2.1 Study design

This study was conducted as a systematic review and meta-analysis to evaluate the association between preoperative serum fructosamine levels and postoperative complications following arthroplasty and other orthopaedic procedures. This study was conducted using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) with ID: CRD420251170735.

2.2 Search strategy

A systematic literature search was performed in PubMed, Embase, and Scopus from inception to September 2025. The search strategy was MeSH terms separated by Boolean operators as: (((fructosamine) OR (fructosamines) OR (glycated albumin) OR (glycated protein)) AND ((arthroplasty) OR (joint replacement) OR (knee arthroplasty) OR (hip arthroplasty) OR (total knee replacement) OR (total hip replacement))). Reference lists of included studies and relevant reviews were screened for additional eligible articles. Two independent reviewers (AR, BBN) screened titles and abstracts, followed by full-text review to determine eligibility, with discrepancies resolved through discussion (Fig. 1).

Close

Fig. 1 PRISMA 2020 flow diagram showing the study selection process.

Export to PPT

2.3 Eligibility criteria

Studies were eligible if they involved adult patients undergoing arthroplasty and other orthopaedic surgery and reported preoperative serum fructosamine measurements along with postoperative outcomes related to infection or wound complications. Both prospective and retrospective cohort studies were considered if they provided sufficient data to estimate risk measures. Studies not reporting relevant clinical outcomes, reviews, case reports, or non-English publications were excluded.

2.4 Data extraction

Data were independently extracted by two reviewers (AR, AS) using a standardized form. Extracted information included study characteristics (author, year, country, study design, surgical procedure, sample size, and follow-up duration), patient demographics (age, prevalence of diabetes), biomarker details (fructosamine, HbA1c, GA, assay methods, and thresholds), and clinical outcomes (infection, wound complications, readmission, or reoperation). Any discrepancies were resolved by discussion with the senior author (VKJ).

2.5 Outcome assessments

The primary outcome of interest was postoperative infection, including periprosthetic joint infection and surgical site infection. Secondary outcomes included wound complications, readmission, and reoperation. Definitions were taken as reported by the individual studies. Comparative assessment with other biomarkers (HbA1c and GA) was also captured when reported.

2.6 Risk-of-bias (RoB) assessment

Methodological quality and risk of bias were assessed using the Newcastle–Ottawa Scale (NOS) for cohort studies. Each study was evaluated across selection, comparability, and outcome domains, and categorized as good, fair, or poor quality based on the NOS scoring system.

2.7 Statistical analysis

Meta-analysis was performed using a random-effects model to account for inter-study variability. Dichotomous outcomes were expressed as risk ratios (RR) with 95% confidence intervals. Heterogeneity was quantified using the I² statistic, with values above 50% considered substantial. Sensitivity analyses were planned based on procedure type, biomarker threshold, and diabetes prevalence to explore potential sources of heterogeneity. Statistical analyses were conducted using Review Manager (RevMan 5.4).

2.8 Ethical considerations

This study was based entirely on previously published, de-identified data. As such, ethical approval and patient consent were not required.

3.1 Study selection and characteristics

A total of seven studies (six arthroplasty and one non-arthroplasty) published between 2017 and 2025 were included in the final analysis.^8–14 In total, it comprises 5217 patients who underwent various orthopaedic procedures, predominantly total hip arthroplasty (THA) and total knee arthroplasty (TKA). Most studies were prospective cohort designs,^8–13 while one used a mixed retrospective–prospective approach.¹⁴

Sample sizes ranged from 304 to 1,212, and the proportion of diabetic patients varied widely (9.2–51%). The mean age across arthroplasty cohorts ranged between 63 and 66 years, while the foot and ankle cohort reported a mean age of 50.8 years.¹² Preoperative optimisation protocols were uniformly implemented, and follow-up durations varied from 90 days to 32 months. Using the Newcastle–Ottawa Scale, five studies were rated as good quality,^8–11,13 and two were rated as fair quality.^12,14 (Table 1)

3.2 Biochemical assessment and testing details

All included studies measured serum fructosamine levels, and six also assessed HbA1c as a comparator biomarker. One recent study additionally evaluated GA.¹³ Fructosamine was measured using spectrophotometric or colorimetric assays,^8–12 while HbA1c was determined by HPLC methods in most studies.

Testing was typically performed within 2–4 weeks before surgery, except in multicenter protocols where “preoperative” timing was variably defined. The fructosamine cut-off thresholds predictive of complications ranged from 238.5 μmol/L in foot and ankle surgery,¹² to 292–293 μmol/L in arthroplasty cohorts.^8,11 Corresponding HbA1c cut-offs were 7–8%. No study found an incremental predictive benefit with albumin-corrected fructosamine.⁸ (Table 2)

3.3 Clinical outcomes

All studies reported postoperative complications as primary or secondary outcomes, most commonly periprosthetic joint infection (PJI) or composite wound-related events. Across all cohorts, elevated fructosamine levels were consistently associated with increased postoperative complications;¹¹

first demonstrated that patients with fructosamine ≥292 μmol/L had a sixfold increased risk of deep infection (adjusted OR 6.2, 95% CI 1.6–24.0, p = 0.009), while HbA1c ≥ 7% was not predictive (p > 0.1).¹¹

In a multicenter expansion, Shohat et al. (2019) confirmed a strong association between elevated fructosamine and PJI (adjusted OR 16.26, 95% CI 4.1–64.4, p < 0.001), with similar trends for readmission (OR 4.62, p = 0.01).⁹ Shohat et al. (2021) extended these findings to THA patients, showing fructosamine ≥293 μmol/L independently predicted PJI (adjusted OR 6.37, 95% CI 1.98–20.49, p = 0.002) and readmission (OR 2.68, p = 0.023), whereas HbA1c remained non-significant.¹⁰

Cetik et al. (2023) corroborated these results in a Turkish multicenter cohort, where fructosamine ≥292 μmol/L was associated with a higher risk of PJI (adjusted OR 13.68, p = 0.025) and overall complications (adjusted OR 3.61, p = 0.001).⁸ In a non-arthroplasty setting, Suh et al. (2024) reported that fructosamine ≥238.5 μmol/L predicted composite wound complications (OR 3.27, p = 0.005).¹²

Tischler et al. (2024) observed that elevated fructosamine correlated with higher perioperative comorbidity burden (ASA ≥3, OR 9.0, p = 0.04).¹⁴ Finally, Tarabichi et al. (2025) incorporated GA as a novel marker; GA ≥ 17.1% predicted 90-day complications (OR 4.82, p = 0.011), whereas fructosamine ≥270 μmol/L did not reach significance (p = 0.51).¹³ Overall, HbA1c was a less reliable predictor of infection, readmission, or reoperation compared to fructosamine (Table 3).

3.4 Subgroup analysis

Subgroup synthesis indicated that high fructosamine (≥292–293 μmol/L) consistently predicted higher infection risk across THA, TKA, and combined arthroplasty populations.^8–11 The strongest association was observed in TKA-only cohorts (Shohat et al., 2019; adjusted OR 16.26), followed by THA cohorts (Shohat et al., 2021; adjusted OR 6.37).^9,10

The single non-arthroplasty study showed a comparable risk elevation (OR 3.27–4.14), supporting the potential generalizability of fructosamine as a short-term glycemic marker in orthopaedic surgery.¹² Albumin-corrected fructosamine offered no additional predictive value,⁸ whereas GA emerged as a promising biomarker for future validation.¹³ (Table 4)

When stratified by biomarker thresholds, patients with high fructosamine levels consistently exhibited higher postoperative event rates compared with those with normal levels.^8–14 In Shohat's series (2017–2021), infection incidence in high fructosamine groups ranged between 7.1% and 9.3%, versus ∼1% in normal groups.^9–11 For HbA1c, differences between high and low categories were less pronounced and often not statistically significant, confirming the superior discriminatory capacity of fructosamine.

3.5 Meta-analysis

3.5.1

3.5.1 High vs. low fructosamine

Data from seven studies including 655 high-fructosamine and 4562 low-fructosamine subjects were pooled using a random-effects Mantel–Haenszel model.^8–14 The analysis showed that elevated fructosamine was associated with a significantly increased risk of postoperative infection or complication (pooled RR = 7.20; 95% CI 1.49–34.91; p < 0.05). Substantial heterogeneity was observed (I² = 91%, p < 0.01), indicating variability in study populations and procedural types (Fig. 2).

Close

Fig. 2 Forest plot comparing postoperative infection or complication risk in patients with high versus low preoperative fructosamine. Data from seven studies (655 high, 4562 low) were pooled using a random-effects Mantel–Haenszel model. Elevated fructosamine was associated with increased risk (RR = 7.20; 95% CI 1.49–34.91; p < 0.05) with substantial heterogeneity (I² = 91%).

Export to PPT

3.5.2

3.5.2 High vs. low HbA1c

Six studies encompassing 797 high HbA1c and 4000 low HbA1c patients demonstrated a modest but significant increase in risk (pooled RR = 2.36; 95% CI 1.04–5.34; p < 0.05)0.^8–13 Heterogeneity remained high (I² = 80%, p < 0.01) (Fig. 3).

Close

Fig. 3 Forest plot comparing postoperative risk in patients with high versus low preoperative HbA1c. Six studies (797 high, 4000 low) were analysed. High HbA1c conferred a modest but significant risk (RR = 2.36; 95% CI 1.04–5.34; p < 0.05), with substantial heterogeneity (I² = 80%).

Export to PPT

3.5.3

3.5.3 High fructosamine vs. high HbA1c

In six studies directly comparing elevated fructosamine and HbA1c cohorts, the pooled estimate indicated no statistically significant difference (RR = 0.98; 95% CI 0.42–2.33; p > 0.05)0.^8–13 However, marked heterogeneity persisted (I² = 76%, p < 0.01). These findings suggest that both markers identify high-risk patients, but fructosamine more accurately reflects short-term glycemic control in the perioperative period (Fig. 4).

Close

Fig. 4 Forest plot comparing postoperative risk between high fructosamine and high HbA1c cohorts. Six studies (589 fructosamine, 797 HbA1c) showed no significant difference (RR = 0.98; 95% CI 0.42–2.33; p > 0.05), with considerable heterogeneity (I² = 76%).

Export to PPT

3.6 Quality assessment

All seven showed moderate-to-high quality on the Newcastle–Ottawa Scale (7–9/9)0.^8–14 Most were prospective cohorts with low risk of selection and outcome bias, though comparability was limited by incomplete adjustment for diabetes and nutritional confounders. Overall, methodological quality supports confidence in the observed association between elevated fructosamine and increased postoperative complication risk (Table 5).

3.7 Summary of evidence

Collectively, the evidence indicates that fructosamine is a robust short-term biomarker for predicting postoperative infections and wound complications following arthroplasty and other orthopaedic procedures. Across multiple prospective cohorts, a threshold around 292–293 μmol/L consistently stratified high-risk patients undergoing arthroplasty,^8–12 while lower thresholds (∼238 μmol/L) were relevant for minor or non-arthroplasty operations. Despite significant heterogeneity, the direction of effect was uniformly positive, underscoring the potential role of fructosamine as a practical and sensitive preoperative screening tool.

4.1 Principal findings

This systematic review and meta-analysis of seven cohort studies demonstrates that elevated preoperative fructosamine is consistently associated with a substantially increased risk of postoperative infection and wound-related complications across arthroplasty and other orthopaedic procedures, most robustly for arthroplasty.^8–14 Pooled analysis showed a large effect (pooled RR ≈ 7.2, 95% CI 1.49–34.91) for high versus low fructosamine, although with very high between-study heterogeneity (I² = 91%). By contrast, elevated HbA1c carried a smaller pooled risk (pooled RR ≈ 2.36, 95% CI 1.04–5.34; I² = 80%), and direct comparisons between high fructosamine and high HbA1c groups did not show a statistically significant difference (RR ≈ 0.98; 95% CI 0.42–2.33)0.^8–13 Taken together, these data indicate that fructosamine is at least as useful, and in many series more discriminating, than HbA1c for identifying patients at short-term perioperative risk.

4.2 Interpretation and comparison with prior literature

The observed superiority of fructosamine in several large prospective cohorts fits mechanistically with the different biological windows measured by the biomarkers: fructosamine reflects glycaemic control over the prior ∼2–3 weeks, whereas HbA1c reflects the prior ∼8–12 weeks.^8–11 In the perioperative context, where short-term glycaemia immediately before surgery likely drives surgical site healing and immune competence, a shorter-window marker like fructosamine may be more relevant.^9,11 The clinical studies in our review support this: fructosamine thresholds around ≈292–293 μmol/L consistently separated higher-risk arthroplasty patients,^8–11 while a lower threshold (∼238.5 μmol/L) was reported in a foot/ankle cohort, suggesting procedure-specific thresholds may be necessary.¹²

Most prior orthopaedic literature has focused on HbA1c as the routine glycaemic biomarker, with mixed associations to infection and wound complications.¹⁵ The present pooled HbA1c effect (RR ≈ 2.36) suggests some predictive value but a smaller magnitude and greater inconsistency than fructosamine. This aligns with the finding that several large cohorts reported non-significant associations for HbA1c while fructosamine remained predictive after multivariable adjustment.^16–19 Thus, our results support a growing body of evidence that fructosamine may better capture the perioperative glycaemic milieu relevant to short-term surgical outcomes.^8,10,11

Two additional biomarker observations deserve attention. First, albumin-corrected fructosamine did not improve predictive performance in the single study that evaluated it, indicating that correction for serum albumin may not meaningfully change risk stratification in this setting.⁸ Second, GA assessed by Tarabichi et al. (2025) predicted 90-day complications (GA ≥17.1%: OR 4.82, p = 0.011), whereas fructosamine ≥270 μmol/L did not in that particular cohort.¹³ GA is another short-term glycation marker (window similar to fructosamine), and these early data suggest GA may warrant further direct comparison and validation in larger, multicenter cohorts.

4.3 Sources of heterogeneity and limitations of the evidence

Important limitations temper the conclusions. Heterogeneity was substantial across pooled analyses (I² 76–91%), driven by several factors: (1) variable case-mix (THA/TKA vs foot and ankle), (2) differences in baseline diabetes prevalence across cohorts (9–51%), (3) heterogeneous biomarker cut-offs (238.5–293 μmol/L) and assay methods (spectrophotometry vs colorimetric/HPLC), (4) differences in outcome definitions and follow-up (90 days to mean 32 months), and (5) variable adjustment for confounders across multivariable models. For example, the very large effect reported by Shohat et al. in some analyses (OR up to ∼16) contrasts with more modest effects in other cohorts.^9–11 a disparity that likely reflects differences in patient selection, outcome adjudication, and sample sizes.^8,9 The single-study findings for GA and albumin correction are hypothesis-generating but require replication.

Methodological limitations across the included studies include the observational design (cohort studies), which carries a risk of residual confounding and potential selection bias. Although most studies were prospective and adjusted for relevant covariates, unmeasured factors, such as perioperative glycemic management protocols, intraoperative variables, and wound care practices, could still influence outcomes. Finally, assay standardisation for fructosamine is not universal; different laboratories and methods may yield non-identical numeric values, complicating the adoption of a single universal cut-off.

4.4 Clinical implications

Despite heterogeneity, the consistent direction of association across multiple independent cohorts suggests fructosamine is a practical, clinically actionable preoperative test for arthroplasty and other orthopaedic patients. For elective arthroplasty, a preoperative fructosamine ≳292–293 μmol/L identifies a subgroup at materially higher risk of PJI and other complications.^8–11 Because fructosamine reflects short-term control, it could be used to: (1) screen patients during the immediate preoperative window, (2) trigger short-term optimisation strategies (like tighter glycaemic control, postponement of elective surgery for targeted interventions), and (3) monitor the effectiveness of preoperative optimisation over weeks rather than months. The emergence of GA as a predictive marker suggests multiple short-window markers merit head-to-head evaluation.¹³

However, clinicians should interpret absolute numeric thresholds with caution until assays and cut-offs are harmonised. Local laboratory methods, patient populations, and the type of procedure should inform institution-specific protocols. In settings with limited access to HbA1c or where short-term glycaemic change is expected (recent medication changes, steroid exposure), fructosamine offers clear advantages.

4.5 Recommendations for future research

Future research should prioritise prospective, multicenter studies to validate standardised fructosamine cut-offs across diverse patient populations and orthopaedic procedures, using protocolized outcome definitions such as MSIS or ICM criteria for periprosthetic joint infection. Such studies would strengthen the evidence base and enhance generalizability.

Comparative studies directly evaluating fructosamine, glycated albumin, and HbA1c with harmonised assay methods are needed to clarify their relative and combined predictive value for perioperative risk stratification. This would help define the most informative glycemic markers for clinical decision-making.

Interventional trials are essential to test whether perioperative strategies guided by fructosamine, such as deferral thresholds or intensified short-term glycemic control, actually reduce infection and complication rates. Observational associations alone cannot establish clinical benefit.

Standardisation of assay methods, reporting units, and clinical cut-offs is critical to ensure that findings are reproducible and transferable across centres. Finally, cost-effectiveness analyses are warranted to assess whether routine preoperative fructosamine testing and subsequent interventions provide economic value compared with standard HbA1c-based care.

4.6 Strengths and limitations

Strengths of this systematic review and meta-analysis include a clearly defined and clinically relevant research question, rigorous methodology, and inclusion of multiple extensive prospective cohort studies, several of which were multicenter in design. The analysis benefitted from standardised extraction of outcome metrics, allowing meaningful comparison across studies, and enabled the calculation of quantitative pooled estimates for both fructosamine and HbA1c. These methodological features enhance the reliability and generalizability of the findings, providing a robust synthesis of current evidence regarding perioperative glycemic control in orthopaedic surgery.

The limitations primarily reflect those inherent to the underlying literature. All included studies were observational, with no randomised controlled trials, which introduces potential for residual confounding. In addition, there was variability in the assays used to measure fructosamine and HbA1c, as well as in the thresholds defining high versus normal levels, which limits direct comparability across studies. Substantial between-study heterogeneity was observed, reducing the precision of pooled effect estimates and necessitating cautious interpretation. Despite these limitations, the evidence base shows increasing consistency in the direction of the association between elevated fructosamine and postoperative complications, supporting the clinical relevance of the findings and underscoring the potential value of fructosamine as a preoperative risk marker.

To summarise, preoperative fructosamine is a promising short-term glycaemic biomarker that consistently identifies arthroplasty and other orthopaedic patients at higher risk of postoperative infection and wound complications, particularly around a threshold of ≈292–293 μmol/L in the arthroplasty cohort.^8–11 Fructosamine frequently outperformed HbA1c in predictive strength, likely because it captures glycaemia in the immediate preoperative period. Before routine adoption, however, assay harmonisation, prospective validation across broader populations, and interventional trials demonstrating that fructosamine-guided care improves outcomes are required.