The Role of Sarcopenia Components in Predicting Osteoporotic Fracture and Its Outcomes of Subsequent Fracture and Mortality in Two Large Prospective Cohorts

Osteoporotic fractures represent a major public health problem worldwide. They are associated with financial costs, disability, subsequent fracture, and premature mortality. Therefore, it is necessary to identify those at higher risk of fracture. Fracture risk assessment tools such as Garvan FRC and FRAX, which estimate absolute fracture risk by incorporating clinical risk factors other than BMD, have shown improved predictive power over BMD alone. However, fracture prediction using these tools remains suboptimal. Sarcopenia components of muscle mass, muscle strength, and physical performance are fall risk factors but their association with fracture risk is controversial. The present thesis reports a series of studies aimed at: determining the contribution of muscle mass, muscle strength, and physical performance and their rate of decline to the risk of fracture; assessing whether the addition of muscle strength and performance improves the predictive accuracy of the existing fracture assessment tools Garvan and FRAX; and examining the contribution of muscle strength and physical performance to the risk of subsequent fracture and mortality in men who already sustained a fracture. Utilising data for 811 community-dwelling women and 440 men aged 60 years and over enrolled in the Dubbo Osteoporosis Epidemiology study and 5665 community-dwelling men aged 65 years and over enrolled in the prospective Osteoporotic Fractures in Men (MrOS) Study, with baseline and serial measurements of BMD and muscle strength and performance, the first study shows that poor quadriceps strength, get up go, and sit to stand test measurements, defined as worst quartiles, but not muscle mass, were associated with a 2-3-fold increase in fracture risk in men independent of bone mineral density (BMD), prior fractures, and falls, while greater rates of deterioration in these measurements were associated with a similar magnitude of fracture risk in both genders. The second study shows that incorporating grip strength and chair stand to Garvan or FRAX significantly improved the prediction of any fracture (net reclassification improvement [NRI] = 3.9% for grip strength and 3.2% for chair stand). The prediction of major osteoporotic fractures has also been improved (NRI = 5.2% for grip strength and 6.1% for chair stands). Gait speed improved the prediction of any hip (7.0%) and initial hip (5.7%) fracture. Combining grip strength and the relevant performance test further improved the models (NRI ranged from 5.7% to 9.4%). The improvement was predominantly driven by the upward reclassification of men with fractures. The third study showed that in 830 men with low-trauma index fracture, muscle strength and performance measured prior to fracture time were not significantly associated with subsequent fracture risk but were significantly associated with mortality. Moreover, the rates of decline in muscle strength and performance were associated with post-fracture mortality, independent of the index values and other confounders. The thesis contributes to clinical practice. Muscle strength and performance tests are simple to perform in GP clinic and have the potential to improve the identification of those at high risk of fracture in order to intervene with the appropriate measures. Our findings stress the importance of physical activity and rehabilitation (physical therapy and occupational therapy) to minimise the risk of fracture and premature death associated with declining muscle strength and physical performance following fracture

Nonstandard lumbar region in predicting fracture risk

Background: Femoral neck BMD is the most commonly used skeletal site to estimate fracture risk. The role of lumbar spine BMD in fracture risk prediction is less clear due to osteophytes that spuriously increase LS BMD, particularly at lower levels. The aim of this study was to compare fracture predictive ability of upper L1-L2 BMD compared to standard L2-L4 BMD and assess whether the addition of either lumbar spine site could improve fracture prediction over FN BMD. Methodology: A prospective cohort of 3016 women and men 60+ years from the Dubbo Osteoporosis Epidemiology Study followed for occurrence of minimal trauma fractures from 1989 to 2014. DXA was used to measure bone mineral density at f L1-L2, L2-L4 and FN at baseline. Fracture risks were estimated using Cox proportional hazards models separately for each site. Predictive performances were compared using ROC curve analyses Results:There were 565 women and 179 men with a minimal trauma fracture during a mean of 11±7 years. L1-L2 BMD T-score was significantly lower than L2-L4 T-score in both genders (p Conclusion: In an elderly population, L1-L2 is as good as but not better than L2-L4 site in predicting fracture risk. The addition of LS BMD to FN BMD provided a modest additional benefit in overall fracture risk. Further studies in individuals with spinal degenerative disease are needed

The association between multimorbidity and osteoporosis investigation and treatment in high-risk fracture patients in Australia: A prospective cohort study.

BackgroundMultimorbidity is common among fracture patients. However, its association with osteoporosis investigation and treatment to prevent future fractures is unclear. This limited knowledge impedes optimal patient care. This study investigated the association between multimorbidity and osteoporosis investigation and treatment in persons at high risk following an osteoporotic fracture.Methods and findingsThe Sax Institute's 45 and Up Study is a prospective population-based cohort of 267,153 people in New South Wales, Australia, recruited between 2005 and 2009. This analysis followed up participants until 2017 for a median of 6 years (IQR: 4 to 8). Questionnaire data were linked to hospital admissions (Admitted Patients Data Collection (APDC)), emergency presentations (Emergency Department Data Collection (EDDC)), Pharmaceutical Benefits Scheme (PBS), and Medicare Benefits Schedule (MBS). Data were linked by the Centre for Health Record Linkage and stored in a secured computing environment. Fractures were identified from APDC and EDDC, Charlson Comorbidity Index (CCI) from APDC, Dual-energy X-ray absorptiometry (DXA) investigation from MBS, and osteoporosis treatment from PBS. Out of 25,280 persons with index fracture, 10,540 were classified as high-risk based on 10-year Garvan Fracture Risk (age, sex, weight, prior fracture and falls) threshold ≥20%. The association of CCI with likelihood of investigation and treatment initiation was determined by logistic regression adjusted for education, socioeconomic and lifestyle factors). The high-risk females and males averaged 77 ± 10 and 86 ± 5 years, respectively; >40% had a CCI ≥2. Only 17% of females and 7% of males received a DXA referral, and 22% of females and 14% males received osteoporosis medication following fracture. A higher CCI was associated with a lower probability of being investigated [adjusted OR, females: 0.73 (95% CI, 0.61 to 0.87) and 0.43 (95% CI, 0.30 to 0.62); males: 0.47 (95% CI, 0.33 to 0.68) and 0.52 (0.31 to 0.85) for CCI: 2 to 3, and ≥4 versus 0 to 1, respectively] and of receiving osteoporosis medication [adjusted OR, females: 0.85 (95% CI, 0.74 to 0.98) and 0.78 (95% CI, 0.61 to 0.99); males: 0.75 (95% CI, 0.59 to 0.94) and 0.37 (95% CI, 0.23 to 0.53) for CCI: 2 to 3, and ≥4 versus 0 to 1, respectively]. The cohort is relatively healthy; therefore, the impact of multimorbidity on osteoporosis management may have been underestimated.ConclusionsMultimorbidity contributed significantly to osteoporosis treatment gap. This suggests that fracture risk is either underestimated or underprioritized in the context of multimorbidity and highlights the need for extra vigilance and improved fracture care in this setting

Muscle Strength and Physical Performance Are Associated With Risk of Postfracture Mortality But Not Subsequent Fracture in Men.

Muscle strength and physical performance are associated with incident fractures and mortality. However, their role in the risk of subsequent fracture and postfracture mortality is not clear. We assessed the association between muscle strength (grip strength) and performance (gait speed and chair stands time) and the risk of subsequent fracture and mortality in 830 men with low-trauma index fracture, who participated in the Osteoporotic Fractures in Men (MrOS) USA Study and had their index measurements assessed within 5 years prior to the index fracture. The annual decline in muscle strength and performance following index fracture, estimated using linear mixed-effects regression, was also examined in relation to mortality. The associations were assessed using Cox proportional hazards models adjusted for age, femoral neck bone mineral density (FN BMD), prior fractures, falls, body mass index (BMI), index fracture site, lifestyle factors, and comorbidities. Over a median follow-up of 3.7 (interquartile range [IQR], 1.3-8.1) years from index fracture to subsequent fracture, 201 (24%) men had a subsequent fracture and over 5.1 (IQR, 1.8-9.6) years to death, and 536 (65%) men died. Index measurements were not associated with subsequent fracture (hazard ratios [HRs] ranging from 0.97 to 1.07). However, they were associated with postfracture mortality. HR (95% confidence interval [CI]) per 1 standard deviation (1-SD) decrement in grip strength: HR 1.12 (95% CI, 1.01-1.25) and gait speed: HR 1.14 (95% CI, 1.02-1.27), and 1-SD increment in chair stands time: HR 1.08 (95% CI, 0.97-1.21). Greater annual declines in these measurements were associated with higher mortality risk, independent of the index values and other covariates. HR (95% CI) per 1-SD annual decrement in change in grip strength: HR 1.15 (95% CI, 1.01-1.33) and in gait speed: HR 1.38 (95% CI, 1.13-1.68), and 1-SD annual increment in chair stands time: HR 1.28 (95% CI, 1.07-1.54). Men who were unable to complete one or multiple tests had greater risk of postfracture mortality (24%-109%) compared to those performed all tests. It remains to be seen whether improvement in these modifiable factors can reduce postfracture mortality. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)

Characteristics at the time of index fracture for females and males in the high-risk group according to DXA referral and treatment initiation.

Characteristics at the time of index fracture for females and males in the high-risk group according to DXA referral and treatment initiation.</p

Clinical risk factors associated with treatment investigation following index hip and vertebral fracture regardless of 10-year Garvan Fracture Risk estimate.

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