Academic Journal
Increased Bone Volume by Ixazomib in Multiple Myeloma:3-Month Results from an Open Label Phase 2 Study
| العنوان: | Increased Bone Volume by Ixazomib in Multiple Myeloma:3-Month Results from an Open Label Phase 2 Study |
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| المؤلفون: | Diaz-delCastillo, Marta, Gundesen, Michael Tveden, Andersen, Christian Walther, Nielsen, Anne Lerberg, Møller, Hanne Elisabeth Højsgaard, Vinholt, Pernille Just, Asmussen, Jon Thor, Kristensen, Ida Bruun, Nyvold, Charlotte Guldborg, Abildgaard, Niels, Andersen, Thomas Levin, Lund, Thomas |
| المصدر: | Diaz-delCastillo , M , Gundesen , M T , Andersen , C W , Nielsen , A L , Møller , H E H , Vinholt , P J , Asmussen , J T , Kristensen , I B , Nyvold , C G , Abildgaard , N , Andersen , T L & Lund , T 2023 , ' Increased Bone Volume by Ixazomib in Multiple Myeloma : 3-Month Results from an Open Label Phase 2 Study ' , Journal of Bone and Mineral Research , vol. 38 , no. 5 , pp. 639-649 . https://doi.org/10.1002/jbmr.4807 |
| سنة النشر: | 2023 |
| المجموعة: | Aarhus University: Research |
| مصطلحات موضوعية: | ANABOLICS, BONE HISTOMORPHOMETRY, OSTEOBLASTS, OSTEOCLASTS, TUMOR-INDUCED BONE DISEASE |
| الوصف: | Multiple myeloma (MM) is an incurable bone marrow cancer characterized by the development of osteolytic lesions due to the myeloma-induced increase in osteoclastogenesis and decrease in osteoblastic activity. The standard treatment of MM often involves proteasome inhibitors (PIs), which can also have a beneficial off-target bone anabolic effect. However, long-term treatment with PIs is unadvised due to their high side-effect burden and inconvenient route of administration. Ixazomib is a new-generation, oral PI that is generally well tolerated; however, its bone effect remains unknown. Here, we describe the 3-month results of a single-center phase II clinical trial investigating the effect of ixazomib treatment on bone formation and bone microstructure. Thirty patients with MM in stable disease not receiving antimyeloma treatment for ≥3 months and presenting ≥2 osteolytic lesions received monthly ixazomib treatment cycles. Serum and plasma samples were collected at baseline and monthly thereafter. Sodium 18 F-Fluoride positron emission tomography (NaF-PET) whole-body scans and trephine iliac crest bone biopsies were collected before and after three treatment cycles. The serum levels of bone remodeling biomarkers suggested an early ixazomib-induced decrease in bone resorption. NaF-PET scans indicated unchanged bone formation ratios; however, histological analyses of bone biopsies revealed a significant increase in bone volume per total volume after treatment. Further analyses of bone biopsies showed unchanged osteoclast number and COLL1A1 High -expressing osteoblasts on bone surfaces. Next, we analyzed the superficial bone structural units (BSUs), which represent each recent microscopic bone remodeling event. Osteopontin staining revealed that following treatment, significantly more BSUs were enlarged (>200,000 μm 2 ), and the distribution frequency of their shape was significantly different from baseline. Overall, our data suggest that ixazomib induces overflow remodeling-based bone formation by decreasing the ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | https://pure.au.dk/portal/en/publications/e0dd0ff8-4d7a-43a3-94ee-d7207da9034e |
| DOI: | 10.1002/jbmr.4807 |
| الاتاحة: | https://pure.au.dk/portal/en/publications/e0dd0ff8-4d7a-43a3-94ee-d7207da9034e https://doi.org/10.1002/jbmr.4807 http://www.scopus.com/inward/record.url?scp=85152774657&partnerID=8YFLogxK |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.AF2AC639 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1002/jbmr.4807 |
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