Rapid Strengthening and Long-term Stabilization – New Strategy for Sequential Treatment of Severe Osteoporosis
Osteoanabolics have long been considered a treatment modality for osteoporosis that is only considered when antiresorptive medication lacks the desired efficacy. However, their role has been shifting in recent years based on new findings from clinical research, as evidenced by the conclusions of the expert working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis, and Musculoskeletal Diseases (ESCEO), whose brief summary we bring.
How High is the Fracture Risk?
The expert panel unequivocally supports the stratification of treatment according to the patient's risk group. Nevertheless, determining the risk of a major osteoporotic fracture in the next few years is currently burdened by inconsistent methodology. Various tools are used (FRAX, Q-Fracture, Garvan, Crystal Bone, FREM, etc.), and different threshold values are applied to define individual risk groups. From a clinical point of view, the most important is the fracture risk in the next 2 years.
Treatment Choice According to Risk
Regardless of the method used to determine the risk of a major osteoporotic fracture, ESCEO recommends that treatment be stratified into 3 groups:
- Low risk – Besides lifestyle adjustments, hormone replacement therapy or a selective estrogen receptor modulator (raloxifene) can be considered during menopause.
- High risk – Antiresorptive therapy (e.g., oral bisphosphonates).
- Very high risk – Sequential therapy with an osteoanabolic (teriparatide, abaloparatide, romosozumab) and an antiresorptive medication (oral bisphosphonates or denosumab) (see fig.).
For all patients, calcium and vitamin D intake should be optimized, appropriate physical activity should be included, and education on fall prevention should be provided.
Fig. Illustration of sequential treatment of osteoporosis in high-risk patients
Sequential Treatment for High-Risk Patients
There is now evidence that osteoanabolics are more effective and work faster than antiresorptive medications for patients at high risk of fractures. However, to maintain their effect – an increase in bone mineral density and fracture prevention – this therapy should be followed by consolidation with antiresorptive medications, i.e., bisphosphonates or denosumab.
The duration of osteoanabolic treatment is derived from changes in the effect of these drugs over time. The maximum effect is achieved in the first months of treatment, after which the effect gradually wanes. For teriparatide, treatment is recommended for a maximum of 2 years, for abaloparatide, it's 18 months, and treatment with romosozumab should not exceed 12 months.
The expected effect of subsequent consolidation therapy is then the stabilization of the condition or gradual slight improvement in density. During consolidation, it is necessary to regularly monitor adherence to treatment, manifestations of adverse effects, and treatment results.
The decision to discontinue antiresorptive treatment is often very complicated, especially because of the lack of data from clinical research. If the patient remains in the group with a high or very high risk of major osteoporotic fracture, it may be appropriate to continue with antiresorptive treatment. If the patient moves to the low-risk group after treatment, it may be appropriate to interrupt antiresorptive treatment for some time. However, the complication of this approach is the risk of rebound fractures. Relatively low risk was described with a one-year interruption of treatment with alendronate and zoledronate, whereas high risk is associated with discontinuation of treatment after long-term administration of denosumab (> 6 years).
Conclusion
Osteoanabolics help reduce the risk of fractures through various mechanisms. Current clinical studies provide evidence that their initiation in the 1st line of treatment is appropriate for patients with a high risk of major osteoporotic fracture in the next few years. After 1-2 years of osteoanabolic treatment, bone mineral density adjusts. It is then recommended to continue with consolidation therapy using antiresorptive medications, which will help stabilize or further improve bone status. The question that remains unanswered is how to discontinue, respectively the safety of extending the consolidation phase of treatment.
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Source: Curtis E. M., Reginster J.-Y., Al-Daghri N. et al. Management of patients at very high risk of osteoporotic fractures through sequential treatments. Aging Clin Exp Res 2022; 34 (4): 695–714, doi: 10.1007/s40520-022-02100-4.
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