Indolent systemic mastocytosis (SM) often takes a toll on bone health, making testing and early treatment essential, according to a review recently published in the International Journal of Molecular Sciences.
How SM impacts bone health
SM often affects the musculoskeletal system, leading to frequent fractures, bone pain and a significant impact on patients’ quality of life.
“Fragility fractures occur in 33% to 43% of patients with SM and in 24% to 41% of patients with ISM,” the authors wrote. “These fractures are frequently multiple and predominantly affect the vertebral bodies, while the peripheral skeleton is affected less commonly.”
Osteoporosis, a pathological decrease in bone density leading to fragility, is the most frequent musculoskeletal complication associated with SM. Multiple mechanisms contribute to osteoporosis in patients with SM. For example, patients with SM often have higher expression of osteoclasts — bone cells specialized in calcium resorption from bone tissue. In addition, the release of certain substances by mast cells can lead to increased production of enzymes called metalloproteinases, which also contribute to bone resorption.
Read more about SM signs and symptoms
Current diagnostic methods have important limitations
Due to the unique mechanisms involved in SM-related osteoporosis, the conventional methods used to diagnose other forms of osteoporosis have limited use in this context.
Therefore, the authors recommend using more advanced imaging techniques such as magnetic resonance imaging (MRI) and computed tomography (CT) scans in patients with SM and suspected osteoporosis to estimate the degree of bone resorption more accurately.
Furthermore, using MastFx, a clinical risk score that estimates the risk of fractures in patients with SM based on clinical and imaging findings, can help identify patients likely to benefit from early prophylactic treatment.
Current and emerging therapeutic strategies
Currently, bone resorption inhibition through bisphosphonates is the most widely used therapy for SM-related osteoporosis. Although some studies have demonstrated their effectiveness, they can sometimes worsen SM-associated gastrointestinal symptoms.
Denosumab, a recently developed anti-resorptive drug, could be an alternative for patients with SM who experience adverse effects from bisphosphonates; however, further investigation regarding its safety is needed. Teriparatide, a drug that promotes bone-producing cells, is another option, but as with denosumab, some safety concerns must be further investigated.
Tyrosine kinase inhibitors (TKIs) such as midostaurin and avapritinib also appear to be viable options for the management of several SM complications, with initial clinical trials showing promising results.
“Ongoing research into novel treatments continues to expand the therapeutic landscape, providing hope for improved outcomes,” the authors concluded.
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