A Risk Assessment Tool for Predicting Fragility Fractures and Mortality in the Elderly
Thach Tran, Dana Bliuc, Hanh M Pham, Tineke van Geel, Jonathan D Adachi, Claudie Berger, Joop van den Bergh, John A Eisman, Piet Geusens, David Goltzman, David A Hanley, Robert G Josse, Stephanie M Kaiser, Christopher S Kovacs, Lisa Langsetmo, Jerilynn C Prior, Tuan V Nguyen, Jacqueline R Center
Existing fracture risk assessment tools are not designed to predict fracture-associated consequences, possibly contributing to the current undermanagement of fragility fractures worldwide. We aimed to develop a risk assessment tool for predicting the conceptual risk of fragility fractures and its consequences. The study involved 8965 people aged ≥60 years from the Dubbo Osteoporosis Epidemiology Study and the Canadian Multicentre Osteoporosis Study. Incident fracture was identified from X-ray reports and questionnaires, and death was ascertained though contact with a family member or obituary review. We used a multistate model to quantify the effects of the predictors on the transition risks to an initial and subsequent incident fracture and mortality, accounting for their complex interrelationships, confounding effects, and death as a competing risk. There were 2364 initial fractures, 755 subsequent fractures, and 3300 deaths during a median follow-up of 13 years (interquartile range [IQR] 7-15). The prediction model included sex, age, bone mineral density, history of falls within 12 previous months, prior fracture after the age of 50 years, cardiovascular diseases, diabetes mellitus, chronic pulmonary diseases, hypertension, and cancer. The model accurately predicted fragility fractures up to 11 years of follow-up and post-fracture mortality up to 9 years, ranging from 7 years after hip fractures to 15 years after non-hip fractures. For example, a 70-year-old woman with a T-score of -1.5 and without other risk factors would have 10% chance of sustaining a fracture and an 8% risk of dying in 5 years. However, after an initial fracture, her risk of sustaining another fracture or dying doubles to 33%, ranging from 26% after a distal to 42% post hip fracture. A robust statistical technique was used to develop a prediction model for individualization of progression to fracture and its consequences, facilitating informed decision making about risk and thus treatment for individuals with different risk profiles.
fracture risk assessment tool elderly mortality prediction, fragility fracture subsequent fracture multistate model, Prior JC CaMos fracture prediction bone mineral density, Dubbo Osteoporosis Epidemiology Study fracture risk model, individualized fracture risk post-fracture mortality prediction, competing risk death fracture prediction elderly, subsequent fracture risk after initial fragility fracture, bone mineral density falls history fracture risk calculator, fracture cascade imminent fracture risk elderly assessment, cardiovascular diabetes comorbidity fracture risk prediction
PMID 32460361 32460361 DOI 10.1002/jbmr.4100 10.1002/jbmr.4100
Cite this article
Tran, T., Bliuc, D., Pham, H. M., van Geel, T., Adachi, J. D., Berger, C., van den Bergh, J., Eisman, J. A., Geusens, P., Goltzman, D., Hanley, D. A., Josse, R. G., Kaiser, S. M., Kovacs, C. S., Langsetmo, L., Prior, J. C., Nguyen, T. V., Center, J. R., & CaMos Research Group (2020). A Risk Assessment Tool for Predicting Fragility Fractures and Mortality in the Elderly. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 35(10), 1923-1934. https://doi.org/10.1002/jbmr.4100
Tran T, Bliuc D, Pham HM, van Geel T, Adachi JD, Berger C, et al. A Risk Assessment Tool for Predicting Fragility Fractures and Mortality in the Elderly. J Bone Miner Res. 2020;35(10):1923-1934. doi:10.1002/jbmr.4100
Tran, T., et al. "A Risk Assessment Tool for Predicting Fragility Fractures and Mortality in the Elderly." Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, vol. 35, no. 10, 2020, pp. 1923-1934.
Related articles
Bone HealthCognitive Decline AssociationMedication EffectsBias by Indication
We are grateful to Dr. Naharci for the interest in our study reporting the association between cognitive decline and bone loss and fracture risk. (1) We agree that bisphosphonates (BPs) have a proven effect on reducing bone loss and fracture risk. (2) Medication with anticholinergic (ACH) side effects may also affect cogni-tive function as well as propensity to fall and fracture, although these effects have not been demonstrated in all studies. (3) We did not include these medication classes in our models because in observational studies the relationship between medication and outcomes is likely driven by factors associated with medication use. This bias by indication can only be avoided by specific study design (ie, propensity score matching), which was beyond the scope of our study. (4) However, we have conducted additional analyses to determine the prevalence of BP and ACH medication in our cohort, the association between these medication classes and our study outcomes and the impact of the addition of these medication classes to our findings. BP and ACH use were self-reported and obtained by questionnaire at baseline, and years 5 and 10. Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry (DXA) and cognitive function using the Mini Mental State Examination (MMSE) test during all clinical visits. Follow-up time for BMD
Bone HealthPredictive ModelsFracture Risk FactorsStructural Equation Modeling
It is recognized that the trabecular bone score (TBS) provides skeletal information, and frailty measurement is significantly associated with increased risks of adverse health outcomes. Given the suboptimal predictive power in fracture risk assessment tools, we aimed to evaluate the combination of frailty and TBS regarding predictive accuracy for risk of major osteoporotic fracture (MOF). Data from the prospective longitudinal study of CaMos (Canadian Multicentre Osteoporosis Study) were used for this study. TBS values were estimated using lumbar spine (L1 to L4 ) dual-energy X-ray absorptiometry (DXA) images; frailty was evaluated by a frailty index (FI) of deficit accumulation. Outcome was time to first incident MOF during the follow-up. We used the Harrell's C-index to compare the model predictive accuracy. The Akaike information criterion, likelihood ratio test, and net reclassification improvement (NRI) were used to compare model performances between the model combining frailty and TBS (subsequently called "FI + TBS"), FI-alone, and TBS-alone models. We included 2730 participants (mean age 69 years; 70% women) for analyses (mean follow-up 7.5 years). There were 243 (8.90%) MOFs observed during follow-up. Participants with MOF had significantly higher FI (0.24 versus 0.20) and lower TBS (1.231 versus 1.285) than those without MOF. FI and TBS were significantly related with MOF risk in the model adjusted for FRAX with bone mineral density (BMD) hazard ratio (HR) = 1.26 (95% confidence interval [CI] 1.11-1.43) for per-SD increase in FI; HR = 1.38 (95% CI 1.21-1.59) for per-SD decrease in TBS; and these associations showed negligible attenuation (HR = 1.24 for per-SD increase in FI, and 1.35 for per-SD decrease in TBS) when combined in the same model. Although the model FI + TBS was a better fit to the data than FI-alone and TBS-alone, only minimal and nonsignificant enhancement of discrimination and NRI were observed in FI + TBS. To conclude, frailty and TBS are significantly and independently related to MOF risk. Larger studies are warranted to determine whether combining frailty and TBS can yield improved predictive accuracy for MOF risk.
Bone HealthBisphosphonatesBone Loss and MortalityMediation Analysis
Bisphosphonates, potent antiresorptive agents, have been found to be associated with mortality reduction. Accelerated bone loss is, in itself, an independent predictor of mortality risk, but the relationship between bisphosphonates, bone loss, and mortality is unknown. This study aimed to determine whether the association between bisphosphonates and mortality is mediated by a reduction in the rate of bone loss. Participants from the population-based Canadian Multicentre Osteoporosis Study were followed prospectively between1996 and 2011. Comorbidities and lifestyle factors were collected at baseline and bone mineral density (BMD) at baseline and at years 3 (for those aged 40 to 60 years), 5, and 10. Rate of bone loss was calculated using linear regression. Information on medication use was obtained yearly. Bisphosphonate users grouped into nitrogen bisphosphonates (nBP; alendronate or risedronate) and etidronate and non-users (NoRx) were matched by propensity score, including all baseline factors as well as time of treatment. Cox's proportional hazards models, unadjusted and adjusted for annual rate of bone loss, were used to determine the association between nBP and etidronate versus NoRx. For the treatment groups with significant mortality risk reduction, the percent of mortality reduction mediated by a reduction in the rate of bone loss was estimated using a causal mediation analysis. There were 271 pairs of nBP and matched NoRx and 327 pairs of etidronate and matched NoRx. nBP but not etidronate use was associated with significant mortality risk reduction (hazard ratios [HR] = 0.61 [95% confidence interval 0.39-0.96] and 1.35 [95% CI 0.86-2.11] for nBP and etidronate, respectively). Rapid bone loss was associated with more than 2-fold increased mortality risk compared with no loss. Mediation analysis indicated that 39% (95% CI 7%-84%) of the nBP association with mortality was related to a reduction in the rate of bone loss. This finding provides an insight into the mechanism of the relationship between nBP and survival benefit in osteoporotic patients.
Bone HealthVertebral Fracture AssessmentRadiographic DiagnosisVertebral Morphometry vs Morphology
Until recently there has been little evidence available to validate any method by which to make an accurate diagnosis of an osteoporotic vertebral fractures (OVFs) from plain radiographs. In part this reflects a lack of a completely satisfactory "gold standard," but primarily it relates to the absence of well-designed prospective studies in this context. Historically, OVFs were recognized by evidence of macroscopic structural failure in vertebrae using the criteria applied elsewhere in the skeleton. This comprised altered alignment, fragmentation, cortical disruptions, and breaks, among other changes. However, these morphological criteria were replaced by vertebral morphometry, referring to the use of quantitative or quasi-quantitative measurement tools for fracture diagnosis. Vertebral morphometry emerged as an understanding of and treatment for osteoporosis evolved, mainly in response to the need for expeditious assessments of large numbers of spine images for epidemiological and pharmaceutical purposes. Although most of the descriptions of such morphometric tools have stressed that they were not to be applied to clinical diagnosis with respect to individual patients, this constraint has been widely disregarded. Here we review the major attempts to develop a diagnostic strategy for OVF and describe their characteristics in adults and children. Recent evidence suggests that morphometric (quantitative; ie, based on measurement of dimensions and shape description) criteria are inferior to morphologic (qualitative; ie, based on structural integrity) vertebral damage assessment in identifying people with low bone density and at an increased risk of future fracture. Thus there is now an evidentiary basis for suggesting that morphological assessment is the preferred strategy for use in diagnosing OVF from radiographs.