Cochrane in CORR®: Nutritional Supplementation for Hip Fracture Aftercare in Older People

Importance of the Topic Hip fractures are one of the most-common reasons for hospital admission and are a substantial source of morbidity and mortality among older patients [5, 6, 12, 16]. Less than half of patients with hip fractures return to their prefracture functional status [17]. As the incidence of hip fractures continues to increase in most Western countries—a trend that parallels the increasing average age of the population—the annual cost of care for patients with hip fractures in the United States is expected to exceed USD 16 billion by the year 2040 [7, 11]. Given the substantial associated mortality, morbidity, and costs, improving outcomes following hip fractures is of great interest. At hospital admission, patients with a hip fracture often present with frailty and poor nutritional status—including inadequate nutritional intake, low BMI, and reduced skeletal muscle mass—which can deteriorate further due to the physical and psychological burden of hospitalization and surgery [3, 4, 14, 15]. Malnutrition may then lead to increased risk for mortality and morbidity and can jeopardize recovery [1, 8]. Nutritional interventions, such as oral, nasogastric, or intravenous supplementation with increased energy, protein, and vitamins and minerals, shortly following a hip fracture, may improve recovery. However, the effectiveness of these interventions is unknown. In their Cochrane Review (see Appendix, https://links.lww.com/CORR/A136), Avenell and colleagues [2] reviewed a total of 41 randomized trials including 3881 patients to determine the efficacy of nutritional supplementation for reducing mortality, complications (such as wound infections, pressure sores, and deep venous thromboses), and unfavorable outcomes (defined as a composite of mortality and complications) following hip fractures. Oral supplementation generally began either just before surgery or within 2 days postoperatively and continued for at least 1 month, whereas nasogastric supplementation generally began within 5 days of surgery and continued until oral intake was sufficient or hospital discharge. Upon Closer Inspection The review did not find evidence that multinutrient supplementation reduces the risk of death after hip-fracture surgery but found that it may reduce complications (relative risk [RR], 0.69, 99% CI, 0.59-0.81) and unfavorable outcomes (RR, 0.67, 99% CI, 0.51-0.89), though the evidence was low- to very low-quality. The authors conducted a subgroup analysis to test whether the effects of multinutrient supplementation differed based on route of administration. The authors found a reduction in complications and unfavorable outcomes for oral supplementation but not for nasogastric supplementation, which was found to be poorly tolerated. The authors also found a reduction in unfavorable outcomes with high-protein supplementation (RR, 0.78, 99% CI, 0.65-0.95). The review only found one small trial (318 participants) on dietetic assistance—a much more intensive and expensive intervention compared to nutritional supplementation. The trial reported reduced mortality with dietetic assistance (RR, 0.57, 95% CI, 0.34-0.95), although these results are highly questionable [9]. The observed effect size is much larger than would be reasonably expected, given the nature of the population and intervention, and is likely inflated because of risk of bias. There was insufficient evidence to conclude whether vitamin, iron, or taurine supplementation impact outcomes. The authors did not conduct subgroup analyses based on type of fracture or surgery. The results of this review are limited by the reporting of composite outcomes, such as complications and unfavorable outcomes. Composite outcomes are combinations of multiple endpoints and can be challenging to interpret if the components of the composite vary in degree of severity or clinical importance. In general, composite endpoints that pool minor events (such as deep-vein thromboses, most of which do not result in lasting harm) with major ones (like death, which always does) may mask important differences in effects across components of the composite. Combining dissimilar outcomes, as was likely done here, increased the statistical power of this meta-analysis to detect between-group differences, but did so by lumping together dissimilar entities that should really be considered separately (such as potentially minor complications with death, in the case of this meta-analysis). Hence, the effects reported in this review may have been driven by trivial components of the composite rather than outcomes that are of direct importance to patients and clinicians. Using the grading of recommendations assessment, development and evaluation (GRADE) system [10], the authors rated the certainty of evidence as low or very low—meaning that the true effects of nutritional supplementation may be substantially different from the estimated effects, primarily because primary studies were at high risk of bias. Most studies were at high or unclear risk of bias for randomization and allocation concealment, blinding of participants, and incomplete outcome data [13]. While these biases may lead to over or underestimation of effects, they most often lead to overestimation. Other reasons for rating down the certainty of evidence included imprecision (small trials with few events) and inconsistency (trials reported varied results). Take-home Messages The review presents insufficient evidence to guide a change in practice because of the poor quality of the underlying evidence. However, oral nutritional supplementation and dietetic assistance represent low-risk interventions that may improve morbidity and mortality. Although dietetic assistance is costly, oral nutritional supplementation by itself may be cost-effective; further evidence on its effectiveness and cost-effectiveness are needed. Additional randomized trials are needed to further elucidate the effects of nutritional supplementation on mortality and morbidity following hip fractures. Ideally, such trials should be large and adequately powered to detect differences in mortality and morbidity and be sufficiently blinded to protect against performance and measurement biases. Furthermore, future trials may also focus on comparing different formulations and durations of multinutrient supplementation, as supplementation is likely to exert different effects depending on its macronutrient and micronutrient content and the duration for which it is administered.

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