Direct comparison of eight national FRAX® tools for fracture prediction and treatment qualification in Canadian women
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We compared the calibration of FRAX tools from Canada, the US (white), UK, Sweden, France, Australia, New Zealand, and China when used to assess fracture risk in 36,730 Canadian women. Our data underscores the importance of applying country-specific FRAX tools that are based upon high-quality national fracture epidemiology.
A FRAX® model for Canada was constructed for prediction of hip fracture and major osteoporotic fracture (MOF) using national hip fracture and mortality data. We examined the calibration of this model in Canadian women and compared it with seven other FRAX tools.
In women aged ≥50 years with baseline bone mineral density (BMD) measures identified from the Manitoba Bone Density Program, Canada (n = 36,730), 10-year fracture probabilities were calculated with and without BMD using selected country-specific FRAX tools. FRAX risk estimates were compared with observed fractures ≤10 years (506 hip, 2,380 MOF). Ten-year fracture risk was compared with predicted probabilities, and proportions exceeding specific treatment thresholds contrasted.
For hip fracture prediction, good calibration was observed for FRAX Canada and most other country-specific FRAX tools, excepting Sweden (risk overestimated) and China (risk underestimated). For MOF prediction, greater between-country differences were seen; FRAX Sweden and FRAX China showed the largest over- and underestimation in this Canadian population. Relative to treatment qualification based upon FRAX Canada, treatment of high-hip fracture probability (≥3 %) was greater by FRAX Sweden (ratio 1.41 without and 1.55 with BMD), and markedly less by FRAX China (ratio 0.09 without and 0.11 with BMD). Greater between-country differences were observed for treat4ment of high MOF (≥20 %); FRAX Sweden again greatly increased (ratio 1.76 without and 1.83 with BMD), and FRAX China severely reduced treatment qualification (ratio 0.00 without and 0.01 with BMD).
The use of country-specific FRAX tools, accurately calibrated to the target population, is essential. Relatively small calibration differences can have large effects on high-risk categorization and treatment qualification.
KeywordsBone mineral density Dual energy x-ray absorptiometry Osteoporosis Fracture prediction models FRAX
The authors are indebted to Manitoba Health for the provision of data (HIPC File No. 2007/2008-49). The results and conclusions are those of the authors, and no official endorsement by Manitoba Health is intended or should be inferred. This article has been reviewed and approved by the members of the Manitoba Bone Density Program Committee. SL Brennan is supported by a National Health and Medical Research Council of Australia Early Career Fellowship (1012472), and a Dyason Fellowship, The University of Melbourne.
Conflicts of interest
William D Leslie has served on advisory boards for Novartis, Amgen, Genzyme; received unrestricted research grants from Amgen; and received speaker fees from Amgen.
Eugene McCloskey has received speaker fees and/or unrestricted research grants from Novartis, Amgen, AstraZeneca, Pfizer, Bayer, Warner-Chilcott/Procter & Gamble, Lilly, Roche, Servier, and Hologic.
John A Kanis is associated with the following industries: Abiogen, Italy; Amgen, USA, Switzerland and Belgium; Bayer, Germany; Besins-Iscovesco, France; Biosintetica, Brazil; Boehringer Ingelheim, UK; Celtrix, USA; D3A, France; Gador, Argentina; General Electric, USA; GSK, UK, USA; Hologic, Belgium and USA; Kissei, Japan; Leiras, Finland; Leo Pharma, Denmark; Lilly, USA, Canada, Japan, Australia and UK; Merck Research Labs, USA; Merlin Ventures, UK; MRL, China; Novartis, Switzerland and USA; Novo Nordisk, Denmark; Nycomed, Norway; Ono, UK and Japan; Organon, Holland; Parke-Davis, USA; Pfizer USA; Pharmexa, Denmark; Procter and Gamble, UK, USA; ProStrakan, UK; Roche, Germany, Australia,Switzerland, USA; Rotta Research, Italy; Sanofi-Aventis, USA; Schering, Germany and Finland; Servier, France and UK; Shire, UK; Solvay, France and Germany; Strathmann, Germany; Tethys, USA; Teijin, Japan; Teva, Israel; UBS, Belgium; Unigene, USA; Warburg-Pincus, UK; Warner-Lambert, USA; Wyeth, USA. He is also associated with the following government organizations and NGOs: National Institute for Health and Clinical Excellence (NICE), UK; International Osteoporosis Foundation; National Osteoporosis Guideline Group (NOGG), UK; INSERM, France; Ministry of Public Health, China; Ministry of Health, Australia; National Osteoporosis Society (UK); WHO.
Helena Johansson is supported by ESCEO-AMGEN Osteoporosis Fellowship Award.
The rest of the authors have no competing interests.
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