Patient Self-Assessment of Walking Ability and Fracture Risk in Older Australian Adults.

Importance: The relationship between self-reported walking limitation, a proxy of muscle function, and fracture risk has not been investigated. Objective: To examine the association between a self-reported walking limitation of 1000 m or less and 5-year risk of fracture. Design, Setting, and Participants: This prospective cohort study compared individuals with various degrees of walking ability limitation at 1000 m (a little limitation and a lot of limitation) and those without limitation (no limitation) accounting for age, falls, prior fractures, and weight. Participants from the ongoing population-based Sax Institute 45 and Up Study were followed from recruitment (2005-2008) for 5 years (2010-2013). Data analysis was conducted from July 2020 to September 2023. Exposure: Self-reported walking limitation. Main Outcomes and Measures: Incident fracture and site-specific fractures (hip, vertebral, and nonhip nonvertebral [NHNV] fractures). Results: Among the 266 912 participants enrolled in the 45 and Up Study, 238 969 were included, with 126 015 (53%) women (mean [SD] age, 63 [11] years) and 112 954 (47%) men (mean [SD] age, 61 [11] years). Approximately 20% reported a degree of limitation in walking 1000 m or less at baseline (39 324 women [24%]; 23 191 men [21%]). During a mean (SD) follow-up of 4.1 (0.8) years, 7190 women and 4267 men experienced an incident fracture. Compared with participants who reported no walking limitations, a little limitation and a lot of limitation were associated with higher risk of fracture (a little limitation among women: hazard ratio [HR], 1.32; 95% CI, 1.23-1.41; a little limitation among men: HR, 1.46; 95% CI, 1.34-1.60; a lot of limitation among women: HR, 1.60; 95% CI, 1.49-1.71; a lot of limitation among men: HR, 2.03; 95% CI, 1.86-2.22). Approximately 60% of fractures were attributable to walking limitation. The association was significant for hip, vertebral, and NHNV fracture and ranged between a 21% increase to a greater than 219% increase. Conclusions and Relevance: In this cohort study of 238 969 participants, self-reported walking limitations were associated with increased risk of fracture. These findings suggest that walking ability should be sought by clinicians to identify high-risk candidates for further assessment.

Predicting Slow Walking Speed From a Pooled Cohort Analysis: Sarcopenia Definitions, Agreement, and Prevalence in Australia and New Zealand.

BACKGROUND: Recent operational definitions of sarcopenia have not been replicated and compared in Australia and New Zealand (ANZ) populations. We aimed to identify sarcopenia measures that discriminate ANZ adults with slow walking speed (<0.8 m/s) and determine the agreement between the Sarcopenia Definitions and Outcomes Consortium (SDOC) and revised European Working Group for Sarcopenia in Older People (EWGSOP2) operational definitions of sarcopenia. METHODS: Eight studies comprising 8 100 ANZ community-dwelling adults (mean age ± standard deviation, 62.0 ± 14.4 years) with walking speed, grip strength (GR), and lean mass data were combined. Replicating the SDOC methodology, 15 candidate variables were included in sex-stratified classification and regression tree models and receiver operating characteristic curves on a pooled cohort with complete data to identify variables and cut points discriminating slow walking speed (<0.8 m/s). Agreement and prevalence estimates were compared using Cohen's Kappa (CK). RESULTS: Receiver operating characteristic curves identified GR as the strongest variable for discriminating slow from normal walking speed in women (GR <20.50 kg, area under curve [AUC] = 0.68) and men (GR <31.05 kg, AUC = 0.64). Near-perfect agreement was found between the derived ANZ cut points and SDOC cut points (CK 0.8-1.0). Sarcopenia prevalence ranged from 1.5% (EWGSOP2) to 37.2% (SDOC) in women and 1.0% (EWGSOP2) to 9.1% (SDOC) in men, with no agreement (CK <0.2) between EWGSOP2 and SDOC. CONCLUSIONS: Grip strength is the primary discriminating characteristic for slow walking speed in ANZ women and men, consistent with findings from the SDOC. Sarcopenia Definitions and Outcomes Consortium and EWGSOP2 definitions showed no agreement suggesting these proposed definitions measure different characteristics and identify people with sarcopenia differently.

Mortality, falls and slow walking speed are predicted by different muscle strength and physical performance measures in women and men.

BACKGROUND: Different measures of muscle strength, physical performance and body size/composition are used in various sarcopenia definitions. This study investigated which baseline measures best predict incident mortality and falls, and prevalent slow walking speed in older women and men. MATERIALS AND METHODS: Data for 899 women (mean age±standard deviation, 68.7 ± 4.3 years) and 497 men (69.4 ± 3.9 years) from the Dubbo Osteoporosis Epidemiology Study 2, comprising sixty variables for muscle strength (quadriceps strength), physical performance (walking speed, timed up and go (TUG) test, sit to stand (STS) test), body size (weight, height, body mass index) and body composition (lean mass, body fat) were included. Sex-stratified Classification and Regression Tree (CART) analyses calculated baseline variable accuracy for predicting incident mortality and falls, and prevalent slow walking speed (<0.8 m/s). RESULTS: Over 14.5 years, 103/899 (11.5%) women and 96/497 (19.3%) men died, 345/899 (38.4%) women and 172/497 (34.6%) men had ≥1 fall, and 304/860 (35.3%) women and 172/461 (31.7%) had baseline slow walking speed (<0.8 m/s). CART models identified age and walking speed adjusted for height as the most important predictors for mortality in women, and quadriceps strength (with adjustments) as the most important predictor for mortality in men. In both sexes, STS (with adjustments) was the most important predictor for incident falls, and TUG test was the most important predictor for prevalent slow walking speed. Body composition measures were not important predictors for any outcome. CONCLUSIONS: Muscle strength and physical performance variables and cut points predict falls and mortality differently in women and men, suggesting targeted sex-specific application of selected measures may improve outcome prediction in older adults.

Muscle strength and physical performance contribute to and improve fracture risk prediction in older people: A narrative review.

Osteoporotic fractures present a major health problem with an increasing prevalence in older people. Fractures are associated with premature mortality, reduced quality of life, subsequent fracture, and increased costs. Hence, it is crucial to identify those at higher risk of fracture. Fracture risk assessment tools incorporated clinical risk factors to improve fracture predictive power over BMD alone. However, fracture risk prediction using these algorithms remains suboptimal, warranting further improvement. Muscle strength and physical performance measurements have been associated with fracture risk. In contrast, the contribution of sarcopenia, the composite condition of low muscle mass, muscle strength and/or physical performance, to fracture risk is unclear. It is uncertain whether this is due to the problematic definition of sarcopenia per se or limitations of the diagnostic tools and cut-off points of the muscle mass component. The recent position statement from the Sarcopenia Definition and Outcomes Consortium confirmed the inclusion of muscle strength and performance in the definition of sarcopenia but not DXA-assessed lean mass. Therefore, clinicians should focus on functional assessment (muscle strength and performance) rather than muscle mass, at least as assessed by DXA, as predictors of fractures. Muscle strength and performance are modifiable risk factors. Resistance exercise improves muscle parameters in the elderly, potentially leading to reduced risk of falls and fractures in the general population and in those who sustained a fracture. Therapists may consider exercise intervention to improve muscle parameters and potentially reduce the risk of fractures. The aim of this review was to explore 1) the contribution of muscle parameters (i.e., muscle mass, strength, and physical performance) to fracture risk in older adults, and 2) the added predictive accuracy of these parameters beyond the existing fracture assessment tools. These topics provide the rationale for investigating strength and physical performance interventions to reduce fracture risk. Most of the included publications showed that muscle mass is not a good predictor of fracture risk, while poor muscle strength and performance are associated with an increased risk of fracture, particularly in men, independent of age, BMD, and other risk factors for fractures. Muscle strength and performance can potentially improve the predictive accuracy in men beyond that obtained by the fracture risk assessment tools, Garvan FRC and FRAX.

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

BACKGROUND: Multimorbidity 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 FINDINGS: The 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. CONCLUSIONS: Multimorbidity 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.

Antiresorptive Medication Use Is not Associated With Acute Cardiovascular Risk: An Observational Study.

CONTEXT: Bisphosphonates have been reported to be cardioprotective in some, but not all, studies. It is unknown whether denosumab (Dmab) use protects against cardiovascular events (CVEs). OBJECTIVE: To determine whether oral bisphosphonate (oBP) or Dmab use is associated with CVEs in persons with incident fracture. METHODS: Participants with an incident minimal trauma fracture from the Sax Institute's 45 and Up Study, a population-based cohort from NSW, Australia, were followed between 2005/2009 and 2017. Questionnaire data were linked to hospital admissions (Admitted Patients Data Collection [APDC]) by the Centre for Health Record Linkage). Medicare Benefit Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) data sets were provided by Services Australia. Data was stored in a secure computing environment (Secure Unified Research Environment). Fractures, CVEs, and comorbidities were identified from the APDC and oBP and Dmab medication from the PBS. oBP and Dmab users were matched to never users (NoRx) by propensity scores. The main outcome measures were association between oBP and Dmab with CVE (acute myocardial infarction, unstable angina, cerebrovascular accident, and transient ischemic attack) and were determined using a stratified Cox's proportional hazards model. RESULTS: There were 880 pairs of oBP and NoRx (616 women) and 770 pairs of Dmab and NoRx (615 women) followed for ∼4.3 years. CVE risk was similar for oBP and NoRx Hazard Ratios (HR) women, 0.88 [95% CI 0.65-1.18]; men, 1.07 [95% CI 0.72-1.57]). Similar findings were obtained for Dmab (Hazard Ratios (HR) women, 1.08 [95% CI 0.78-1.50]; men, 1.55 [95% CI 0.96-2.48]). CONCLUSION: oBP and Dmab use was not associated with CVEs.

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).

Muscle Strength and Physical Performance Improve Fracture Risk Prediction Beyond Garvan and FRAX: The Osteoporotic Fractures in Men (MrOS) Study.

Muscle strength and physical performance are associated with fracture risk in men. However, it is not known whether these measurements enhance fracture prediction beyond Garvan and FRAX tools. A total of 5665 community-dwelling men, aged ≥65 years, from the Osteoporotic Fractures in Men (MrOS) Study, who had data on muscle strength (grip strength) and physical performance (gait speed and chair stand tests), were followed from 2000 to 2019 for any fracture, major osteoporotic fracture (MOF), initial hip, and any hip fracture. The contributions to different fracture outcomes were assessed using Cox's proportional hazard models. Tool-specific analysis approaches and outcome definitions were used. The added predictive values of muscle strength and physical performance beyond Garvan and FRAX were assessed using categorical net reclassification improvement (NRI) and relative importance analyses. During a median follow-up of 13 (interquartile range 7-17) years, there were 1014 fractures, 536 MOFs, 215 initial hip, and 274 any hip fractures. Grip strength and chair stand improved prediction of any fracture (NRI for grip strength 3.9% and for chair stand 3.2%) and MOF (5.2% and 6.1%). Gait speed improved prediction of initial hip (5.7%) and any hip (7.0%) fracture. Combining grip strength and the relevant performance test further improved the models (5.7%, 8.9%, 9.4%, and 7.0% for any, MOF, initial, and any hip fractures, respectively). The improvements were predominantly driven by reclassification of those with fracture to higher risk categories. Apart from age and femoral neck bone mineral density, muscle strength and performance were ranked equal to or better than the other risk factors included in fracture models, including prior fractures, falls, smoking, alcohol, and glucocorticoid use. Muscle strength and performance measurements improved fracture risk prediction in men beyond Garvan and FRAX. They were as or more important than other established risk factors. These measures should be considered for inclusion in fracture risk assessment tools. © 2021 American Society for Bone and Mineral Research (ASBMR).

Decline in Muscle Strength and Performance Predicts Fracture Risk in Elderly Women and Men.

CONTEXT: Muscle strength and performance are associated with fractures. However, the contribution of their rate of decline is unclear. OBJECTIVE: To assess the independent contribution of the rate of decline in muscle strength and performance to fracture risk. DESIGN, SETTING, AND PARTICIPANTS: Community-dwelling women (n = 811) and men (n = 440) aged 60 years or older from the prospective Dubbo Osteoporosis Epidemiology Study followed from 2000 to 2018 for incident fracture. Clinical data, appendicular lean mass/height2 (ht)2, bone mineral density, quadricep strength/ht (QS), timed get-up-and-go (TGUG), 5 times repeated sit-to-stand (5xSTS), and gait speed (GS) measured biennially. Rates of decline in muscle parameters were calculated using ordinary least squares regression and fracture risk was assessed using Cox's models. MAIN OUTCOME: Incident low-trauma fracture ascertained by x-ray report. RESULTS: Apart from lean mass in women, all muscle parameters declined over time. Greater rates of decline in physical performance were associated with increased fracture risk in women (Hazard ratios [HRs] ranging from 2.1 (95% CI: 1.5-2.9) for GS to 2.7 (95% CI: 1.9-3.6) for 5xSTS, while in men only the decline in GS was associated with fracture risk (HR: 3.4 [95% CI: 1.8-6.3]). Baseline performance and strength were also associated with increased fracture risk in men (HRs ranging from 1.8 (95% CI: 1.1-3.0) for QS to 2.5 (95% CI: 1.5-4.1) for TGUG, but not in women. CONCLUSION: Rate of decline in physical performance in both genders, and baseline strength and performance in men, contributed independently to fracture risk. Sit-to-stand and GS were the tests most consistently associated with fractures. Further studies are required to determine whether muscle strength and/or performance improve the predictive accuracy of fracture prediction models.

Nonstandard Lumbar Region in Predicting Fracture Risk.

Femoral neck (FN) bone mineral density (BMD) is the most commonly used skeletal site to estimate fracture risk. The role of lumbar spine (LS) 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 with standard L2-L4 BMD and assess whether the addition of either LS site could improve fracture prediction over FN BMD. This study comprised a prospective cohort of 3016 women and men over 60 yr from the Dubbo Osteoporosis Epidemiology Study followed up for occurrence of minimal trauma fractures from 1989 to 2014. Dual-energy X-ray absorptiometry was used to measure BMD at 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 receiver operating characteristic curve analyses. There were 565 women and 179 men with a minimal trauma fracture during a mean of 11 ± 7 yr. L1-L2 BMD T-score was significantly lower than L2-L4 T-score in both genders (p < 0.0001). L1-L2 and L2-L4 BMD models had a similar fracture predictive ability. LS BMD was better than FN BMD in predicting vertebral fracture risk in women [area under the curve 0.73 (95% confidence interval, 0.68-0.79) vs 0.68 (95% confidence interval, 0.62-0.74), but FN was superior for hip fractures prediction in both women and men. The addition of L1-L2 or L2-L4 to FN BMD in women increased overall and vertebral predictive power compared with FN BMD alone by 1% and 4%, respectively (p < 0.05). 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.