A reference standard for the description of osteoporosis

Self Cite

115

Ten-year fracture risk assessment with the fracture risk assessment system (FRAX) is increasingly used to guide treatment decisions. Osteoporosis pharmacotherapy reduces fracture risk, but the effect is greater than can be explained from the increase in bone mineral density (BMD). Whether this invalidates fracture predictions with FRAX is uncertain. A total of 35,764 women (age !50 years) and baseline BMD testing (1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007) had FRAX probabilities retroactively calculated. A provincial pharmacy database was used to identify osteoporosis medication use. Women were categorized as untreated, current high adherence users [medication possession ratio (MPR) !0.80 in the year after BMD testing], current low adherence users (MPR <0.80), and past users. Fractures outcomes to 10 years were established form a population-based health data repository. FRAX and femoral neck BMD alone stratified major osteoporotic and hip fracture risk within untreated and each treated subgroup (all p-values <0.001) with similar area under the receiver operating characteristic curve. In untreated and each treated subgroup, a stepwise gradient in observed 10-year major osteoporotic and hip fracture incidence was found as a function of the predicted probability tertile (all p-values <0.001 for linear trend). Concordance (calibration) plots for major osteoporotic fractures and hip fractures showed good agreement between the predicted and observed 10-year fracture incidence in untreated women and each treated subgroup. Only in the highest risk tertile of women highly adherent to at least 5 years of bisphosphonate use was observed hip fracture risk significantly less than predicted, though major osteoporotic fracture risk was similar to predicted. In summary, this work suggests that the FRAX tool can be used to predict fracture probability in women currently or previously treated for osteoporosis. Although FRAX should not be used to assess the reduction in fracture risk in individuals on treatment, it may still have value for guiding the need for continued treatment or treatment withdrawal. ß

Section: Bone Density Measurementsmentioning

confidence: 99%

Does osteoporosis therapy invalidate FRAX for fracture prediction?

Leslie

Lix

Johansson

et al. 2012

Self Cite

115

“…We assessed BMD by DXA (reference standard for BMD measurements) (27) at sites not previously studied in relation to Cd, as well as the risk of various types of fractures, including multiple incident fractures. U-Cd was assessed with high analytical precision giving low uncertainty even in our low-dose range.…”

Section: Discussionmentioning

confidence: 99%

Long-term cadmium exposure and the association with bone mineral density and fractures in a population-based study among women

Engström

Michaëlsson

Suwazono

et al. 2010

127

All people are exposed to cadmium (Cd) via food; smokers are additionally exposed. High Cd exposure is associated with severe bone damage, but the public health impact in relation to osteoporosis and fractures at low environmental exposure remains to be clarified. Within the population-based Swedish Mammography Cohort, we assessed urinary Cd [U-Cd, mg/g of creatinine (cr)] as a marker of lifetime exposure and bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) among 2688 women. Register-based information on fractures was retrieved from 1997 to 2009. Associations were evaluated by multivariable regression analyses. In linear regression, U-Cd was inversely associated with BMD at the total body ( p < .001), femoral neck ( p ¼ .025), total hip ( p ¼ .004), lumbar spine ( p ¼ .088), and volumetric femoral neck ( p ¼ .013). In comparison with women with U-Cd < 0.50 mg/g of cr, those with U-Cd ! 0.75 mg/g of cr had odds ratios (ORs) of 2.45 [95% confidence interval (CI) 1.51-3.97] and 1.97 (95% CI 1.24-3.14) for osteoporosis at the femoral neck and lumbar spine, respectively. Among never-smokers, the corresponding ORs were 3.47 (95% CI 1.46-8.23) and 3.26 (95% CI 1.44-7.38). For any first fracture (n ¼ 395), the OR was 1.16 (95% CI 0.89-1.50) comparing U-Cd ! 0.50 mg/g of cr with lower levels. Among never-smokers, the ORs (95% CIs) were 2.03 (1.33-3.09) for any first fracture, 2.06 (1.28-3.32) for first osteoporotic fracture, 2.18 (1.20-3.94) for first distal forearm fracture, and 1.89 (1.25-2.85) for multiple incident fractures. U-Cd at low environmental exposure from food in a general population of women showed modest but significant association with both BMD and fractures, especially in neversmokers, indicating a larger concern than previously known. ß

“…(8,10) The WHO coordinating center has reviewed the available data and suggested that a common (sex-independent) reference database be used for T-score generation, (4) and for the femoral neck, the recommended database is NHANES III for young white females. (3) As fracture risk assessment moves globally from a T-scorebased approach to absolute 10-year fracture risk using the WHO fracture risk assessment (FRAX) tool, controversies regarding choice of BMD reference population become less critical. FRAX tools could be calibrated equally well with sex-matched or sexindependent T-scores.…”

Section: Discussionmentioning

confidence: 99%

“…We used NHANES III non-Hispanic whites (ages 20 to 29 years) as the reference population for all models. (3) In model 1, BMD was centered using a common reference mean and SD based on the NHANES III women. In model 2, BMD was centered separately using a sex-specific mean, but we still used the SD derived from women only.…”

Section: Methodsmentioning

confidence: 99%

Using the same bone density reference database for men and women provides a simpler estimation of fracture risk

Langsetmo

Leslie

Zhou

et al. 2010

Although low bone mineral density (BMD) predicts fractures, there are postulated sex differences in the fracture ''threshold.'' Some studies demonstrate a higher mean BMD for men with fractures than for women, whereas others note similar absolute risk at the same level of BMD. Our objective was to test the preceding observations in the population-based Canadian Multicentre Osteoporosis Study (CaMOS). We included participants 50þ years of age at baseline. Mean BMD in men was higher than in women among both fracture cases and noncases. Three methods of BMD normalization were compared in age-adjusted Cox proportional hazards models. In a model using the same reference population mean and standard deviation (SD), there were strong effects of age and total-hip BMD for prediction of fractures but no significant effect of sex [hazard ratio (HR) ¼ 0.97, 95% confidence interval (CI) 0.78-1.20] for men versus women. In a model using sex-specific reference means but a common SD, an apparent sex difference emerged (HR ¼ 0.66, 95% CI 0.54-0.81) for men versus women. The sex term in the second model counterbalanced the higher risk introduced by the lower normalized BMD in men. A third model using sex-specific reference means and SDs gave nearly identical results. Parallel results for the three methods of normalization were seen when adjusting for clinical risk factors, excluding antiresorptive users and considering death as a competing risk. We conclude that no adjustment for sex is necessary when using common reference data for both men and women, whereas using sex-specific reference data requires a substantial secondary adjustment for sex. ß