MON-798 - A Case of Severe Osteoporosis Secondary to Aggressive Systemic Mastocytosis

Background:
In patients with severe osteoporosis, particularly those with worsening bone mineral density despite antiresorptive therapy, screening for systemic mastocytosis should be performed as part of a secondary workup. Given the rarity of systemic mastocytosis and variability in clinical presentation, diagnosis of this disorder is often delayed. We present the case of a patient with osteoporosis with worsening T scores despite denosumab treatment, found to have underlying aggressive systemic mastocytosis.

Case:
A 72-year old male with hypothyroidism, diabetes mellitus, and IgM Kappa Monoclonal Gammopathy of Undetermined Significance presented in 2017 with back pain and was found to have a T11 vertebral compression fracture. Dual-Energy X-ray Absorptiometry (DXA) scan showed T scores of -4.4 in the L1-L4 spine, -2.1 in the left femoral neck, and -2.2 in the left total hip. The patient denied a history of nephrolithiasis, previous fractures, chronic glucocorticoid or proton pump inhibitor use. He denied symptoms of flushing, gastrointestinal distress, headaches, or bone pain. Laboratory testing showed normal 25-OH vitamin D, phosphate, magnesium, calcium, parathyroid hormone, thyroid stimulating hormone, and 24-hour urine calcium levels.

The patient was initiated on denosumab 60 mg every six months in early 2018. Subsequent DXA scans showed an overall 8.6% decrease in bone mineral density in the lumbar spine despite therapy. In 2022, after a delay in receiving denosumab, imaging showed new vertebral compression fractures at T12, L2, and L4, with an incomplete fracture of the left ilium. He underwent vertebral augmentation kyphoplasty in July 2022 and was initiated on teriparatide 20 mcg daily in addition to denosumab therapy.

Additional workup was obtained and notable for a tryptase of 30.2 ug/L (normal ≤ 10.9 ug/L). Bone marrow biopsy showed 5-10% cellularity of mast cells with clusters of at least 15 cells, some CD25 positive. Peripheral C kit mutation D816V was detected, and the patient was diagnosed with aggressive systemic mastocytosis. He was initiated on avapritinib in December 2022.

Tryptase levels normalized within one year on avapritinib treatment. Following two years of teriparatide treatment, the patient was continued on denosumab therapy. Repeat DXA scan in March 2025 showed osteopenia at all sites, with a T score -1.4 at the lumbar spine and over 20% total increase in bone mineral density at the spine.

Conclusions:
Systemic mastocytosis is an underrecognized etiology of osteoporosis, particularly in patients who present with osteoporosis or fractures as the first clinical manifestation of the disease. Physicians should be prompted to screen for systemic mastocytosis as part of the secondary workup for osteoporosis, especially in cases with severe osteoporosis at presentation, as treatment of this disease can lead to dramatic improvements in bone mineral density.

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