JAMDA xxx (2014) 1e6
JAMDA journal homepage: www.jamda.com
Original Study
Sarcopenia Combined With FRAX Probabilities Improves Fracture Risk Prediction in Older Chinese Men Ruby Yu PhD a, *, Jason Leung MSc b, Jean Woo MD a a b
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China Jockey Club Centre for Osteoporosis Care and Control, The Chinese University of Hong Kong, Hong Kong, China
a b s t r a c t Keywords: FRAX fracture probability sarcopenia fracture prediction elderly
Objectives: To examine whether the inclusion of sarcopenia in prediction models adds any incremental value to fracture risk assessment tool (FRAX). Design, Setting, and Participants: Data from a prospective cohort of 4000 community-dwelling Chinese men and women aged 65 years and older with adjudicated fracture outcomes were analyzed. Measurements: At baseline, femoral neck bone mineral density (BMD) was assessed, as were the clinical risk factors included in FRAX, along with additional appendicular skeletal muscle mass, grip strength, and gait speed. Sarcopenia was defined according to the Asian Working Group for Sarcopenia algorithm. Incident fractures were documented during the follow-up period from 2001 to 2013. Results: Of 4000 participants, 565 experienced at least 1 incident fracture of all types combined and 132 experienced a hip fracture during a follow-up of 10.2 years. Hazard ratios (HRs) for 1-unit increase in FRAX score without BMD in men were 1.12 [95% confidence interval (CI) 1.08e1.16] for all fractures combined and 1.19 (95% CI 1.13e1.27) for hip fracture, and in women were 1.04 (95% CI 1.03e1.06) for all fractures combined and 1.08 (95% CI 1.06e1.11) for hip fracture. Similar to results of the FRAX score without BMD, HRs for 1-unit increase in FRAX score with BMD in men were, 1.04 (95% CI 1.03e1.06) for all fractures combined and 1.19 (95% CI 1.13e1.25) for hip fracture, and in women were 1.04 (95% CI 1.03e 1.05) for all fractures combined and 1.06 (95% CI 1.05e1.08) for hip fracture. Sarcopenia was significantly associated with all fractures combined (Adjusted HR 1.87; 95% CI 1.30e2.68) and hip fracture (Adjusted HR 2.67; 95% CI 1.46e4.90) in men but not in women. The discriminative values for fracture, as measured by the area under the receiver operating characteristic curve, were 0.60e0.73 and 0.62e0.76 for FRAX without and with BMD, respectively. Adding sarcopenia did not significantly improve the discriminatory capacity over FRAX (P > .05). Using reclassification techniques, sarcopenia significantly enhanced the integrated discrimination improvement by 0.6% to 1.2% and the net reclassification improvement by 7.2% to 20.8% in men, but it did not contribute to predictive accuracy in women. Conclusions: Sarcopenia added incremental value to FRAX in predicting incident fracture in older Chinese men. Ó 2014 AMDA e The Society for Post-Acute and Long-Term Care Medicine.
Osteoporotic fractures represent a major public health problem and are a leading cause of morbidity, mortality, and hospitalization in older adults.1 Screening for low bone mass by using dual energy X-ray absorptiometry is an important part of geriatric assessment because detection of osteoporosis offers treatment opportunities to delay further decline and prevent fractures.2,3 However, approximately one-half of all clinical fractures occur in persons without osteoporosis based on bone mineral density (BMD).4 Therefore, there is a need to
The authors declare no conflicts of interest. * Address correspondence to Ruby Yu, PhD, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China. E-mail address: [email protected] (R. Yu). http://dx.doi.org/10.1016/j.jamda.2014.07.011 1525-8610/Ó 2014 AMDA e The Society for Post-Acute and Long-Term Care Medicine.
identify other risk factors that may help to identify people at high risk for fracture. For example, the fracture risk assessment tool (FRAX) was developed by the World Health Organization (WHO) in 2008. It uses clinical risk factors, with or without consideration of femoral neck BMD measurement, to estimate the 10-year probability of hip fracture and major osteoporotic fracture (hip, clinical vertebral, proximal humerus, distal forearm).5 Although FRAX has been most widely used for national osteoporosis guidelines,6 fracture risk prediction of FRAX may not be perfect as not all people at high risk do have fractures and vice versa for some people in the low risk category.7 Other models using fewer clinical risk factors (based on age and BMD alone) predicted 10-year risk of any clinical fracture and hip fracture as well as FRAX with BMD.8 This
2
R. Yu et al. / JAMDA xxx (2014) 1e6
raises the question of whether adjustment to FRAX might improve its ability to identify individuals at high risk of fracture.9 In the past decade, there is an increasing volume of literature on the impact of sarcopenia on health outcomes including frailty, falls, and disability.10e12 It represents the loss of skeletal muscle mass and strength that occurs with aging,13 which may predispose older individuals to an increased fracture risk. Previous studies among older women have suggested that slow gait speed, a component in the definition of sarcopenia, is predictive of hip fracture, independent of BMD,14 and repeated chair stand performance (lower-limb muscle strength) is also highly predictive of hip fracture among older men.15 We have previously reported that sarcopenia was an independent predictor of fracture, which also provided incremental predictive value for fracture over the integration of BMD and other clinical risk factors in a cohort of older Chinese men.16 However, there are a limited number of studies examining the incremental predictive value of sarcopenia combined with FRAX for prediction of fracture. Using data from a large-scale cohort study conducted in Hong Kong on bone health, we, therefore, examined whether the inclusion of the diagnosis of sarcopenia to FRAX improves its predicative power. Methods Participants Four thousand community-dwelling Chinese men and women at least 65 years old were invited to attend a health check carried out in the School of Public Health of the Chinese University of Hong Kong between August 2001 and February 2003. Recruitment was conducted by placing recruitment notices in community centers for older adults and in housing estates. Participants were volunteers, and the aim was to recruit a stratified sample so that approximately 33% would each be aged 65e69, 70e74, and 75 years and older. Those who were unable to walk independently, had a history of bilateral hip replacements, were not competent to give informed consent, or had medical conditions judged by the study physicians on the likelihood that they would not survive the duration of the primary study were excluded. All participants gave written consent, and the study was approved by the Clinical Research Ethics Committee of the Chinese University of Hong Kong.
Diagnosis of Sarcopenia Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia algorithm,18 in which a person who has low muscle mass, low muscle strength, and/or low physical performance was categorized as having sarcopenia. As suggested by the Asian Working Group for Sarcopenia, low muscle mass was defined as appendicular skeletal muscle mass (ASM) index (ASM/height2)
JAMDA journal homepage: www.jamda.com
Original Study
Sarcopenia Combined With FRAX Probabilities Improves Fracture Risk Prediction in Older Chinese Men Ruby Yu PhD a, *, Jason Leung MSc b, Jean Woo MD a a b
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China Jockey Club Centre for Osteoporosis Care and Control, The Chinese University of Hong Kong, Hong Kong, China
a b s t r a c t Keywords: FRAX fracture probability sarcopenia fracture prediction elderly
Objectives: To examine whether the inclusion of sarcopenia in prediction models adds any incremental value to fracture risk assessment tool (FRAX). Design, Setting, and Participants: Data from a prospective cohort of 4000 community-dwelling Chinese men and women aged 65 years and older with adjudicated fracture outcomes were analyzed. Measurements: At baseline, femoral neck bone mineral density (BMD) was assessed, as were the clinical risk factors included in FRAX, along with additional appendicular skeletal muscle mass, grip strength, and gait speed. Sarcopenia was defined according to the Asian Working Group for Sarcopenia algorithm. Incident fractures were documented during the follow-up period from 2001 to 2013. Results: Of 4000 participants, 565 experienced at least 1 incident fracture of all types combined and 132 experienced a hip fracture during a follow-up of 10.2 years. Hazard ratios (HRs) for 1-unit increase in FRAX score without BMD in men were 1.12 [95% confidence interval (CI) 1.08e1.16] for all fractures combined and 1.19 (95% CI 1.13e1.27) for hip fracture, and in women were 1.04 (95% CI 1.03e1.06) for all fractures combined and 1.08 (95% CI 1.06e1.11) for hip fracture. Similar to results of the FRAX score without BMD, HRs for 1-unit increase in FRAX score with BMD in men were, 1.04 (95% CI 1.03e1.06) for all fractures combined and 1.19 (95% CI 1.13e1.25) for hip fracture, and in women were 1.04 (95% CI 1.03e 1.05) for all fractures combined and 1.06 (95% CI 1.05e1.08) for hip fracture. Sarcopenia was significantly associated with all fractures combined (Adjusted HR 1.87; 95% CI 1.30e2.68) and hip fracture (Adjusted HR 2.67; 95% CI 1.46e4.90) in men but not in women. The discriminative values for fracture, as measured by the area under the receiver operating characteristic curve, were 0.60e0.73 and 0.62e0.76 for FRAX without and with BMD, respectively. Adding sarcopenia did not significantly improve the discriminatory capacity over FRAX (P > .05). Using reclassification techniques, sarcopenia significantly enhanced the integrated discrimination improvement by 0.6% to 1.2% and the net reclassification improvement by 7.2% to 20.8% in men, but it did not contribute to predictive accuracy in women. Conclusions: Sarcopenia added incremental value to FRAX in predicting incident fracture in older Chinese men. Ó 2014 AMDA e The Society for Post-Acute and Long-Term Care Medicine.
Osteoporotic fractures represent a major public health problem and are a leading cause of morbidity, mortality, and hospitalization in older adults.1 Screening for low bone mass by using dual energy X-ray absorptiometry is an important part of geriatric assessment because detection of osteoporosis offers treatment opportunities to delay further decline and prevent fractures.2,3 However, approximately one-half of all clinical fractures occur in persons without osteoporosis based on bone mineral density (BMD).4 Therefore, there is a need to
The authors declare no conflicts of interest. * Address correspondence to Ruby Yu, PhD, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China. E-mail address: [email protected] (R. Yu). http://dx.doi.org/10.1016/j.jamda.2014.07.011 1525-8610/Ó 2014 AMDA e The Society for Post-Acute and Long-Term Care Medicine.
identify other risk factors that may help to identify people at high risk for fracture. For example, the fracture risk assessment tool (FRAX) was developed by the World Health Organization (WHO) in 2008. It uses clinical risk factors, with or without consideration of femoral neck BMD measurement, to estimate the 10-year probability of hip fracture and major osteoporotic fracture (hip, clinical vertebral, proximal humerus, distal forearm).5 Although FRAX has been most widely used for national osteoporosis guidelines,6 fracture risk prediction of FRAX may not be perfect as not all people at high risk do have fractures and vice versa for some people in the low risk category.7 Other models using fewer clinical risk factors (based on age and BMD alone) predicted 10-year risk of any clinical fracture and hip fracture as well as FRAX with BMD.8 This
2
R. Yu et al. / JAMDA xxx (2014) 1e6
raises the question of whether adjustment to FRAX might improve its ability to identify individuals at high risk of fracture.9 In the past decade, there is an increasing volume of literature on the impact of sarcopenia on health outcomes including frailty, falls, and disability.10e12 It represents the loss of skeletal muscle mass and strength that occurs with aging,13 which may predispose older individuals to an increased fracture risk. Previous studies among older women have suggested that slow gait speed, a component in the definition of sarcopenia, is predictive of hip fracture, independent of BMD,14 and repeated chair stand performance (lower-limb muscle strength) is also highly predictive of hip fracture among older men.15 We have previously reported that sarcopenia was an independent predictor of fracture, which also provided incremental predictive value for fracture over the integration of BMD and other clinical risk factors in a cohort of older Chinese men.16 However, there are a limited number of studies examining the incremental predictive value of sarcopenia combined with FRAX for prediction of fracture. Using data from a large-scale cohort study conducted in Hong Kong on bone health, we, therefore, examined whether the inclusion of the diagnosis of sarcopenia to FRAX improves its predicative power. Methods Participants Four thousand community-dwelling Chinese men and women at least 65 years old were invited to attend a health check carried out in the School of Public Health of the Chinese University of Hong Kong between August 2001 and February 2003. Recruitment was conducted by placing recruitment notices in community centers for older adults and in housing estates. Participants were volunteers, and the aim was to recruit a stratified sample so that approximately 33% would each be aged 65e69, 70e74, and 75 years and older. Those who were unable to walk independently, had a history of bilateral hip replacements, were not competent to give informed consent, or had medical conditions judged by the study physicians on the likelihood that they would not survive the duration of the primary study were excluded. All participants gave written consent, and the study was approved by the Clinical Research Ethics Committee of the Chinese University of Hong Kong.
Diagnosis of Sarcopenia Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia algorithm,18 in which a person who has low muscle mass, low muscle strength, and/or low physical performance was categorized as having sarcopenia. As suggested by the Asian Working Group for Sarcopenia, low muscle mass was defined as appendicular skeletal muscle mass (ASM) index (ASM/height2)
