Incidence of fractures among patients with rheumatoid arthritis: a systematic review and meta-analysis

Jin, Shunqian; Hsieh, Evelyn; Li, Peng; Yu, Chengbo; Wang, Y.; Wu, Caimei; Wang, Q.; Li, M.; Zeng, Xiaofeng

doi:10.1007/s00198-018-4473-1

Cited by 89 publications

(49 citation statements)

References 45 publications

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“…Also, due to the lack of data about trauma level, some of the traumatic fractures might be misclassified as osteoporotic fractures. Despite that, our fracture incidence rates were comparable to the reported rates in a recent meta-analysis of 25 cohort studies in patients with RA (pooled incidence rates of fragility fractures 15.31 (95% CI 10.43 to 22.47) per 1000 person-years) 48. Additionally, the majority of the vertebral fractures are not clinically recognisable at early stages, and the diagnosis of these fractures requires ≥2 radiographic assessments at appropriate intervals.…”

Section: Discussionsupporting

confidence: 80%

Medications associated with fracture risk in patients with rheumatoid arthritis

et al. 2019

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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.

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Section: Discussionsupporting

confidence: 80%

Medications associated with fracture risk in patients with rheumatoid arthritis

et al. 2019

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“…Our study only shows the osteoporosis site fracture incidence in patients with RA. As we indicated in our manuscript, the incidence rate of osteoporotic fractures in our cohort is similar to a recent meta-analysis of 25 cohort studies in patients with RA 3…”

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confidence: 90%

Response to: ‘Medications associated with fracture risk in patients with rheumatoid arthritis’ by Chen et al

Özen

Michaud

2019

Ann Rheum Dis

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We appreciate the interest shown by Dr Chen 1 concerning our recent study on medications associated with fracture risk in patients with rheumatoid arthritis (RA). 2 We would like to clarify some issues Chen et al indicated. First, we agree that osteoporotic fractures are more common in patients with inflammatory diseases. However, in our study, we excluded all patients with prevalent fractures to estimate the risk related to new fractures. Our study only shows the osteoporosis site fracture incidence in patients with RA. As we indicated in our manuscript, the incidence rate of osteoporotic fractures in our cohort is similar to a recent meta-analysis of 25 cohort studies in patients with RA. 3 Second, it is possible that high-intensity statin regimens may prevent fractures better than moderate-intensity ones especially if the protective effects are assumed to be due to anti-inflammatory properties of statins. Moreover, as Chen et al indicate, some antihypertensives may have protective effects on osteoporotic fracture risk. However, the only randomised controlled trial for this association is with thiazide diuretics 4 5 of which effect is also more biologically plausible compared with other antihypertensives. 6 The fracture risk change with high-intensity statins and antihypertensives should be investigated further in patients with RA. Lastly, we appreciate the comment about our outcome-only osteoporosis site fractures. It is well-known that patients with RA have increased fall risk, which can also cause fractures. Unfortunately, we do not have any data for the level of trauma and fall risk other than disability scores. Regardless, we believe that including all types of fractures would make our outcome very heterogeneous. A significant trauma could cause a fracture in any patient even in the absence of risk factors. We are planning to collect more data regarding fall risk to better assess the fracture risk in our cohort.

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“…A recent systematic review and meta-analysis not only confirmed this result, but also conducted site-specific analyses in RA patients on fractures in the vertebrae, hip, forearm, and proximal humerus. Incidence rates were found to be highest in the vertebrae, leading the authors to suggest vertebral imaging specifically in these patients to assess clinical deterioration of bone structure in the spine, in addition to assessment of other known osteoporotic risk factors, including those specific to RA [ 25 ]. This is consistent with previous data, demonstrating vertebral facture rates in RA to be as high as twice the expected value in the general population [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Predictors of fragility fracture and low bone mineral density in patients with a history of parental fracture

Dey

Bukhari

2019

Osteoporosis and Sarcopenia

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Objectives Bone mineral density (BMD) and fragility fracture (FF) have high heritability, but few data exist on impact of other factors on families with fracture history. We aimed to evaluate predictors of FF and low BMD, in patients with family history of FF. Methods This was a retrospective study on patients undergoing dual energy X-ray absorptiometry at a district general hospital (DGH), 2004–2016. Parameters recorded (in addition to standard dual energy X-ray absorptiometry parameters): age, smoking, alcohol, corticosteroids, aromatase inhibitors, Depo-Provera, hormone replacement therapy, rheumatoid arthritis, polymyalgia rheumatica, breast or prostate cancer, coeliac disease, and fracture site. Logistic regression was used to model fracture risk and site, and linear regression for impact of factors on L1–4 and femoral BMD. Factor analyses with polychoric correlation matrices and calculation of Eigenvalues were applied to determine association between fracture sites and associated risk factors. Results A total of 6053 patients were included, 91.1% female. 2094 had sustained at least one FF. Smoking, alcoholism, increased age, height, and fat mass increased FF risk. Sites analysed: femur, tibia/fibula, humerus, forearm, ribs, and vertebrae. Alcoholism, and increasing tissue thickness and fat mass significantly increased FF risk. Decreased right femoral and vertebral BMD increased overall FF risk. Conclusions Our study confirms the effect of certain factors on vertebral BMD, but suggests a differential effect on the upper and lower spine, as well as in the dominant and nondominant hip. Different sites of fracture are associated with different risk factors, the most common sites of fracture being the peripheral long bones and vertebrae.

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Incidence of fractures among patients with rheumatoid arthritis: a systematic review and meta-analysis

Abstract: Patients with RA are at high risk of incident overall and fragility fractures. Consideration of vertebral imaging for patients with additional OP risk factors, including RA-specific risk factors, may help with early OP diagnosis and timely intervention.

Cited by 89 publications

References 45 publications

Medications associated with fracture risk in patients with rheumatoid arthritis

Medications associated with fracture risk in patients with rheumatoid arthritis

Response to: ‘Medications associated with fracture risk in patients with rheumatoid arthritis’ by Chen et al

Predictors of fragility fracture and low bone mineral density in patients with a history of parental fracture

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