Researchers reported the case of a female patient with progressive systemic mastocytosis (SM) and loss of bone mineral density (BMD), and discussed the difficulties of managing her clinical condition in Endocrinology, Diabetes & Metabolism Case Reports.

“This case highlights the complexities of systemic mastocytosis-related bone disease and the interplay of numerous mediators contributing to a phenotype of both increased bone resorption and formation,” the researchers said.

At the age of 56, the patient was referred for bone health assessment after a fall that caused a left greater tuberosity fracture. Osteoporosis screening returned normal and the patient had no significant clinical risk factors for bone loss.

Ten years later, her BMD had declined. She initiated antiresorptive therapy (zoledronic acid) but she had a significant acute phase reaction and the therapy was terminated. The patient was monitored with bone density scans every 2 years.

Read more about SM etiology

At the age of 69, the patient presented with asymptomatic pigmented macules and papules, with a pattern consistent with urticaria pigmentosa. Positive Darier sign raised suspicion for mast cell degranulation.

Further investigations revealed CD117-positive mast cells, consistent with cutaneous mastocytosis. The patient also complained of other cutaneous symptoms suggestive of mast cell degranulation, together with gastrointestinal and constitutional symptoms.

Her serum tryptase level was elevated and her bone marrow was infiltrated by mast cells expressing CD117, CD2, CD25, and tryptase. The identification of a KIT D816V mutation confirmed the SM diagnosis.

A bone density scan repeated at the time of SM diagnosis showed a further decline in BMD at the spine. In addition, a computerized tomography scan performed due to her lower back pain revealed multiple sclerotic foci with surrounding osteolysis in multiple areas.

Read more about SM diagnosis

“Due to osteosclerosis in the lumbar spine, it was difficult to interpret her true BMD, although it was expected to decline further as a result of her SM if not treated with antiresorptive therapy,” the study’s authors explained.

The clinical condition of the patient was managed with cetirizine, ranitidine, topical corticosteroids, and midostaurin (Rydapt®), which was gradually increased to the maximum dose of 100 mg, twice daily, and denosumab.

As denosumab has a theoretical risk of anaphylaxis, the patient was closely monitored for side effects following initial administration. The treatment was well-tolerated and she continued on denosumab for the following 5.5 years. At follow-up, she had improved her BMD.


Wang M, Seibel MJ. Skin and bones: systemic mastocytosis and bone. Endocrinol Diabetes Metab Case Reports. Published online May 11, 2023. doi:10.1530/EDM-22-0408