Indolent Mastocytosis and Bone Health: Molecular Mechanisms and Emerging Treatment Options
Abstract
1. Introduction
2. Manifestations of Bone Health Impairment
3. Mechanisms Underlying Bone Impairment
4. Methods of Evaluation
4.1. Dual-Energy X-Ray Assessment
4.2. X-Ray
4.3. Assessment of Microarchitecture and Bone Strength
4.4. Bone Turnover Markers
5. Constraints of Evaluation Methods
6. Therapeutic Approaches
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
References
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Drug/Treatment | Mechanism | Therapeutic Effects/Benefits | Adverse Effects/Limitations |
---|---|---|---|
Bisphosphonates (aminobisphosphonate Zoledronate) [17,37,40,65] | Antiresorptive agents | ↑ lumbar and hip BMD (~2%/year); ↓ bone turnover markers; ↓ bone pain; no new fractures observed | GI symptoms (oral bisphosphonates); acute phase reaction after 1st dose (usually temporary, can be pre-medicated); caution in reproductive-age women; atypical femoral fracture; osteonecrosis of the jaw; hypocalcemia; |
Denosumab [17,57] | Biologic anti-resorptive drug (anti-RANKL monoclonal antibody) | ↑ BMD (lumbar, femoral); ↓ serum tryptase, bALP, CTX; no new vertebral fractures; (short term—12 months, small cohort N = 4); useful in bisphosphonate intolerance | Allergy risk; lacks long-term data in SM; rebound fractures (in case of delay/discontinuation after >1 application); atypical femoral fracture; osteonecrosis of the jaw; hypocalcemia; |
Teriparatide [17,68] | Recombinant PTH | Stimulates osteoblasts (theoretical benefit) | May ↑ atypical MC proliferation; potential for disease worsening; not recommended in SM |
IFN-α [22,70] | TKI | ↓ MC burden; ↓ MC mediator symptoms; improved BMD in severe cases; ↓ BM MC infiltration; reduced mastocytosis-related osteoporosis | Toxicities: flu-like symptoms, depression, hepatic/cardiac contraindications |
Cladribine (2-CdA) [16,70] | TKI | ↓ MC burden; potential for disease control in severe cases | Myelosuppression, lymphopenia, infection risk (needs prophylaxis) |
Midostaurin (PKC412) [16,70,72] | TKI | ↓ serum tryptase, ↓ BM MC burden; salvage therapy option | GI side effects; requires monitoring (for labs and ECG); long-term safety under investigation |
Avapritinib [16,75] | TKI | ↓ tryptase, ↓ KIT VAF, ↓ BM MCs; ↑ symptom control | CNS side effects (confusion, dizziness); intracranial bleeding risk |
Bezuclastinib [16,77] | TKI | ↓ tryptase (>50% in all treated); ↓ BM MC burden; some complete MC clearance in early trials | Low CNS penetration; safety profile still emerging |
BLU-263 [16,78] | TKI | Similar target to Avapritinib; designed to limit CNS penetration | Limited CNS penetration; long-term data pending |
Masitinib [76] | TKI | Symptom improvement; ↓ mean tryptase | Mild side effects; no life-threatening toxicities |
Supportive Therapies [22] | Calcium, vitamin D, estrogen | Treats osteopenia/osteoporosis; improves calcium balance; sodium cromolyn improves absorption | Malabsorption can limit efficacy; estrogen contraindicated in some populations |
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Jankovski, L.; Rakusa, M.; Koceva, A.; Janež, A.; Kopač, P.; Jensterle, M. Indolent Mastocytosis and Bone Health: Molecular Mechanisms and Emerging Treatment Options. Int. J. Mol. Sci. 2025, 26, 5649. https://doi.org/10.3390/ijms26125649
Jankovski L, Rakusa M, Koceva A, Janež A, Kopač P, Jensterle M. Indolent Mastocytosis and Bone Health: Molecular Mechanisms and Emerging Treatment Options. International Journal of Molecular Sciences. 2025; 26(12):5649. https://doi.org/10.3390/ijms26125649
Chicago/Turabian StyleJankovski, Lucia, Matej Rakusa, Andrijana Koceva, Andrej Janež, Peter Kopač, and Mojca Jensterle. 2025. "Indolent Mastocytosis and Bone Health: Molecular Mechanisms and Emerging Treatment Options" International Journal of Molecular Sciences 26, no. 12: 5649. https://doi.org/10.3390/ijms26125649
APA StyleJankovski, L., Rakusa, M., Koceva, A., Janež, A., Kopač, P., & Jensterle, M. (2025). Indolent Mastocytosis and Bone Health: Molecular Mechanisms and Emerging Treatment Options. International Journal of Molecular Sciences, 26(12), 5649. https://doi.org/10.3390/ijms26125649