Early and targeted osteoporosis treatment can help reduce painful spine and peripheral fractures in patients with indolent systemic mastocytosis (SM) caused by a KIT mutation, according to a study published recently in Bone.
What is a KIT gene mutation?
SM is usually caused by a sporadic mutation in the KIT gene, which codes for a protein called CD117 transmembrane tyrosine kinase. The protein is involved in the growth, survival and migration of mast cells. The most common KIT mutation associated with SM is the D816V mutation, which results in the amino acid aspartic acid being replaced by the amino acid valine in the protein chain.
In this study, 42% of people with ISM had osteoporosis, and fractures were common, highlighting the need for patients and doctors to focus on bone health right after diagnosis.
“[W]e identified the KIT-mutation in bone biopsies as relevant to the severity of osteoporosis on analysis of the osteoporosis patient subgroup with proven ISM with and without fractures,” the study’s authors said.
Spinal fractures occurred in 43% of patients, while 19% experienced peripheral fractures (fractures occurring in the limbs); both types of fracture were seen in 14% of patients. Fractures led to significant back pain in many cases. Even small injuries could trigger peripheral fractures, making daily activities riskier for patients.
Read more about SM prognosis
A major factor raising fracture risk was the KIT mutation found in bone biopsy samples. Patients with this mutation faced over five times higher odds of spine fractures. While many factors can contribute to bone weakness, KIT mutation stood out as a clear predictor of severe spinal involvement. Smoking also increased fracture risk but this effect faded once KIT mutation was considered, suggesting genetic factors play a larger role.
Skin lesions, seen in about 80% of patients, seemed to be associated with a protective effect. Patients with ISM with these lesions generally had better bone density at the femur and femoral neck. Those without skin lesions had lower bone mineral density (BMD) scores in these regions, putting them at higher risk for fractures. Notably, spinal BMD did not differ much between patients with or without skin lesions, making hip measurements more useful for assessment of risk.
Bone density scores provided valuable clues, with those scoring below –2.5 (the osteoporosis range) suffering more fractures. Yet some patients with higher BMD still experienced breaks, showing the need for a careful, individualized approach. Doctors used bone biopsies in nearly all patients to confirm ISM and check for KIT mutations, which helped identify those most at risk.
For patients living with ISM, these results stress the importance of early osteoporosis screening and treatment. Recognizing high-risk factors such as KIT mutations, smoking and low femoral BMD can help clinicians act quickly to prevent painful fractures, improve quality of life and avoid complications that come with weakened bones.
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