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      Mandibular Reconstruction with Free Fibula Flap for Medication-related Osteonecrosis of the Jaw in Patients with Multiple Myeloma

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          Summary:

          While bisphosphonates are the cornerstone for management of multiple myeloma, they are associated with medication-related osteonecrosis of the jaw (MRONJ). There are many controversies in the management of MRONJ in this patient population. In this article, we describe a representative case and, along with a literature review, we report the outcomes of our 3 cases with multiple myeloma who underwent mandible reconstruction with vascularized fibula bone grafts after segmental mandible resection for Stage 3 MRONJ over a 3-year period. All patients were male with a mean age of 59 years. All patients had undergone therapy with bisphosphonates and had no other identifiable cause of mandible osteonecrosis. All patients had pathologic mandible fractures associated with intraoral fistulae and exposed bone. Nonsurgical management was attempted in all patients. One patient also underwent debridement of the mandible without resolution of the disease. Mandible reconstruction with an osteocutaneous free fibula flap after segmental mandible resection was performed in all 3 cases without major complications or donor site morbidity. Different bacteria were isolated from the intraoperative tissue cultures in all cases. Computed tomographic imaging revealed bony union without hardware complications in all cases. Mean follow-up was 28 months. In conclusion, we demonstrated that patients with multiple myeloma and advanced MRONJ lesions of the mandible can be managed successfully and safely by segmental resection and reconstruction with vascularized fibula bone graft.

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          Most cited references14

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          American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws--2009 update.

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            Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment.

            Bisphosphonates inhibit bone resorption and thus bone renewal by suppressing the recruitment and activity of osteoclasts thus shortening their life span. Recently three bisphosphonates, Pamidronate (Aredia; Novartis Pharmaceuticals, East Haven, NJ), Zoledronate (Zometa; Novartis Pharmaceuticals), and Alendronate (Fosamax; Merck Co, West Point, VA) have been linked to painful refractory bone exposures in the jaws. One hundred-nineteen total cases of bisphosphonate-related bone exposure were reviewed. Thirty-two of 119 patients (26%) received Aredia, 48 (40.3%) received Zometa, 36 (30.2%) received Aredia later changed to Zometa, and 3 (2.5%) received Fosamax. The mean induction time for clinical bone exposure and symptoms was 14.3 months for those who received Aredia, 12.1 months for those who received both, 9.4 months for those who received Zometa, and 3 years for those who received Fosamax. Sixty-two (52.1%) were treated for multiple myeloma, 50 (42%) for metastatic breast cancer, 4 (3.4%) for metastatic prostate cancer and 3 (2.5%) for osteoporosis. Presenting findings in addition to exposed bone were 37 (31.1%) asymptomatic, 82 (68.9%) with pain, 28 (23.5%) mobile teeth, and 21 (17.6%) with nonhealing fistulas. Eighty-one (68.1%) bone exposures occurred in the mandible alone, 33 (27.7%) in the maxilla, and 5 (4.2%) occurred in both jaws. Medical comorbidities included the malignancy itself 97.5%, previous and/or maintenance chemotherapy 97.5%, Dexamethasone 59.7%. Dental comorbidities included the presence of periodontitis 84%, dental caries 28.6%, abscessed teeth 13.4% root canal treatments 10.9%, and the presence of mandibular tori 9.2%. The precipitating event that produced the bone exposures were spontaneous 25.2%, tooth removals 37.8%, advanced periodontitis 28.6%, periodontal surgery 11.2%, dental implants 3.4% and root canal surgery 0.8%. Complete prevention of this complication in not currently possible. However, pre-therapy dental care reduces this incidence, and non-surgical dental procedures can prevent new cases. For those who present with painful exposed bone, effective control to a pain free state without resolution of the exposed bone is 90.1% effective using a regimen of antibiotics along with 0.12% chlorohexidine antiseptic mouth.
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              Multiple myeloma in the marrow: pathogenesis and treatments.

              Multiple myeloma (MM) is a B cell malignancy resulting in osteolytic lesions and fractures. In the disease state, bone healing is limited owing to increased osteoclastic and decreased osteoblastic activity, as well as an MM-induced forward-feedback cycle where bone-embedded growth factors further enhance tumor progression as bone is resorbed. Recent work on somatic mutation in MM tumors has provided insight into cytogenetic changes associated with this disease; the initiating driver mutations causing MM are diverse because of the complexity and multitude of mutations inherent in MM tumor cells. This manuscript provides an overview of MM pathogenesis by summarizing cytogenic changes related to oncogenes and tumor suppressors associated with MM, reviewing risk factors, and describing the disease progression from monoclonal gammopathy of undetermined significance to overt MM. It also highlights the importance of the bone marrow microenvironment (BMM) in the establishment and progression of MM, as well as associated MM-induced bone disease, and the relationship of the bone marrow to current and future therapeutics. This review highlights why understanding the basic biology of the healthy and diseased BMM is crucial in the quest for better treatments and work toward a cure for genetically diverse diseases such as MM.
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                Author and article information

                Journal
                Plast Reconstr Surg Glob Open
                Plast Reconstr Surg Glob Open
                GOX
                Plastic and Reconstructive Surgery Global Open
                Lippincott Williams & Wilkins (Hagerstown, MD )
                2169-7574
                October 2020
                28 October 2020
                : 8
                : 10
                : e3186
                Affiliations
                From the [* ]Division of Plastic and Reconstructive Surgery, Department of Surgery, UCHealth University of Colorado Hospital, Aurora, Colo.
                []Section of Oral and Maxillofacial Surgery, UCLA School of Dentistry; Division of Plastic and Reconstructive Surgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, Calif.
                []Hansjörg Wyss Department of Plastic Surgery, NYU Langone Health, New York, N.Y.
                [§ ]Division of Oral and Maxillofacial Surgery, Department of Surgery, NYU Langone Health, New York, N.Y.
                Author notes
                Christodoulos Kaoutzanis, MD, Division of Plastic & Reconstructive Surgery, Department of Surgery, UCHealth University of Colorado Hospital, Academic Office 1 (AO1), 12631 E. 17th Ave, C309, Aurora, CO 80045, E-mail: ckaoutzanis@ 123456gmail.com
                Article
                00046
                10.1097/GOX.0000000000003186
                7647497
                aade6b7b-0efe-4f12-8457-d3f3961d8ad9
                Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

                History
                : 6 July 2020
                : 22 August 2020
                Categories
                Reconstructive
                Case Report
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                UNITED STATES

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