Research progress on the predictive role of sarcopenia in the course and prognosis of inflammatory bowel disease

Imaging methods for assessing muscle mass.

Muscle mass can be assessed using DXA to evaluate the ASMM, BIA to assess the total body SMM (or limb muscle mass), and magnetic resonance imaging (MRI) or computed tomography (CT) to measure the cross-sectional muscle area of the lumbar spine. DXA can provide repeatable ASMM measurements within minutes using the same equipment and diagnostic thresholds. However, DXA equipment is not portable and cannot be widely used in community settings. Conversely, BIA is a low-cost, widely used, portable single-frequency device that can be adapted using muscle mass measurements from specific populations determined through DXA as a reference. However, BIA measurements are more likely to be influenced by the hydration status of patients (Cruz-Jentoft et al., 2019). MRI and CT are the gold standards for noninvasive assessment of muscle mass; however, their application is limited due to their high cost, low portability, and need for specially trained personnel. DXA, a noninvasive technique, is widely used to determine muscle mass.

The diagnostic thresholds for sarcopenia depend on the examination techniques and reference population used in the study. While quantifying muscle mass, absolute levels of SMM or ASMM should be adjusted for body parameters, including height squared (ASMM/height²), weight (ASMM/weight), or body mass index (ASMM/BMI) (Kim, Jang & Lim, 2016). Several cohort studies have defined sarcopenia using the skeletal muscle index (SMI) as the ratio of the cross-sectional area of skeletal muscle at the third lumbar vertebra (L3) level determined via CT scan to height squared. Due to the variation in the currently used measurement methods, it is unclear whether the same method can be used to assess sarcopenia in all population groups, resulting in heterogeneity in sarcopenia assessment among IBD patients.

Assessment of muscle strength and physical performance.

In addition to the assessment of body mass, the diagnosis of sarcopenia includes the following two aspects: (1) Muscle strength measurement using grip strength or chair stand tests, and (2) physical performance assessment using functional tests, such as gait speed, short physical performance battery, timed up-and-go, and 400-m walk tests, which are objective, measurable, exercise-related methods to assess overall body function (Cruz-Jentoft & Sayer, 2019).

Sarcopenia is a manifestation of malnutrition for Patients with IBD.

Several blood biomarkers, including albumin, prealbumin, total protein, and BMI, are widely used in clinical practice for nutritional assessment and are considered standard diagnostic criteria for malnutrition. However, recent studies have shown that sarcopenia can develop in IBD patients with normal, reduced, or elevated BMI, indicating that sarcopenia can occur at any time in IBD patients and is not limited by BMI (Adams et al., 2017; Ünal et al., 2021). Several cohort studies investigating sarcopenia in individuals with inflammatory bowel disease (IBD) have indicated that gender, age, serum albumin levels, and body weight may play a role in determining the risk of developing sarcopenia. A recent systematic review of the outcomes of visceral fat and IBD revealed no significant difference between the BMI of patients with and without sarcopenia (Berger et al., 2020). A retrospective study discovered that 22% of IBD patients with a normal or elevated BMI and 36% with hypoalbuminemia had sarcopenia (Campbell et al., 2022). Although patients with low BMI and albumin levels are more likely to develop sarcopenia, these clinical indicators have no predictive or diagnostic value. A prospective study including 110 IBD patients suggested that low BMI and serum albumin levels are risk factors for sarcopenia, and these two easily accessible clinical indicators can help clinicians in the early diagnosis of sarcopenia in IBD patients (Liu et al., 2022).

Studies reported that the predictive value of BMI is limited to body fat assessment. Patients with high body fat and low muscle mass can still have normal BMI values. These findings highlight the importance of sarcopenia as an independent measurement indicator. Moreover, it can be inferred that using sarcopenia as a risk stratification criterion for disease severity positively affects the diagnosis and treatment of IBD patients.

Association of Sarcopenia with the disease course and prognosis of patients with IBD.

Currently, over 15% of UC and 80% of CD patients undergo surgical treatment. The effects of sarcopenia on the prediction of surgery and prognosis of patients with IBD are still being investigated by researchers.

Some studies (Cravo et al., 2017; Kurban et al., 2020; Labarthe et al., 2020; Boparai et al., 2021) show that the evaluation of body composition can be used as a marker of disease severity of patients with IBD. It can also be used as an independent predictor of IBD-related surgery.

Two studies (Grillot et al., 2020; Ge et al., 2022) clearly show that, the IBD patients with sarcopenia have a higher risk of surgery (OR 4.48, p = 0.00) (22.0% vs 7.1%, p = 0.001). Sarcopenia has a unique predictive function for surger y (HR 0.318, CI [0.126–0.802], p = 0.015) (Bamba et al., 2017). In addition to the predictive value for surgery, patients with sarcopenia are more likely to fail in drug treatment (anti-TNF therapy) (OR 4.69, P = 0.001) and need rescue treatment more frequently (like colectomy) (Ding et al., 2017). The results of a study evaluating IBD patients who had started taking new antitumor necrosis factor (TNF) medications demonstrated that skeletal muscle loss could predict the likelihood of surgery in overweight patients (P = 0.002); however, it had no predictive value for clinical outcomes, such as hospitalization or medication changes (Adams et al., 2017). The intervals between readmissions in the control, pre-sarcopenia, and sarcopenia groups gradually decreased during the follow-up (89 vs 85 vs 57 days, P < 0.001) (Liu et al., 2022).

Surgical planning and risk assessment are essential components of the preoperative evaluation of IBD patients. Numerous comorbidities have been identified as risk factors for postoperative complications; however, these factors do not adequately measure the overall physical function and are not associated with the physiological reserve required for surgical recovery (Hasselager & Gögenur, 2014; Erős et al., 2020). Therefore, as an indicator of physiological reserve, muscle mass is a valuable factor that can help design treatment plans, determine surgical suitability, and predict outcomes (OR 9.24, P = 0.04) (Zhang et al., 2017a). Studies have shown a significant link between sarcopenia and intestinal resection in CD patients (p = 0.01), whereas no difference in the cumulative rate of surgery-free survival between sarcopenic and nonsarcopenic patients with UC (p = 0.152) (Bamba et al., 2021).

In addition, the relationship between sarcopenia and postoperative complications is also worth exploring. Campbell et al. (2022) observed that the proportion of patients with skeletal muscle loss is significantly higher in surgical cohorts (32%; mean PAI 5.29 cm²/m²) than in medical treatment cohorts (16%; mean PAI 5.86 cm²/m²)(P < 0.02), indicating that these patients are more susceptible to malnutrition, cachexia, and subsequent loss of lean muscle mass. Sarcopenia is a potent independent predictor of major postoperative complications in CD patients, including transfusion, ICU admission, postoperative sepsis, and venous thromboembolism. These risks can be mitigated through preoperative interventions to improve the nutritional status of patients. A recent meta-analysis discovered that sarcopenia increased the risk of postoperative complications in patients with IBD by more than sixfold (Erős et al., 2020). There is significant correlation between IBD patients with sarcopenia and some infectious postoperative complications. For example, wound infection or dehiscence, anastomotic leak, abscess, sepsis, fistula, pulmonary infection, and urinary tract infection (Pedersen, Cromwell & Nau, 2017; Zhang et al., 2017a; Ge et al., 2022), no significant association with non-infection complications (small bowel obstruction, ileus, deep vein thrombus, pulmonary embolism, bleeding, hematoma, or anemia) and sarcopenia (Berger et al., 2020). Clinicians can use SMI as an objective assessment tool to determine the surgical risk in CD patients and prevent complications related to preoperative nutritional management in sarcopenic patients with CD undergoing elective surgery (Zhang et al., 2017a).

In contrast, no association was between sarcopenia and surgery (p = 0.066), hospitalization (p = 0.772), or the initial use of new medications (biologics, p = 0.481; immunomodulators, p = 0.320; corticosteroid, p = 0.842) (Lee et al., 2020). Patients with skeletal muscle loss frequently underwent surgery, developed abscesses, and were re-hospitalized during the follow-up period. However, no correlation was identified between skeletal muscle loss and the use of new medication dosages (p = 0.259) (Grillot et al., 2020). Although subcutaneous fat and visceral fat are related to the poor outcome of IBD patients, sarcopenia does not have this effect (Thiberge et al., 2018). A retrospective study involving 1,027 IBD patients discovered no significant differences in the cumulative risks of using corticosteroids (p = 0.073), immunomodulators (p = 0.116), and biologics (p = 0.743) and undergoing intestinal resection (p = 0.115) during the follow-up period between patients with and without sarcopenia (Nam et al., 2023). In the univariate analysis, sarcopenia was a significant risk factor for perianal surgery in patients with CD, but multivariate logistic regression and Cox proportional hazard analyses revealed that sarcopenia is not a significant risk factor for perianal surgery (Nam et al., 2023). The heterogeneity in results can be attributed to various factors such as gender imbalance in this study, the impact of muscle loss diminishing over time, and this study only examining the short-term effects of muscle loss before and after diagnosis (Table 3).

In summary, sarcopenia may affect the prognosis of inflammatory bowel disease (IBD) in the following ways: (1) Slow recovery: Sarcopenia is related to the increased systemic inflammation levels in IBD patients, affecting the course of IBD; (2) Increased risk of complications: Some IBD patients require surgical treatment, and the risk of postoperative complications and infections increases in IBD patients with sarcopenia; (3) Decreased quality of life: IBD patients experience psychological stress, fatigue, and weakness, which may be related to sarcopenia; (4) Reduced treatment tolerance: IBD patients with sarcopenia have a reduced treatment response, a higher risk of adverse drug reactions, and difficulties with subsequent rehabilitation training (Fig. 2).