What Are the Barriers to Incorporating Nutrition Interventions Into Care of Older Adults With Femoral Fragility Fractures?

Abstract

Femoral fragility fractures cause substantial morbidity and mortality in older adults. Mortality has generally been approximated between 10-20% in the first year after fracture and among those who do survive, another 20-60% require assistance with basic activities within 1-2 years following fracture.¹ Malnutrition is common and perpetuates these poor outcomes. Nutrition supplementation has potential to prevent post-injury malnutrition, preserve functional muscle mass, and improve outcomes in older adults with femoral fragility fractures, however high-quality evidence is lacking, thus limiting translation of interventions into clinical practice. This review article is designed to highlight gaps in the evidence investigating nutrition interventions in this population and identify barriers for translation to clinical practice. Our goal is to guide future nutrition intervention research in older adults with femoral fragility fractures.

Level of Evidence: V

Introduction

Femoral fragility fractures, which include hip and distal femur fractures, are devastating complications of osteoporotic disease in the elderly. Over 75% of fragility fractures occur in people aged 75 years or older, resulting in dramatic loss of independence, physical function, and mortality in an already frail population.^2,3 Many of these complications are associated with loss of muscle mass and progression to sarcopenia. Significant loss of muscle mass occurs during the first six weeks after injury and is directly due to disuse and nutritional deficiencies.⁴ Postoperative nutritional supplementation provides an opportunity to preserve muscle mass and accelerate return to functional status, as well as reduce surgical complications and mortality.^5-6

Various modalities of postoperative nutrition interventions have been explored in the context of fragility fracture. Protein supplementation has shown promise in reducing surgical complications in addition to enhancing walking recovery and body weight maintenance in the acute phase of recovery.^7-10 Formal dietician evaluation, in conjunction with diet modification and supplementation, is also utilized to provide multimodal, individualized care to patients. Evidence suggests that these interventions have the potential to improve postoperative nutritional status, blunt reduction in quality-of-life, and shorten length of hospital stay.^11-13 Select previous clinical trials of nutrition interventions in older adults with femoral fragility fractures are summarized in Table 1.

Table 1.

Summary of Randomized Clinical Trials Evaluating the Impact of Protein/Amino Acid Supplementation in Patients with Femur Fractures

First Author	Injury Treated	Age Criteria	Number Enrolled	Random- ization	Intervention	Duration	Primary Outcome(s)	Secondary Outcome(s)
Anbar16	Hip Fracture	≥65 years	50	1:1.3	Ensure Plus® or Glucarna®	14d or un- til hospital discharge	Postoperative complications and hospital LOS	Energy intake and calculated energy balance
Botella- Carretero54	Hip Fracture	≥65 years	60	1:1	Oral nutritional supple- ment (ONS) 40 g protein and 400 kcal of energy daily	Duration of hospital stay	Change in serum albumin, prealbumin, and RBP	Tolerance to supplementation, LOS, postoperative complications, time to start of mobilization
Botella- Carretero21	Hip Fracture	≥65 years	90	1:1:1	Protein group: ONS of 36g protein daily Protein-energy group: ONS of 37.6g protein and 500kcal energy daily	Duration of hospital stay	Change in serum albumin, prealbumin, and RBP	Tolerance to supplementation, LOS, postoperative complications, time to start of mobilization
Bruce49	Hip Fracture	All	109	1:1.2	235 mL daily ONS of 352 kcal energy, 17.6 g protein, 11.8 g fat, 44.2 g carbohydrate, vitamins, and minerals	28d	Weight change	Mortality rate, discharge destination, ADL, LOS
Delmi15	Femoral Neck Fracture	≥60 years	59	1:1.2	250 mL ONS of 20 g protein and 254 kcal energy daily	Mean = 32d	Postoperative complications, mortality	LOS, anthropometric measures (triceps skinfold, upper arm circumference), Biochemical measures (e.g. albumin, 25(OH) D, prealbumin, alkaline phosphatase)
Ekinci28	Hip Fracture	≥65 years	75	1:1	Enteral 3 g cal- cium β-hydroxy-β- methylbutyrate, 1000 IU vitamin D, and 36 g protein twice daily	30d	Weight and BMI	Wound healing time, LOS, arm circumference, calf circumference, muscle strength, CRP
Espaule- lla55	Proximal Femur Fracture	≥70 years	171	1:1	20 g protein, 800 mg calcium, 25 IU vitamin D3, 149 calorie ONS daily	60d	Functional recovery, fracture-related mortality	Postoperative complications, discharge outcome, compliance, LOS
Houwing19	Hip Fracture	All	103	1:1	400 mL daily ONS of 125 kcal, 10 g protein, 1.5 mg l-arginine, 5 mg zinc, 125 mg vitamin C, 50 mg vitamin E, 1 mg carotenoids	4 weeks or until discharge	Incidence of pressure ulcers	Severity of pressure ulcers, time of ulcer onset
Invernizzi56	Hip Fracture	≥65 years	32	1:1	Aminotrofic® 4 g daily in conjunction with physical exercise rehabilitation program (performed in both groups)	2 months	Hand grip strength, Timed Up and Go Test, Iowa Level of Assistance scale	Daily caloric and protein intake, health-related quality-of-life
Malafa- rina5	Hip Fracture	≥65 years	107	1.1:1	Ensure Plus® en- riched with 0.7 g/100 mL CaHMB, 227 IU/100 mL 25(OH)D, and 227 mg/100 mL of calcium twice daily	Duration of hospital stay	Body composi- tion measures (e.g. BMI, ap- pendicular lean mass) and nutritional markers (e.g. albumin, triglycerides, 25(OH)D)	Postoperative complications, functional status, inflammatory markers (e.g. CRP, IL-1, IL-6)
Olofsson57	Femoral Neck Fracture	≥70 years	199	1.1:1	Multidisciplinary program on ortho- pedic-geriatric unit consisting of dietician consult, systematic food and liquid intake, nutritional and protein drinks twice daily, and protein-enriched meals as necessary.	≥4d postopera- tively	Postoperative complications and nutritional status	None noted
Schürch42	Hip Fracture	≥60 years	82	1:1	ONS of 250 kcal energy, 20 g proteins, 3.1 g lipids, 35.7 g car- bohydrates, 1000 IU vi- tamin A, 30 μg vitamin K1, 20 mg vitamin C, 550 mg calcium, 91 mg magnesium, 429 mg phosphorus, and 228 mg sodium 5 days per week	6 months	Function and LOS	Nutrition (e.g. albumin, prealbumin, IGF-1) and immunologic (e.g. IgG, IgM) status, bone mass and remodeling
Tider- mark53	Femoral Neck Fracture	≥70 years	60	1:1:1	Protein group: 20 g/ day Protein-steroid group: 20 g/day protein and 25 mg/3 weeks nandrolone All groups received 400 IU vitamin D and 1 g calcium daily	6 months	Nutritional Status (body composition), Function, Quality-of-life	Postoperative complications
Van Stijn58	Hip Fracture	≥75 years	236	1:1.1	≥31.2 g taurine	6d postop- eratively	Mortality and morbidity (e.g. infectious, cardiovascular event)	LOS, ADL index, oxidative stress
Wyers25	Hip Fracture	≥55 years	152	1:1.1	400 mL Cubitan® daily	3 months	LOS in hospital and rehabilita- tion units, read- missions within 6 months	Nutritional status, functional status, cognition, quality of life, postoperative complications, subsequent fracture, all-cause mortality

ONS= oral nutritional supplement, LOS=length of stay, RBP=retinol binding globulin, BMI=body mass index, ADL=activities of daily living, CRP=C-reactive protein.

Inconsistent interventions in the current literature limit ability to draw definitive conclusions about the efficacy and feasibility of nutritional interventions following fracture fixation. Low enrollment, varying supplement type, composition, and duration, and lack of clinically significant outcomes make it difficult to establish widespread practice guidelines. The 2021 American Academy of Orthopedic Surgeons guidelines strongly recommended that nutrition assessment should be a part of the inter-disciplinary team, however the two studies cited are dated and do not recommend specific nutrition supplementation.¹⁴ Additionally, a relative dearth of basic science evidence supporting benefits of nutritional interventions, exploration into the cost-effectiveness of these modalities, and inconsistent patient compliance in trials further serve as roadblocks toward future use of nutritional interventions in the context of orthopedic trauma such as fragility fractures.

The objectives of this literature review are to summarize the current evidence for postoperative nutritional interventions in patients with femoral fragility fracture, critically evaluate limitations, and provide guidance for establishing a more complete and uniform knowledge base for future research. We highlight areas of controversy in nutrition interventions and opportunities to fill gaps in the clinical and mechanistic evidence that, once addressed, may accelerate translation to clinical practice.

Limitations of Previous Clinical Trials

Sample Size

Limited enrollment in clinical trials can lead to type II error and inability to apply findings to a general population. Previous clinical trials demonstrate promising benefits but were not sufficiently powered for general application. A multicenter trial performed by Delmi et al. randomized 59 older adults with femoral neck fractures to standard diet or an intervention with 20 g protein supplement twice daily for a mean 32 days postoperatively.¹⁵ Compared to controls, patients that received supplementation had lower rates of malnutrition (as determined by serum albumin levels) and lower rates of bedsores, severe anemia, and surgical-site infections. Six-month mortality was also greater in patients that did not receive supplementation. No power analysis was performed.

Another prospective cohort study of 50 patients showed promising benefits of Ensure plus® and Glucarna® supplementation on energy balance, hospital course, and infection rate in patients over 65 admitted for hip fracture.¹⁶ Supplementation and follow-up was limited to the duration of the hospital stay, and slow recruitment led to failure to reach the enrollment required to provide definitive conclusions. Similarly, Hitz et al. suffered from insufficient power due to small sample size in their trial examining the effect of one year of daily 3000 mg calcium carbonate along with 1400 IU cholecalciferol on bone mineral density in patients with low-energy hip fractures.¹⁷ Hip bone mineral density was similar at 12-month follow-up, but differences were observed in spine bone mineral density in patients ≤70. Their trial included only 29 hip fracture patients, leading to a poststudy power calculation of 73.2% for their lumbar spine measurements and 29.9% for hip bone mineral density calculations.

In another example, a randomized, double-parallel trial by Neumann et al. enrolled hip fracture patients aged over 60 years, randomizing them to either two eight-ounce cans daily of Ensure® or Boost HP® postoperatively for a 28-day period.¹⁸ Once again, recruitment goals were not reached due to lower-than-expected rates of eligible subjects in addition to high refusal rates, leading to inclusion of 46 patients. No significant differences were found between functional independence measures up to three months post-discharge in addition to length of stay on the rehabilitation unit. The underpowered nature of the study, in addition to the lack of a true control arm, increases the probability of type II error, as greater recruitment may have revealed significant differences in functional outcomes between the two groups. Low recruitment in these trials highlights the challenges of enrolling older adults with femoral fragility fractures in nutrition intervention trials and limits the reliability of conclusions. Future clinical trials of nutrition interventions should be multi-center to increase enrollment and diversity of the patient population, so that definitive conclusions can be applied to clinical practice.

Clinically Meaningful Outcomes

Another obstacle to demonstrating clinical benefit of nutritional interventions is the lack of clinically meaningful outcomes in previous trials. Houwing et al. investigated the effect of supplementing a standard hospital diet with 400 mL daily of 500 kcal energy, 40 g protein, along with arginine, zinc, vitamin C and E, and carotenoids on the incidence and severity of pressure ulcers in the acute phase of recovery from hip fracture patients.¹⁹ Significant differences were found in relative severity, but not incidence, of pressure ulcers between the control (n=52) and intervention (n=51) arms, but there were no other clinical or functional outcomes reported to clarify the somewhat mixed results.

Wyers et al. assessed the efficacy in improving nutritional status and reducing postoperative complications of 400 mL daily of Cubitan® (500 kcal energy, 40g protein) in conjunction with scheduled dietetic counseling for three months after surgery for a low-energy hip fracture.¹¹ Although significant improvements in nutritional status and fewer surgical complications were found in the intervention arm (n=73) when compared to the control arm (n=79), these improvements did not translate to reduced postoperative complications, including infections, cardiovascular events, pressure ulcers, delirium, and anemia. Additionally, fracture incidence and all-cause mortality did not differ between the two groups at one-and five-year follow-up.

A single-blinded randomized control trial conducted by Torbergsen et al. found that supplementation of a regular orthogeriatric unit diet with 150 μg vitamin A, 10 mg vitamin E, 1.2 g ω-3 fatty acids, as well as calcium, vitamin D3, and vitamin K1 fortification improved 25(OH)D and vitamin K1 levels at four month follow-up, but once again the improved nutritional profile in the 31 experimental patients did not translate to improved profiles of other vitamins or bone turnover markers when compared to controls.²⁰ Functional and clinical outcome measures were not compared between the two groups.

Last, a parallel, three-arm trial led by Botella-Carretero and Vázquez investigated biochemical and anthropometric changes in three groups of moderate-to-severely malnourished patients, one taking 36 g of supplemental protein daily, one taking 37.6 g of supplemental protein in conjunction with 500 kcal of energy supplement per day, and the other receiving no nutrition intervention (n=30 in all groups).²¹ There was a significant increase in serum albumin from admission to discharge, but the extent of this increase did not differ between any of the three groups. Additionally, there were no statistically significant differences in hospital time and postoperative complication rates between the groups, leading to inconclusive findings on the impact of the regimen on clinical outcomes. Future clinical trials should focus on outcomes important to older adults that sustain hip fractures including improved physical function and independence with reduced medical and surgical complication.²²

Variability in Type and Composition of Nutritional Intervention

A significant roadblock to translating nutritional interventions into clinical practice is the widespread variability in type and composition of intervention studied. While EAAs have shown promise in improving functional outcomes and reducing complications, there are significant differences in the composition of EAAs administered. For example, Hendrickson et al. provided twice daily supplementation of 7 g arginine, 7 g glutamine, and 1.5 g of beta-hydroxymethylbutyrate (HMB), demonstrating reductions in postoperative complications, nonunion, and mortality in acute fracture patients randomized to standard diet and EAA supplementation (n=200) versus placebo.⁷ Rondanelli et al. administered a supplement consisting of 1500 mg leucine, 1000 mg lysine, 750 mg glutamine, 550 mg valine, 450 mg threonine, 250 mg phenylalanine, 350 mg tyrosine, 350 mg histidine, 200 mg cysteine, 125 mg methionine, and 75 mg tryptophan twice daily for four weeks in randomized groups of 19 hip fracture patients.⁹ This small study demonstrated a reduction in post-operative pain and increase in time spent in physiotherapy up to 45 days post-operatively, but there were no statistically significant improvements in mental or physical health measures.

A single-center trial by Eneroth et al. found that the commercially available Fortimel® (protein, vitamins, minerals) along with Vitrimix® (EAAs, minerals) infusions reduced postoperative infectious complications at 10, 30, and 120-day timepoints, largely due to reduced incidence of pneumonia and wound infections in the intervention group.²³ Subjects were given 1000 mL of IV Vitrimix® daily for three days postoperatively, then 400 mL of enteral Fortimel® daily for seven days. This protocol also attenuated mortality in the intervention group (n=40) at four-month follow-up.

Boost HP®, a commercially available drink with 20 g of protein per serving, was also explored in an underpowered trial that did not yield any statistically significant improvement in functional recovery or shortening of hospital stay when compared to Ensure® supplementation.¹⁸ This trial brings to light an additional concern not sufficiently addressed: added sugar content in commercially available oral protein supplements. Both Boost HP® and Ensure® contain glucose, sugar, and/or maltodextrin, in the first three ingredients. Yet, a clinical assessment of blood glucose or hemoglobin A1c levels were not included, which is an important clinical outcome to monitor when supplementing a product containing more than 10 g of added sugar per serving.

Nutrition interventions have been frequently paired with participant engagement with a registered dietician, which leaves it difficult to discern improvement attributed to supplementation alone. In isolation, registered dietician intervention can positively affect postoperative nutritional and functional outcomes. Duncan et al. investigated dietician evaluation in women over 65 years old with non-pathologic hip fracture.²⁴ Patients who received dietetic care in addition to their standard care had lower mortality in both the trauma unit and at four-month follow-up compared to controls. There were also improvements in energy intake, handgrip strength, anthropometric measurements, weight, and biochemical values such as albumin, hemoglobin, and lymphocyte count in the experimental group. There were no significant differences in length-of-stay or complications in any of the settings studied.

A series of studies describe the outcomes of multi-modal approaches. Wyers et al. utilized an oral regimen of a milk-protein based, yogurt, or juice style supplement (Cubitan®, Nutridrink Yogurt®, Nutridrink® Juice) combined with five dietetic visits over a three month span.²⁵ Hoekstra et al. assessed the impact of implementing a multidisciplinary nutritional program on nutritional status, body cell mass, and quality-of-life in patients with low-energy hip fracture at a single hospital.²⁶ Patients whose care followed the multidisciplinary protocol (n=61) had improved energy and nutritional intake, attenuated reduction in quality-of-life scores, lower risk of malnutrition, and reduced VAS pain scores three months post-operatively when compared to patients receiving standard care.

High-dose vitamin D and calcium regimens have been explored both in isolation and in conjunction with other interventional modalities for recovering hip fracture patients. As previously mentioned, Hitz et al. found no differences in hip bone mineral density at one-year follow-up in patients given 1400 IU cholecalciferol and 3000 mg calcium carbonate when compared to controls.¹⁷ In a four-arm randomized control trial that was part of the Nottingham Neck of Femur (NoNof) study, patients within seven days of surgery for hip fracture received either a single injection of 30000 units vitamin D2 (n=25), 30000 units of vitamin D2 with one gram daily calcium (n=20), 800 units of daily vitamin D3 with one gram daily calcium (n=26), or no treatment (n=32).²⁷ The NoNof study group found that all modalities of vitamin D supplementation improved neck of femur, trochanter, and total hip bone mineral density while also reducing falls when compared to the placebo arm, with oral vitamin D and calcium supplementation showing the most drastic increases in total hip bone mineral density of the three treatment modalities.

Ekinci et al. supplemented 1000 IU vitamin D alongside 3 g calcium beta-hydroxy-beta-methylbutyrate (CaHMB) and 36 g protein twice daily.²⁸ Their formulation shortened wound healing, increased patient mobility, and reduced postoperative complications within 30 days of surgery. Malafarina et al. used a similar formulation of Ensure Plus® enriched with 0.7 g/100 mL CaHMB, 227 IU/100 mL 25(OH)D, and 227 mg/100 mL of calcium to assess impact on anthropometric measures, inflammatory markers, and functional recovery.²⁹ From admission to discharge in two rehabilitation facilities (mean=42.3 days), patients in the intervention group (n=49) had stable body mass index, appendicular lean mass, and muscle mass, all of which decreased significantly in controls. Activities of daily living recovery trended toward positive association with the intervention but did not reach statistical significance. The CaHMB, vitamin D, and calcium enriched Ensure Plus® reduced sarcopenic markers in patients while on the rehabilitation unit. Based on our review, future clinical trials should continue to focus on outcomes specific for the intervention chosen in the trial. For example, EAA supplementation has a known positive impact on body composition and muscle mass. Clinical trials focusing on EAA supplementation should focus on outcomes related to muscle mass, physiology, and function.

Lack of Mechanistic Evidence

A limiting factor in the clinical application of nutrition interventions in fragility fracture patients is the lack of mechanistic evidence to serve as a basis explaining how supplementation affects physiologic and metabolic processes. Much of the mechanistic data for supplementation and bone health or healing outcomes have been performed in rodent models, which can be difficult to use as the basis for translation to patient populations. In a study by Yoneme et al., mice that received water supplemented with milk-based proteins experienced higher expression levels of genes associated with chondrogenesis and osteogenesis up to 56 days after fracture when compared to controls.³⁰ Meesters et al. found that supplementation with citrulline, a non-essential amino acid, enhanced post-operative maintenance of body weight and expedited callus formation in mice after a controlled femoral osteotomy.³¹ Roberts et al. investigated probiotic supplementation of the bacterium bifidobacterium adolescentis in mice healing from bone fracture.³² Their results indicated that probiotics with bifidobacterium adolescentis decreased systemic inflammation after bone fracture and increased the rate of bone healing while also protecting the intact skeleton. A final example by Küçükalp et al. found no statistically significant difference in fibular fracture healing in rabbits after giving the experimental group 2 mL/kg/day of 20% L-arginine L-glutamine solution, but this may have been due to an underpowered sample, as positive radiographic, histopathologic, and clinical outcomes trends were noted.³³

While few human studies have sought to explain the mechanisms by which nutritional interventions affect clinical and functional outcomes following femoral fragility fractures, much of the rationale supporting nutritional supplementation originates from the current understanding of underlying physiology of bone growth and healing. Vitamin D, calcium, and phosphorous supplementation have been frequently investigated in the pre-clinical setting due to their important role in bone growth. Vitamin D supplementation has been investigated in numerous basic science research studies with positive results suggesting bone healing benefits, but direct translation of these results to clinical practice is limited due to the necessary inclusion of calcium supplementation to assist absorption.^34-36 Zinc’s role in osteoblast and osteoclast differentiation may allow it to serve as a promoter of fracture healing by increasing alkaline phosphatase activity and osteocalcin.^37-38 Additionally, antioxidants have been suggested as potential accelerators of bone healing in the setting of fracture.^37,39 Investigation of these compounds, amongst others, is warranted for improvements to translational research.

Populations at highest risk for femoral fragility fractures, particularly osteopenic and osteoporotic patients, commonly have nutritional deficiencies present before injury occurs, giving rise to another theoretical source of support for nutritional intervention – identifying existing nutritional deficiencies present in patients at higher risk for poor clinical and functional outcomes. Insulin-like growth factor 1 (IGF-1) represents an example of such theories. Implicated in early satellite cell activation and proliferation, increased IGF-1 levels could theoretically improve recovery and rehabilitation outcomes for patients following femoral fragility fracture.⁴⁰ The importance of differences in IGF-1 is well-outlined by Ohlsson et al., who established increased risk for fractures, especially hip fractures, in elderly men with low IGF-1 levels.⁴¹ Protein supplementation in patients with osteoporotic hip fractures was associated with increased serum levels of IGF-1 compared to controls.⁴² Patients that received protein supplementation had significantly less loss of proximal femur bone mineral density at 12 months, as well as fewer new vertebral deformities and shorter rehabilitation ward stays (although not statistically significant). Although these studies suggested a mechanistic contribution for which nutritional supplementation impacts outcomes following femoral fragility fractures, the precise mechanisms are unclear and future investigation is warranted.

Cost of Interventions

Compared to the efficacy and safety of interventions, cost-effectiveness remains a poorly explored dimension of post-operative nutrition programs in orthopedics, and even moreso in the context of fragility fracture. Shafrin et al. explored the cost-effectiveness of conditionally essential amino acids after in adults ≥18 after fracture fixation of the lower extremity, upper extremity, or pelvis.⁴³ Their model indicated that a two-week, twice daily regimen would provide a net incremental cost savings per patient of $4,902, largely due to reduced postoperative complications. Application to the US population yielded an expected annual savings of $316 million with 813 quality-of-life-years added. In a retrospective cohort study by Williams et al., malnourished patients who underwent either a hip or femur fracture repair during a ten-year period were grouped by exposure to oral nutrition supplements, tube feed formulas, or modular nutritional supplements within one day postoperatively.⁴⁴ Early supplement exposure was associated with significantly reduced length of hospital stay without a statistically significant difference in hospital cost. There were no reported differences in infection rates, intensive care unit admission, or hospital mortality.

There is limited evidence regarding cost-effectiveness of nutritional care in this setting, including registered dietician referral and use. This article has highlighted the efficacy and outcomes of various explored nutritional supplements, of which multiple have shown promise in reducing complications, shortening length-of-stay, and reducing disability within various follow-up periods. These outcomes likely translate to less cost both for patients and healthcare systems. Future work should prioritize inclusion of cost metrics and health-related quality of life assessments that allow for assessment of incremental cost effectiveness ratios alongside clinical and functional outcomes.

Variability in dose and Duration of Nutrition Interventions

Among fragility fracture patients, malnutrition frequently underlies the presenting clinical problem and complicates physicians’ ability to optimize clinical outcomes.⁴⁵ While interventions like nutritional supplementation and dietician consultation have produced positive results, best practices for dosing and duration of these interventions remain unclear. To find a solution to the question of “how long is long enough” for nutritional interventions in this population, one must first consider how long significant complications of hip fragility fracture may occur. Some of the most severe complications include acute loss of skeletal muscle due to disuse, decreased physical function, pain, and resulting loss of independence and quality of life. Mortality is also a reported complication among this population, for which risk is as high as 10% within the first 30 days postoperatively.⁴⁶

Outcomes also greatly improve with intervention beyond the time they are admitted to the hospital, yet many studies limit intervention and follow-up to the acute phase of recovery due to logistical barriers. The greatest amount of recovery occurs within the first six months postoperatively, but patients continue to improve their pain status and functional ability out to one year.⁴⁷ Because many fragility hip fracture patients are malnourished prior to injury, it is reasonable to conclude that most would benefit from lifelong nutritional supplementation.^5-6 This should certainly be considered, but may not be feasible considering the cost of nutritional interventions and low compliance in long-term studies. Trials cited throughout this review have found variable success in extending intervention beyond hospital stay due to compliance concerns. As addressed later, coupling successful tools used by prior trials to increase compliance with extension of supplementation length would provide more impactful assessment of the long-term efficacy of interventions.

Supplement dosing is highly heterogenous, making it difficult to compare trials. Rarely has a clinical trial evaluating a nutritional supplement addressed potential differences in body weight, sex, or even pre-nutritional status by altering supplement dose. Gunnarsson et al. tailored preoperative and postoperative supplementation to reach 30 kcal/kg of energy intake for hip fracture patients.⁴⁸ Nasogastric and tube feeds, in addition to glucose infusions, were given if patients did not reach their energy intake goal. Their regimen reduced incidence of pressure ulcers and nosocomial infections within five days postoperatively in the experimental group, while also serving as a potential guide for future interventions in terms of individualized dosing.

Compliance with Nutritional Interventions

Reported Compliance in Randomized Clinical Trials

Compliance with nutrition supplementation regimen remains a significant challenge and is highly variable depending on duration and mode of supplementation. A trial by Bruce et al. illustrates this concept, as their results showed significantly increased postoperative weight loss with decreased compliance to nutritional supplementation.⁴⁹ Flodin et al. provided 200 mL of twice daily protein and energy supplement for six months.⁵⁰ Of the 18 patients in the intervention group, only seven reported taking the full supplement as prescribed, with the remaining 11 taking half of their prescribed doses, a compliance rate of 39%.

Adherence to intervention is highly variable depending on length and mode of supplementation. Myint et al. finished their trial with a 78% compliance rate with twice daily oral nutritional supplementation for four weeks.⁵¹ Many trials with similar length of intervention have comparable compliance rates. A four-week trial by Chevalley et al. had a compliance rate of 73% in the intervention arm, and Houwing et al. had 75% of subjects consume 75% or more of their prescribed supplementation.¹⁹

Nutritional supplementation has the potential to enhance clinical outcomes in older adults with fragility fracture. However, trials provide evidence of persistent difficulties with prescribed compliance. To realize translation to clinical practice, it is necessary that investigators improve approaches to measuring and assuring consistent adherence to the intervention.

Measures to Improve Oral Nutrition Supplementation Compliance

Higher compliance rates have been achieved in prior trials through shorter duration of prescription, scheduled days off from treatment, and home nurse visits. Tidermark et al. reported 100% compliance in their trial investigating anabolic steroid injections and oral protein supplement in patients after fixation of femoral neck fractures.⁵³ In their trial, a research nurse was assigned to visit subjects at home to administer the nandrolone injections. Schurch et al. investigated protein supplementation over a six-month period.⁴² However, they required their subjects to only take prescribed supplements for five days per week. Compliance was 73% in the intervention group and 80% in the control group.

Conclusion

Postoperative nutritional interventions show promise for improving outcomes after fragility fracture in older adults. Implementation into clinical practice has been complicated by an inconsistent literature supporting supplement composition, dose, and duration. Future trials should aim to achieve consistency in the characteristics of interventions studied through dose standardization and use of widely available products. In addition, issues with compliance and small sample size limit reliability of findings. Investigators should adopt tools from past research to increase compliance and strengthen approaches for improving subject recruitment and retention. Further, clinical trials aiming to demonstrate the impact of nutrition interventions on the clinical and functional outcomes in patients with femoral fragility fractures should also include key economic indicators that will allow clinicians, hospitals, and policy makers to better evaluate and compare cost-effectiveness. Last, there is a great need for basic science research into the mechanisms by which supplementation may improve clinical and functional outcomes. Without basic science and mechanistic literature as a foundation, it will be difficult to fully understand and explain the efficacy, safety, and cost-effectiveness of nutritional interventions.