Medications associated with fracture risk in patients with rheumatoid arthritis

Abstract

ObjectiveTo examine the fracture risk with use of disease-modifying antirheumatic drugs (DMARDs), statins, proton pump inhibitors (PPIs), opioids, non-opioid analgesics and psychotropic medications in a US-wide observational rheumatoid arthritis (RA) cohort.MethodsPatients with RA without prior fracture from 2001 through 2017 in FORWARD, a longitudinal observational registry, were assessed for osteoporosis-related site fractures (vertebra, hip, forearm and humerus). DMARD exposure was assessed in four mutually exclusive groups: (1) methotrexate monotherapy-reference, (2) tumour necrosis factor-α inhibitors (TNFi), (3) non-TNFi biologics and (4) others. Non-DMARDs and glucocorticoids were classified as current/ever use and based on treatment duration. Fracture Risk Assessment Tool (FRAX) scores estimating for 10-year major osteoporotic fractures were calculated. Cox proportional hazard models stratified by FRAX were used to adjust for confounders.ResultsDuring median (IQR) 3.0 (1.5–6.0) years of follow-up in 11 412 patients, 914 fractures were observed. The adjusted models showed a significant fracture risk increase with use of any dose glucocorticoids ≥3 months (HR (95% CI) for <7.5 mg/day 1.26 (1.07 to 1.48) and for ≥7.5 mg/day 1.57 (1.27 to 1.94)), opioids (for weak: 1.37 (1.18 to 1.59); strong: 1.53 (1.24 to 1.88)) and selective serotonin reuptake inhibitors (SSRIs) (1.37 (1.15 to 1.63)). Fracture risk with opioids increased within 1 month of use (1.66 (1.36 to 2.04)) and with SSRIs >3 months of use (1.25 (1.01 to 1.55)). Statins (0.77 (0.62 to 0.96)) and TNFi (0.72 (0.54 to 0.97)) were associated with reduction in vertebral fracture risk only. PPIs and other psychotropic medications were not associated with increased fracture risk.ConclusionUse of opioids, SSRIs and glucocorticoids were associated with increased risk of any fracture in patients with RA, whereas statins and TNFi were associated with decreased vertebral fractures.

Medications associated with fracture risk in patients with rheumatoid arthritis

“…These findings were published in the August 2019 issue of the Annals of the Rheumatic Diseases . Certainly, the findings of Ozen et al 5 will be significant for clinicians; however, four points remain unaddressed that we would like to communicate with the authors.…”

“…In particular, statins may influence bone metabolism by increasing bone formation 3 4. Recently, Ozen et al 5 reported that medication with opioids, selective serotonin reuptake inhibitors, and glucocorticoids were associated with an increased risk of osteoporosis-related site fractures (vertebra, hip, forearm and humerus) in patients with rheumatoid arthritis, whereas statins and tumour necrosis factor-α inhibitors were associated with a decreased risk of vertebral fractures. These findings were published in the August 2019 issue of the Annals of the Rheumatic Diseases .…”

Association between proton pump inhibitors therapy and fracture risk in patients with rheumatoid arthritis

“…1 Recently, a cohort study in USA conducted by Ozen et al published in the Annals of the Rheumatic Diseases reported that proton pump inhibitors therapy was not associated with increased fracture risk in patients with rheumatoid arthritis (HR=0.92; 95% CI 0.80 to 1.06). 2 Ozen et al's study is an important one and deserves a practical value. Some points not shown in the original article are shared with the readers.…”

“…Table 1 shows that the incidence of major osteoporotic fractures is 1.33-fold higher in patients with proton pump inhibitors therapy than those without use, but it does not reach statistic significance (1.24 vs 0.94 per 100 person-years; 95% CI 0.86 to 2.06, p=0.2049) which was compatible with Ozen et al's study reporting that no association could be observed between proton pump inhibitors therapy and fracture risk in patients with rheumatoid arthritis. 2 Second, previous research has suggested that no significant association can be detected between proton pump inhibitors therapy and fracture risk in older adults. 4 Ozen et al's and our studies further confirm that even in patients with rheumatoid arthritis, such an association still does not exist.…”

Rheumatoid arthritis: glucocorticoids are associated with nearly double infection risk post-surgery

“…In another study, published in the Annals of Rheumatic Diseases, researchers looked at the fracture risk of several drugs often used alongside disease modifying antirheumatic drugs, including statins, proton pump inhibitors, opioids, non-opioid analgesics, and psychotropic drugs 3…”