Primary Sjogren syndrome increases the risk of bisphosphonate-related osteonecrosis of the jaw

Abstract

The risk of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in primary Sjogren syndrome (pSS) has rarely been explored. To explore the association between BRONJ and pSS, we conducted a population-based propensity-score-matched cohort study using Taiwan’s National Health Insurance Research Database, including pSS patients receiving antiosteoporotic therapy and patients without pSS receiving antiosteoporotic therapy. A 1:4 matched-pair cohort based on propensity score was created. The stratified Cox proportional hazards model compared the risk of BRONJ in the pSS and non-pSS groups. In the study, 23,280 pSS patients and 28,712,152 controls were enrolled. After matching, 348 patients with pSS receiving antiosteoporotic drugs and 50,145 without pSS receiving antiosteoporotic drugs were included for analysis. The risk of developing BRONJ was 1.96 times higher in pSS patients compared with non-pSS patients after adjustment for age, sex, and comorbidities. No dose–response effect was observed in the bisphosphonate-treated pSS cohorts, documented as the cumulative defined daily doses of either < 224 or ≥ 224 (hazard ratio [HR]: 2.407, 95% confidence interval [CI] 1.412–7.790; HR: 2.143, 95% CI 1.046–4.393, respectively) increased risk of developing osteonecrosis of the jaw. In conclusion, the risk of BRONJ is significantly higher in patients with pSS compared with the general population.

Are medication-induced salivary changes the culprit of osteonecrosis of the jaw? A systematic review

“…Based on the qualitative synthesis, a reduction in salivary flow and changes in salivary protein levels led to the development of MRONJ. Two studies revealed a significant association between SS and MRONJ, following the administration of bisphosphonates, steroids, and chemotherapy ( 25 , 27 ). In two studies, patients with a history of bisphosphonates, steroids, chemotherapy, thalidomide, interferon, and hormone therapy showed a significantly higher association between salivary flow and MRONJ development ( 26 , 30 ).…”

“…All these factors increase the risk of MRONJ, and the health-related quality of life of these patients is severely diminished. It should be noted that patients with SS were more susceptible to bisphosphonate-related osteonecrosis of the jaw, which might be due to the shared risk factors and molecular pathways ( 25 , 27 ). Low salivary flow in combination with acid reflux might result in an oral environment of low pH, which promotes the growth of acidophilic bacteria, in turn, leading to tooth destruction and mucosal degradation ( 40 ).…”

Mechanism of bisphosphonate-related osteonecrosis of the jaw (BRONJ) revealed by targeted removal of legacy bisphosphonate from jawbone using competing inert hydroxymethylene diphosphonate

“…Therefore, other confounding factors may be involved in the pathogenesis of MRONJ. Clinical case studies proposed an increased risk of BRONJ in patients with autoimmune diseases such as rheumatoid arthritis ( Fujieda et al, 2020 ), autoimmune hepatitis ( de Boer et al, 2012 ), and Sjogren syndrome ( Kuo et al, 2021 ; Liao et al, 2019 ). N-BP-treated rodent models combined with experimental rheumatoid arthritis ( de Molon et al, 2016 ) or concurrent dexamethasone treatment ( Inoue et al, 2021 ) developed exacerbated BRONJ lesion supporting the susceptibility of compromised systemic immunity.…”

Incidence and Risk of Anti-Resorptive Agent-Related Osteonecrosis of the Jaw after Tooth Extraction: A Retrospective Study

“…The mechanisms of ONJ development with BMA use include impaired bone remodeling, inflammation or infection, immune changes due to anticancer drugs and diabetes, and healing failure due to impaired angiogenesis. Since hypoparathyroidism causes a bone remodeling disorder, it is considered that the risk of ARONJ increases due to the synergistic effect with BMA administration [ 13 ]. In addition, PTH therapy is administered in hypoparathyroidism, and hormone therapy is suggested as a high risk for ARONJ in this study because of its correlation with hypoparathyroidism.…”