Fracture Risk Reduction by Bisphosphonates in Mastocytosis

Abstract Background Fragility fractures (FFxs) and osteoporosis are frequent manifestations of indolent systemic mastocytosis (ISM). So far, the effect of anti-osteoporotic therapy on FFxs has scarcely been investigated. Objective This study evaluates the long-term effect of bisphosphonate treatment on FFxs, bone mineral density (BMD) and bone resorption in ISM patients in daily clinical practice. Methods ISM patients who received bisphosphonates because of osteoporosis and/or FFxs were retrospectively analysed (n=58). Fractures were recorded by vertebral fracture assessment, X-rays of thoracolumbar spine, medical records and a questionnaire. Five-year analysis (n=30) was made by comparing observed 5-year FFx risk with MastFx predicted FFx risk for ISM patients not treated with anti-osteoporotic drugs and analysing 5-year change in BMD and serum collagen C telopeptide (sCTx) Z-scores. Results During median follow-up of 7.3 years, 14 of 58 patients suffered 40 FFxs. Five- and ten-year FFx-free survival were 81.9% (SE 5.5%) and 67.0% (SE 7.7%). FFx risk was significantly higher in patients with previous vertebral FFxs (P=0.004), lower femoral BMD at baseline (P=0.042), and history of anaphylaxis (P=0.028). No 5-year FFx risk reduction could be proven, possibly due to small sample size. Lumbar BMD Z-score significantly increased from median (IQR) -2.20 (-2.80 to -1.50) to -1.50 (-2.30 to -0.60) (P Conclusion Bisphosphonates significantly increase BMD and decrease sCTx in ISM patients. However, FFxs still frequently occur. Especially patients with previous FFxs remain at high risk of new FFxs.