{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T23:29:53Z","timestamp":1784071793050,"version":"3.55.0"},"reference-count":99,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Systemic mastocytosis comprises a group of clonal mast cell disorders characterized by multisystem involvement. Bone involvement represents a major source of morbidity, particularly in young men affected by indolent systemic mastocytosis. This review provides an integrated and up-to-date overview of SM-related bone disease. We dissect the dual and context-dependent role of mast cells in bone remodeling, detailing how they promote osteoclastogenesis, suppress osteoblast function, and, in advanced disease, drive osteosclerosis. We critically appraise available treatments, including classic anti-resorptive therapy and emerging anabolic strategies. We further discuss the transformative impact of KIT-directed tyrosine kinase inhibitors, particularly avapritinib, which has demonstrated for the first time the ability to reverse not only osteoporosis but also osteosclerosis. Finally, we explore the emerging role of machine learning models in SM, proposing their application to individualized prediction of osteoporosis and fracture risk in SM. By bridging clinical care, bone biology, and therapeutic advances, this review underscores the need for a paradigm shift in which SM-related bone disease is recognized as a dynamic process requiring early identification, integrated risk stratification, and coordinated use of anti-resorptive, disease-modifying, and data-driven precision approaches to prevent fractures and improve long-term outcomes and quality of life in this delicate category of patients.<\/jats:p>","DOI":"10.3390\/cells15030307","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T16:32:59Z","timestamp":1770395579000},"page":"307","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Skeletal Involvement in Systemic Mastocytosis: Pathophysiology, Clinical Management, Standards of Care, and Novel Therapeutic Strategies"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8804-2640","authenticated-orcid":false,"given":"Manlio","family":"Fazio","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Human Pathology in Adulthood and Childhood \u201cGaetano Barresi\u201d, University of Messina, Via Consolare Valeria 1, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adele","family":"Bottaro","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Human Pathology in Adulthood and Childhood \u201cGaetano Barresi\u201d, University of Messina, Via Consolare Valeria 1, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Elisa","family":"Nasso","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Human Pathology in Adulthood and Childhood \u201cGaetano Barresi\u201d, University of Messina, Via Consolare Valeria 1, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7947-158X","authenticated-orcid":false,"given":"Fabio","family":"Stagno","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Human Pathology in Adulthood and Childhood \u201cGaetano Barresi\u201d, University of Messina, Via Consolare Valeria 1, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6156-8239","authenticated-orcid":false,"given":"Alessandro","family":"Allegra","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Human Pathology in Adulthood and Childhood \u201cGaetano Barresi\u201d, University of Messina, Via Consolare Valeria 1, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1038\/s41375-022-01613-1","article-title":"The 5th Edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic\/Dendritic Neoplasms","volume":"36","author":"Khoury","year":"2022","journal-title":"Leukemia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e7134","DOI":"10.1002\/ccr3.7134","article-title":"A Case of High-risk AML in a Patient with Advanced Systemic Mastocytosis","volume":"11","author":"Fazio","year":"2023","journal-title":"Clin. Case Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7315","DOI":"10.1182\/blood-2025-7315","article-title":"Systemic Mastocytosis with Associated Lymphoid Neoplasms (SM-ALN): A Distinct Subset with Indolent Clinical Course and Favorable Outcomes","volume":"146","author":"Munoz","year":"2025","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Fazio, M., Elena, C., Ferrari, J., Camilotto, V., Stella, S., Leotta, D., Palumbo, G.A., Di Raimondo, F., and Romano, A. (2025). Is Bruton Tyrosine Kinase a Potential Target to Treat Mast Cell Neoplasms? Systemic Mastocytosis Associated with Chronic Lymphoid Leukemia Successfully Treated with Acalabrutinib Monotherapy: A Case Report and Review of the Literature. Haematologica, early view.","DOI":"10.3324\/haematol.2025.289116"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1111\/j.1468-3083.2010.03599.x","article-title":"Association of Adult Mastocytosis with M541L in the Transmembrane Domain of KIT","volume":"24","author":"Rocha","year":"2010","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"521","DOI":"10.18632\/oncotarget.28614","article-title":"Prevalence and Impact of the KIT M541L Variant in Patients with Mastocytosis","volume":"15","author":"Aldama","year":"2024","journal-title":"Oncotarget"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1097\/00005131-199509060-00005","article-title":"Fracture Healing and Mast Cells","volume":"9","author":"Banovac","year":"1995","journal-title":"J. Orthop. Trauma"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"684","DOI":"10.3899\/jrheum.120845","article-title":"RANKL\/OPG Ratio and DKK-1 Expression in Primary Osteoblastic Cultures from Osteoarthritic and Osteoporotic Subjects","volume":"40","author":"Corrado","year":"2013","journal-title":"J. Rheumatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1007\/s00011-022-01608-9","article-title":"Human Mast Cells Induce Osteoclastogenesis through Cell Surface RANKL","volume":"71","author":"Ng","year":"2022","journal-title":"Inflamm. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.iac.2014.01.011","article-title":"Bone Involvement and Osteoporosis in Mastocytosis","volume":"34","author":"Rossini","year":"2014","journal-title":"Immunol. Allergy Clin. N. Am."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.7150\/ijms.108763","article-title":"Unraveling the Role of N6-Methylation Modification: From Bone Biology to Osteoporosis","volume":"22","author":"Liu","year":"2025","journal-title":"Int. J. Med. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e63402","DOI":"10.7554\/eLife.63402","article-title":"Sclerostin Small-Molecule Inhibitors Promote Osteogenesis by Activating Canonical Wnt and BMP Pathways","volume":"12","author":"Sangadala","year":"2023","journal-title":"eLife"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Letizia Mauro, G., Accomando, J., Tomasello, S., Duca, A., Mangano, M.S., de Sire, A., Vecchio, M., and Scaturro, D. (2024). Osteoporosis in Systemic Mastocytosis: A Scoping Review. Medicina, 60.","DOI":"10.3390\/medicina60111752"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1016\/j.jaci.2013.06.019","article-title":"Serum Levels of Bone Cytokines Are Increased in Indolent Systemic Mastocytosis Associated with Osteopenia or Osteoporosis","volume":"132","author":"Rabenhorst","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1038\/s41598-024-83851-0","article-title":"Role of Sclerostin in Mastocytosis Bone Disease","volume":"15","author":"Mlak","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ragipoglu, D., Dudeck, A., Haffner-Luntzer, M., Voss, M., Kroner, J., Ignatius, A., and Fischer, V. (2020). The Role of Mast Cells in Bone Metabolism and Bone Disorders. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00163"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"521754","DOI":"10.1155\/2014\/521754","article-title":"Transforming Growth Factor-Beta and Matrix Metalloproteinases: Functional Interactions in Tumor Stroma-Infiltrating Myeloid Cells","volume":"2014","author":"Krstic","year":"2014","journal-title":"Sci. World J."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Norrby, K. (2024). On Connective Tissue Mast Cells as Protectors of Life, Reproduction, and Progeny. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202403.1200.v1"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"124","DOI":"10.3324\/haematol.2018.212126","article-title":"Oncogenic D816V-KIT Signaling in Mast Cells Causes Persistent IL-6 Production","volume":"105","author":"Bandara","year":"2020","journal-title":"Haematologica"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/jbmr.4455","article-title":"Mast Cells Trigger Disturbed Bone Healing in Osteoporotic Mice","volume":"37","author":"Fischer","year":"2020","journal-title":"J. Bone Miner. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2527","DOI":"10.1038\/s41467-021-22754-4","article-title":"Mastocytosis-Derived Extracellular Vesicles Deliver MiR-23a and MiR-30a into Pre-Osteoblasts and Prevent Osteoblastogenesis and Bone Formation","volume":"12","author":"Kim","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Fazio, M., Stagno, F., Penna, G., Mirabile, G., and Allegra, A. (2025). Navigating the Landscape of Exosomal MicroRNAs: Charting Their Pivotal Role as Biomarkers in Hematological Malignancies. Non-Coding RNA, 11.","DOI":"10.3390\/ncrna11050064"},{"key":"ref_23","first-page":"22-0408","article-title":"Skin and Bones: Systemic Mastocytosis and Bone","volume":"2023","author":"Wang","year":"2023","journal-title":"Endocrinol. Diabetes Metab. Case Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.humpath.2017.01.007","article-title":"Transforming Growth Factor \u03b2\u2014And Interleukin 13\u2013Producing Mast Cells Are Associated with Fibrosis in Bone Marrow","volume":"62","author":"Nakayama","year":"2017","journal-title":"Hum. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"16009","DOI":"10.1038\/boneres.2016.9","article-title":"TGF-\u03b2 and BMP Signaling in Osteoblast, Skeletal Development, and Bone Formation, Homeostasis and Disease","volume":"4","author":"Wu","year":"2016","journal-title":"Bone Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Han, Y., Gao, H., Gan, X., Liu, J., Bao, C., and He, C. (2024). Roles of IL-11 in the Regulation of Bone Metabolism. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1290130"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"You, J., Liu, M., Li, M., Zhai, S., Quni, S., Zhang, L., Liu, X., Jia, K., Zhang, Y., and Zhou, Y. (2023). The Role of HIF-1\u03b1 in Bone Regeneration: A New Direction and Challenge in Bone Tissue Engineering. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24098029"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1007\/s12016-019-08729-w","article-title":"A Review of the Contribution of Mast Cells in Wound Healing: Involved Molecular and Cellular Mechanisms","volume":"58","author":"Komi","year":"2020","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.4252\/wjsc.v13.i11.1667","article-title":"Effects of Immune Cells on Mesenchymal Stem Cells during Fracture Healing","volume":"13","author":"Ehnert","year":"2021","journal-title":"World J. Stem Cells"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1016\/j.jaip.2023.02.007","article-title":"Bone and Cytokine Markers Associated with Bone Disease in Systemic Mastocytosis","volume":"11","author":"Rama","year":"2023","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_31","first-page":"75","article-title":"Calcium ion signals are fundamental in viral infection","volume":"9","author":"Lobefalo","year":"2025","journal-title":"Int. J. Infect."},{"key":"ref_32","first-page":"46","article-title":"Inhibition of PI3K\u03b2 and mtor influence the immune response and the defense mechanism against pathogens","volume":"7","year":"2023","journal-title":"Int. J. Infect."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1111\/bjh.12916","article-title":"Epidemiology of Systemic Mastocytosis in Denmark","volume":"166","author":"Cohen","year":"2014","journal-title":"Br. J. Haematol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"52","DOI":"10.55563\/clinexprheumatol\/y4ksv9","article-title":"Bone Mineral Density in Patients with Systemic Mastocytosis: Correlations with Clinical and Histopathological Features","volume":"39","author":"Meyer","year":"2021","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Jankovski, L., Rakusa, M., Koceva, A., Jane\u017e, A., Kopa\u010d, P., and Jensterle, M. (2025). Indolent Mastocytosis and Bone Health: Molecular Mechanisms and Emerging Treatment Options. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26125649"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1111\/j.1398-9995.2011.02780.x","article-title":"High Prevalence of Fractures and Osteoporosis in Patients with Indolent Systemic Mastocytosis","volume":"67","year":"2012","journal-title":"Allergy"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1007\/s00223-021-00887-4","article-title":"Osteoporosis Caused by Systemic Mastocytosis: Prevalence in a Cohort of 8392 Patients with Osteoporosis","volume":"109","author":"Gehlen","year":"2021","journal-title":"Calcif. Tissue Int."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1007\/s00432-019-03119-3","article-title":"An Increased Bone Mineral Density Is an Adverse Prognostic Factor in Patients with Systemic Mastocytosis","volume":"146","author":"Riffel","year":"2020","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Zanotti, R., Bonifacio, M., Isolan, C., Tanasi, I., Crosera, L., Olivieri, F., Orsolini, G., Schena, D., and Bonadonna, P. (2021). A Multidisciplinary Diagnostic Approach Reveals a Higher Prevalence of Indolent Systemic Mastocytosis: 15-Years\u2019 Experience of the GISM Network. Cancers, 13.","DOI":"10.3390\/cancers13246380"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zanotti, R., Tanasi, I., Bernardelli, A., Orsolini, G., and Bonadonna, P. (2021). Bone Marrow Mastocytosis: A Diagnostic Challenge. J. Clin. Med., 10.","DOI":"10.3390\/jcm10071420"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1038\/s41375-021-01406-y","article-title":"Refined Diagnostic Criteria for Bone Marrow Mastocytosis: A Proposal of the European Competence Network on Mastocytosis","volume":"36","author":"Zanotti","year":"2022","journal-title":"Leukemia"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1007\/s00198-019-04918-7","article-title":"Higher Prevalence of Vertebral Fractures in Systemic Mastocytosis, but Not in Cutaneous Mastocytosis and Idiopathic Mast Cell Activation Syndrome","volume":"30","author":"Eischen","year":"2019","journal-title":"Osteoporos. Int."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1016\/j.jaip.2024.02.021","article-title":"The Prevalence of Osteoporosis Is Low in Adult Cutaneous Mastocytosis Patients","volume":"12","author":"Couture","year":"2024","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_44","first-page":"92813","article-title":"Mast Cell Activation Syndrome: An up-to-Date Review of Literature","volume":"13","author":"Bak","year":"2024","journal-title":"World J. Clin. Pediatr."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Hermine, O., Lortholary, O., Leventhal, P.S., Catteau, A., Soppelsa, F., Baude, C., Cohen-Akenine, A., Palm\u00e9rini, F., Hanssens, K., and Yang, Y. (2008). Case-Control Cohort Study of Patients\u2019 Perceptions of Disability in Mastocytosis. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0002266"},{"key":"ref_46","unstructured":"Williams, C., Anastasopoulou, C., and Sapra, A. (2025). Biochemical Markers of Osteoporosis, StatPearls Publishing."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e638","DOI":"10.1016\/S2352-3026(19)30166-8","article-title":"International Prognostic Scoring System for Mastocytosis (IPSM): A Retrospective Cohort Study","volume":"6","author":"Sperr","year":"2019","journal-title":"Lancet Haematol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e194","DOI":"10.1016\/S2352-3026(20)30400-2","article-title":"Proposed Global Prognostic Score for Systemic Mastocytosis: A Retrospective Prognostic Modelling Study","volume":"8","author":"Zanotti","year":"2021","journal-title":"Lancet Haematol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"75.e1","DOI":"10.1016\/j.amjmed.2012.07.018","article-title":"Bone Complications of Mastocytosis: A Link between Clinical and Biological Characteristics","volume":"126","author":"Guillaume","year":"2013","journal-title":"Am. J. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1016\/j.bone.2011.07.004","article-title":"Bone Mineral Density, Bone Turnover Markers and Fractures in Patients with Indolent Systemic Mastocytosis","volume":"49","author":"Rossini","year":"2011","journal-title":"Bone"},{"key":"ref_51","unstructured":"National Clinical Guideline Centre (2012). Osteoporosis: Fragility Fracture Risk: Osteoporosis: Assessing the Risk of Fragility Fracture, Royal College of Physicians."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1016\/j.jaci.2014.05.003","article-title":"Predictors of New Fragility Fractures after Diagnosis of Indolent Systemic Mastocytosis","volume":"134","author":"Arends","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4081\/reumatismo.2016.870","article-title":"Guidelines for the Diagnosis, Prevention and Management of Osteoporosis","volume":"68","author":"Rossini","year":"2016","journal-title":"Reumatismo"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e2021056","DOI":"10.4084\/MJHID.2021.056","article-title":"Systemic Mastocytosis: Radiological Point of View","volume":"13","author":"Leone","year":"2021","journal-title":"Mediterr. J. Hematol. Infect. Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1007\/s11547-020-01306-8","article-title":"Systemic Mastocytosis Revisited with an Emphasis on Skeletal Manifestations","volume":"126","author":"Leone","year":"2021","journal-title":"Radiol. Med."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Murdaca, G., Allegra, A., Tonacci, A., Musolino, C., Ricciardi, L., and Gangemi, S. (2022). Mast Cells and Vitamin D Status: A Clinical and Biological Link in the Onset of Allergy and Bone Diseases. Biomedicines, 10.","DOI":"10.3390\/biomedicines10081877"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.3892\/etm.2021.10815","article-title":"Osteoporosis Therapies and Their Mechanisms of Action (Review)","volume":"22","author":"Kim","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"D\u00f6m\u00f6t\u00f6r, Z.R., V\u00f6rhendi, N., Han\u00e1k, L., Hegyi, P., Kiss, S., Csiki, E., Szak\u00f3, L., P\u00e1rniczky, A., and Er\u0151ss, B. (2020). Oral Treatment with Bisphosphonates of Osteoporosis Does Not Increase the Risk of Severe Gastrointestinal Side Effects: A Meta-Analysis of Randomized Controlled Trials. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.573976"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.bone.2011.01.003","article-title":"Safety of Bisphosphonates","volume":"49","author":"Pazianas","year":"2011","journal-title":"Bone"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1002\/jbmr.4235","article-title":"Safety of Oral Bisphosphonates in Moderate-to-Severe Chronic Kidney Disease: A Binational Cohort Analysis","volume":"36","author":"Robinson","year":"2020","journal-title":"J. Bone Miner. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"360","DOI":"10.7861\/clinmedicine.16-4-360","article-title":"Recent Advances in the Pathogenesis and Treatment of Osteoporosis","volume":"16","author":"Curtis","year":"2016","journal-title":"Clin. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1007\/s10067-009-1165-4","article-title":"Systemic Mastocytosis Presenting as Osteoporosis\u2014A Case Report","volume":"28","author":"Mathew","year":"2009","journal-title":"Clin. Rheumatol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1127.e1","DOI":"10.1016\/j.amjmed.2014.06.015","article-title":"Zoledronic Acid in Osteoporosis Secondary to Mastocytosis","volume":"127","author":"Rossini","year":"2014","journal-title":"Am. J. Med."},{"key":"ref_64","first-page":"2","article-title":"A 48-Year-Old Man with a Hip Fracture and Skin Rash: A Case Report","volume":"10","author":"Parker","year":"2024","journal-title":"AACE Clin. Case Rep."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1093\/rheumatology\/36.3.393","article-title":"The Effect of Pamidronate on Lumbar Spine Bone Density and Pain in Osteoporosis Secondary to Systemic Mastocytosis","volume":"36","author":"Marshall","year":"1997","journal-title":"Rheumatology"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1007\/s10067-006-0369-0","article-title":"Clinical and Densitometric Efficacy of the Association of Interferon Alpha and Pamidronate in the Treatment of Osteoporosis in Patients with Systemic Mastocytosis","volume":"26","author":"Laroche","year":"2006","journal-title":"Clin. Rheumatol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1016\/j.amjmed.2011.02.038","article-title":"Interferon Alpha and Pamidronate in Osteoporosis with Fracture Secondary to Mastocytosis","volume":"124","author":"Laroche","year":"2011","journal-title":"Am. J. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1136\/annrheumdis-2023-eular.3302","article-title":"Pos0496\u2005Management of Osteoporosis in Patients with Systemic Mastocytosis: A Monocentric Expert Centre Experience","volume":"82","author":"Nezzar","year":"2023","journal-title":"Ann. Rheum. Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/BF00663015","article-title":"Successful Treatment of Osteoporosis in Systemic Mastocytosis with Interferon Alpha-2b","volume":"72","author":"Weide","year":"1996","journal-title":"Ann. Hematol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1093\/rheumatology\/35.9.898","article-title":"Severe osteoporosis due to systemic mast cell disease: Successful treatment with interferon alpha-2B","volume":"35","author":"Lehmann","year":"1996","journal-title":"Rheumatology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1007\/s12325-021-01936-y","article-title":"Denosumab in the Treatment of Osteoporosis: 10 Years Later: A Narrative Review","volume":"39","author":"Kendler","year":"2022","journal-title":"Adv. Ther."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1111\/ijcp.12022","article-title":"Denosumab: Mechanism of Action and Clinical Outcomes","volume":"66","author":"Hanley","year":"2012","journal-title":"Int. J. Clin. Pract."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/S2213-8587(17)30138-9","article-title":"10 Years of Denosumab Treatment in Postmenopausal Women with Osteoporosis: Results from the Phase 3 Randomised FREEDOM Trial and Open-Label Extension","volume":"5","author":"Bone","year":"2017","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.bone.2017.08.003","article-title":"Discontinuation of Denosumab Therapy for Osteoporosis: A Systematic Review and Position Statement by ECTS","volume":"105","author":"Tsourdi","year":"2017","journal-title":"Bone"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.1007\/s00198-016-3539-1","article-title":"Prevalence, Pathogenesis, and Treatment Options for Mastocytosis-Related Osteoporosis","volume":"27","author":"Rossini","year":"2016","journal-title":"Osteoporos. Int."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1007\/s00223-017-0241-z","article-title":"Denosumab for the Treatment of Mastocytosis-Related Osteoporosis: A Case Series","volume":"100","author":"Orsolini","year":"2017","journal-title":"Calcif. Tissue Int."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.medcli.2017.10.010","article-title":"Osteonecrosis Maxilar Asociada a Tratamiento Con Denosumab En Una Paciente Con Mastocitosis Sist\u00e9mica","volume":"151","author":"Cariati","year":"2018","journal-title":"Med. Clin."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"bvaf149.535","DOI":"10.1210\/jendso\/bvaf149.535","article-title":"MON-793 Long-Term Denosumab Treatment in a Patient with Low Bone Mass Associated with Indolent Systemic Mastocytosis","volume":"9","author":"Joven","year":"2025","journal-title":"J. Endocr. Soc."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"luaf272","DOI":"10.1210\/jcemcr\/luaf272","article-title":"Denosumab as a Potential Disease-Modifying Treatment in Indolent Systemic Mastocytosis-Related Osteoporosis","volume":"4","author":"Abbas","year":"2025","journal-title":"JCEM Case Rep."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2530","DOI":"10.1056\/NEJMoa1513098","article-title":"Efficacy and Safety of Midostaurin in Advanced Systemic Mastocytosis","volume":"374","author":"Gotlib","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1038\/s41591-021-01538-9","article-title":"Safety and Efficacy of Avapritinib in Advanced Systemic Mastocytosis: The Phase 1 EXPLORER Trial","volume":"27","author":"DeAngelo","year":"2021","journal-title":"Nat. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2565","DOI":"10.1182\/blood-2021-146873","article-title":"Efficacy of Avapritinib in Patients with Advanced Systemic Mastocytosis: Hematologic and Bone Marrow Responses from the Phase 2 Open-Label, Single-Arm, Pathfinder Study","volume":"138","author":"George","year":"2021","journal-title":"Blood"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1038\/s41591-021-01539-8","article-title":"Efficacy and Safety of Avapritinib in Advanced Systemic Mastocytosis: Interim Analysis of the Phase 2 PATHFINDER Trial","volume":"27","author":"Gotlib","year":"2021","journal-title":"Nat. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1056\/EVIDoa2200339","article-title":"Avapritinib versus Placebo in Indolent Systemic Mastocytosis","volume":"2","author":"Gotlib","year":"2023","journal-title":"NEJM Evid."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"5582","DOI":"10.1182\/blood-2025-5582","article-title":"Changes in Long-Term Bone Health in Patients Receiving Avapritinib for the Treatment of Indolent Systemic Mastocytosis in the Pioneer Study","volume":"146","author":"Castells","year":"2025","journal-title":"Blood"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1182\/blood-2025-1022","article-title":"Avapritinib Treatment of Patients with Advanced Systemic Mastocytosis: 4-Year Safety, Effect on Bone and First-Line Efficacy Results of the Pathfinder Clinical Study","volume":"146","author":"Reiter","year":"2025","journal-title":"Blood"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3813","DOI":"10.1182\/blood-2025-3813","article-title":"Clinical, Molecular, and Demographic Features of Systemic Mastocytosis: Analysis of a Large Cohort","volume":"146","author":"Nguyen","year":"2025","journal-title":"Blood"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1186\/1752-1947-4-193","article-title":"Oral and Inhaled Sodium Cromoglicate in the Management of Systemic Mastocytosis: A Case Report","volume":"4","author":"Edwards","year":"2010","journal-title":"J. Med. Case Rep."},{"key":"ref_89","first-page":"342","article-title":"Innovative Therapeutic Approaches in Systemic Mastocytosis: An Updated Review","volume":"20","author":"Soare","year":"2025","journal-title":"Maedica\u2014J. Clin. Med."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Szudy-Szczyrek, A., Bachanek-Mitura, O., Gromek, T., Chromik, K., Mital, A., Szczyrek, M., Krupski, W., Szumi\u0142o, J., Kandu\u0142a, Z., and Helbig, G. (2021). Real-World Efficacy of Midostaurin in Aggressive Systemic Mastocytosis. J. Clin. Med., 10.","DOI":"10.3390\/jcm10051109"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1007\/s00223-015-9969-5","article-title":"Dickkopf-1 and Sclerostin Serum Levels in Patients with Systemic Mastocytosis","volume":"96","author":"Rossini","year":"2015","journal-title":"Calcif. Tissue Int."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.drudis.2013.04.001","article-title":"Sclerostin: How Human Mutations Have Helped Reveal a New Target for the Treatment of Osteoporosis","volume":"18","author":"Robinson","year":"2013","journal-title":"Drug Discov. Today"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/s40259-017-0229-2","article-title":"Targeting Sclerostin in Postmenopausal Osteoporosis: Focus on Romosozumab and Blosozumab","volume":"31","author":"Reid","year":"2017","journal-title":"BioDrugs"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1056\/NEJMoa1607948","article-title":"Romosozumab Treatment in Postmenopausal Women with Osteoporosis","volume":"375","author":"Cosman","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1002\/jbmr.3735","article-title":"Bone-Forming and Antiresorptive Effects of Romosozumab in Postmenopausal Women with Osteoporosis: Bone Histomorphometry and Microcomputed Tomography Analysis After 2 and 12 Months of Treatment","volume":"34","author":"Chavassieux","year":"2019","journal-title":"J. Bone Miner. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"4544","DOI":"10.1182\/blood-2024-193774","article-title":"Disease-Modifying Effects of Avapritinib in Patients with Advanced Systemic Mastocytosis: Improvements in Bone Density","volume":"144","author":"Luebke","year":"2024","journal-title":"Blood"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1007\/s00198-025-07541-x","article-title":"Machine Learning Is Changing Osteoporosis Detection: An Integrative Review","volume":"36","author":"Zhang","year":"2025","journal-title":"Osteoporos. Int."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"102948","DOI":"10.1016\/j.arr.2025.102948","article-title":"Artificial Intelligence for Fall Detection in Older Adults: A Comprehensive Survey of Machine Learning, Deep Learning Approaches, and Future Directions","volume":"113","author":"Gattani","year":"2026","journal-title":"Ageing Res. Rev."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2610079","DOI":"10.1080\/07853890.2025.2610079","article-title":"Enhanced fracture detection on radiographs with AI assistance for clinicians: A systematic review and meta-analysis","volume":"58","author":"Qin","year":"2026","journal-title":"Ann. Med."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/3\/307\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T11:30:51Z","timestamp":1770809451000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/3\/307"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,6]]},"references-count":99,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["cells15030307"],"URL":"https:\/\/doi.org\/10.3390\/cells15030307","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,6]]}}}