The use of clinical risk factors enhances the performance of BMD in the prediction of hip and osteoporotic fractures in men and women

Kanis, JA; Odén, Anders; Johnell, Olof; Johansson, Helena; Laet, Chris De; Brown, Jacques P.; Burckhardt, P.; Cooper, Cyrus; Christiansen, Claus; Cummings, Steven R.; Eisman, John A.; Fujiwara, Saeko; Glüer, Claus C.; Goltzman, David; Hans, Didier; Ma, Kui; Croix, AZ La; McCloskey, Eugène; Mellström, Dan; Melton, L. Joseph; Pols, Huibert A. P.; Reeve, J.; Sanders, Kerrie M.; Schott, Anne-Marie; Silman, Alan J.; Torgerson, David; Staa, Tjeerd van; Watts, Nelson B.; Yoshimura, Nagahisa

doi:10.1007/s00198-007-0343-y

Cited by 1,033 publications

(785 citation statements)

References 69 publications

Supporting

Mentioning

715

Contrasting

Unclassified

Order By: Relevance

“…Accordingly, in the meta-analyses using data from the FRAX cohorts, all CRFs except a personal history of fracture were more strongly associated with the risk of hip fracture than with the risk of other OP fractures. (5) At the age of 50 years, the gradient of risk with BMD alone was 3.7 per SD, but with the addition of CRFs, it increased to 4.2 per SD. For other major OP fractures, the gradient of risk with BMD alone was lower, and adding CRFs only modestly improved it.…”

Section: Discussionmentioning

confidence: 92%

“…Hence the predictive value of a family history of fracture, corticosteroid use, and some other infrequent CRFs would need to be further studied in larger cohorts of young postmenopausal women. One of the main differences between our cohort and the cohorts used to develop the FRAX tool (5) is that our cohort is, on average, 10 years younger (53 versus 63 years in the FRAX cohorts). The mix of fractures is likely different in early postmenopausal than in elderly women.…”

Section: Discussionmentioning

confidence: 99%

“…(3) However, even though a low BMD is strongly associated with the risk of fracture, it is well recognized that different risk factors, such as age, history of a prior fragility fracture, steroid use, and many others, are independent contributors to the risk of fracture and improve the sensitivity of BMD measurement in identifying patients at high risk of fracture. (4,5) Current guidelines thus have emphasized the usefulness of combining BMD and clinical risk factors to determine an absolute risk of fracture and decide which patient has to be treated and which patient has a sufficiently low fracture risk to be observed without treatment. In this regard, the WHO's fracture risk assessment tool (FRAX), which has just been launched during this last year, allows one to calculate the 10-year probability of fractures in men and women from several clinical risk factors (CRFs) with or without the measurement of femoral neck BMD.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Fracture risk prediction using BMD and clinical risk factors in early postmenopausal women: Sensitivity of the WHO FRAX tool

Trémollières

Pouillès

Drewniak

et al. 2010

Journal of Bone and Mineral Research

177

110

View full text Add to dashboard Cite

The aim of this prospective study was (1) to identify significant and independent clinical risk factors (CRFs) for major osteoporotic (OP) fracture among peri-and early postmenopausal women, (2) to assess, in this population, the discriminatory capacity of FRAX and bone mineral density (BMD) for the identification of women at high risk of fracture, and (3) to assess whether adding risk factors to either FRAX or BMD would improve discriminatory capacity. The study population included 2651 peri-and early postmenopausal women [mean age (AE SD): 54 AE 4 years] with a mean follow-up period of 13.4 years (AE1.4 years). At baseline, a large set of CRFs was recorded, and vertebral BMD was measured (Lunar, DPX) in all women. Femoral neck BMD also was measured in 1399 women in addition to spine BMD. Women with current or past OP treatment for more than 3 months at baseline (n ¼ 454) were excluded from the analyses. Over the follow-up period, 415 women sustained a first low-energy fracture, including 145 major OP fractures (108 wrist, 44 spine, 20 proximal humerus, and 13 hip). In Cox multivariate regression models, only 3 CRFs were significant predictors of a major OP fracture independent of BMD and age: a personal history of fracture, three or more pregnancies, and current postmenopausal hormone therapy. In the subsample of women who had a hip BMD measurement and who were not receiving OP therapy (including hormone-replacement therapy) at baseline, mean FRAX value was 3.8% (AE2.4%). The overall discriminative value for fracture, as measured by the area under the Receiver Operating Characteristic (ROC) curve (AUC), was equal to 0.63 [95% confidence interval (CI) 0.56-0.69] and 0.66 (95% CI 0.60-0.73), respectively, for FRAX and hip BMD. Sensitivity of both tools was low (ie, around 50% for 30% of the women classified as the highest risk). Adding parity to the predictive model including FRAX or using a simple risk score based on the best predictive model in our population did not significantly improve the discriminatory capacity over BMD alone. Only a limited number of clinical risk factors were found associated with the risk of major OP fracture in peri-and early postmenopausal women. In this population, the FRAX tool, like other risk scores combining CRFs to either BMD or FRAX, had a poor sensitivity for fracture prediction and did not significantly improve the discriminatory value of hip BMD alone. ß

show abstract

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Fracture risk prediction using BMD and clinical risk factors in early postmenopausal women: Sensitivity of the WHO FRAX tool

Trémollières

Pouillès

Drewniak

et al. 2010

Journal of Bone and Mineral Research

177

110

View full text Add to dashboard Cite

show abstract

“…The clinical risk factors were body mass index, prior low-trauma fracture after age 50, parental fracture, alcohol intake, current smoking, rheumatoid arthritis, and glucocorticoid use because these are part of the WHO fracture risk assessment (FRAX) paradigm. (19) We also repeated all the preceding analyses using femoral neck BMD rather than total-hip BMD. The analyses were performed using SAS Version 9.1 (SAS Institute, Cary, NC, USA) and Stata Version 9.2 (Stata, Inc., College Station, TX, USA) for Windows.…”

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

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

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

show abstract

“…However, there are numerous other risk factors for osteoporotic fractures and a WHO working party has been developing an approach for the estimation of 10-year fracture risk based on these factors (7) . Recently, attention has turned to the role of biochemical markers of bone turnover as predictors of fracture.…”

mentioning

confidence: 99%

Biomarkers of bone health and osteoporosis risk

2008

View full text Add to dashboard Cite

The assay features of biochemical markers of bone turnover have markedly improved in the past few years. The most sensitive and specific markers of bone formation include serum bone alkaline phosphatase, total osteocalcin (including the intact molecule and the large N-mid fragment) and the procollagen type I N-terminal propeptide assay. Among the various markers of bone resorption, measurements of the urinary excretion of N-and C-terminal cross-linked telopeptides) and of serum C-terminal cross-linked telopeptides are the most sensitive and specific. Markers of bone turnover can be used to predict the rate of bone loss in postmenopausal women and can also be used to assess the risk of fractures. In osteoporosistreatment studies (with alendronate, risedronate, raloxifene) markers of bone turnover appear even more strongly associated with fracture risk reduction than bone mineral density (BMD). These observations support the use of markers of bone turnover as surrogates for fracture risk reduction, perhaps even more so than BMD. Bone markers can also be used to monitor the efficacy of antiresorptive therapy such as hormone-replacement therapy, raloxifene and bisphosphonates in individual patients. Furthermore, they have also proved to be helpful in monitoring the response to nutritional interventions and have the advantage over BMD in that they provide information about mechanism of effect and changes are often observed much more rapidly.Bone turnover markers: Bone mineral density: Bone health: Osteoporosis Osteoporotic fractures have a considerable impact on the individual and on health economics. There is a substantial increase in mortality and morbidity, particularly after a hip fracture; 10-20 % more women die subsequent to a hip fracture than would be expected for their age, and for those who survive £ 50% cease to be able to live independently (1) . In health economic terms it is estimated that there are >160 000 osteoporotic fractures per year in the UK alone, which cost the National Health Service £1 . 7 · 10 9 . Antiresorptive therapies are now available that have been shown to rapidly reduce fracture incidence even in elderly women (2)(3)(4)(5) . However, in developing a fracture prevention strategy it is important to be able to identify those women at greatest risk of a fracture.It is now well established that fracture risk is higher in women with low bone mineral density (BMD), with a decrease of 1 SD in BMD leading to a doubling of the risk of fracture (6) . However, there are numerous other risk factors for osteoporotic fractures and a WHO working party has been developing an approach for the estimation of 10-year fracture risk based on these factors (7) . Recently, attention has turned to the role of biochemical markers of bone turnover as predictors of fracture. Bone turnover may predict fracture in two ways: (a) via BMD, since high bone turnover is associated with low BMD (8) ; (b) independently of BMD, since increased bone turnover has a detrimental effect on bone microarchitecture and fragility ...

show abstract

The use of clinical risk factors enhances the performance of BMD in the prediction of hip and osteoporotic fractures in men and women

Abstract: The models developed provide the basis for the integrated use of validated clinical risk factors in men and women to aid in fracture risk prediction.

Cited by 1,033 publications

References 69 publications

Fracture risk prediction using BMD and clinical risk factors in early postmenopausal women: Sensitivity of the WHO FRAX tool

Fracture risk prediction using BMD and clinical risk factors in early postmenopausal women: Sensitivity of the WHO FRAX tool

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

Biomarkers of bone health and osteoporosis risk

Contact Info

Product

Resources

About