The number of vertebral fractures in indolent systemic mastocytosis is influenced by presence of the KIT-mutation

Systemic mastocytosis (SM) is a rare disease characterized by aggregation of mast cells in the skin or extracutaneous organs. Disease subtypes range from cutaneous to systemic mastocytosis with highly malignant forms, indolent systemic mastocytosis (ISM) being the most frequent subtype. In ISM, mast cells infiltrate bone marrow, with some patients developing osteoporosis and fractures. However, fractures do not occur in all ISM patients.

In this retrospective one-center study, we analyzed data from patients evaluated for osteoporosis diagnosed with ISM according to WHO criteria between 2006 and 2019. ISM patients (n = 42) comprised 76.2 % women (n = 32), had a mean age of 52.2 ± 12 years, and presented with skin lesions in 80.5 % (n = 33). Osteoporosis was diagnosed in 42 % (n = 15) according to the WHO definition (T-score ≤ −2.5). Fractures were either peripheral in 19 % (n = 8), or to the spine in 43 % (n = 18); both fracture types presented in 14 % (n = 6). All fracture types correlated to femoral BMD T-scores. The presence of the somatic gain-of-function mutation in the KIT receptor tyrosine kinase (KIT-mutation) in bone biopsy was associated with a significantly greater number of fractures (p = 0.024) and correlated to the number of vertebral fractures in individual patients (p = 0.03). Neither tryptase levels, postmenopausal status, nor bone turnover markers were indicators of an increase in vertebral or peripheral fractures in ISM patients. Smoking was associated with more fractures, however the effect disappeared dependent on KIT-mutation. Those with skin lesions had better femoral BMD T-scores (right femur: −1.05 ± 0.99 vs −2.26 ± 0.59, p = 0.008; right femoral neck: −1.21 ± 0.99 vs −2.22 ± 0.55, p = 0.0023).

In conclusion, we demonstrate the influence of the KIT-mutation on the severity of fractures in osteoporosis patients with the final diagnosis of ISM. Our results suggest that, in the presence of the KIT-mutation in ISM patients without skin lesions, the timely onset of anti-osteoporotic treatment might be of value.