Abstract
Objective: This nested case–control study aimed to investigate the effects of VEGFA polymorphisms on the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in women with osteoporosis. Methods: Eleven single nucleotide polymorphisms (SNPs) of the VEGFA were assessed in a total of 125 patients. Logistic regression was performed for multivariable analysis. Machine learning algorithms, namely, fivefold cross-validated multivariate logistic regression, elastic net, random forest, and support vector machine, were developed to predict risk factors for BRONJ occurrence. Area under the receiver-operating curve (AUROC) analysis was conducted to assess clinical performance. Results: The VEGFA rs881858 was significantly associated with BRONJ development. The odds of BRONJ development were 6.45 times (95% CI, 1.69–24.65) higher among carriers of the wild-type rs881858 allele compared with variant homozygote carriers after adjusting for covariates. Additionally, variant homozygote (GG) carriers of rs10434 had higher odds than those with wild-type allele (OR, 3.16). Age ≥ 65 years (OR, 16.05) and bisphosphonate exposure ≥ 36 months (OR, 3.67) were also significant risk factors for BRONJ occurrence. AUROC values were higher than 0.78 for all machine learning methods employed in this study. Conclusion: Our study showed that the BRONJ occurrence was associated with VEGFA polymorphisms in osteoporotic women.
Highlights
Bisphosphonates are widely used to treat various bone diseases, including osteoporosis and cancer-induced bone metastasis
Since bisphosphonate-related osteonecrosis of the jaw (BRONJ) was first described in 2003, denosumab, which is a new antiresorptive; tyrosine kinase inhibitors; mammalian target of rapamycin inhibitors; monoclonal antibodies; radiopharmaceuticals; selective estrogen receptor modulators; and immunosuppressants have been implicated in ONJ [3]
After adjusting for demographic variables with p < 0.05, we found that the odds of BRONJ development were about 6.45 times higher among the G allele carriers of rs881858 than the odds among variant homozygote carriers (p < 0.01)
Summary
Bisphosphonates are widely used to treat various bone diseases, including osteoporosis and cancer-induced bone metastasis. The majority of ONJ cases occur after dental surgery, such as tooth extraction [6], and wound healing processes may be involved. Complementary treatment, such as laser, ozone therapy and application of platelet concentrates in solid and liquid form, would allow both to prevent ONJ and improve healing after surgical treatment of bone lesions [7,8,9]. It is assumed that ONJ may develop, at least in part, due to the effect of bisphosphonates on angiogenic gene expression in healing tissues
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