Denosumab: The Optimal Choice for Bone Health and Osteoporosis Treatment

This study investigated the efficacy of various interventions for osteoporosis over different time periods. Bisphosphonates, including alendronate, clodronate, and zoledronate, initially demonstrated promising preventive effects. However, alendronate's efficacy decreased over time, possibly due to increased tolerance or a balance in bone remodeling. While bisphosphonates inhibit bone resorption, bone remodeling may eventually return to equilibrium, leading to diminished therapeutic effects.

Clodronate, with its higher absorption rate compared to alendronate sodium, showed potential for long-term treatment. Its efficacy at 12 months surpassed that at 6 months, suggesting sustained benefit. Zoledronate, a long-acting bisphosphonate, exhibited stable effects for extended periods. This may be attributed to its inhibition of farnesyl pyrophosphate synthase (FPPS), a key enzyme involved in bone resorption, providing continuous protection for bone tissue.

However, the study strongly recommends denosumab as a more favorable option. This monoclonal antibody targets receptor activator of nuclear factor-kB ligand (RANKL), a key regulator of bone resorption. Long-term denosumab use has demonstrated increased bone density for up to 10 years, with a low incidence of adverse events. Switching from long-term oral bisphosphonate therapy to denosumab has also been associated with greater gains in postmenopausal osteoporosis patients.

Teriparatide, which stimulates bone formation and inhibits bone loss by acting on the PTH receptor 1, may be superior to alendronate in improving lumbar bone mineral density (BMD) in postmenopausal osteoporosis patients. However, due to its higher cost, teriparatide is less recommended compared to denosumab. Raloxifene, a selective estrogen receptor modulator (SERM), can produce estrogen-like effects on bones, reducing absorption and increasing BMD in postmenopausal women. While raloxifene is commonly used, denosumab offers broader applicability and is superior in reducing the risk of death and ischemic stroke in women with osteoporosis.

Previous meta-analyses have shown that both denosumab and zoledronate significantly reduce periprosthetic BMD loss after total hip arthroplasty (THA), particularly in the proximal femur, and improve hip joint function. Another study ranked anti-osteoporotic drugs for total hip BMD in postmenopausal women as denosumab > zoledronate > teriparatide. Denosumab is considered the optimal choice for improving total hip BMD. The research conducted in this study fills the gap in data on denosumab at 6 months and confirms its superior efficacy, a key strength of the study.

In conclusion, the study revealed that different interventions for osteoporosis have varying efficacy over time. While bisphosphonates initially demonstrated promising preventive effects, their efficacy may decrease over time. Clodronate and zoledronate may be more effective for long-term treatment, but denosumab stands out as the most favorable option due to its long-term efficacy and low incidence of adverse events. Teriparatide and raloxifene have also shown interesting effects, but denosumab is considered superior. Previous studies have demonstrated the effectiveness of denosumab and zoledronate in reducing periprosthetic BMD loss after THA and improving hip joint function. Overall, denosumab is considered the optimal choice for improving total hip BMD.