Undernutrition, Sarcopenia, and Frailty in Fragility Hip Fracture: Advanced Strategies for Improving Clinical Outcomes

1Hip fractures are a global public health problem and result in hospitalization, disability, and death. Globally, as the population ages, the number of hip fractures is increasing, and it is expected that 6.3 million people will suffer from hip fracture in 2050. Hip fracture patients have high mortality, experience prolonged disability, and require substantial costs for postoperative management. Therefore, management after hip fracture is a critical issue to be resolved.

2Hip fracture patients experience multiple geriatric nutritional problems, often including undernutrition, sarcopenia, and frailty at admission, all of which overlap (Figure 1), (Supplementary Figures S1–S3). These geriatric nutritional problems have significant impacts on disability, the occurrence of complications, and mortality after hip fracture. Therefore, interventions for these factors are a key strategy for improving postoperative clinical outcomes in patients with hip fracture.

3Conversely, the effect of interventions for geriatric nutritional problems in patients with hip fracture remains unclear. Nutritional therapy alone was not shown to reduce mortality. Medical professionals often ignore undernutrition, sarcopenia, and frailty, and this unawareness inhibits improvements in clinical outcomes. A focus must be placed on geriatric nutritional problems in hip fracture patients, and effective interventions should be considered. Our review aims to summarize the impact of undernutrition, sarcopenia, and frailty on clinical outcomes and to identify effective interventions combined with nutrition and rehabilitation for hip fracture patients.

4This review adhered to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched for relevant literature in PubMed (MEDLINE) and Cochrane Central Register of Controlled Trials (CENTRAL). To review recent studies on undernutrition, sarcopenia, and frailty of patients with hip fracture, we selected observational and intervention studies published in English 10 years since the European Working Group on Sarcopenia in Older People (EWGSOP) was published in 2010. We used the search terms hip fractures, femoral neck fractures, nutritional status, malnutrition, sarcopenia, muscle atrophy, and frailty.

5The inclusion criteria for the included studies in this review were as follows: (1) Assessment of patients with fragility hip fracture; (2) inclusion of both genders and all races; (3) examination of the impact of undernutrition, sarcopenia, and frailty on clinical outcomes; (4) application of validated nutritional assessments, such as nutritional screening tools, anthropometric parameters, and blood concentrations; (5) evaluation of muscle strength and/or muscle mass for diagnosing sarcopenia; (6) utilization of diagnostic criteria that address multiple factors reflecting vulnerability in the absence of established diagnostic criteria for frailty; (7) clinical outcomes, such as death, complications, hospital stay, discharge disposition, activities of daily living (ADL), mobility, etc.; and (8) observational and intervention study design.

6Editorials, case reports, letters to the editor, review articles, animal studies, and conference abstracts were excluded from this review.

7We extracted the following information from the included studies: Name of the first author, year of publication, country of origin, study design, setting, age, gender prevalence, sample size, screening or assessment tool of nutritional status, diagnostic criteria of sarcopenia and frailty, prevalence of undernutrition, sarcopenia, and frailty, main study outcomes, and main results.

8We assessed the quality of the included studies using both the National Institutes of Health (NIH) Quality Assessment tool for Observational Cohort and Cross-Sectional Studies and the Quality Assessment of Controlled Intervention Studies. This quality assessment tool comprised 14 items per study design. We scored these items and classified the included studies as “good”, “fair”, or “poor” (Supplementary Tables S1–S3).

9The prevalence of undernutrition with hip fracture is high and varies based on the evaluation tool used, ranging from about 7% to 26% (Table 1). The Mini Nutritional Assessment-Short Form (MNA-SF) and the Mini Nutritional Assessment-Full Form (MNA-FF) are the most commonly used tools for evaluating nutritional status in patients with hip fracture. The Malnutrition Screening Tool (MST), Controlling Nutritional Status (CONUT), Geriatric Nutritional Risk Index (GNRI), Malnutrition Universal Screening Tool (MUST), body mass index (BMI), serum albumin, prealbumin, total protein, vitamin D and lymphocyte count are also used. These evaluation tools are useful for assessing the nutritional status of patients with hip fracture.

10A large number of observational studies reported a significant association between undernutrition and clinical outcomes in patients with hip fracture. Most studies set mortality or ADL as clinical outcomes and the occurrence of postoperative complications, length of hospital stay, discharge disposition, readmission, mobility, and failure after internal fixation as additional outcomes. Inoue et al. and Goisser et al. reported that undernutrition, as evaluated via the MNA-SF and MNA-FF, respectively, was a significant predictor of improved ADL at discharge from acute hospitals and six months postsurgery. Nishioka et al. revealed that improvement in nutritional status via MNA-SF screening during hospitalization in a convalescent hospital was associated with ADL at discharge. Miu and Lam reported that, compared with at-risk and well-nourished patients, malnourished patients screened via the MNA-SF had a higher rate of in-hospital mortality. Gumieiro et al. reported that the MNA-FF score was a predictor of mortality after six months. Vosoughi et al. reported that BMI was an independent risk factor of mortality at one and three years. Conversely, Koren-Hakim et al. reported that the MNA-SF score was not associated with mortality at 36 months. Overall, most of the studies found an association between nutritional status and clinical outcomes in hip fracture patients.

11Several studies examining the appropriate nutritional screening tools recommended the use of the MNA-SF for hip fracture patients. The European Society for Clinical Nutrition and Metabolism also recommended the MNA-SF and the Malnutrition Universal Screening Tool and the Nutritional Risk Score 2002 (NRS-2002), which is known as a validated nutritional screening tool. In their comparisons of these validated screening tools, Inoue et al. and Koren-Hakim et al. reported that the MNA-SF was a good predictor of ADL at discharge from an acute hospital, readmission during six months, and mortality at 36 months. In a study comparing the MNA-FF and NRS-2002, only the MNA-FF could predict walking ability and mortality after six months. These results suggested that the use of the MNA-SF or MNA-FF is appropriate for predicting clinical outcomes in patients with hip fracture.

12Evaluation of nutritional status is important, because undernutrition is a significant risk factor for clinical outcomes in hip fracture patients. The MNA-SF and MNA-FF are the most commonly used tools for nutritional status evaluation and were reported to be significant independent predictors of clinical outcomes. The MNA-SF is a simple and quick nutritional screening tool for nutritional status. Furthermore, calf circumference rather than BMI can be used in the scoring of the MNA-SF, which is an advantage because of the difficulty in accurately measuring body weight on admission for patients with hip fracture. Moreover, the scoring for the MNA-SF includes the following components: functional, psychological, and cognitive aspects. Thus, the MNA-SF can accurately reflect the characteristics of elderly patients with hip fracture and might be the most appropriate nutritional screening tool for clinical outcomes in patients with hip fracture.

13Sarcopenia is defined as a muscle disease characterized by progressive and generalized decreased muscle strength and loss of muscle mass. Sarcopenia is associated with functional disability, death, and other adverse outcomes. Sarcopenia is also associated with osteoporosis and falls, therefore, patients with hip fracture are more likely to be sarcopenic.

14The prevalence of sarcopenia is high in patients with hip fracture. Although the prevalence varies on the basis of the diagnostic criteria, the overall prevalence (for both sexes combined) of sarcopenia ranges from 11% to 76.4% (Table 2). The prevalence ranges from 12% to 81% in males and from 18% to 76% in females. The EWGSOP, updated EWGSOP2, Asian Working Group for Sarcopenia (AWGS), and updated AWGS 2019 are often used for diagnosis, and the Foundation for the National Institutes of Health and SARC-F were also used in reported studies.

15Previous studies reported two ways to diagnose sarcopenia, i.e., using either a combination of muscle strength and muscle mass or muscle mass alone. In all of the studies referenced in the present review, handgrip strength was used to evaluate muscle strength. Dual-energy X-ray absorptiometry and bioimpedance analysis (BIA) were mostly used to evaluate muscle mass, with computed tomography and anthropometric measurement also used. Postoperative hip fracture patients have implantation of metal in the lower extremity, and the BIA may overestimate the muscle mass of the operative lower extremity because of its methodological limitations. Therefore, whether BIA is a suitable method for measuring muscle mass in patients with hip fractures is unclear. The criteria for sarcopenia diagnosis are becoming standardized, and further research using standardized diagnostic criteria is necessary in patients with hip fracture.

16Most observational studies reported a significant association between sarcopenia and clinical outcomes in patients with hip fractures. Many studies set outcomes for mortality and ADL. Others reported an association between sarcopenia and mobility, quality of life (QOL), length of hospital stay, discharge disposition, and the development of dysphagia. Di Monaco et al. reported the association between sarcopenia and ADL at admission to a convalescent hospital. Landi et al. reported the association between sarcopenia and ADL at discharge from a rehabilitation hospital and after 3 months, and Steihaug et al. reported the association between sarcopenia and mobility after 1 year. Nagano et al. reported an association between sarcopenia and the development of dysphagia after hip fracture. Regarding mortality, Kim et al. reported that sarcopenia was not associated with mortality at one year postoperatively but was associated with mortality at five years. Conversely, Byun et al. reported an association between sarcopenia in women and one-year mortality. Malafarina et al. reported sarcopenia was a predictor of mortality at seven years. Overall, sarcopenia was found to be a significant independent predictor of postoperative clinical outcomes, and the diagnosis of sarcopenia is important to improve clinical outcomes.

17The prevalence of sarcopenia is very high, and sarcopenia is a significant predictor of adverse outcomes in patients with hip fractures. The diagnostic criteria of the EWGSOP, updated EWGSOP2, AWGS, and updated AWGS 2019 are mainly used for the diagnosis of sarcopenia, depending on the race of the patients. The use of standardized diagnostic criteria has had a positive impact on the increase in sarcopenia research in patients with hip fracture. However, sarcopenia is often overlooked in clinical practice, and there are no intervention studies in hip fracture patients with sarcopenia. Thus, this type of study in hip fracture patients with sarcopenia is strongly needed.

18Frailty is defined as a state of vulnerability accompanied by various preliminary reductions in the ability to maintain or regain homeostasis when exposed to stressors. However, no standardized diagnostic criteria of frailty exist, and various tools were used in reported studies. A previous study reported an association between frailty and the incidence of hip fractures, with a large proportion of hip fracture patients expected to have frailty.

19The diagnosis of frailty in patients with hip fracture is hindered by a lack of standardized diagnostic criteria for frailty. These criteria vary in the studies referenced in the present review (Table 3). Therefore, discussing the prevalence of frailty in hip fracture patients is difficult. The most commonly used criteria are the frailty phenotype reported by Fried et al. and the frailty index reported by Rockwood et al.. Frailty phenotype has the following five features or criteria: Weakness, slow gait speed, low physical activity, exhaustion, and unintentional weight loss. Frailty is diagnosed if a positive score is obtained for three or more symptoms or signs out of the five criteria.

20The concept of the frailty index consists of the accumulation of health-related deficits, such as signs, symptoms, disease, and disability. The frailty index is easy to use in clinical practice because it consists mainly of medical conditions and can be evaluated from the medical record. Patel et al., Inoue et al., Vasu et al., and Pizzonia M et al. adopted 19 items and Krishnan et al. adopted 51 items to develop the modified frailty index for hip fracture patients. These models suggest that frailty is a continuous score that considers disability, comorbidity, and symptoms. Higher scores are considered to be associated with greater frailty. They reported an association of the modified frailty index with mortality, occurrences of complications, length of hospital stay, discharge disposition from acute hospital, and low functional recovery. Further studies are needed to enable an easy diagnosis of frailty in clinical practice for hip fracture patients.

21Many previous studies reported that frailty was a predictor of adverse outcomes. The clinical outcomes included mortality, the occurrence of complications, length of hospital stay, ADL, QOL, and discharge disposition. However, few well-designed studies were conducted. Thus, it is necessary to develop diagnostic criteria that are simple, highly accurate, able to predict adverse outcomes, and suitable for hip fracture patients.

22Based on the current evidence, the effectiveness of nutritional therapy alone for hip fracture patients is unclear. A systematic review of nutritional interventions for hip fracture patients reported only low-quality evidence to reduce complications and no clear effect on mortality. Many intervention studies examined the effect of oral administration of protein, β-hydroxy-β-methylbutyrate, vitamin D, whey protein, or combined calcium β-hydroxy-β-methylbutyrate (CaHMB), vitamin D, and protein intake on clinical outcomes. One randomized controlled trial for hip fracture patients conducted an intervention to calculate energy requirements by measuring the resting energy expenditure using an indirect calorimeter. In individual randomized controlled trials, the group that received the nutritional intervention had better outcomes than the control group in terms of occurrence of complications, severity of pressure ulcers, length of hospital stay, readmission rate, nutritional status, muscle strength, muscle mass, and wound-healing period. Conversely, there was no significant difference in nutritional status or mortality between the group that received a nutritional intervention alone and the control group. The effects of nutritional intervention on ADL are not consistent. There were no intervention studies that reported enhanced rehabilitation used in combination with nutritional therapy. These discrepancies might suggest that nutritional interventions alone are insufficient to improve clinical outcomes.

23A combination of nutrition and exercise interventions is effective for elderly patients with sarcopenia. A combination of amino acid intake and exercise improved muscle strength, muscle mass, and ADL of community-dwelling women with sarcopenia and sarcopenic patients with cerebrovascular disease. A meta-analysis reported that the combination of nutrition and exercise had a positive effect on physical function in community-dwelling elderly individuals. Combined nutrition and exercise interventions promoted muscle protein synthesis compared with each of these interventions alone. Thus, these combination interventions for hip fracture patients may contribute to improved clinical outcomes.

24To improve clinical outcomes effectively, medical professionals should be aware of geriatric nutritional problems in hip fracture patients (Figure 2). On the basis of geriatric nutritional evaluation, we must be careful about iatrogenic sarcopenia. Iatrogenic sarcopenia is caused by hospitalization and is drug-related. Hospitalization-related iatrogenic sarcopenia is caused by physicians, nurses, and other medical professionals. Iatrogenic sarcopenia mainly comprises inactivity- and nutritional-related factors. Inactivity-related iatrogenic sarcopenia is mainly caused by unnecessary inactivity during the perioperative period. In hospitalized hip fracture patients, approximately 99% of the day consists of sedentary time. The incidence of sarcopenia in acute hospitals is approximately 15%, and the duration of bed rest is associated with the incidence of sarcopenia. In patients in rehabilitation hospitals, increased time away from bed is more effective in improving ADL. Medical professionals should pay close attention to iatrogenic sarcopenia, and avoiding unnecessary bed rest, immobility, and deconditioning in patients could prevent activity-related sarcopenia.

25In hip fracture patients, nutritional-related iatrogenic sarcopenia requires a comprehensive approach. Only 17.5% of patients meet their energy requirements in the first week after hip surgery. Additionally, multiple factors are associated with reduced food intake after fractures, and it is clear that interventions that merely administer supplements are insufficient for improving clinical outcomes. Bell et al. reported that intensive individualized, multidisciplinary (orthopedic and geriatric physician, nursing staff, physiotherapists and occupational therapists, dietitian, pharmacist, etc.) interventions reduced barriers to food intake; food intake increased in the group with multidisciplinary intervention (mean 1489.0 kcal/day, protein intake of 1.13 g/body weight) compared with the group with conventional care (mean 707.4 kcal/day, protein intake of 0.60 g/body weight) in hip fracture patients. Additionally, medical professionals should pay attention to sarcopenic dysphagia accompanied by deterioration in nutritional status after hip surgery. A multidisciplinary, comprehensive pragmatic intervention trial is required for hip fractures with overlapping undernutrition, sarcopenia, and frailty. Compared with randomized controlled trials, pragmatic trials can be routinely conducted with less stringent inclusion and exclusion criteria. Therefore, selection bias can be controlled, and the results can be easily generalized to routine clinical practice. Comprehensive multidisciplinary interventions are necessary to prevent nutritional-related iatrogenic sarcopenia in patients with hip fracture.

26The geriatric nutritional evaluation, a comprehensive approach that combines nutritional management and rehabilitation, is a key strategy for improving clinical outcomes. The concept of “rehabilitation nutrition” invented in Japan may be effective for managing geriatric nutritional problems in fragility hip fracture patients. “Rehabilitation nutrition” is defined as that which (i) holistically evaluates the presence and causes of nutritional disorders, sarcopenia, and excess or deficiency of nutrient intake as per the International Classification of Functioning, Disability and Health; (ii) conducts rehabilitation nutrition diagnosis and rehabilitation nutrition goal setting; and (iii) elicits the highest body functions, activities, participations, and QOL by improving nutritional status, sarcopenia, and frailty using “nutrition care management in consideration of rehabilitation” and “rehabilitation in consideration of nutrition” in people with a disability and frail older people. This rehabilitation nutrition concept can maximize functional recovery and QOL through the diagnosis and intervention of undernutrition, sarcopenia, and frailty. Previous studies reported the usefulness of this comprehensive approach, which combines nutritional management and rehabilitation. Future research on comprehensive interventions combined with nutrition and rehabilitation, specifically for hip fracture patients, is strongly needed.

27The strength of this review is that we summarized recent research that focused on the nutritional problem of elderly patients with hip fracture and mentioned new intervention strategies for geriatric nutritional problems. However, this review also has methodological limitations. For example, we did not use a strict literature search for a systematic review, which is necessary to further explore the impact of sarcopenia and frailty on the clinical outcomes of hip fractures.

28The overlap between undernutrition, sarcopenia, and frailty is a characteristic of fragility hip fracture patients. Geriatric nutritional problems have a strong impact on adverse outcomes after hip fracture. To improve clinical outcomes effectively, medical professionals should be aware of geriatric nutritional problems in hip fracture patients. A comprehensive approach that combines nutritional management and rehabilitation is a key strategy for improving clinical outcomes. New, comprehensive, advanced, and hip-fracture-specific intervention strategies are strongly needed.