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Predicting the 10-year risk of hip and major osteoporotic fracture in rheumatoid arthritis and in the general population: an independent validation and update of UK FRAX without bone mineral density
  1. Corinne Klop1,
  2. Frank de Vries1,2,3,4,
  3. Johannes W J Bijlsma5,
  4. Hubert G M Leufkens1,
  5. Paco M J Welsing5,6
  1. 1Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
  2. 2MRC Lifecourse Epidemiology Unit, Southampton General Hospital, Southampton, UK
  3. 3Department of Clinical Pharmacy & Toxicology, Maastricht University Medical Centre, Maastricht, The Netherlands
  4. 4Department of Epidemiology, Maastricht University/CAPHRI, Maastricht, The Netherlands
  5. 5Department of Rheumatology & Clinical Immunology, University Medical Center, Utrecht, The Netherlands
  6. 6Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands
  1. Correspondence to Corinne Klop, Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Obbinklaan 100, Utrecht 3571 NJ, The Netherlands; C.Klop{at}uu.nl

Abstract

Objectives FRAX incorporates rheumatoid arthritis (RA) as a dichotomous predictor for predicting the 10-year risk of hip and major osteoporotic fracture (MOF). However, fracture risk may deviate with disease severity, duration or treatment. Aims were to validate, and if needed to update, UK FRAX for patients with RA and to compare predictive performance with the general population (GP).

Methods Cohort study within UK Clinical Practice Research Datalink (CPRD) (RA: n=11 582, GP: n=38 755), also linked to hospital admissions for hip fracture (CPRD-Hospital Episode Statistics, HES) (RA: n=7221, GP: n=24 227). Predictive performance of UK FRAX without bone mineral density was assessed by discrimination and calibration. Updating methods included recalibration and extension. Differences in predictive performance were assessed by the C-statistic and Net Reclassification Improvement (NRI) using the UK National Osteoporosis Guideline Group intervention thresholds.

Results UK FRAX significantly overestimated fracture risk in patients with RA, both for MOF (mean predicted vs observed 10-year risk: 13.3% vs 8.4%) and hip fracture (CPRD: 5.5% vs 3.1%, CPRD-HES: 5.5% vs 4.1%). Calibration was good for hip fracture in the GP (CPRD-HES: 2.7% vs 2.4%). Discrimination was good for hip fracture (RA: 0.78, GP: 0.83) and moderate for MOF (RA: 0.69, GP: 0.71). Extension of the recalibrated UK FRAX using CPRD-HES with duration of RA disease, glucocorticoids (>7.5 mg/day) and secondary osteoporosis did not improve the NRI (0.01, 95% CI −0.04 to 0.05) or C-statistic (0.78).

Conclusions UK FRAX overestimated fracture risk in RA, but performed well for hip fracture in the GP after linkage to hospitalisations. Extension of the recalibrated UK FRAX did not improve predictive performance.

  • Epidemiology
  • Osteoporosis
  • Rheumatoid Arthritis

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Footnotes

  • Handling editor Tore K Kvien

  • Contributors Conceived and designed the experiments: CK FdV JWJB, HGML and PMJW. Analysed the data: CK and PMJW. Wrote the paper: CK. Reviewed the manuscript: CK, FdV, JWJB, HGML and PMJW.

  • Funding This study was supported by a research grant from the Netherlands Organization for Health Research and Development (ZonMw; grant number 113101007).

  • Competing interests The Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, employing authors CK and FdV, has received unrestricted funding from the Netherlands Organisation for Health Research and Development (ZonMW), the Dutch Health Care Insurance Board (ZIN), the Royal Dutch Pharmacists Association (KNMP), the private–public funded Top Institute Pharma (http://www.tipharma.nl), includes cofunding from universities, government and industry, the EU Innovative Medicines Initiative (IMI), the EU 7th Framework Program (FP7), the Dutch Ministry of Health and industry (including GlaxoSmithKline, Pfizer and others); HGML is a researcher at The WHO Collaborating Centre for Pharmaceutical Policy and Regulation, which receives no direct funding or donations from private parties, including pharma industry. Research funding from public–private partnerships, for example, IMI, TI Pharma (http://www.tipharma.nl) is accepted under the condition that no company-specific product or company-related study is conducted. The Centre has received unrestricted research funding from public sources, for example, the Netherlands Organisation for Health Research and Development (ZonMW), the Dutch Health Care Insurance Board (CVZ), the EU 7th Framework Program (FP7), the Dutch Medicines Evaluation Board (MEB) and the Dutch Ministry of Health.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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