Preoperative malnutrition is associated with increased postoperative complications following lumbar fusion: a propensity-matched analysis

Introduction

Lumbar fusion (LF) is a common surgical intervention used to manage a variety of spinal conditions, including degenerative disc disease, spondylolisthesis, and spinal instability (1). While effective for improving pain and function in select patients, LF is also associated with significant short- and long-term risks, including surgical site infection, pseudoarthrosis, readmission, and the need for revision procedures (2). Given the increasing demand for spine surgery in aging and medically complex populations, optimizing preoperative risk factors is essential to improving outcomes and reducing healthcare utilization.

One increasingly recognized yet under-addressed modifiable risk factor is preoperative malnutrition. Malnutrition is associated with impaired wound healing, increased susceptibility to infection, and reduced physiologic reserve (3-6). Malnutrition is a multidimensional syndrome involving inadequate energy intake, weight loss, changes in body composition, and diminished functional status. Validated screening tools, including the Malnutrition Universal Screening Tool (MUST), Nutritional Risk Screening 2002 (NRS2002), and the Subjective Global Assessment (SGA) integrate anthropometric measures, weight loss, and dietary intake to improve sensitivity for identifying highrisk patients (7). It is typically quantified using surrogate laboratory markers, including serum albumin and total leukocyte count, which reflect nutritional and immunologic status, respectively (3,4,8,9). Though malnutrition has been strongly linked to increased morbidity across multiple surgical subspecialties, including general, oncologic, and arthroplasty populations, it remains poorly defined and underexplored in the spine literature (9-11).

Existing studies investigating malnutrition in spine surgery are limited by small sample sizes, heterogenous definitions of nutritional status, and lack of long-term follow-up. Most have relied on retrospective chart review without adequate adjustment for confounding variables such as comorbid burden, obesity, or surgical approach. Furthermore, malnutrition is often viewed as an end-stage consequence of severe systemic disease; however, emerging data suggest that even moderate nutritional deficiencies, particularly when chronic or uncorrected, may significantly influence surgical recovery and complication risk (12,13).

In the context of LF, where outcomes are already influenced by multifactorial biomechanical, metabolic, and patient-level factors, the presence of malnutrition may exacerbate healing complications and undermine fusion integrity (4-6). Yet, malnutrition remains excluded from most current risk calculators and perioperative optimization protocols (14,15). As healthcare systems shift toward value-based care and bundled payment models, identifying high-risk patients for targeted preoperative intervention has become increasingly critical.

This study aims to evaluate the association between preoperative malnutrition and postoperative complications in patients undergoing LF using a large, real-world, multicenter cohort. We define malnutrition based on clinically validated laboratory thresholds (albumin <3.5 g/dL or leukocytes <1,500/mm³) measured within 1 year prior to surgery. Using 1:1 propensity score matching across demographic, clinical, and procedural variables, we compare both short-term (90-day) and long-term (5-year) outcomes between malnourished and non-malnourished patients. We hypothesize that preoperative malnutrition will be independently associated with increased postoperative complications, including reoperation, infection, and readmission, thereby underscoring the importance of nutritional screening and optimization in the LF population. We present this article in accordance with the STROBE reporting checklist (available at https://jss.amegroups.com/article/view/10.21037/jss-25-150/rc).

Methods

Patient selection

We conducted a retrospective cohort study using the TriNetX US Collaborative Network, a real-world, federated health research platform that aggregates de-identified electronic medical records from more than 90 large healthcare organizations across the United States. Data available through TriNetX include demographic information, diagnoses, procedures, medications, and laboratory values. All queries for this study were executed on April 10, 2025. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

We identified adult patients who underwent LF surgery between January 1, 2003, and January 31, 2023. LF was defined using the following Current Procedural Terminology (CPT) codes: 22558 (anterior interbody technique), 22612 (posterior or posterolateral technique), 22630 (posterior interbody technique), and 22633 (combined posterior or posterolateral with posterior interbody technique). Patients were included if they had at least one qualifying fusion procedure and a minimum of 1 year of follow-up after the index operation.

Patients were then stratified based on nutritional status prior to surgery. Because TriNetX lacks uniform anthropometric data or validated screening scores, we defined malnutrition using laboratory surrogates: a serum albumin level <3.5 g/dL or a leukocyte count <1,500/mm³ measured within 365 days before surgery. Although these markers are commonly used as indicators of protein-calorie deficiency and immune status, they are influenced by inflammation, hydration and comorbid conditions (16). We selected these cut-offs to align with prior database studies investigating the effects of malnutrition. Patients meeting either criterion were included. The comparison cohort consisted of patients undergoing LF who had no laboratory evidence of malnutrition within the same preoperative time window. A total of 52,671 patients met inclusion criteria for the malnutrition cohort and 21,454 for the non-malnutrition cohort. After propensity score matching, 20,693 patients remained in each group for analysis (Figure 1).

Figure 1 Flow diagram illustrating patient selection from the TriNetX US Collaborative Network (2003–2023), including inclusion and exclusion criteria, cohort stratification by nutritional status, and 1:1 propensity score matching between malnourished and non-malnourished patients undergoing lumbar fusion.

Outcomes evaluated

We assessed both short-term (90-day) and long-term (5-year) postoperative outcomes. The 90-day outcomes included anemia, complications of surgical care, myocardial infarction (MI), postoperative infection, pulmonary embolism (PE), deep vein thrombosis (DVT), stroke, hospitalization, pneumonia, transfusion, acute renal failure, emergency department (ED) visits, opioid use, wound complications, and sepsis. Long-term outcomes were assessed using Kaplan-Meier survival estimates and included pseudoarthrosis, adjacent segment disease, instrumentation removal, repeat LF, revision surgery, foot drop, compression fractures, long-term surgical site infection, and all-cause mortality.

Procedural and diagnostic events were identified using CPT and International Classification of Diseases-10-Clinical Modification/Procedure Coding System (ICD-10-CM/PCS) codes which are listed in the provided Table S1. Event timing was calculated relative to the index LF date. Survival-based outcomes were censored at 5 years postoperatively. All outcomes were assessed in both unmatched and propensity-matched cohorts.

Statistical analysis

All statistical analyses were performed using the built-in analytic tools within the TriNetX platform. Descriptive statistics were reported as means with standard deviations (SDs) for continuous variables and counts with percentages for categorical variables. Baseline differences between cohorts were assessed using independent-sample t-tests and Chi-squared tests, respectively.

To account for baseline differences, 1:1 propensity score matching was performed using a greedy nearest-neighbor algorithm with a caliper of 0.01 pooled SDs of the logit of the propensity scores. Covariates included in the matching model were age, sex, race, body mass index (BMI), and comorbidities [hypertension, heart failure, liver disease, chronic kidney disease (CKD), obesity, type 1 and type 2 diabetes, osteoporosis with and without fracture], as well as surgical approach and preoperative metformin use. All matched cohorts showed a standardized mean difference (SMD) of less than 0.1 for each matched covariate.

Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models for survival-based outcomes. A two-sided P value <0.05 was considered statistically significant for all analyses.

Results

Baseline characteristics

After propensity score matching, each cohort comprised 20,693 patients: those undergoing LF with preoperative malnutrition and those without. Malnutrition was defined as albumin <3.5 g/dL or leukocyte count <1,500/mm³ obtained within 1 year prior to surgery. Baseline characteristics were well balanced between groups (Table 1). The mean age was 59.6 (SD 14.5) years in the malnourished cohort and 59.7 (SD 14.5) years in the non-malnourished group (P=0.43). Female sex represented 54.8% of the malnourished group and 55.3% of controls (P=0.29). BMI was similar [29.5 (SD 6.4) vs. 29.8 (SD 6.1) kg/m², P=0.48]. Surgical technique distributions were comparable, though anterior lumbar interbody fusion (ALIF) was more common among malnourished patients (18.0% vs. 12.0%, P<0.001). Comorbidities such as hypertension, diabetes, CKD, and osteoporosis were evenly distributed after matching (all P>0.05).

Five-year outcomes

At 5 years postoperatively, patients with preoperative malnutrition experienced higher rates of numerous complications (Table 2). Pseudoarthrosis occurred in 25.8% of malnourished patients compared to 20.5% in controls (HR 1.32, 95% CI: 1.26–1.38, P<0.001). Revision LF was also more common in the malnourished group (12.7% vs. 9.3%, HR 1.40, 95% CI: 1.32–1.49, P<0.001). Instrumentation removal occurred in 4.2% vs. 3.5% (HR 1.21, 95% CI: 1.10–1.34, P<0.001), and revision surgery in 16.2% vs. 11.9% (HR 1.41, 95% CI: 1.34–1.49, P<0.001). Foot drop (2.8% vs. 1.9%, HR 1.54, 95% CI: 1.35–1.76, P<0.001), compression fractures (5.8% vs. 3.7%, HR 1.60, 95% CI: 1.46–1.76, P<0.001), and long-term surgical site infections (1.4% vs. 0.9%, HR 1.47, 95% CI: 1.22–1.77, P<0.001) were also significantly elevated.

Interestingly, all-cause 5-year mortality was lower in the malnourished cohort (4.3% vs. 5.8%, HR 0.75, 95% CI: 0.69–0.82, P<0.001), possibly reflecting selection bias, survivorship effects, or healthcare utilization patterns.

Ninety-day outcomes

Short-term outcomes at 90 days demonstrated consistent trends (Table 3). Transfusion was required in 8.4% of malnourished patients compared to 4.5% of controls (HR 1.87, 95% CI: 1.73–2.02, P<0.001). Surgical complications were more frequent (9.1% vs. 6.6%, HR 1.39, 95% CI: 1.30–1.48, P<0.001), as were wound complications (2.6% vs. 1.5%, HR 1.70, 95% CI: 1.48–1.95, P<0.001). Hospital readmissions occurred in 17.3% vs. 13.8% (HR 1.26, 95% CI: 1.20–1.32, P<0.001), and ED visits in 10.6% vs. 8.5% (HR 1.25, 95% CI: 1.18–1.33, P<0.001). Opioid use was nearly ubiquitous in the malnourished group (92.1% vs. 78.3%, HR 1.18, 95% CI: 1.17–1.19, P<0.001).

Malnourished patients were also at higher risk for infection (3.2% vs. 2.3%, HR 1.37, 95% CI: 1.22–1.54, P<0.001), renal failure (2.1% vs. 1.8%, HR 1.21, 95% CI: 1.06–1.39, P=0.006), and ED utilization. Foot drop occurred more often (0.7% vs. 0.4%, HR 1.64, 95% CI: 1.26–2.15, P<0.001), and compression fractures were elevated (2.0% vs. 1.2%, HR 1.72, 95% CI: 1.47–2.03, P<0.001). Revision surgery (4.2% vs. 2.8%, HR 1.52, 95% CI: 1.37–1.69, P<0.001) and repeat LF (3.5% vs. 2.2%, HR 1.56, 95% CI: 1.39–1.76, P<0.001) were also more frequent in the malnourished cohort.

Conversely, several outcomes occurred less frequently among malnourished patients. MI (0.5% vs. 0.8%, HR 0.63, 95% CI: 0.50–0.81, P<0.001), stroke (0.4% vs. 0.7%, HR 0.60, 95% CI: 0.46–0.79, P<0.001), pneumonia (1.2% vs. 1.5%, HR 0.83, 95% CI: 0.70–0.97, P=0.02), and 90-day mortality (0.2% vs. 0.4%, HR 0.39, 95% CI: 0.26–0.57, P<0.001) were all significantly reduced. There were no statistically significant differences in DVT (HR 0.92, 95% CI: 0.80–1.06, P=0.26) or sepsis (HR 1.20, 95% CI: 0.52–2.78, P=0.67).

Discussion

Preoperative malnutrition has long been recognized as a risk factor for adverse surgical outcomes, yet its specific impact on LF, has remained poorly characterized. In this large, multicenter, propensity-matched cohort study, we demonstrate that malnutrition, as defined by either hypoalbuminemia or leukopenia within 1 year prior to LF, is independently associated with increased postoperative complications at both 90-day and 5-year follow-up. These complications include higher rates of surgical site infection, wound complications, pseudoarthrosis, transfusion, hospital readmission, revision surgery, opioid dependence, and multiple secondary complications (Tables 2,3). Our findings align with and expand upon existing literature, reinforcing the concept that nutritional status exerts a profound influence on surgical morbidity in spine patients (6).

Importantly, our analysis highlights that nearly every clinically meaningful 90-day complication was significantly more common in malnourished patients. These include higher rates of anemia, surgical complications, transfusion, infection, pneumonia, renal failure, sepsis, ED visits, hospital readmissions, and prolonged opioid use (Table 3). From a perioperative risk standpoint, complications such as transfusion, surgical site infection, wound complications, and unplanned readmissions are particularly clinically significant, as they directly influence immediate recovery, healthcare cost, and patient safety. Meanwhile, others like sepsis and renal failure, though less frequent, are unexpected and potentially catastrophic. These complications represent not only key quality metrics but also major contributors to patient morbidity and healthcare cost. Spine surgeries, particularly LFs, are among the most resource-intensive orthopedic procedures, and increased rates of early complications can disrupt recovery trajectories and delay return to function (17).

Similarly, the 5-year outcomes, often the focus of long-term spine surgery follow-up, can be categorized into those reflecting surgical failure and those indicating systemic or neurologic complications. Surgical failure-related outcomes such as pseudoarthrosis, revision LF, and instrumentation removal were significantly more common in malnourished patients (Table 2), indicating impaired healing and construct durability. Meanwhile, complications like foot drop and surgical site infection may reflect systemic vulnerability or perioperative management challenges. This distinction is critical for guiding both surgical planning and postoperative monitoring strategies. Pseudoarthrosis, observed in 25.8% of malnourished patients compared to 20.5% of controls (HR 1.32), is a particularly devastating failure with well-documented consequences on patient-reported outcomes, disability, and pain. Similarly, revision surgery (HR 1.41) and adjacent segment disease (HR 0.82, indicating lower incidence likely due to earlier failure modes) further reinforce the link between systemic vulnerability and local surgical breakdown.

A deeper pathophysiological understanding helps contextualize these outcomes. Hypoalbuminemia reflects both protein-calorie malnutrition and systemic inflammation, impairing fibroblast proliferation, collagen synthesis, angiogenesis, and immune response, processes critical to wound healing and bone fusion (4,18-20). Beyond serving as a nutritional surrogate, hypoalbuminemia represents a systemic inflammatory and endothelial dysfunction state rather than an isolated representation of malnutrition (21,22). Thus, patients presenting with preoperative hypoalbuminemia enter surgery in a pro-inflammatory state, which disrupts the normal, sequential inflammatory response required for effective postoperative healing (22). During the wound healing process, Pro-inflammatory cytokines such as platelet-derived growth factor (PDGF), interleukin (IL)-6, and vascular endothelial growth factor (VEGF) are highly expressed, increasing the permeability of the capillary endothelium and allowing the release of albumin into the tissue interstitium (22). When in the interstitium, albumin acts as a potent antioxidant and, to a limited extent, supplies protein precursors for the wound healing process (22). The link shown between hypoalbuminemia and worse post-operative outcomes may be attributed to a decrease in the body’s ability to combat reactive oxygen species (ROS), leading to prolonged, excessive oxidative stress at the site of the wound (23). ROS play an essential role in the early stages of wound healing by promoting microbial defense and initiating inflammatory signaling. However, excessive or prolonged ROS activity disrupts angiogenesis, extracellular matrix (ECM) formation, and keratinocyte proliferation and migration (23). In addition, ROS have been shown to stimulate the differentiation of osteoclast precursors into mature osteoclasts while simultaneously exerting pro-apoptotic effects on osteoblasts and osteocytes, thereby shifting bone metabolism toward chronic resorption (24). This proposed mechanism may account for the increased incidence of pseudoarthrosis observed in the malnourished cohort. Albumin is also essential for drug transport, oncotic balance, and detoxification, and its depletion has been linked to capillary leakage, impaired tissue perfusion, and susceptibility to infection. Similarly, leukopenia may signal underlying immunosuppression or bone marrow dysfunction, limiting host defense against pathogens and increasing infection risk. Recruitment of neutrophils and macrophages to the fracture or fusion site is critical for clearing necrotic tissue, producing pro-inflammatory cytokines, and recruiting mesenchymal stem cells and osteoprogenitors that form the callus and new bone (25,26). Leukopenia limits this initial inflammatory response and increases the risk of infection (27). These mechanisms likely contribute to our observed increases in surgical site infection (HR 1.47), wound complications (HR 1.70), and transfusion needs (HR 1.87).

Experimental studies in animal models corroborate these findings, demonstrating that malnutrition delays callus formation, reduces mineral apposition, and impairs osteoblastic differentiation (28,29). Thus, our findings not only confirm clinical associations but are mechanistically plausible.

Transfusion needs (8.4% vs. 4.5%) also support a biologic explanation: poor erythropoietin response, reduced marrow reserve, and impaired hemostasis are all hallmarks of chronic nutritional compromise. These elements may exacerbate intraoperative blood loss or impair compensatory mechanisms. Anemia and malnutrition frequently coexist, and their combination has been shown to synergistically worsen postoperative outcomes (30,31).

The implications extend to pain management as well. Opioid use within 90 days of surgery was markedly more common in malnourished patients (92.1% vs. 78.3%, HR 1.18), suggesting that poor nutritional status may be associated with heightened postoperative pain perception, altered pharmacokinetics, or delayed recovery. Malnutrition-induced neuroinflammation and cytokine dysregulation may sensitize central and peripheral pain pathways. Chronic opioid exposure following spine surgery has been independently linked to increased length of stay, worse functional outcomes, and prolonged disability (32-35), and our findings point to nutrition as a potential upstream modifier of this trajectory.

A paradoxical finding in our study was the lower incidence of MI, stroke, pneumonia, and mortality in malnourished patients (Tables 2,3). These counterintuitive results are likely attributable to survivorship and selection bias introduced by the study’s cohort design. To be included in our analysis, patients were required to have at least 90-day (for short-term outcomes) or 1-year (for long-term outcomes) postoperative follow-up. Severely malnourished individuals may not be offered elective fusion or may succumb to early catastrophic events before the 90-day inclusion window and would have been excluded from the final analytic cohort due to lack of sufficient follow-up, creating an immortal-time effect. As such, the malnourished patients who remained for inclusion represent a healthier, survivor subset with inherently lower risk of these outcomes. Moreover, malnourished patients who do undergo surgery may receive heightened perioperative surveillance, prophylaxis, or more conservative indications, leading to lower observed rates of cardiopulmonary events. Therefore, our mortality findings should be interpreted cautiously. This immortal time bias artificially reduces the incidence of high-severity events in the malnourished group and highlights a key limitation in retrospective database studies using mandatory follow-up thresholds.

Our findings should also be interpreted with additional limitations in mind. First, our operational definition of malnutrition, based on serum albumin and leukocyte count, may not capture the full spectrum of nutritional deficiency. While these metrics are validated and widely used (3,4,8,9,19), they do not reflect other important variables such as vitamin deficiencies, sarcopenia, or micronutrient status. Second, the use of laboratory values from up to 365 days before surgery may not accurately reflect nutritional status at the time of the operation. However, this mirrors real-world clinical workflows in which repeat labs may not be routinely obtained preoperatively. Third, residual confounding may remain despite matching, particularly regarding unmeasured factors such as frailty, smoking status, socioeconomic position, or functional capacity. Frailty has been shown to synergize with malnutrition to predict major complications after thoracolumbar fusion (36). Socioeconomic factors such as net worth and home ownership are associated with readmission and complications (37), and smoking increases the risk of pseudoarthrosis and infection following spinal fusion (38). These variables, while clinically relevant, are not available in TriNetX and may confound our results and their interpretation. Fourth, although our cohort is large, the TriNetX network predominantly comprises U.S. academic centers, and baseline nutrition, socioeconomic conditions, and perioperative protocols may vary in community hospitals or internationally; therefore, caution is warranted when extrapolating these findings to other healthcare settings. For example, baseline malnutrition prevalence varies in different regions across the globe. Healthcare access and postoperative rehabilitation resources differ substantially as well, which can drastically affect complication rates. Future studies in diverse international cohorts are needed to confirm the generalizability of these findings and to tailor nutritional screening and intervention strategies to specific populations. Lastly, as with all real-world evidence studies relying on Electronic Health Record (EHR)-derived datasets, inaccuracies in coding or data entry may contribute to misclassification.

Taken together, our findings demonstrate that malnutrition is not only associated with a wide array of short- and long-term postoperative complications, but also contributes to increased resource utilization, poorer healing, and prolonged recovery in the LF population. Despite these limitations, this study provides compelling evidence that preoperative malnutrition is a significant and modifiable risk factor in patients undergoing LF. Nutritional assessment is rarely included in modern surgical risk calculators for spine surgery (14,15), yet our findings support its integration into routine preoperative workups. Previous evidence also supports nutritional interventions: a 2023 randomized controlled trial found that patients receiving perioperative protein supplementation showed significantly lower rates of in-hospital minor complications (2.1% vs. 23.2%), wound healing complications (3.4% vs. 17.9%), regardless of preoperative nutritional status. A subgroup analysis of malnourished patients demonstrated that nutritional intervention had significantly lower rates of minor complications during admission (0% vs. 34.4%) and return to the operating room within 90 days (0% vs. 12.4%) (20). Early identification of at-risk patients and timely nutritional intervention, such as dietary counseling, protein supplementation, or referral to a nutrition specialist, may provide a cost-effective strategy to improve surgical outcomes and reduce complications.

The potential impact of addressing malnutrition extends beyond the individual patient level. As healthcare systems increasingly embrace bundled payments and episode-based reimbursement for spine procedures, preventable complications like infection, pseudoarthrosis, and unplanned readmissions may trigger financial penalties. Integrating preoperative nutritional screening and intervention into enhanced recovery after surgery (ERAS) pathways or perioperative surgical home models may improve patient outcomes while also reducing institutional costs. Prospective trials evaluating nutritional supplementation protocols in spine surgery patients, particularly those with laboratory evidence of risk, are urgently needed to confirm whether these strategies can translate into meaningful clinical and economic benefits.

Future directions should include prospective interventional studies evaluating whether nutritional optimization leads to improved fusion rates, reduced infection, and fewer reoperations. Further, incorporating comprehensive nutritional screening tools such as the SGA or Mini Nutritional Assessment (MNA) into routine preoperative pathways could enhance risk prediction and targeted care.

Conclusions

Preoperative malnutrition, defined by hypoalbuminemia or leukopenia, was independently associated with increased perioperative morbidity and compromised long-term outcomes following LF. Malnourished patients experienced higher rates of transfusion, wound complications, infection, readmission, pseudoarthrosis, revision surgery, and compression fractures compared with matched controls. These findings highlight the need for routine nutritional assessment and optimization in the preoperative evaluation of LF candidates. Targeted nutritional interventions may mitigate complications and improve surgical success, and future research should investigate whether correcting malnutrition before surgery reduces adverse outcomes.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jss.amegroups.com/article/view/10.21037/jss-25-150/rc

Peer Review File: Available at https://jss.amegroups.com/article/view/10.21037/jss-25-150/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jss.amegroups.com/article/view/10.21037/jss-25-150/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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