Nutritional Status and Nutritional Treatment Are Related to Outcomes and Mortality in Older Adults with Hip Fracture

1Hip fractures represent a significant health risk for older populations because the incidence of fractures increases notably with age.

2Hip fractures in geriatric patients have a negative impact on functional status and quality of life, and are associated with high mortality. Despite the reduction in pre-surgery hospital stay (surgery performed in the first 24 h, or 48 h after admission, is associated with fewer post-operative complications), and improvements in the management of complications, many patients with hip fracture presented functional deterioration. Identifying the risk factors that predict functional loss after a hip fracture could reduce the costs associated with the need for help resulting from loss of autonomy and institutionalization, and could also improve the treatment of post-operative complications. The need for help in order to be able to walk within a patient’s home, Parkinson’s disease, smoking, having suffered delirium in the previous month, having a Body Mass Index (BMI) < 22 kg/m2, and age are among the independent risk factors for hip fractures. Poor nutritional status, defined by the Mini Nutritional Assessment (MNA), was associated with a higher risk of fracture at any site. Among risk factors for hip fracture as well as functional loss after the fracture, malnutrition represents an area of great interest, principally because it is a modifiable risk factor. The identification of malnutrition is widely accepted as an appropriate procedure, which may help to give patients better care. This review represents an actualization of the evidence previously published on this topic. The novelty of this review is that we included not only studies with nutritional interventions, but also studies that have assessed the nutritional status in older patients with hip fracture.

3The principal objective of this review is to describe how both nutritional status, as revealed by malnutrition biomarkers, influences the clinical evolution and mortality of older people with hip fracture, as well as the impact of nutritional intervention. We therefore structured this paper into four chapters concerning subjects with hip fracture: (1) prevalence of malnutrition and nutritional status aspects (including anthropometry, blood biomarkers, and energy intake), (2) influence upon outcomes and complications, (3) mortality, and (4) effects of nutritional intervention.

4A search was carried out on the electronic database MEDLINE for papers published from January 1990 until December 2017. The search strategy is detailed in Supplementary data. The search was restricted to articles in English, Spanish, or Italian. The references of the selected articles were manually revised in the search for eligible articles. Whenever there were studies with multiple publications about the same population, the study with the largest sample was selected, as long as it respected our inclusion criteria.

5We included observational and cohort studies that evaluated the presence of malnutrition (defined by MNA, BMI, albumin concentration, or weight loss), and the influence of malnutrition, as revealed by nutritional biomarkers, on functional recovery, post-operative complications, and mortality in hip fracture patients. We considered as nutritional biomarkers: (1) anthropometric parameters, such as BMI, mid-arm circumference, and triceps skinfold; (2) blood concentrations of total proteins, albumin, and micronutrients such as vitamin D and calcium. We also included controlled clinical trials with nutritional intervention. We defined an intervention as cases where patients received supplements (either orally, by tube, or intravenously) or advice on the characteristics of the diet (by a specialized nurse or dietician). We consider studies (which included only males, only females, or both sexes) carried out in populations with an average age of 70 years or above. Reviews and protocols that did not provide results were excluded.

6The title and abstract of papers compiled from the search were evaluated by two researchers who carried out data extraction. Doubts and queries were discussed and whenever these could not be solved, the opinion of a third reviewer was requested. Studies were grouped according to their main objective. When necessary we contacted the corresponding author to request data that did not appear in the paper.

7The quality of the selected studies was determined with 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. These tools have been designed to evaluate internal validity and bias risk for both types of observational and intervention studies, and each consists of 14 evaluation criteria. The criteria for observational studies are: aims of the study, sources of bias, sampling, participation rate, study power, data collection methods, and confounding. The criteria for intervention studies are: objective of the study, population characteristics, sampling, selection criteria, sample size justification, exposure measured, timeframe, categories of exposure, independent variables, exposure over the time, dependent variables, blinded, drop-out, and confounding. The criteria were rated as either yes, no, or “other” (i.e., CD, cannot determine; NA, not applicable; NR, not reported). The overall assessment of the studies were classified as “good”, “fair”, or “poor”.

8This review included 44 papers, which totaled 26,281 subjects with a mean age 83.6 ± 7.2 years. The population was mostly female (73.5%). The overall quality of the included studies was rated as fair (Supplementary Tables S1 and S2).

9In all of the studies included, malnutrition was identified by a validated nutritional assessment tool. Nevertheless, the prevalence of malnutrition changed according to diagnostic tool used. The prevalence of malnutrition was 18.7% using the MNA (long or short form), but it was greater if other diagnostic criteria were used (BMI, albumin, or weight loss) (45.7%). The prevalence of malnutrition, of risk of malnutrition, and the diagnostic tool used in each study are presented in Table 1.

10In this section we included 10 studies that assessed the nutritional status of older people with hip fracture, with a total of 1575 subjects (88.3% female, mean age 79.6 ± 4 years). The design of the studies, the general characteristics of the populations studied, and the main results are presented in Table 2.

11Patients with hip fracture present malnutrition, as demonstrated by the presence of low values of the anthropometric indices. Several studies showed that energy intake in older people is smaller than that required and recommended. They also showed that calorie and protein intake are significantly lower in geriatric patients with hip fracture compared to patients without fracture. Both the reduced intake observed in hip fracture patients and the increase of the energy requirement secondary to the inflammatory state lead to weight loss and a reduction in muscle mass and fat tissue indicators, and this hypercatabolism situation may continue up to 4 months after the fracture.

12The importance of a good nutritional status was backed up by studies that observed how higher BMI scores were associated with a lower incidence of hip fractures. An interesting and original study showed that patients with intracapsular fractures presented lower BMI scores than patients with intertrochanteric fractures. Almost half of the subjects with intracapsular fractures presented BMI scores lower than 18 kg/m2, versus only one-fifth of patients with intertrochanteric fractures.

13The general characteristics of the studies included in this section can be found in Table 3.

14Espaulella et al. showed how after 6 months’ follow-up only slightly over half of the patients subject to follow-up had recovered the functional status they had before the fracture. The MNA was an independent predictor of functional status upon discharge, at four and at 12 months. Malnourished patients are more likely to suffer postoperative delirium, as well as other post-operative complications such as sepsis and pressure ulcers.

15Malnutrition is of double importance as it is a risk factor for hip fracture, and in patients with hip fracture it reduces the ability to recover pre-fracture functional capacity. Indeed, malnutrition is a risk factor for fracture, and malnourished older people generally present a worse functional status before the fracture and frequently recover only partially their pre-fracture level of independency in activities of daily living (ADL) following a hip fracture. Conversely, well-nourished older people tend to improve their functional status at discharge after a hip fracture, as revealed by the motor-Functional Independence Measure (FIM) scale.

16Malnutrition and risk of malnutrition are more prevalent in geriatric patients with a higher comorbidity, in addition to being risk factors for complications following hip fracture surgery, such as pressure ulcers.

17Albumin could be a good blood marker of malnutrition. In this context, Bohl et al. studied a large database (17,651 patients with hip fracture, mean age 84.4 ± 7.2 years) and observed a prevalence of malnutrition of 45.9%, defined as albumin values below 3.5 g/dL prior to surgery. These authors reported that patients with hypoalbuminemia presented a higher prevalence of sepsis (p < 0.001), longer hospital stay (p < 0.001), and higher prevalence of readmission (p = 0.054). The benefits of a good nutritional status were also observed in other studies.

18In this section we included those studies whose main objective was to assess the impact of malnutrition, as revealed by nutritional biomarkers, on mortality. In addition, we considered studies where a multivariable analysis was carried out and which included malnutrition biomarkers. A summary of the design, characteristics, and main results of the included studies can be found in Table 4. We included five studies, with a total of 2518 patients (71.8% females), mean age 84.3 ± 7.2 years.

19Mortality was inversely associated with pre-surgery albumin levels, and patients with hypoalbuminemia had a relative risk of dying of 1.52 (95% Confidence Interval (CI) 1.37–1.70, p < 0.001). Regardless of the tool used to diagnose malnutrition, low values of albumin or BMI or low MNA were associated with an increase in mortality. Albumin concentrations of less than 36 g/L were associated with a 4-year mortality nearly six times greater (Odd-Ratio (OR) 5.85, 95% CI 2.3–16.5). Furthermore, BMI values of less than 22 kg/m2 were associated with an increase of almost seven times the mortality at 1 year, as compared to values higher than 25 kg/m2 (Hazard Ratio (HR) 7.25, 95% CI 1.6–33.7). Studies such as that of Flodin and collaborators confirm the anterior outcome, observing that subjects with a BMI greater than 26 kg/m2 had a risk almost three times less of dying after 1 year from the fracture (OR 2.6, 95%CI 1.4–5.0).

20Cenzer et al. showed that difficulty preparing meals after hip fracture predicts 1-year mortality (and this predictor factor has the same points as congestive heart failure). Others factors such as age, male sex, congestive heart failure, and not being able to drive complete the risk stratification scale.

21Mortality increases progressively after a hip fracture, from an in-hospital mortality of 7%, to 11% in the first 6 months after the fracture, up to 30% in the first year and 40% at 3 years. To highlight the importance of this health problem, we summarized total mortality and the follow-up periods of the included studies in Table 5.

22In this section we included the studies in which nutritional interventions were carried out. The general characteristics of the populations included, the design, and the main results of the studies included are presented in Table 6.

23We included 18 studies, 14 of which were carried out in Europe, one in the USA, one in Australia, and two in Asia, totaling 2248 patients (each study including between 23 and 420 subjects), with an mean age of 81.6 ± 5.4. Five studies were carried out only on women, whereas the rest had mixed samples (66.8% women).

24A majority of the studies (n 14) used oral nutritional supplements. One was preceded by supplementation with parenteral nutrition. In one study the supplement was administered via naso-gastric tube, and in one other study only dietary advice was used. One study did not specify the type of intervention. The characteristics of the interventions, calories used, protein content, and duration of the treatment are summarized in Table 7.

25Regarding duration, in seven studies intervention was maintained during hospital stay, in four studies the duration was ≤3 months, and in two it was up to 6 months. Two of the studies did not specify the duration of treatment.

26The results demonstrated that a good compliance in the use of oral supplements was associated with an increase in total energy, protein, and liquid intake during hospital stay. This is important because higher nutritional intake was associated with less postoperative complications. This improvement in intake brought on an increase of IGF-1, a decrease of bone loss 1 year after the fracture, lesser prevalence and intensity of delirium, and lower production of oxidative stress-derived products. Nutritional supplementation could also lead to a decrease in the incidence and duration of pressure ulcers, as well as delay their onset. Weight loss was found among subjects who received no supplementation (the control group), probably due to a loss of muscle mass. Two recent studies used supplements enriched with Calcium β-Hydroxy-β-Methylbutyrate (CaHMB); these studies observed an improvement in muscle indices in the intervention groups but no improvement in the control groups.

27A multidisciplinary approach is required in order to reduce malnourishment in subjects admitted to hospital. Having a dietician on the team as well as nurses trained in nutrition was associated with an increase in energy, protein, and supplement intake. In addition, a multidisciplinary approach was shown to counteract increases in the incidence of malnutrition after discharge. Furthermore, nutritional intervention was associated with lower short- and long-term mortality rate as well as with an increase in quality of life (as revealed by the EuroQol-5D scale). Nutritional advice for well-nourished patients was associated with better performance in the ADL, and with a better recovery of the ability to walk.

28Malnutrition is a subject under intense discussion in geriatric research, as it is very prevalent in older people with hip fracture, it negatively influences functional recovery after fracture, it increases healthcare spending, and it is associated with high mortality. It appears that nutritional intervention aids the prevention of complications in geriatric patients with hip fracture. This review is an attempt to summarize existing evidence of these aspects. To our knowledge, this is the first review to assess the nutritional status of older people with hip fracture and how it influences complications and mortality.

29Despite the variability in the main objective of the included studies, the results are homogeneous in the evidence that subjects with hip fracture have anthropometric indices indicative of malnutrition (Table 2). In addition, there is evidence that subjects with worse nutritional status have more complications (Table 3) and increased mortality (Table 4). There is a lot of variability in the main objective, as well as in the type of nutritional intervention (dietary advice, use of nutritional supplements) and in the amount of calories used in the included studies (Table 7). Despite this variability in the methods used in the studies, overall nutritional intervention has been shown to reduce complications and avoid weight loss in elderly subjects with hip fracture (Table 6).

30The prevalence of malnutrition in older patients with hip fracture is higher than in community-dwelling older adults. A further problem was associated with an increase in calorie expenditure, secondary to systemic inflammatory response, without a corresponding intake increase, whereby nutritional intake remained smaller than requirements due to factors such as pain, being bedridden, and reduced mobility.

31A reduction in intake is often observed in older people, causing it to be lower than requirements. These changes in intake have a multi-factor origin, among which the most frequent factors are alterations in sensory organs, loss of teeth, lack of a principal caregiver, and, in some cases, the adverse effects of certain drugs. These intake alterations constitute a well-known geriatric syndrome defined as anorexia of ageing. Calorie and/or protein deficits can contribute to the pathophysiology of fractures, especially through two mechanisms: (1) loss of strength and muscle mass (sarcopenia), which increases the risk of falls; and (2) low bone mineral density (osteoporosis), which reduces the resistance of bones to trauma, increasing the risk of fracture.

32The observed variability in the parameters of nutritional status in hip fracture patients could be due to the lack of a universal consensus as to the best measure to diagnose protein-energy malnutrition. This lack of universality limits our comparison of the various studies, also making it difficult to carry out a consistent malnutrition diagnosis, which, in certain cases, can delay the clinical decision to prescribe nutritional treatment for these patients.

33Despite this, the observed trend is uniform and shows that malnourished older people are at a greater risk of fracture and that the prevalence of malnutrition is high in geriatric patients admitted with hip fracture. Patients with intracapsular fracture usually have low BMI, while patients with trochanteric fracture tend to have high BMI. Low BMI is associated with protein deficit (type II nutrients, important for maintaining weight) and type I nutrients are important for bone metabolism. In relation to this, “BMI paradox” is valid in the elderly, in which an increase in fat mass and a decrease of muscle mass are observed, and for this reason falsely high values of BMI can mask the presence of sarcopenia. Despite the important limitations of the prognostic meaning of BMI in the elderly, this remains a fundamental index to assess the nutritional status for its simplicity and repeatability, and most validated nutrition assessment tools include BMI. Recent articles have proposed that the normal cut-off considered by the World Health Organization (WHO) (18.5–20.0 kg/m2) should be modified with the values that have been shown to be associated with lower mortality in the elderly (23–29 kg/m2). It would be advisable to complete the nutritional assessment by evaluating the body composition (with dual-energy absorptiometry (DXA) or with bioimpedance analysis). The problem is different if we consider the concentration of albumin for the diagnosis of malnutrition. The blood concentration of albumin may be a good nutritional index if the inflammatory state is taken into account, considering that its concentration does not depend only on nutritional status. On the other hand, albumin has been shown to be a good prognostic index in hospitalized patients.

34Screening tools such as the Mini-Nutritional Assessment Short-Form (MNA-SF) were able to diagnose a nutritional problem before it manifested through changes in the biochemical markers of malnutrition (such as albumin or total protein). Factors such as cognitive impairment and disability in the basic activities of daily living (ADL) were associated with lower scores in the MNA-SF. This tool was also shown to be a predictive factor of destination upon discharge following the fracture. Selective deficiencies such as lack of vitamin D are very prevalent in older people.

35As well as the known effects of this deficiency on bone metabolism, there is a high concentration of vitamin D receptors in muscle tissue. This situation could explain why the lack of this vitamin (scant diet input, little exposure to the sun, and the ability to make vitamin D within the skin declines with age) is so obviously associated with reduced muscle strength and a worse functional status, involving factors that increase the risk of fall and fracture.

36The high prevalence of malnutrition in people with dementia could be one of the pathophysiological mechanisms for the high risk of falls and fractures, as well as for their poor functional recovery after a fracture. People with dementia suffered an increase in incidence of hip fracture, as dementia is a risk factor for hip fracture. Strategies for the prevention of hip fractures are very important in people with dementia because they present a higher prevalence of complications, higher risk of institutionalization, and worse functional recovery. Moreover, dementia is an independent predictor for mortality.

37Malnutrition, which is very prevalent in geriatric patients with hip fracture, is associated with the incidence of complications, with length of hospital stay (and thus increase in cost), and with mortality. Hip fracture continues to be a pathology with high mortality. In spite of the achievement of a reduction in the incidence of hip fractures, mortality has not decreased. Intra-hospital mortality of elderly patients with hip fracture (7.4%) is comparable with mortality of elderly patients with heart failure (8%). The problem is that hip fracture represents an acute potentially preventable disease, for example by implanting exercise programs that have been shown to reduce the risk of falling. It will be necessary to improve the post-surgical treatment to reduce complications and mortality, which at 3 years is almost twice that of patients with heart failure.

38Patients with hip fracture show a state of hypercatabolism secondary to reduced intake, loss of blood, and inflammation, which leads to a reduction in plasma proteins, which are important mechanisms for the defense of oxidative stress. Cell regeneration determines an increase in the production of free radicals at the site of the fracture. Plasma oxidant markers malondialdehyde (MDA) and advanced oxidation protein products (AOPP) were significantly positively, while albumin and total antioxidant capacity (TAC) are significantly negatively associated with the duration of hospitalization.

39Several studies observed lower scores in nutritional indices, such as BMI, in geriatric patients who died following a hip fracture, as compared to those who lived. It may be possible to reduce mortality with adequate nutritional intervention. A difficult question to answer is whether nutritional supplementation is indicated for all patients with hip fracture or only for malnourished patients. Supplementation prevented weight loss in both malnourished and well-nourished patients. This association was directly related to the dose administered. A higher protein intake was associated with a lower risk of post-surgery complications, and an adequate energy intake reduced the development of complications and was associated with a shorter duration of hospital stay.

40Therefore, the results of this review support the indications of the European Society of Parenteral and Enteral Nutrition (ESPEN) guidelines, according to which all older adult patients with hip fracture should receive nutritional supplements during hospitalization.

41The prevalence of malnutrition is very high in older people and increases further in older people with high comorbidities as well as in geriatric patients. Malnutrition is associated to functional alterations and this can be a cause as well as a consequence of fractures.

42Malnutrition prevention could be associated with a reduction in the incidence of fractures, and with a better functional recovery following hip fracture. Fall prevention campaigns as well as advice on healthy and active ageing have contributed to the reduction in the incidence of hip fractures. The inclusion in care plans for geriatric patients with hip fracture of both nutritional assessments and the treatment of malnutrition could contribute to a better functional recovery and a reduction of mortality.