Microarchitecture of medication-related osteonecrosis of the jaw (MRONJ); a retrospective micro-CT and morphometric analysis |
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| Authors: | Rouven Schoenhof Adelheid Munz Anna Yuan Ashraf ElAyouti Hans Boesmueller Gunnar Blumenstock Siegmar Reinert Sebastian Hoefert |
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| Affiliation: | 1. Department of Oral and Maxillofacial Surgery, University Hospital Tuebingen, Osianderstrasse 2-8, 72076, Tuebingen, Germany;2. Department of Conservative Dentistry and Periodontology, University Hospital Tuebingen, Osianderstrasse 2-8, 72076, Tuebingen, Germany;3. Institute of Pathology, Liebermeisterstrasse 8, 72076, Tuebingen, Germany;4. Institute for Clinical Epidemiology and Applied Biometry, University Hospital Tuebingen, Silcherstrasse 5, 72076, Tuebingen, Germany;1. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Oral Maxillofacial Surgery, West China School of Stomatology, Sichuan University, Chengdu, 610041, China;2. Department of Health Statistics, School of Preventive Medicine, Fourth Military Medical University, Changlexilu Road #169, Shaanxi, 710032, China;3. Division of Plastic Surgery, The Children''s Hospital of Philadelphia, Philadelphia, PA, 19104, USA;1. Maxillofacial Surgery and Diagnostic Science, College of Dentistry, Qassim University, Saudi Arabia;2. Anaesthesia, Intensive Care, and Pain, Faculty of Medicine for Girls, Al Azhar University, 11727, Nasr City, Cairo, Egypt;3. Oral and Maxillofacial Surgery, Faculty of Dentistry, Deraya University, Minya, Egypt;4. Dental Medicine for Girls, Al Azhar University, 11727, Nasr City, Cairo, Egypt;1. Department of Oral and Maxillofacial Surgery, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Glueckstrasse 11, 91054, Erlangen, Germany;2. James Cook University Hospital, South Tees NHS Trust, Middlesbrough, UK;3. Department of Medical Informatics, Biometry and Epidemiology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Waldstrasse 6, 91054, Erlangen, Germany;4. Department of Radiology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Krankenhausstrasse 12, 91054, Erlangen, Germany;5. Practice for Oral, Maxillofacial and Plastic Surgery, Fürther Straße 4a, 90429, Nürnberg, Germany;1. Department of Head and Neck Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, Japan;2. Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, Nagoya, Japan;3. Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, 65-banchi, Tsurumai-cho, Showa-ku, Nagoya-shi, Aichi, Nagoya, Japan |
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| Abstract: | ![]()
Medication-related osteonecrosis of the jaw (MRONJ) is a severe side effect of antiresorptive (AR) drugs such as bisphosphonates (BP) and denosumab (Dmab). Although several risk factors are described, the etiology of MRONJ is still not fully elucidated. Bone-strengthening is the primary aim of antiresorptive therapy; however, overly increased bone mass and microcrack accumulation are also discussed in MRONJ etiologies. The aim of this study is to evaluate the microarchitecture of jaw bones with micro?computed tomography (micro-CT) in AR-treated patients with or without MRONJ.Human jaw bone samples of AR-treated patients were separated into 11 groups by AR treatment bisphosphonate (BP), denosumab (Dmab), both (M) and control groups. Subgroups were divided according to the clinical localization as AR-exposed vital jaw bone (BPexp, Dmabexp, Mexp), osteonecrosis–margin of a sequestrum (BPOmar, DmabOmar, MOmar) and osteonecrosis–sequestrum (BPOseq, DmabOseq, MOseq). Healthy jaw bone (CHB) and osteoporotic jaw bone (COP) represent control groups. Samples underwent retrospective micro-CT and morphometric analysis in representative units by bone volume fraction (BV/TV), bone surface density (BS/BV), trabecular thickness (Tr.Th.), trabecular number (Tr.N.), trabecular space (Tr.Sp.), Euler characteristic for bone connectivity, bone mineral density (BMD) and tissue mineral density (TMD).A total of 141 samples from 78 patients were analyzed. BV/TV of Mexp group (mean: 0.46 ± 0.27) was significantly higher than in the COP group (mean: 0.14 ± 0.05; p = 0.0053). Tr.Th. differed significantly between the BPexp group (mean: 0.32 ± 0.15) and the Mexp group (mean: 0.57 ± 0.20; p = 0.0452) as well as between the BPOseq group (mean: 0.25 ± 0.10) and the MOseq group (mean: 0.39 ± 0.18; p = 0.0417). Signs of trabecular thickening and unorganized trabecular microarchitecture from AR-exposed- to sequestrum groups, were analyzed in 3D reconstructions. However, BS/BV, Tr.N., and Tr.Sp. showed no significant differences. Euler characteristic of the BPOseq group (median: 7.46) doubled compared to that of the BPexp group (median: 14.97; p = 0.0064). Mineralization parameters BMD and TMD were similar in all groups.Findings show evidence of enhanced bone mass and suspect microarchitecture in some AR-treated jaw bone compared to osteoporotic jaw bone. Despite increased bone mass, some MRONJ samples showed decreased trabecular connectivity by Euler characteristic compared to AR-treated jaw bone. These samples may indicate extensive ossification and ineffective bone mass with superficially higher bone mass without existing or even reduced mechanical stability, indicated by connectivity loss. This result might also suggest a high risk to microcrack accumulation. At some point, possibly some kind of over-ossification could lead to under-nourishment and microarchitectural weakness, creating instability, subsequently increasing vulnerability to MRONJ. |
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| Keywords: | MRONJ Microarchitecture Euler-characteristics Bone mass |
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