Denosumab vs. Other Interventions for Osteoporosis: A Comprehensive Comparison

In addition to denosumab, other interventions such as alendronate, zoledronate, clodronate, teriparatide, and raloxifene have also shown positive effects at various time points. Alendronate, clodronate, and zoledronate are bisphosphonates that reduce bone loss by inhibiting bone resorption49. However, it has been found that the effectiveness of alendronate decreases over time, possibly due to the gradual increase in tolerance or the balance of bone remodeling. On the other hand, clodronate is more effective at 12 months compared to 6 months, potentially because it has a higher rate of absorption50. Zoledronate, being a long-acting bisphosphonate, consistently exhibits stable effects for most of the time, which can be attributed to its unique mechanism of inhibiting bone resorption51. However, in our study, both denosumab and other RANKL receptor inhibitors, represented by it, have shown better effects, whether comparing individual drugs or classifying drugs based on mechanisms. Previous studies have shown that in postmenopausal osteoporosis patients who had been on long-term oral bisphosphonate therapy, switching to denosumab was associated with greater gains than zoledronate55, which supports our viewpoint. Additionally, teriparatide and raloxifene have shown interesting effects. Teriparatide acts on the PTH receptor 1, inducing a significant increase in bone formation markers while simultaneously inhibiting bone loss caused by sustained elevation of parathyroid hormone levels56. A meta-analysis57 has shown that teriparatide may be superior to alendronate in improving lumbar BMD in postmenopausal osteoporosis patients. However, due to its higher cost, teriparatide is less recommended compared to drugs such as denosumab58. Raloxifene, a second-generation selective estrogen receptor modulator (SERM), can bind to estrogen receptors and produce estrogen-like effects on the bones, reducing absorption and increasing BMD in postmenopausal women59. Raloxifene is commonly used in clinical practice for women, while denosumab exhibits broader applicability. Furthermore, denosumab is superior to raloxifene in reducing the risk of death and ischemic stroke in women with osteoporosis60.