Frailty Predicts Osteoporotic Fracture Risk in US Veterans With Rheumatoid Arthritis

Key Clinical Summary

• US Veterans Affairs Rheumatoid Arthritis Registry cohort (n=2,912): Baseline frailty, measured using the Veterans Affairs Frailty Index (VAFI), was independently associated with a stepwise increase in incident osteoporotic fracture risk after multivariable adjustment.
• Fracture risk increased with frailty severity: Compared with robust patients, adjusted hazard ratios (aHRs) were 2.02 for mild frailty, 2.99 for moderate frailty, and 4.67 for severe frailty (P for trend <0.001).
• Functional deficits were major contributors: Failure to thrive, muscular issues, and gait abnormalities were among the strongest individual frailty components associated with incident osteoporotic fractures, supporting further evaluation of VAFI as a fracture risk assessment tool in RA.

Rheumatoid arthritis is associated with elevated risks of both frailty and osteoporosis, yet the relationship between frailty and future osteoporotic fractures has remained insufficiently characterized. In a study published online in Arthritis Care & Research, investigators analyzed data from the US Veterans Affairs (VA) Rheumatoid Arthritis Registry to determine whether frailty independently predicts incident osteoporotic fractures in this high-risk population.

Study Findings / Main News

Investigators evaluated 2,912 patients enrolled in the VA Rheumatoid Arthritis Registry. Frailty was assessed at baseline using the Veterans Affairs Frailty Index (VAFI), while incident osteoporotic fractures were identified through administrative codes and confirmed by physician chart review.

The study population had a mean age of 64.3 years (standard deviation, 11.0 years); 88% were men and 76% were White. During follow-up, 248 participants (9%) experienced an incident osteoporotic fracture.

At baseline, 30% of participants were classified as robust, 38% as prefrail, 18% as mildly frail, 7% as moderately frail, and 3% as severely frail.

After adjustment for age, sex, race, anti-cyclic citrullinated peptide (anti-CCP) positivity, previous fracture, body mass index, smoking status, disease duration, disease activity, prednisone use, and RA and osteoporosis medication use, increasing frailty severity was associated with progressively higher fracture risk.

Compared with robust participants, adjusted hazard ratios for incident osteoporotic fracture were:

• Mild frailty: aHR 2.02 (95% CI, 1.37–2.97)
• Moderate frailty: aHR 2.99 (95% CI, 1.83–4.87)
• Severe frailty: aHR 4.67 (95% CI, 2.41–9.03)

The association demonstrated a significant dose-response relationship (P for trend <0.001).

Secondary analyses identified several individual frailty components that contributed strongly to fracture risk. Three of the five leading contributors reflected functional impairment: failure to thrive (aHR 4.57; 95% CI, 1.10–18.94), muscular issues (aHR 2.42; 95% CI, 1.69–3.40), and gait abnormality (aHR 2.01; 95% CI, 1.39–2.93). All associations were statistically significant (P<0.05).

Clinical Implications

These findings suggest that frailty provides clinically meaningful prognostic information beyond established fracture risk factors in patients with RA. Even after accounting for demographic characteristics, disease-related variables, glucocorticoid exposure, previous fractures, and osteoporosis treatment, progressively greater frailty remained associated with higher rates of incident osteoporotic fracture.

The study also highlights the importance of functional impairments—including gait abnormalities, muscular deficits, and failure to thrive—as components of frailty associated with fracture risk. According to the authors, these findings support further investigation of frailty assessment as part of fracture risk evaluation in patients with RA.

The investigators note that additional research comparing the predictive performance of the Veterans Affairs Frailty Index with established fracture prediction models is needed to determine whether VAFI could improve osteoporosis screening and treatment strategies in this high-risk population.

Expert Commentary

The authors concluded that "frailty is associated with an increased risk of incident osteoporotic fracture in RA." They further stated that comparing the predictive ability of the Veterans Affairs Frailty Index with established fracture prediction models is needed to determine whether it can be deployed to improve osteoporosis screening and treatment among patients with rheumatoid arthritis.

Frailty was independently associated with progressively higher osteoporotic fracture risk in this cohort of US veterans with rheumatoid arthritis. The findings support additional research to determine whether incorporating frailty assessment into fracture prediction models could enhance osteoporosis risk stratification and guide preventive care in patients with RA.

Reference: 

Wysham KD, Brubeck HF, Baraff A, et al. Frailty predicts incident osteoporotic fractures in veterans with rheumatoid arthritis. Arthritis Care Res. Published online June 22, 2026. https://doi.org/10.1002/acr.80107