A Oden

Publications (70)298.09 Total impact

• Article: Pitfalls in the external validation of FRAX: response to Bolland et al.

  J A Kanis, A Oden, H Johansson, E McCloskey
  Osteoporosis International 05/2012; · 4.58 Impact Factor
• Article: A comparative study of using non-hip bone density inputs with FRAX®

  W. D. Leslie, L. M. Lix, H. Johansson, A. Oden, E. McCloskey, J. A. Kanis, for the Manitoba Bone Density Program
  [show abstract] [hide abstract]
  ABSTRACT: SummaryUse of lumbar spine T-score or minimum T-score as a bone mineral density (BMD) input to the FRAX® algorithm led to miscalibration compared with the recommended femoral neck input. Use of a weighted mean between the lumbar spine and femoral neck T-scores was found to provide an arithmetically equivalent result to a previously described offset adjustment. IntroductionFRAX assumes that the BMD input, when used in the calculation, is from the femoral neck. Use of other BMD inputs is not recommended, but there are no studies describing how this affects the performance of FRAX. MethodsTen-year probabilities of a major osteoporotic fracture were calculated with different BMD inputs for 20,477 women and men aged 50years and older from Manitoba, Canada. FRAX probability calculated with femoral neck BMD was designated the reference method. We also derived FRAX probabilities where the BMD input was based upon the lumbar spine T-score, minimum T-score (lumbar spine or femoral neck), weighted mean T-score (lumbar spine or femoral neck), or used an adjustment for the spine–hip T-score difference (offset). Fracture outcomes were assessed using a population-based administrative data repository. ResultsAll FRAX models showed good risk stratification with minimal differences. There was no consistent improvement in FRAX performance when lumbar spine or minimum T-score were used as inputs, but calibration was adversely affected due to higher mean fracture probabilities compared with the femoral neck. The weighted mean T-score was found to be equivalent to the spine–hip T-score offset adjustment, and both slightly improved risk classification without a change in calibration. ConclusionsThe choice of BMD input to the FRAX model has a large effect on performance. The lumbar spine T-score or minimum T-score should not be used as inputs to the FRAX algorithm. Use of a weighted mean between the lumbar spine and femoral neck T-scores slightly improves risk classification. KeywordsBone mineral density–Clinical risk factors–Fracture prediction–FRAX®–Osteoporosis
  Osteoporosis International 04/2012; 23(3):853-860. · 4.58 Impact Factor
• Article: Fracture risk assessment without bone density measurement in routine clinical practice

  W. D. Leslie, S. Morin, L. M. Lix, H. Johansson, A. Oden, E. McCloskey, J. A. Kanis, for the Manitoba Bone Density Program
  [show abstract] [hide abstract]
  ABSTRACT: SummaryFracture probability assessed without bone mineral density (BMD) could potentially be sufficient for clinical decision making in many individuals categorized as low or high fracture risk. For individuals falling in a moderate risk range, there is incremental value in using BMD in the probability calculation as this appropriately reclassifies risk in over one third of the individuals. IntroductionA new fracture risk assessment tool from the World Health Organization (FRAX®) estimates 10-year major osteoporotic and hip fracture probabilities from multiple clinical risk factors with or without hip BMD. The objective of this study is to determine whether fracture probability derived without BMD can be used to identify individuals who would be designated for treatment. MethodsA historical cohort of 36,730 women and 2,873 men aged 50years and older drawn from the Manitoba Bone Density Program database, which contains clinical BMD results for the Province of Manitoba, Canada, was included in the study. ResultsWhen 10-year probability for major osteoporotic fracture estimated without knowledge of BMD was high (≥20%), the vast majority (92.8%) qualified for intervention under the National Osteoporosis Foundation (NOF) guidelines, whereas among those at low risk (<10%), the vast majority (80.5%) did not satisfy any NOF intervention criteria. The benefit of including BMD in the risk assessment was greatest among those initially at moderate risk (10–19%) when fracture probability was derived without BMD, but this represented only 29.4% of the cohort (9.3% of those aged <65years and 48.7% of those ≥65years). ConclusionsFracture probability derived without BMD is able to risk stratify women in terms of future fracture risk and could potentially be sufficient for clinical decision making in many of those designated at low or high fracture risk. KeywordsAdministrative data–Bone mineral density–Dual-energy X-ray absorptiometry–Fracture prediction–FRAX–Osteoporosis
  Osteoporosis International 04/2012; 23(1):75-85. · 4.58 Impact Factor
• Article: The use of multiple sites for the diagnosis of osteoporosis

  J. A. Kanis, O. Johnell, A. Oden, H. Johansson, J. A. Eisman, S. Fujiwara, H. Kroger, R. Honkanen, L. J. Melton, T. O’Neill, J. Reeve, A. Silman, A. Tenenhouse
  [show abstract] [hide abstract]
  ABSTRACT: IntroductionIt has been suggested that bone mineral density (BMD) measurements should be made at multiple sites, and that the lowest T–score should be taken for the purpose of diagnosing osteoporosis. PurposeThe aim of this study was to examine the use of BMD measurements at the femoral neck and lumbar spine alone and in combination for fracture prediction. MethodsWe studied 19,071 individuals (68% women) from six prospective population-based cohorts in whom BMD was measured at both sites and fracture outcomes documented over 73,499 patient years. BMD values were converted to Z-scores, and the gradient of risk for any osteoporotic fracture and for hip fracture was examined by using a Poisson model in each cohort and each gender separately. Results of the different studies were merged using weighted β-coefficients. ResultsThe gradients of risk for osteoporotic fracture and for hip fracture were similar in men and women. In men and women combined, the risk of any osteoporotic fracture increased by 1.51 [95% confidence interval (CI)=1.42–1.61] per standard deviation (SD) decrease in femoral-neck BMD. For measurements made at the lumbar spine, the gradient of risk was 1.47 (95% CI=1.38–1.56). Where the minimum of the two values was used, the gradient of risk was similar (1.55; 95% CI=1.45–1.64). Higher gradients of risk were observed for hip fracture outcomes: with BMD at the femoral neck, the gradient of risk was 2.45 (95% CI=2.10–2.87), with lumbar BMD was 1.57 (95% CI=1.36–1.82), and with the minimum value of either femoral neck and lumbar spine was 2.11 (95% CI=1.81–2.45). Thus, selecting the lowest value for BMD at either the femoral neck or lumbar spine did not increase the predictive ability of BMD tests. By contrast, the sensitivity increased so that more individuals were identified but at the expense of specificity. Thus, the same effect could be achieved by using a less stringent T–score for the diagnosis of osteoporosis. ConclusionsSince taking the minimum value of the two measurements does not improve predictive ability, its clinical utility for the diagnosis of osteoporosis is low.
  Osteoporosis International 04/2012; 17(4):527-534. · 4.58 Impact Factor
• Article: High fracture probability with FRAX® usually indicates densitometric osteoporosis: implications for clinical practice

  W. D. Leslie, S. R. Majumdar, L. M. Lix, H. Johansson, A. Oden, E. McCloskey, J. A. Kanis, for the Manitoba Bone Density Program
  [show abstract] [hide abstract]
  ABSTRACT: SummaryMost patients designated as high risk of fracture using fracture risk assessment tool (FRAX®) with femoral neck bone mineral density (BMD) (i.e., 10-year major osteoporotic fracture probability exceeding 20% or hip fracture exceeding 3%) have one or more T-scores in the osteoporotic range; conversely, almost no high risk patients have normal T-scores at all bone mineral density measurement sites. IntroductionWe determined the agreement between a FRAX® designation of high risk of fracture [defined as 10-year major osteoporotic fracture probability (≥20%) or hip fracture probability (≥3%)] and the WHO categorizations of bone mineral density according to T-score. MethodsTen-year FRAX® probabilities calculated with femoral neck BMD were derived using both Canadian and US white tools for a large clinical cohort of 36,730 women and 2,873 men age 50years and older from Manitoba, Canada. Individuals were classified according to FRAX fracture probability and BMD T-scores alone. ResultsMost individuals designated by FRAX as high risk of major osteoporotic fracture had a T-score in the osteoporotic range at one or more BMD measurement sites (85% with Canadian tool and 83% with US white tool). The majority of individuals deemed at high risk of hip fracture had one or more T-scores in the osteoporotic range (66% with Canadian tool and 64% with US white tool). Conversely, there were extremely few individuals (<1%) who were at high risk of major osteoporotic or hip fracture with normal T-scores at all BMD measurement sites. ConclusionsA FRAX designation of high risk of fracture is usually associated with a densitometric diagnosis of osteoporosis. KeywordsBone mineral density–Clinical risk factors–Fracture prediction–FRAX® –Osteoporosis
  Osteoporosis International 04/2012; 23(1):391-397. · 4.58 Impact Factor
• Article: A comparative study of using non-hip bone density inputs with FRAX®.

  W D Leslie, L M Lix, H Johansson, A Oden, E McCloskey, J A Kanis
  [show abstract] [hide abstract]
  ABSTRACT: Use of lumbar spine T-score or minimum T-score as a bone mineral density (BMD) input to the FRAX® algorithm led to miscalibration compared with the recommended femoral neck input. Use of a weighted mean between the lumbar spine and femoral neck T-scores was found to provide an arithmetically equivalent result to a previously described offset adjustment. FRAX assumes that the BMD input, when used in the calculation, is from the femoral neck. Use of other BMD inputs is not recommended, but there are no studies describing how this affects the performance of FRAX. Ten-year probabilities of a major osteoporotic fracture were calculated with different BMD inputs for 20,477 women and men aged 50 years and older from Manitoba, Canada. FRAX probability calculated with femoral neck BMD was designated the reference method. We also derived FRAX probabilities where the BMD input was based upon the lumbar spine T-score, minimum T-score (lumbar spine or femoral neck), weighted mean T-score (lumbar spine or femoral neck), or used an adjustment for the spine-hip T-score difference (offset). Fracture outcomes were assessed using a population-based administrative data repository. All FRAX models showed good risk stratification with minimal differences. There was no consistent improvement in FRAX performance when lumbar spine or minimum T-score were used as inputs, but calibration was adversely affected due to higher mean fracture probabilities compared with the femoral neck. The weighted mean T-score was found to be equivalent to the spine-hip T-score offset adjustment, and both slightly improved risk classification without a change in calibration. The choice of BMD input to the FRAX model has a large effect on performance. The lumbar spine T-score or minimum T-score should not be used as inputs to the FRAX algorithm. Use of a weighted mean between the lumbar spine and femoral neck T-scores slightly improves risk classification.
  Osteoporosis International 03/2012; 23(3):853-60. · 4.58 Impact Factor
• Article: A comparison of case-finding strategies in the UK for the management of hip fractures.

  H Johansson, J A Kanis, A Oden, J Compston, E McCloskey
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  ABSTRACT: Treatment criteria published by the National Osteoporosis Guideline Group (NOGG) in the UK make more efficient use of bone mineral density (BMD) resources than the previous Royal College of Physicians (RCP) guideline. We compared the effectiveness of the RCP case-finding strategy previously used in the UK and the updated guideline published by NOGG, which incorporates the FRAX® fracture probability tool. Comparisons were made by simulating population samples of 1000 women at ages between 50 and 85 years, using age-specific prevalence of risk factors and UK-derived fracture and mortality rates. Comparators comprised the number identified at high risk, the incidence of hip fracture and the femoral neck BMD in those identified, the number needed to scan to identify a hip fracture, the acquisition cost and the cost per hip fracture averted Compared with the RCP strategy, NOGG identified slightly reduced numbers of women at high risk (average 34.6% vs. 35.7% across all ages), but with lower numbers of scans required at each age. For example, NOGG required only 3.5 scans at the age of 50 years to identify one case of hip fracture, whereas RCP required 13.9. At 75 years, the corresponding numbers were 0.9 and 1.5. Thus, the acquisition costs for identifying a hip fracture case and the total costs (acquisition and treatment) per hip fracture averted were lower. Compared to the RCP strategy, the FRAX-based NOGG strategy uses BMD resources more efficiently with lower acquisition costs and lower costs per hip fracture averted.
  Osteoporosis International 03/2012; 23(3):907-15. · 4.58 Impact Factor
• Article: Pitfalls in the external validation of FRAX.

  J A Kanis, A Oden, H Johansson, E McCloskey
  [show abstract] [hide abstract]
  ABSTRACT: Recent studies have evaluated the performance of FRAX® in independent cohorts. The interpretation of most is problematic for reasons summarised in this perspective. FRAX is an extensively validated assessment tool for the prediction of fracture in men and women. The aim of this study was to review the methods used since the launch of FRAX to further evaluate this instrument. This covers a critical review of studies investigating the calibration of FRAX or assessing its performance characteristics in external cohorts. Most studies used inappropriate methodologies to compare the performance characteristics of FRAX with other models. These included discordant parameters of risk (comparing incidence with probabilities), comparison with internally derived predictors and inappropriate use and interpretation of receiver operating characteristic curves. These deficits markedly impair interpretation of these studies. Cohort studies that have evaluated the performance of FRAX need to be interpreted with caution and preferably re-evaluated.
  Osteoporosis International 11/2011; 23(2):423-31. · 4.58 Impact Factor
• Article: FRAX underestimates fracture risk in patients with diabetes.

  Lora M Giangregorio, William D Leslie, Lisa M Lix, Helena Johansson, Anders Oden, Eugene McCloskey, John A Kanis
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  ABSTRACT: The study objective was to determine whether diabetes is a risk factor for incident hip or major osteoporotic fractures independent of the WHO fracture risk assessment tool (FRAX). Men and women with diabetes (n = 3518) and nondiabetics (n = 36,085) aged ≥50 years at the time of bone mineral density (BMD) testing (1990 to 2007) were identified in a large clinical database from Manitoba, Canada. FRAX probabilities were calculated, and fracture outcomes to 2008 were established via linkage with a population-based data repository. Multivariable Cox proportional hazards models were used to determine if diabetes was associated with incident hip fractures or major osteoporotic fractures after controlling for FRAX risk factors. Mean 10-year probabilities of fracture were similar between groups for major fractures (diabetic 11.1 ± 7.2 versus nondiabetic 10.9 ± 7.3, p = 0.116) and hip fractures (diabetic 2.9 ± 4.4 versus nondiabetic 2.8 ± 4.4, p = 0.400). Diabetes was a significant predictor of subsequent major osteoporotic fracture (hazard ratio [HR] = 1.61, 95% confidence interval [CI] 1.42-1.83) after controlling for age, sex, medication use, and FRAX risk factors including BMD. Similar results were seen after adjusting for FRAX probability directly (HR = 1.59, 95% CI 1.40-1.79). Diabetes was also associated with significantly higher risk for hip fractures (p < 0.001). Higher mortality from diabetes attenuated but did not eliminate the excess fracture risk. FRAX underestimated observed major osteoporotic and hip fracture risk in diabetics (adjusted for competing mortality) but demonstrated good concordance with observed fractures for nondiabetics. We conclude that diabetes confers an increased risk of fracture that is independent of FRAX derived with BMD. This suggests that diabetes might be considered for inclusion in future iterations of FRAX.
  Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 11/2011; 27(2):301-8. · 6.04 Impact Factor
• Article: Interpretation and use of FRAX in clinical practice.

  J A Kanis, D Hans, C Cooper, S Baim, J P Bilezikian, N Binkley, J A Cauley, J E Compston, B Dawson-Hughes, G El-Hajj Fuleihan, H Johansson, W D Leslie, E M Lewiecki, M Luckey, A Oden, S E Papapoulos, C Poiana, R Rizzoli, D A Wahl, E V McCloskey
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  ABSTRACT: The introduction of the WHO FRAX® algorithms has facilitated the assessment of fracture risk on the basis of fracture probability. Its use in fracture risk prediction has strengths, but also limitations of which the clinician should be aware and are the focus of this review The International Osteoporosis Foundation (IOF) and the International Society for Clinical Densitometry (ISCD) appointed a joint Task Force to develop resource documents in order to make recommendations on how to improve FRAX and better inform clinicians who use FRAX. The Task Force met in November 2010 for 3 days to discuss these topics which form the focus of this review. This study reviews the resource documents and joint position statements of ISCD and IOF. Details on the clinical risk factors currently used in FRAX are provided, and the reasons for the exclusion of others are provided. Recommendations are made for the development of surrogate models where country-specific FRAX models are not available. The wish list of clinicians for the modulation of FRAX is large, but in many instances, these wishes cannot presently be fulfilled; however, an explanation and understanding of the reasons may be helpful in translating the information provided by FRAX into clinical practice.
  Osteoporosis International 09/2011; 22(9):2395-411. · 4.58 Impact Factor
• Article: Fracture risk assessment without bone density measurement in routine clinical practice.

  W D Leslie, S Morin, L M Lix, H Johansson, A Oden, E McCloskey, J A Kanis
  [show abstract] [hide abstract]
  ABSTRACT: Fracture probability assessed without bone mineral density (BMD) could potentially be sufficient for clinical decision making in many individuals categorized as low or high fracture risk. For individuals falling in a moderate risk range, there is incremental value in using BMD in the probability calculation as this appropriately reclassifies risk in over one third of the individuals. A new fracture risk assessment tool from the World Health Organization (FRAX) estimates 10-year major osteoporotic and hip fracture probabilities from multiple clinical risk factors with or without hip BMD. The objective of this study is to determine whether fracture probability derived without BMD can be used to identify individuals who would be designated for treatment. A historical cohort of 36,730 women and 2,873 men aged 50 years and older drawn from the Manitoba Bone Density Program database, which contains clinical BMD results for the Province of Manitoba, Canada, was included in the study. When 10-year probability for major osteoporotic fracture estimated without knowledge of BMD was high (≥ 20%), the vast majority (92.8%) qualified for intervention under the National Osteoporosis Foundation (NOF) guidelines, whereas among those at low risk (<10%), the vast majority (80.5%) did not satisfy any NOF intervention criteria. The benefit of including BMD in the risk assessment was greatest among those initially at moderate risk (10-19%) when fracture probability was derived without BMD, but this represented only 29.4% of the cohort (9.3% of those aged < 65 years and 48.7% of those ≥ 65 years). Fracture probability derived without BMD is able to risk stratify women in terms of future fracture risk and could potentially be sufficient for clinical decision making in many of those designated at low or high fracture risk.
  Osteoporosis International 08/2011; 23(1):75-85. · 4.58 Impact Factor
• Article: Erratum to: A meta-analysis of the effect of strontium ranelate on the risk of vertebral and non-vertebral fracture in postmenopausal osteoporosis and the interaction with FRAX(®).

  J A Kanis, H Johansson, A Oden, E V McCloskey
  Osteoporosis International 05/2011; · 4.58 Impact Factor
• Article: Fracture prediction and calibration of a Canadian FRAX® tool: a population-based report from CaMos.

  L-A Fraser, L Langsetmo, C Berger, G Ioannidis, D Goltzman, J D Adachi, A Papaioannou, R Josse, C S Kovacs, W P Olszynski, [......], S M Kaiser, J Prior, S Jamal, N Kreiger, J P Brown, H Johansson, A Oden, E McCloskey, J A Kanis, W D Leslie
  [show abstract] [hide abstract]
  ABSTRACT: A new Canadian WHO fracture risk assessment (FRAX®) tool to predict 10-year fracture probability was compared with observed 10-year fracture outcomes in a large Canadian population-based study (CaMos). The Canadian FRAX tool showed good calibration and discrimination for both hip and major osteoporotic fractures. The purpose of this study was to validate a new Canadian WHO fracture risk assessment (FRAX®) tool in a prospective, population-based cohort, the Canadian Multicentre Osteoporosis Study (CaMos). A FRAX tool calibrated to the Canadian population was developed by the WHO Collaborating Centre for Metabolic Bone Diseases using national hip fracture and mortality data. Ten-year FRAX probabilities with and without bone mineral density (BMD) were derived for CaMos women (N = 4,778) and men (N = 1,919) and compared with observed fracture outcomes to 10 years (Kaplan-Meier method). Cox proportional hazard models were used to investigate the contribution of individual FRAX variables. Mean overall 10-year FRAX probability with BMD for major osteoporotic fractures was not significantly different from the observed value in men [predicted 5.4% vs. observed 6.4% (95%CI 5.2-7.5%)] and only slightly lower in women [predicted 10.8% vs. observed 12.0% (95%CI 11.0-12.9%)]. FRAX was well calibrated for hip fracture assessment in women [predicted 2.7% vs. observed 2.7% (95%CI 2.2-3.2%)] but underestimated risk in men [predicted 1.3% vs. observed 2.4% (95%CI 1.7-3.1%)]. FRAX with BMD showed better fracture discrimination than FRAX without BMD or BMD alone. Age, body mass index, prior fragility fracture and femoral neck BMD were significant independent predictors of major osteoporotic fractures; sex, age, prior fragility fracture and femoral neck BMD were significant independent predictors of hip fractures. The Canadian FRAX tool provides predictions consistent with observed fracture rates in Canadian women and men, thereby providing a valuable tool for Canadian clinicians assessing patients at risk of fracture.
  Osteoporosis International 03/2011; 22(3):829-37. · 4.58 Impact Factor
• Article: Construction of a FRAX® model for the assessment of fracture probability in Canada and implications for treatment.

  W D Leslie, L M Lix, L Langsetmo, C Berger, D Goltzman, D A Hanley, J D Adachi, H Johansson, A Oden, E McCloskey, J A Kanis
  [show abstract] [hide abstract]
  ABSTRACT: We describe the creation of a FRAX® model for the assessment of fracture probability in Canadian men and women, calibrated from national hip fracture and mortality data. This FRAX tool was used to examine possible thresholds for therapeutic intervention in Canada in two large complementary cohorts of women and men. To evaluate a Canadian World Health Organization (WHO) fracture risk assessment (FRAX®) tool for computing 10-year probabilities of osteoporotic fracture. Fracture probabilities were computed from national hip fracture data (2005) and death hazards (2004) for Canada. Probabilities took account of age, sex, clinical risk factors (CRFs), and femoral neck bone mineral density (BMD). Treatment implications were studied in two large cohorts of individuals age 50 years and older: the population-based Canadian Multicentre Osteoporosis Study (4,778 women and 1,919 men) and the clinically referred Manitoba BMD Cohort (36,730 women and 2,873 men). Fracture probabilities increased with age, decreasing femoral neck T-score, and number of CRFs. Among women, 10.1-11.3% would be designated high risk based upon 10-year major osteoporotic fracture probability exceeding 20%. A much larger proportion would be designated high risk based upon 10-year hip fracture probability exceeding 3% (25.7-28.0%) or osteoporotic BMD (27.1-30.9%), and relatively few from prior hip or clinical spine fracture (1.6-4.2%). One or more criteria for intervention were met by 29.2-34.0% of women excluding hip fracture probability (35.3-41.0% including hip fracture probability). Lower intervention rates were seen among CaMos (Canadian Multicentre Osteoporosis Study) men (6.8-12.9%), but in clinically referred men from the Manitoba BMD Cohort, one or more criteria for high risk were seen for 26.4% excluding hip fracture probability (42.4% including hip fracture probability). The FRAX tool can be used to identify intervention thresholds in Canada. The FRAX model supports a shift from a dual X-ray absorptiometry (DXA)-based intervention strategy, towards a strategy based on fracture probability for a major osteoporotic fracture.
  Osteoporosis International 03/2011; 22(3):817-27. · 4.58 Impact Factor
• Article: Guidance for the adjustment of FRAX according to the dose of glucocorticoids.

  J A Kanis, H Johansson, A Oden, E V McCloskey
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  ABSTRACT: We examined the effect of glucocorticoid dose on FRAX® derived fracture probabilities in a UK setting. A relatively simple adjustment of conventional FRAX estimates of probabilities of hip fracture and a major osteoporotic fracture can be applied to modulate the risk assessment with knowledge of the dose of glucocorticoids. The WHO fracture risk assessment (FRAX) tool estimates 10-year probability of fracture based upon multiple clinical risk factors and an optional femoral neck BMD measurement. Ever (past and current) use of systemic glucocorticoids is a dichotomous risk factor (yes/no) and does not therefore take account of the dose of glucocorticoids. The aim of this work was to estimate the adjustment for fracture probability based upon the dose of glucocorticoids. Dose responses for fracture risk during exposure to glucocorticoids were taken from the General Practice Research Database and used to adjust the relative risks for glucocorticoids in FRAX. In addition to fracture risk, a dose response for the death hazard was estimated and both variables were used to populate the FRAX model for the UK. The exposure to glucocorticoids was found to significantly affect fracture probability. The following rule was formulated. For low-dose exposure (< 2.5 mg daily of prednisolone or equivalent), the probability of a major fracture is decreased by about 20% depending on age. For medium doses (2.5-7.5 mg daily), the unadjusted FRAX value can be used. For high doses (> 7.5 mg daily), probabilities can be upward revised by about 15%. Conversion factors were also determined for the adjustment of hip fracture probability. A relatively simple adjustment of conventional FRAX estimates of probabilities of hip fracture and a major osteoporotic fracture can be applied to modulate the risk assessment with knowledge of the dose of glucocorticoids.
  Osteoporosis International 03/2011; 22(3):809-16. · 4.58 Impact Factor
• Article: High fracture probability with FRAX usually indicates densitometric osteoporosis: implications for clinical practice.

  W D Leslie, S R Majumdar, L M Lix, H Johansson, A Oden, E McCloskey, J A Kanis
  [show abstract] [hide abstract]
  ABSTRACT: Most patients designated as high risk of fracture using fracture risk assessment tool (FRAX) with femoral neck bone mineral density (BMD) (i.e., 10-year major osteoporotic fracture probability exceeding 20% or hip fracture exceeding 3%) have one or more T-scores in the osteoporotic range; conversely, almost no high risk patients have normal T-scores at all bone mineral density measurement sites. We determined the agreement between a FRAX designation of high risk of fracture [defined as 10-year major osteoporotic fracture probability (≥ 20%) or hip fracture probability (≥ 3%)] and the WHO categorizations of bone mineral density according to T-score. Ten-year FRAX probabilities calculated with femoral neck BMD were derived using both Canadian and US white tools for a large clinical cohort of 36,730 women and 2,873 men age 50 years and older from Manitoba, Canada. Individuals were classified according to FRAX fracture probability and BMD T-scores alone. Most individuals designated by FRAX as high risk of major osteoporotic fracture had a T-score in the osteoporotic range at one or more BMD measurement sites (85% with Canadian tool and 83% with US white tool). The majority of individuals deemed at high risk of hip fracture had one or more T-scores in the osteoporotic range (66% with Canadian tool and 64% with US white tool). Conversely, there were extremely few individuals (<1%) who were at high risk of major osteoporotic or hip fracture with normal T-scores at all BMD measurement sites. A FRAX designation of high risk of fracture is usually associated with a densitometric diagnosis of osteoporosis.
  Osteoporosis International 03/2011; 23(1):391-7. · 4.58 Impact Factor
• Article: A meta-analysis of the effect of strontium ranelate on the risk of vertebral and non-vertebral fracture in postmenopausal osteoporosis and the interaction with FRAX(®).

  J A Kanis, H Johansson, A Oden, E V McCloskey
  [show abstract] [hide abstract]
  ABSTRACT: The aim of the present study was to determine the efficacy of strontium ranelate as a function of baseline fracture risk. Treatment with strontium ranelate was associated with a significant 31% decrease in all clinical osteoporotic fractures (vertebral fractures included). Hazard ratios for the effect of strontium ranelate on the fracture outcome did not change significantly with increasing fracture probability. Two previous studies have suggested that the efficacy of intervention may be greater in the segment of the population at highest fracture risk as assessed by the FRAX(®) algorithms. The aim of the present study was to determine whether the anti-fracture efficacy of strontium ranelate was dependent of the level of fracture risk. The primary data of the two phase III studies (SOTI and TROPOS) of the effects of strontium ranelate in postmenopausal osteoporosis were combined. Country-specific probabilities were computed using the FRAX(®) tool (version 2.0). The primary outcome variable comprised all clinical osteoporotic fractures (including clinical vertebral fractures). Interactions between fracture probability and efficacy were explored by Poisson regression. The 10-year probability of major osteoporotic fractures (with BMD) ranged from 2.5% to 90.8%. FRAX(®)-based hip fracture probabilities ranged from 0.1% to 90.3%. The incidence of clinical osteoporotic fractures (vertebral fractures excluded) and morphometric vertebral fractures increased with increasing baseline fracture probabilities. Treatment with strontium ranelate was associated with a 31% (95% CI = 20-39%) decrease in osteoporotic clinical fractures and a 40% decrease in vertebral fractures assessed by semiquantitative morphometry (95% CI = 31-48%) Hazard ratios for the effect of strontium ranelate on the fracture outcomes did not change significantly with increasing fracture probability. Strontium ranelate significantly decreased the risk of osteoporotic clinical fractures, non vertebral fractures and morphometric vertebral fractures in women. Overall, the efficacy of strontium ranelate was not dependent of the level of fracture risk assessed by FRAX.
  Osteoporosis International 02/2011; 22(8):2347-55. · 4.58 Impact Factor
• Source

  Available from: Patricia Clark

  Article: Increasing age- and sex-specific rates of hip fracture in Mexico: a survey of the Mexican Institute of Social Security.

  H Johansson, P Clark, F Carlos, A Oden, E V McCloskey, J A Kanis
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  ABSTRACT: This study, characterising the incidence of hip fracture in Mexico, showed that age- and sex-specific rates increased between 2000 and 2006. The demographic changes estimated for Mexico indicate that the annual number of hip fractures will rise from 29,732 in 2005 to 155,874 in 2050. If the age-specific incidence of hip fracture continues, the number of hip fractures would increase by a further 46%. The aim of the present study was to determine time trends, if any, in hip fracture rates for Mexico and to forecast the number of hip fractures expected in Mexico over the coming years up to 2050. All hip fracture cases registered during the years 2000-2006 were collected at all the second and tertiary-care hospitals across the country from one of the largest health systems in Mexico, The Instituto Mexicano del Seguro Social (IMSS). Between the years 2000 and 2006, the age-specific incidence of hip fracture increased significantly both for men and women by 1% per year (p = 0.016 and p < 0.001, respectively). In 2005, there were there were 29,732 hip fractures estimated in Mexico, 68% of which were found in women. Assuming no change in the age- and sex-specific incidence of hip fracture, the number of hip fractures was expected to increase markedly with time to 155,874 in 2050. Assuming that the age-specific incidence continues, the number of hip fractures in men and women would increase by a further 46% to 226,886 in 2050. Demographic changes estimated for Mexico indicate that the annual number of hip fractures will rise from 29,732 in 2005 to 155,874 expected in 2050. If the age-specific incidence of hip fracture continues to rise, the number of hip fractures would increase by a further 46%.
  Osteoporosis International 12/2010; 22(8):2359-64. · 4.58 Impact Factor
• Source

  Available from: esceo.org

  Article: Spine-hip discordance and fracture risk assessment: a physician-friendly FRAX enhancement.

  W D Leslie, L M Lix, H Johansson, A Oden, E McCloskey, J A Kanis
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  ABSTRACT: The FRAX® tool estimates a 10-year probability of fracture based upon multiple clinical risk factors and an optional bone mineral density (BMD) measurement obtained from the femoral neck. We describe a simple procedure for using lumbar spine BMD to enhance fracture risk assessment under the FRAX system. Discordance between lumbar spine (LS) and femoral neck (FN) T-scores is common and a source of clinical confusion since the LS measurement is not an input variable for the FRAX algorithm. The purpose of this study is to develop a procedure for adjusting FRAX probability based upon the T-score difference between the LS and FN (termed offset). The Manitoba BMD database was used to identify baseline LS and FN dual-energy X-ray absorptiometry examinations (33,850 women and 2,518 men age 50 and older) with FRAX estimates for a major osteoporotic fracture categorized as low (<10%), moderate (10-20%), and high (>20%). Fracture outcomes were assessed from population-based administrative data. An approach was developed and internally validated using a split-cohort design. The offset was found to significantly affect fracture risk [HR, 1.12 (95% CI, 1.06-1.18) per SD LS below FN] independent of the FRAX probability. The following rule was formulated: "Increase/decrease FRAX estimate for a major fracture by one tenth for each rounded T-score difference between LS and FN." In the validation subgroup, there was a significant improvement in the fracture prediction using FRAX with the proposed offset adjustment for major osteoporotic (P = 0.007) and vertebral fracture prediction (P < 0.001). For those at moderate risk under FRAX, 12.6% showed reclassification using the offset to a risk level that more accurately reflected their observed risk (25.2% reclassification for moderate risk discordant cases). A simple procedure that incorporates the offset between the LS and FN T-scores can enhance fracture risk prediction under the FRAX system.
  Osteoporosis International 10/2010; 22(3):839-47. · 4.58 Impact Factor
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  Available from: Oskar Ström

  Article: Development and use of FRAX in osteoporosis.

  J A Kanis, E V McCloskey, H Johansson, A Oden, O Ström, F Borgström
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  ABSTRACT: This paper reviews briefly the development and clinical use of FRAX in the development of assessment guidelines for osteoporosis.Fractures are the clinical consequence of osteoporosis and are a major cause of morbidity and mortality worldwide. Several treatments are available that have been shown to decrease the risk of fracture, but problems arise in identifying individuals at high fracture risk so that treatments can be effectively targeted. Case finding can be enhanced by the consideration of clinical risk factors that provide information on fracture risk over and above that provided by bone mineral density measurements. The FRAX tool integrates information on fracture risk from clinical risk factors with or without the use of BMD and can be used to improve the targeting of individuals at high fracture risk.
  Osteoporosis International 06/2010; 21 Suppl 2:S407-13. · 4.58 Impact Factor