerging promise in autosomal dominant hypoparathyroidism. In contrast, zoledronic acid has not demonstrated consistent clinical benefit in knee osteoarthritis. Strontium ranelate, despite showing structure-modifying effects in osteoarthritis, is no longer marketed due to safety concerns. Alendronate and denosumab in fibrous dysplasia yielded mixed results, with concerns about rebound effects after denosumab withdrawal.

Repurposing osteoporosis medications represents a cost-effective, timely strategy to expand treatment options across diverse clinical indications. While promising outcomes have been demonstrated-particularly in rare diseases-rigorous, indication-specific clinical trials are essential to confirm efficacy, safety, and long-term outcomes. The accumulated pharmacologic and clinical experience with these agents offers a strong foundation for their continued exploration beyond osteoporosis.

Osteoporotic bone presents a compromised regenerative niche, with reduced osteoblast function and an imbalance between bone formation and resorption, limiting the success of conventional defect filling strategies. Injectable biomaterials that conform to irregular defects and provide localized osteogenic cues are particularly relevant. Here, we developed injectable sodium alginate hydrogels (HPs) incorporating 45S5 bioactive glass (HB) or the same glass functionalized with two osteoporosis-relevant osteotropic drugs deliberately selected for distinct mechanisms of action: raloxifene hydrochloride (HBRx; selective estrogen receptor modulation) and strontium ranelate (HBSr; dual action on bone remodeling). Within the scope of this work, we established material feasibility and comparative in vitro performance through quantitative assessment of microstructure and surface behavior, together with cytocompatibility and osteogenic readouts. Glass incorporation remodeled the scaffold microstructure, increasing mean pore size from 54.0 ± 17.9 µm (HP) to 139.9 ± 51.5 µm (HB), while drug functionalization produced intermediate pores (84.8 ± 26.3 µm for HBRx; 85.5 ± 37.4 µm for HBSr). The increased inorganic contribution in the composites was reflected by higher residual mass at 800 °C (from 33.5% in HP to 45.0%–48.3% in glass-containing groups) and by shifts in wettability, with all formulations remaining hydrophilic ( θ < 90°) but differing between functionalizations (44.2 ± 9.1° for HBRx vs 62.4 ± 11.8° for HBSr). All HPs were cytocompatible (day 7 relative viability ⩾70%) and supported osteogenic readouts (protein production, alkaline phosphatase activity, calcium deposition, and mineralized nodules), with HBSr showing the most favorable overall cellular response among the composites. Collectively, these findings indicate that osteoporosis-relevant drug-functionalized 45S5 within injectable alginate HPs provides a quantitative route to tune microstructure and interfacial behavior while preserving cytocompatibility and osteogenic potential. Future work will prioritize in vivo validation in osteoporotic models to assess bone repair efficacy and determine whether localized delivery mitigates drug-specific drawbacks associated with systemic therapies.