Anabolic Antiosteoporotic Treatment as a First Step in Patients with Very High Fracture Risk
According to the 2022 opinion of the ESCEO (European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases) working group, it is advisable to identify patients with osteoporosis who have a very high risk of fracture and to use an anabolic antiosteoporotic drug as the initial pharmacotherapeutic intervention, followed by necessary antiresorptive treatment to be addressed over the entire expected length of life.
Antiresorptive and Anabolic Treatment of Osteoporosis
In the care of individuals with osteoporosis, we currently have a clear definition of the disease, validated methods for assessing fracture risk, and several effective therapeutic options. Anabolic antiosteoporotic drugs are now used in many countries for patients with continuing decreases in bone mineral density (BMD), repeated fractures, or fractures even while undergoing antiresorptive treatment. However, direct comparisons show that anabolic drugs reduce fracture risk more quickly and effectively than antiresorptive agents. There is growing evidence that stratifying patients with osteoporosis by initial fracture risk allows for the use of the most effective treatment in patients with the highest risk.
The ESCEO working group concluded, based on existing evidence, that for patients with osteoporosis who have a very high fracture risk, initial therapy with an anabolic drug followed by an antiresorptive agent is appropriate. However, implementing such an approach can be challenging. How to identify a patient at very high risk of osteoporotic fracture? Which anabolic to choose and for how long? Can the cycle of anabolic − antiresorptive treatment be repeated?
How to Identify Patients with Very High Risk of Osteoporotic Fracture
Modern methods of identifying such patients include procedures assisted by machine learning. Artificial intelligence can estimate a 1−2-year fracture risk based on medical record data for patients over 50 years old. However, this system will likely be used in the future.
ESCEO recommends the FRAX questionnaire. It uses 10 clinical risk factors to assess the probability of an osteoporotic fracture (proximal femur, humerus, pelvis, radius, or clinical vertebral fracture) over a 10-year horizon. If BMD values are available, it also considers them. Modern versions of the questionnaire also take into account previous fractures.
ESCEO defines very high fracture risk as a probability of a major osteoporotic fracture over the next 10 years according to FRAX ≥ 20%. High immediate fracture risk is defined as a 10% risk over the next 2 years. This includes, for example, individuals over 65 years old after suffering a major osteoporotic fracture.
Reevaluating the Role of Anabolic Drugs in Osteoporosis Treatment
Anabolic antiosteoporotic drugs include teriparatide, abaloparatide, and romosozumab. The first two are parathyroid hormone analogs, and the third is a monoclonal antibody that inhibits sclerostin. They increase bone tissue density through their mechanisms of action, leading to reduced risk of osteoporotic fractures. Their effects must subsequently be maintained with antiresorptive treatment.
The order of drugs is important based on available evidence. It is hypothesized that the above process (anabolic for 18 months, followed by antiresorptive for 10 years) could hypothetically prevent nearly 34 hip fractures annually per 1,000 women over 70 years old with a recent osteoporotic fracture. If therapy starts with an antiresorptive followed by an anabolic drug, it is hypothesized that 20 hip fractures per 1,000 patients annually would be prevented. These findings reevaluate the view of anabolics as a "last resort" and make them a first-line therapy for patients with high risk of osteoporotic fractures. Choosing a specific anabolic is beyond the study's scope, and their availability varies by country.
Treatment in Cycles?
It is hypothesized that treatment cycles of anabolic − antiresorptive could be repeated in some patients. Some study authors propose that a cyclic approach (alternating drugs in 6-month intervals) could benefit patients with an immediate fracture risk, though more data is needed for clearer conclusions. Authors allow that for well-treated patients showing BMD increases during long-term antiresorptive treatment, the drug could be paused temporarily (for a maximum of a few years).
Conclusion
According to the expert group, initial therapy with an anabolic agent followed by antiresorptive treatment is a suitable strategy for patients with osteoporosis and very high fracture risk. This strategy changes the perspective on anabolics and their place in osteoporosis 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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