MON-793 Long-term Denosumab Treatment in a Patient with Low Bone Mass Associated with Indolent Systemic Mastocytosis

Abstract Disclosure: M. Joven: None. K. Diemer: None. INTRODUCTION Systemic mastocytosis (SM) is a hematologic neoplasm caused by proliferation of mast cells with heterogenous presentations, including osteoporosis and fractures. Osteoporosis treatment in indolent SM with bisphosphonates have been characterized; however, its effect on BMD increase is variable with some studies showing no significant changes. Histamine, an abundant mediator of mast cells, stimulates osteoclasts and its precursors thereby leading to bone loss. We report a patient with indolent SM-associated low bone mass treated with long term denosumab. CASE PRESENTATION A 38-year-old man was referred for SM-associated osteoporosis. He had bone marrow biopsy-proven indolent SM after presenting with a 6-year history of rash, later diagnosed to be urticaria pigmentosa. Initial bone mineral density (BMD) of the spine and total hip showed low bone mass with Z-scores of -2.8 and -2.5 respectively. He did not have prior fractures. He initially received 3 consecutive annual doses of zoledronic acid 5 mg infusions. He had significant BMD gains on the lumbar spine (+3.1% and +5.3%) during the first two years but had a -4.1% drop after the last zoledronic acid dose. No significant changes were observed in the total hip BMD. Because of this, he subsequently received denosumab 60 mg subcutaneously every 6 months for the next 5 years and had substantial BMD gains in both the spine and the total hip, around 24.6% and 39.9% from baseline respectively. Serum tryptase levels remained elevated (18.2-30.2 ng/ml (ref, <11.5)) and did not change with either zoledronic acid or denosumab treatment. The patient has remained fracture-free. DISCUSSION Our data shows significant BMD gains with long term denosumab treatment. As RANKL expression in osteoblasts in SM results in osteoporosis, denosumab may potentially be used in patients with indolent SM who are treatment naïve, who do not respond to or are intolerant to bisphosphonates. Currently, there are only a few reported cases in the literature without reports on long-term denosumab use in SM-associated osteoporosis. Conclusion Denosumab can be used in managing SM-associated osteoporosis. More additional studies including its long-term are needed to show its benefit in reducing fracture events associated with this condition. Presentation: Monday, July 14, 2025