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(a) Stage I MRONJ presence of fistulas on the maxillary alveolar ridge extending to the underlying bone. (b) Stage I MRONJ: site of exposed bone left mandible distal to the premolar that is confined to the alveolar bone superior to the inferior alveolar nerve canal. (c) Stage II: MRONJ exposed bone involving the ascending ramus of the left mandible showing both the radiographic and clinical presentation. (d) Stage III: cone beam CT demonstrating MRONJ of the left mandible extending below the inferior dental nerve canal. (e) Stage III MRONJ; cone Beam CT of the right alveolar processes showing MRONJ associated with upper right molars and the right maxillary sinus.
Source publication
Myeloma is a common haematological malignancy in which adverse skeletal related events are frequently seen. Over recent years, treatment for myeloma has evolved leading to improved survival. Antiresorptive therapy is an important adjunct therapy to reduce the risk of bone fractures and to improve the quality of life for myeloma patients; however, t...
Citations
... Several hypotheses can explain the overall pathophysiology of MRONJ [4,5]. Antiresorptive and antiangiogenic reagents, including bisphosphonates and denosumab, inhibit bone remodeling by affecting osteoclast formation and differentiation, or they directly inhibit angiogenesis by reducing blood flow to the bone [5,6]. Genetic factors such as single nucleotide polymorphisms (SNPs) and mutations are significantly associated with MRONJ development by regulating bone remodeling, angiogenesis, and immune responses [7,8]. ...
Background:
Bisphosphonates are antiresorptive and antiangiogenic drugs that prevent and treat bone loss and mineralization in women with postmenopausal osteoporosis and cancer patients. Medication-related osteonecrosis of the jaw (MRONJ) is commonly caused by tooth extraction and dental trauma. Although genetic and pathological studies about MRONJ have been conducted, the pathogenesis of MRONJ still remains unclear.
Methods:
We aimed to identify genetic variants associated with MRONJ, using whole-exome sequencing (WES). Ten MRONJ patients prescribed bisphosphonates were recruited for WES, and jawbone tissue and blood samples were collected from the patients.
Results:
The analysis of the WES data found a total of 1866 SNP and 40 InDel variants which are specific to MRONJ. The functional classification assay using Gene Ontology and pathway analysis discovered that genes bearing the MRONJ variants are significantly enriched for keratinization and calcium ion transport. Some of the variants are potential pathogenic variants (24 missense mutations and seven frameshift mutations) with MAF < 0.01.
Conclusions:
The variants are located in eight different genes (KRT18, MUC5AC, NBPF9, PABPC3, MST1L, ASPN, ATN1, and SLAIN1). Nine deleterious SNPs significantly associated with MRONJ were found in the KRT18 and PABPC3 genes. It suggests that KRT18 and PABPC3 could be MRONJ-related key genes.
... Several hypotheses can explain the overall pathophysiology of MRONJ [4,5]. Antiresorptive and antiangiogenic reagents, including bisphosphonates and denosumab, inhibit bone remodeling by affecting osteoclast formation and differentiation, or they directly inhibit angiogenesis by reducing blood flow to the bone [5,6]. Genetic factors such as single nucleotide polymorphisms (SNPs) and mutations are significantly associated with MRONJ development by regulating bone remodeling, angiogenesis, and immune responses [7,8]. ...
Ovarian granulosa cell tumor (OGCT) is a rare ovarian tumor that accounts for about 2-5% of all ovarian tumors. Despite the low grade of ovarian tumors, high and late recurrences are common in OGCT patients. Even though this tumor usually occurs in adult women with high estrogen levels, the cause of OGCT is still unknown. To screen genetic variants associated with OGCT, we collected normal and matched-tumor formalin-fixed paraffin-embedded (FFPE) from 11 OGCT patients and performed whole-exome sequencing (WES) using Illumina NovaSeq 6000. A total of 1,067,219 single nucleotide polymorphisms (SNPs) and 162,155 insertions/deletions (indels) were identified from 11 pairs of samples. Of these, we identified 44 tumor-specific SNPs in 22 genes and four tumor-specific indels in one gene that were common to 11 patients. We used three cancer databases (TCGA, COSMIC, and ICGC) to investigate genes associated with ovarian cancers. Nine genes (SEC22B, FEZ2, ANKRD36B, GYPA, MUC3A, PRSS3, NUTM2A, OR8U1, and KRTAP10-6) associated with ovarian cancers were found in all three databases. In addition, we identified seven rare variants with MAF ≤ 0.05 in two genes (PRSS3 and MUC3A). Of seven rare variants, five variants in MUC3A are potentially pathogenic. Furthermore, we conducted gene enrichment analysis of tumor-specific 417 genes in SNPs and 106 genes in indels using cytoscape and metascape. In GO analysis, these genes were highly enriched in “selective autophagy”, and “regulation of anoikis”. Taken together, we suggest that MUC3A is implicated in OGCT development, and MUC3A could be used as a potential biomarker for OGCT diagnosis.
... Due to the improving survival, the level of exposure to these drugs becomes longer, and we might expect to see more such complications. Therefore, prevention and early intervention is important, as Beaumont and co-workers [10] emphasize in their paper. The risk of MRONJ is higher in malignancy than in non-malignant osteoporosis. ...
It was Bart Barlogie who made a clear point by stating in one of his lectures that any myeloma that is not cured will eventually turn into a resistant disease with aggressive clinical behaviour [...]
