ArticleClinical rheumatology2026
Osteoporosis and fracture severity as independent risk factors for osteonecrosis of the jaw in rheumatoid arthritis: a TriNetX cohort study.
Article in Clinical rheumatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectivesTo investigate the independent impact of osteoporosis and its severity, characterised by bone fractures, on osteonecrosis of the jaw (ONJ) risk in patients with rheumatoid arthritis (RA) using a global real-world database. We hypothesised that osteoporosis independently increases ONJ risk in patients with RA, irrespective of medication exposure.
methodsThis retrospective cohort study utilised the TriNetX database. Primary analysis estimated the association between osteoporosis and incident ONJ (primary outcome) after propensity score matching (PSM). Secondary analysis evaluated the impact of bone fractures using multivariable Cox proportional hazards models. Sensitivity analyses assessed robustness.
resultsIn the primary PSM analysis (160,789 pairs), osteoporosis was the strongest independent risk factor for ONJ (adjusted hazard ratio [aHR] 3.135, 95% confidence interval [CI] 2.740-3.584, P < 0.001). Among patients with osteoporosis (22,821 pairs), ONJ incidence was higher in those with bone fractures (P = 0.047). Multivariable analysis identified bone fractures (aHR 1.522, 95% CI 1.202-1.931, P < 0.001) and denosumab use (aHR 1.970, 95% CI 1.397-2.777, P < 0.001) as independent risk factors. Sensitivity analyses confirmed that the association between osteoporosis and ONJ remained robust in antiresorptive-naïve and glucocorticoid-naïve patients after excluding bone metastasis and high-dose antiresorptive therapy (aHR 3.125, 95% CI 2.564-3.817, P < 0.0001).
conclusionOsteoporosis and fracture history are independent risk factors for ONJ in patients with RA. These findings support a disease-driven paradigm where underlying bone fragility drives ONJ development beyond antiresorptive or glucocorticoid effects, highlighting the need for comprehensive bone health management in this population. Future prospective studies are needed to evaluate targeted screening interventions. Key points • Osteoporosis is a stronger independent risk factor for ONJ than antiresorptive medication. • Prior bone fractures significantly increase ONJ risk among patients with rheumatoid arthritis and osteoporosis. • Managing underlying bone fragility is crucial for ONJ prevention, beyond monitoring osteoporosis medication use.
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