Unmasking indolent systemic mastocytosis in patients with unexplained or treatment-refractory osteoporosis : a case series with diagnostic and therapeutic implications

Jankovski, Lucia (avtor), Herman, Rok (avtor), Rakuša, Matej (avtor), Kopač, Peter (avtor), Kačar, Mark (avtor), Škerget, Matevž (avtor), Janež, Andrej (avtor), Jensterle Sever, Mojca (avtor)

Indolent systemic mastocytosis (ISM) is an under-recognised cause of secondary osteoporosis, and skeletal fragility may be the only presenting feature, delaying diagnosis. We describe four adults referred to a tertiary endocrinology service for unexplained osteoporosis or low-trauma fractures, in whom systemic mastocytosis (SM) was identified during work-up. All had elevated basal serum tryptase (41.4–87.0 µg/L), bone-marrow biopsy showing atypical mast cells and the KIT D816V variant; cutaneous lesions were absent in every case. Three patients fulfilled WHO 2022 criteria for ISM. The fourth had coexistent JAK2 V617F-positive post-essential-thrombocythaemia myelofibrosis and was classified as SM with associated haematological neoplasm (SM-AHN); his mast cell clone (tryptase 43.7 µg/L; KIT D816V VAF 0.391%) behaved indolently and contributed clinically through osteoporosis alone, illustrating that an indolent mast cell component can be overlooked when a chronic myeloid neoplasm dominates the picture. Presentations ranged from an isolated low-energy L5 fracture in a 55-year-old man, to multiple vertebral compression fractures despite denosumab in a 71-year-old woman with primary hyperparathyroidism, to severe wasp-sting anaphylaxis in a 43-year-old man. After multidisciplinary review, all received intravenous zoledronic acid with vitamin D repletion; KIT-targeted therapy is under consideration in selected patients. Although causal inferences cannot be drawn from four retrospectively identified cases, the series illustrates how ISM may be missed in unexplained or treatment-refractory osteoporosis—particularly in younger men, those with prior severe anaphylaxis, and those fracturing on antiresorptive therapy—and supports combining basal serum tryptase with high-sensitivity peripheral-blood KIT D816V testing, in line with the WHO/ICC/AIM-ECNM 2022–2024 criteria. Prospective studies are needed.

• Jezik: Angleški jezik
• Ključne besede: indolent systemic mastocytosis, osteoporosis, bone mineral density
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: MF - Medicinska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2026
• Št. strani: 15 str.
• Številčenje: Vol. 16, iss. 6, art. 821
• PID: 20.500.12556/RUL-185578
• UDK: 616.4
• ISSN pri članku: 2218-273X
• DOI: 10.3390/biom16060821
• COBISS.SI-ID: 280057859
• Datum objave v RUL: 11.08.2026

Gradivo je del revije

• Naslov: Biomolecules
• Založnik: MDPI
• ISSN: 2218-273X
• COBISS.SI-ID: 519952921

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: indolentna sistemska mastocitoza, agregacija proteinov, osteoporoza, mineralna gostota kosti