Lower-extremity osteoarthritis (OA) is a prevalent musculoskeletal disease in elder population. The main symptom of OA is pain which leads to muscle weakness and physical disability. Recently, muscle weakness, function limitation, and severity of disease in OA are addressed to aging-related muscle attenuations. Therefore, elder individuals with OA are under potential sarcopenia risks. In addition, obesity, which exerts negative impacts on disease outcomes, has become a burden in OA population. Under multifactor risks of OA, it is important to identify effectiveness of multidisciplinary management for such elder population to prevent sarcopenic obesity and maintain physical function. Previous studies have indicated that diet intervention (DI) using protein supplement, dietary protein, or weight loss enhances exercise efficacy in terms of additional muscle mass and strength gains to exercise training (ET) for elder individuals with high sarcopenia and frailty risks. However, it remains unclear whether DI in combination with ET augments any benefit for older adults with lower-extremity OA. This chapter aimed to review the effects of DI plus ET on muscle mass, strength, and physical function outcomes in older individuals with lower-extremity OA.
- protein supplement
- exercise training
- muscle mass
- function outcome
Elderly population aged 65 and over is a substantially growing population which is estimated to exceed 16% of global population worldwide in the year of 2050 . Elongation of life expectancy is accompanied with an increase of chronic diseases leading to restricted physical function and disabilities in daily life [2, 3], among which musculoskeletal disorder is a significant public health issue with 7.5–35.2% of the elder people having mild to moderate musculoskeletal conditions [3, 4] and has become the second cause of global burden worldwide compared with other causes of morbidity-mortality .
Among the age-related musculoskeletal disorders, osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases from the sixth to the ninth decade of lifespan, especially the OA in lower extremities is closely associated with limitations of functional activities and participation . In addition, sarcopenia, obesity, or in combination of both called sarcopenic obesity have great impacts on physical function in older adults [7, 8]. The impacts of sarcopenia on musculoskeletal system are accounted to the risks of physical limitation in elder individuals, especially those with hip or knee OA [9, 10]. The age-related muscle dysfunction can be addressed to impairments in musculoskeletal system as well as neuromuscular system [11, 12]. With respective to the underlying mechanisms of sarcopenia in older population, muscle atrophy (i.e., decline in muscle size) plays a key role in muscle attenuation , especially the type II myofiber . The loss of muscle mass occurs progressively from middle-age by a rate of 0.47% per year in men and 0.37% per year in women ; in people aged 75 years, muscle mass is decreased at a rapid rate of 0.64–0.70% per year in women and 0.80–0.98% per year in men and in severe diseases can lead to a loss of approximate 50% by the 8–9th decade of life . Loss of skeletal muscle mass is commonly accompanied with deficits in muscle function such as muscle weakness, which is relevant to clinical presentation of sarcopenia as well as OA. Reid et al. indicated that leg lean mass is strongly associated with muscle strength (r = 0.78,
Recently, the disease progression of knee and hip OA has been attributed to age-related decline in muscle mass (i.e., sarcopenia). Toda et al. reported that older women with knee OA experienced significantly lower leg lean mass relative to body weight (%) by a mean ± standard deviation of 19.2 ± 2.7%, compared with the healthy control (21.0 ± 2.9%;
The sarcopenia, obesity, and OA are becoming major threats to aging society and have been recognized as important health issues [8, 25, 26, 27]. The relationships among sarcopenia, obesity (i.e., sarcopenic obesity), and OA have been discussed. Kemmler et al. conducted an observational study to investigate the prevalence of sarcopenia in community-dwelled women who aged 70 years and older; the results indicated that elder women with lower-extremity OA exhibited a significantly higher rate of sarcopenia (9.1%) than nonarthritic peers (3.5%) . Jin et al. reported that elder men and women with sarcopenic obesity showed significantly higher risks of exhibiting knee OA (OR = 1.92–2.43) compared with the healthy control groups . Misra et al. conducted a longitudinal study of the risk of radiographic OA in relation to sarcopenic obesity; the result showed that elder people with sarcopenic obesity (RR = 1.91) had increased risks of exhibiting knee OA within a 5-year interval of follow up . Therefore, preventive efforts for the obese elder individuals may need to focus not only on reducing sarcopenia but also on improving sarcopenic obesity to reduce the growing incidence and prevalence of knee OA.
2. Treatments and management for sarcopenia in elderly
Sarcopenic obesity originates from a multifactorial consequence of aging and its related physical inactivity , which especially exerts negative impacts to obese elderly populations . Several approaches for management of sarcopenic obesity have been recommended including pharmacological interventions, exercise interventions, and nutrition interventions to counteract muscle loss and physical declines in obese older adults . According to the recommendations from the European Society for Clinical Nutrition and Metabolism Expert Group , there are urgent needs for elder people with a risk of sarcopenic obesity to incorporate nutrition intervention and muscle strengthening exercise to prevent the functional decline.
2.1 Protein supplement plus exercise training for sarcopenic obesity
Obesity has become epidemic burden in elderly population . Sarcopenic obesity, a recently identified phenotype of obese elderly population, is developed based on an underling additive effect of sarcopenia and obesity and is referred by the coexistence of diminished muscle mass and increased fat mass. Sarcopenia has been characterized by age-related muscle degeneration , and obesity with an increased body fat exerts negative impacts on the skeletal muscle turnover and its homeostasis . Such deteriorations of muscle mass loss originated from aging process result in muscle dysfunction which may further lead to physical deficits in frail elderly . Furthermore, older adults who are identified as overweight or obesity have been observed suffering high risks of physical disability [37, 38]. Accordingly, sarcopenic obesity had been identified to be associated with more physical limit than either pure sarcopenia or obesity and was served as a risk to disability and frail life style [8, 39]. Therefore, the preservation of muscle mass and strength are vital for obese older adults to yield physical activities in daily life.
Aging-related attenuation of skeletal muscle mass had been addressed to a smaller muscle fiber size rather than loss of fiber number and characterized of type II myofiber phenotype dominant [13, 40]. In addition, sarcopenic muscles remain in a state of failing compensatory effort in an attempt to stave off muscular degeneration and atrophy . Given the facts that myofiber hypertrophy activated by satellite cells is largely dependent on both net muscle protein synthesis and satellite cell recruitment through serious cellular processing mechanism [42, 43], and that both age-associated sarcopenia and obesity are associated with an over expression of myostatin which functions as a protein inhibitor negatively regulating the skeletal muscle growth and homeostasis with inhibiting the myoblasts proliferation and differentiation [44, 45, 46], it is important to identify whether resistance exercises exert any effect on the myofiber type-specific muscle mass loss in obese aged people. In such scenarios, previous trials claimed that age-related Type II myofiber phenotype atrophy would be improved following resistance exercise training by means of satellite cell proliferation and an increase in the rate of muscle contractile and mitochondrial protein synthesis, which further contributed to myofiber hypertrophy [40, 42, 47, 48, 49, 50, 51].
Progressive resistance exercise training (RET) has been used as an effective way of improving muscle function and increasing muscle mass by stimulating muscle protein synthesis in elder people [31, 49, 52, 53]. Liao et al. further indicate that elastic RET exerts benefits on lean mass and physical mobility in older women with sarcopenic obesity . With respective to multidisciplinary interventions for prevention of sarcopenia in elder populations, an additional protein supplements (PS) has also been believed to augment the effects of resistance training on muscle mass gain in older adults [55, 56]. For obese elderly individuals with energy restricted diet, PS has its effect on reduction of losing muscle mass during caloric restriction-induced weight loss . However, the effects of PS plus RET on muscle mass and strength gains for obese elder people remain controversy. While several studies identified the effects of PS on muscle mass accretion and strength gain during resistance training in sarcopenic or obese elderly individuals , some concluded that PS provides no additional benefit in resistance-trained obese elder individuals [59, 60]. Furthermore, few systemic review studies have summarized these results in obese elder individuals. Whether PS during RET exerts any benefit on augmentation of muscular and functional performance in obese elder people remains unclear.
Liao et al. conducted a systemic review and meta-analysis study to investigate effects of PS plus RET for obese elder people . Main results of Liao’s study showed an overall effect on lean body mass (LBM) and fat mass with significant standardized mean differences (SMDs) of 0.58 (95% CI = 0.32, 0.84,
2.2 Associations of muscle mass changes with intervention effects on muscle strength and physical capability after protein supplement plus exercise training
Multidisciplinary approaches are recommended for elderly individuals who have high sarcopenia or frailty risks, including nutrient intervention alone, exercise training alone, or combination of both [62, 63, 64, 65, 66], and among which protein supplement combined with exercise training (PS + ET) has been widely employed to augment lean mass gain, strength gain, and physical function enhancement in elderly individuals, irrespective of PS types and exercise protocols [65, 67, 68, 69]. However, whether intervention-induced changes in muscle mass contribute to strength gain and physical mobility improvement after PS + ET remains unclear. Several previous meta-analysis studies have reported that an increase in lean mass is accompanied by significant increases in strength gain [61, 68, 70, 71, 72] as well as physical mobility [68, 72] following PS + ET; however, such simultaneous increases in lean mass with strength [67, 73] (or physical function [61, 71]) were not observed by other researchers. Low muscle mass strongly predicts strength loss and mobility limitations in older adults [17, 74]; in addition, sarcopenia has been addressed to suppressed muscle protein turnover and homeostasis [75, 76]; therefore, identification of relationship between the muscle mass changes and physical improvements in response to PS + ET can facilitate clinical practitioners to efficiently make optimal decisions and set appropriate intervention strategies for elderly patients who are diagnosed as sarcopenia or frailty.
Liao et al. conducted a systemic review and meta-regression study to determine the associations of lean mass changes with treatment effects on strength and physical mobility after PS + ET . Main results of Liao’s study showed an overall effect on LBM and appendicular lean mass (ALM) with significant SMDs of 0.66 (95%CI: 0.41–0.91,
3. Management of muscle deficits for mild to moderate severity of osteoarthritis
Since OA has been recognized as a serious musculoskeletal disease , managements of OA comprise multidisciplinary interventions including pain medications and nonpharmacological treatments for those patients who exhibit mild to moderate symptoms. However, surgical treatments such as total joint arthroplasty that could help to relief pain and improve joint function (e.g., range of motion and strength)  are commonly recommended at the end stage of OA.
Evidences regarding the effects of ET alone or PS plus ET on muscle mass, strength, and physical mobility have been well established in elderly populations with sarcopenia (Figure 1). However, whether ET alone or PS plus ET exert any benefit on muscle mass and function outcomes remains unclear. Based on that low muscle mass is closely associated with OA and elder individuals with OA have high sarcopenia risk [10, 28], it is urgent to generate effective strategy to manage this condition for the rapidly growing OA population. In addition, it is necessary to identify evidence of intervention effects on muscle mass and strength gains for elder people with OA.
3.1 Exercise training
Among the interventions of OA, exercise therapy is recommended as one of the first-line treatments . Exercise exerts benefits on pain reduction, muscle strength, and physical function in elder individuals with OA, regardless of exercise types . Especially, the muscle strength-based exercise training (MSE) has been encouraged to minimize degenerative muscular function associated with aging [82, 83], because of that elder individuals experience well muscular adaptations in terms of muscle morphological and architectural changes responding to MSE . Therefore, MSE has been recommended for elder people with OA to augment muscle volume and enhance muscle hypertrophy .
Previous results have shown that MSE exerts benefits on muscle mass gain in elderly people. Churchward-Venne et al. indicated that older individuals achieved significantly temporal changes in whole body lean mass at 12-week and 24-week follow up by 0.9 ± 0.1 kg (
The MSE has been served as the most promising intervention for sarcopenic elderly [62, 86] as well as those with OA [87, 88, 89, 90] to increase strength and improve mobility. Due to that MSE enables older adults to yield increased muscle anabolic resistance occurring with advancing age [91, 92], resistance-type exercise training (RET) as well as multicomponent exercise training (MET) have been considered beneficial for preserving lean muscle mass in older populations, even in those with sarcopenia [53, 93]. In addition, muscle protein synthesis and myofiber proliferation can be effectively activated through MSE , which further contribute to skeletal muscle hypertrophy and muscle mass gains even in elder population [42, 43]. Therefore, MSE is recommend to be employed for management of OA since elder individuals with OA has been considered having low muscle mass .
However, it remains unclear that whether MSE has any effect on muscle mass gain and morphological changes in older individuals with lower extremities of OA. Studies have reported that patients with OA exhibited increased changes in the muscle cross-sectional area or muscle thickness after MSE [95, 96, 97], whereas other authors have reported conflicting conclusions that MSE exerted no beneficial effects on fat-free mass or muscle remodeling [98, 99, 100]. In addition, both sarcopenia and OA are associated with decreased muscle protein synthesis and homeostasis [75, 76], and exercise-induced muscular hypertrophy contributes to the increase of muscle strength . Moreover, most of previous systematic reviews investigating the treatment efficacy of MSE for individuals with OA have focused on muscular strength and physical outcomes rather than the muscle mass or volume measures [87, 88, 89, 90]. Therefore, identifying the effects of MSE on increasing muscle mass and volume helps clinical practitioners to develop appropriate treatment strategies for older people with OA.
Liao et al. conducted a systemic review and meta-analysis study to investigate effects of MSE for elder people with lower extremity OA . Main results of systemic review and meta-analyses showed MSE has effects on changes in muscle mass gain (SMD = 0.49, 95% CI: 0.28, 0.71;
3.2 Protein supplement
Diet intervention such as dietary protein or protein supplementation (PS) has been incorporated to multidisciplinary managements for OA , since elder patients with OA have potential risks of age-related sarcopenia. In addition, alternative and complementary therapeutic approaches, such as the use of a wide array of nutritional and physical manipulations, are becoming popular for relieving symptoms of OA. Several previous studies had investigated clinical efficacy of protein supplementation (PS) for elder individuals with knee OA [103, 104, 105, 106]. Colker et al. employed a 6-week milk PS for elder individuals with OA and the results showed that PS achieved significant improved changes of daily activity and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) per week compared with the placebo group (
3.3 Protein supplement combined with exercise training
Nutritional intervention, especially the protein supplementation (PS), can influence outcomes for elder individuals undergoing exercise interventions such as resistance-based exercise training (RET) or multicomponent exercise training (MET). Several systematic review studies had identified benefits of PS plus exercise training for elder population. For healthy elder individuals, Morton et al. reported that prolonged PS plus RET has effects on fat free mass, mid-thigh cross-sectional area, and one-repetition maximum strength by significant pooled mean differences of 0.30 kg (95%CI: 0.09–0.52 kg;
3.4 Weight loss plus exercise for sarcopenic obesity in osteoarthritis
Given that obesity has become a burden in OA population , weight loss (WL) should be considered as an option while setting the treatment goals and planning rehabilitation strategies for elder people with OA. Previous studies had shown that maintaining or lowering BMI to the normal range (usually within 20.0–24.9, regardless of ethic) may reduce risks or improve symptoms of OA [107, 108]. Felson et al. indicated that a decrease of over 50% in odds of developing OA (odds ratio = 0.46;
An WL intervention may exert negative impacts on lean mass since obesity often masks the age-associated loss of muscle mass. Recently, WL in combination with exercise has been recommended as the optimal approach to managing obese patients with OA. Several previous trials had targeted weight management for obese older adults with OA including the Intensive Diet and Exercise for Arthritis Trial , the Arthritis, Diet and Activity Promotion Trial , and the Physical Activity, Inflammation, and Body Composition Trial . These registered clinical trials employed weight-loss protocols which targeted 5–10% reduction of body weight over 6–18 months and incorporated partial meal replacements, nutrition class, and behavior therapy for diet habit changes and lifestyle modifications. Results from such previous trials showed that exercise training in combination with a weight-loss program in obese adults with knee OA achieved significantly greater changes in pain and function compared to the control groups. In addition, several systemic reviews regarding WL with or without exercise for elder OA populations also provide evidences for treatment efficacy on pain relief and function recovery [114, 115, 116, 117]. However, the effects of WL plus exercise on lean mass remain inconsistency among the results of previous trials and few systemic review and meta-analysis studies focused on the treatment efficacy on muscle mass outcome in obese elder individuals with OA who received WL plus exercise. Future studies should be warranted to investigate effects of WL plus exercise on muscle mass in order to prevent sarcopenia in such elder population with OA.
Liao et al. conducted a systemic review and meta-analysis study to investigate effects of diet intervention plus ET for elder people with mild to moderate OA . Among the included trials in Liao’s study, all of the included trials which reported muscle mass outcomes conducted a WL plus ET intervention for obese elder patients with knee OA  and the results showed that during an overall follow-up duration, the WL plus ET group achieved significant effects on muscle mass gains (SMD = 0.61; 95%CI: 0.30–0.91,
4. Management of muscle dysfunction after total joint replacement for patients with end-stage osteoarthritis
4.1 Postoperative rehabilitation for muscle recovery after total joint replacement
Total joint replacement has been recommended for patients with end-stage of OA who experience poor response to pharmacological medication or conventional therapy [119, 120, 121]. Total knee replacement (TKR) as well as total hip replacement (THR) has profound benefits for pain relief, which is the main determinant of functional recovery following surgery.
Enhanced recovery programs after a TKR or THR surgery, which require a multidisciplinary team of dedicated professionals, have been well-established . Among the perioperative interventions producing better surgery outcome, rehabilitation plays an important role in physical reconditioning and functional recovery . As mentioned in the Section 2.1, muscle strengthening exercise (MSE) exerts benefits on muscle mass and strength gains in elder people with OA, and an MSE has been effectively employed following TKR or THR surgery as well to improve postoperative muscle and joint function . However, it remains unclear that whether MSE exerts any effect on muscle mass after total joint replacement. It is important to identify the effects of MSE on muscle mass outcome following total joint replacement since patient who were undergoing TKR or THR may experience acute sarcopenia immediately after surgery [125, 126]. Due to that sarcopenia may have impacts on function outcome after TKR or THR, further studies should be conducted to warrant effective interventions for preserve muscle mass for elderly population with OA who recently underwent total joint replacement.
Liao et al. conducted a randomized control trial to investigate effects of post-TKR MSE for elder women with OA . Liao’s study demonstrated that an intervention of 12-week elastic RET following TKR surgery exerted benefits for muscle mass gain and physical recovery among elderly women with KOA. The results of this study suggest that elastic RET should be incorporated to post-TKR rehabilitation for patients with KOA to achieve well postoperative outcomes, especially muscle mass gains and physical mobility improvements. Liao further stated that the elastic RET is relatively safe and easily performed at home. The elastic RET protocol used in Liao’s study will help clinical practitioners and physiotherapists and to establish prompt treatment strategies for elderly people with KOA, especially those who have undergone a recent TKR and are considered to have high sarcopenia risk. The findings of this study indicated post-TKR elastic RET exerted benefits on muscle mass and function and can potentially assist clinician decision-making concerning the optimal treatment strategy for elderly women who are undergoing a primary TKR.
4.2 Protein supplement plus exercise training after surgery
The previous observational study has indicated that low protein intake occurring in patients with OA may place themselves at high risks of sarcopenia . Therefore, perioperative interventions including protein supplement may prevent elder patients from suffering acute sarcopenia and poor surgical outcome at early stage after total joint replacement (i.e., TKR or THR) [129, 130, 131]. Alito et al. employed 5-day protein-contained (23%) supplements (PS) before surgery for patients who were undergoing THR and the results demonstrated that comparing with the non-supplement control group, the PS group experienced significantly a lower level of C-reactive protein (mean 80.6 vs. 66.5 mg/L,
On the basis that either perioperative diet interventions or early rehabilitation programs exerts benefits on surgical outcome, combination of both may provide additional effects on function recovery after TKR or THR. The evidences regarding effects of PS plus exercise for healthy, sarcopenic, and frail elder populations have been well established by previous systemic review and meta-analysis studies [61, 68, 132]. However, the elder population with OA as well as those who underwent total joint replacement are less targeted by previous systemic reviews investigating efficacy of PS plus exercise. Future studies are necessary to be warranted in order to identify whether PS plus exercise following TKR or THR exerts any effect on postoperative function outcomes.
Liao et al. conducted a systemic review and meta-analysis study to investigate effects of diet intervention plus ET for elder people with OA . Among the included trials in Liao’s study, all of the included trials which reported muscle mass outcomes conducted a PS plus ET intervention for older patients who recently received a TKR or THR  and the results showed that during an overall follow-up duration, the PS plus ET group achieved significant effects on muscle mass gains (SMD = 0.81; 95%CI: 0.45–1.17,
This review provides evidence that DI incorporated with ET is effective for promoting gains in muscle mass and strength and enhancing performance in physical mobility for the elder adults with lower-extremity OA, compared to placebo, DI-alone or ET-alone controls. In addition, muscle mass gains have effects on strength gain and global function recovery. Furthermore, the results of this study showed that PS plus ET appears to be the optimal treatment strategy for those who were undergoing total joint replacement whereas WL plus ET is most preferred for those who experienced mild to moderate severity of OA disease. Therefore, we concluded that DI additional to ET may have extra effects to prevent or offset muscle loss and function decline for elder individuals with OA who have high sarcopenia risks.
6. Implications for clinical practice
This review adds current evidences of interdisciplinary approach practices which comprise effective nutrient and exercise intervention strategies for KOA populations who have potential risks of sarcopenic obesity. This review also provides references for clinical practitioners to develop efficient and effective interventions for such population to prevent sarcopenic obesity.
This study was funded by grants from the Taipei Medical University-Shuang Ho Hospital, Ministry of Health and Welfare, Taiwan (grant no. 109TMU-SHH-13) and Taipei Medical University (grant no. IIT-1072-3).
Conflict of interest
The authors declare that they have no conflict of interest to the publication of this review.