Sarcopenia in pediatric gastroenterology and hepatology: an updated review

1. Pediatric sarcopenia vs. adult sarcopenia

The conceptual framework of sarcopenia originated in geriatric medicine, where it is defined by the age-related loss of muscle mass and function. In adults, consensus guidelines such as those from the EWGSOP and AWGS utilize fixed, absolute cutoff values for diagnosis [3-6]. For example, EWGSOP2 thresholds include grip strength <27 kg for men and <16 kg for women, and appendicular lean mass (ALM) index <7.0 and <5.5 kg/m², respectively, in European populations [3]. The AWGS guidelines use similar parameters with slightly different cutoffs (e.g. grip <26 kg in men, <18 kg in women) appropriate for Asian body composition, and they emphasize walking speed or chair stand performance as additional criteria [5,6].

Applying these adult definitions to pediatrics, however, is inappropriate due to the dynamic nature of childhood growth. In children, muscle mass and strength naturally increase with age and somatic development [20]. Therefore, a single absolute threshold cannot differentiate a pathological deficit from a developmental stage. Instead, pediatric sarcopenia must be defined relative to a healthy reference population. Current approaches rely on z scores or percentiles normalized for age, sex, and height. This need for reference-based interpretation is reinforced by the developmental biology of body composition: birth weight and subsequent growth trajectories influence later lean and fat mass, while muscle-related parameters rise nonlinearly across childhood and puberty, with more pronounced pubertal gains in boys [21,22]. A commonly cited definition for low muscle mass is a value <5th percentile or a z score < -2 relative to a healthy reference population [7].

A critical divergence from adult criteria lies in the assessment of muscle function. While adult diagnoses mandate the presence of both low muscle mass and low strength, functional testing in pediatrics is limited by developmental feasibility. Handgrip dynamometry is reproducible in children aged 5–6 years and older using appropriate devices [23]. However, in infants and toddlers—a population frequently requiring liver transplantation—direct strength measures are impossible. Clinicians must resort to developmental motor scales (e.g., Alberta Infant Motor Scale [AIMS]) to infer functional impairment [24]. Consequently, the majority of pediatric studies currently rely on muscle mass quantification (via imaging or dual-energy x-ray absorptiometry [DXA]) as the primary diagnostic criterion [7], although the integration of functional metrics remains the gold standard for older children.

2. Sarcopenic obesity

A particularly relevant concept in pediatric GI/hepatology is sarcopenic obesity, defined as the coexistence of high adiposity with low muscle mass/quality [19,23,24]. This condition is “two-hit,” combining risks from obesity (e.g., metabolic and mechanical complications) and sarcopenia (frailty and functional impairment) [24]. In adults, sarcopenic obesity confers synergistically worse outcomes than either condition alone [25]. In children, obesity has become common, and notably MASLD—now the most prevalent pediatric chronic liver disease—often affects children with overweight/obesity [26]. Sarcopenic obesity in pediatrics is an emerging area of study, and there is no consensus pediatric definition yet [23]. Sarcopenic obesity is of special concern because excess fat may mask the muscle deficiency if one only looks at weight or BMI [23]. In parallel, the recent concept of “clinical obesity” highlights that obesity should not be interpreted by BMI alone, but in the context of confirmed adiposity, fat distribution, and obesity-related tissue or organ dysfunction. Within this framework, sarcopenic obesity represents a particularly high-risk phenotype because excess adiposity and muscle depletion may coexist while remaining obscured by body weight alone [10]. Children with sarcopenic obesity might appear “well-nourished” or even overweight by BMI, yet have diminished strength and metabolic issues. Indeed, low relative muscle mass in obese youth correlates with worse insulin resistance and metabolic syndrome features [27]. In pediatric MASLD, children with lower muscle mass indices have more severe liver steatosis and inflammation – suggesting that sarcopenic obesity could exacerbate liver disease progression [19]. Overall, recognizing sarcopenic obesity requires clinicians to assess body composition (not just BMI) in children with overweight, as this subgroup may benefit from targeted exercise and nutrition interventions to improve muscle mass while managing weight.

3. Distinguishing sarcopenia, malnutrition, and frailty

In clinical practice, the terms sarcopenia, malnutrition, and frailty are often used interchangeably, yet they represent distinct pathophysiological entities with varying overlaps (Fig. 1).

Fig. 1.

Conceptual relationships between malnutrition, sarcopenia, and frailty in children. Malnutrition reflects inadequate intake or absorption and impaired growth; sarcopenia refers to low muscle mass with or without low strength or physical function; frailty denotes reduced physiologic reserve and increased vulnerability to stressors. These entities frequently overlap in children with chronic gastrointestinal and liver diseases, but sarcopenia may also occur in children with normal body mass index or obesity.

• Malnutrition is traditionally defined by deficits in dietary intake or uptake resulting in measurable anthropometric changes, such as low weight-for-height or BMI [28]. While chronic malnutrition often causes sarcopenia due to the catabolism of muscle protein, the two are not synonymous.

• Frailty is a multidimensional syndrome of reduced physiologic reserve and increased vulnerability to stressors [29]. Sarcopenia is a key biological driver of physical frailty, but frailty also encompasses cardiovascular, immunological, and psychosocial deficits [30].

These conditions frequently coexist in children with chronic GI or liver diseases [31]. However, their dissociation is clinically critical. In advanced chronic liver disease, while virtually all frail patients are sarcopenic, sarcopenia can exist without overt frailty, serving as an early warning sign of physiologic decline [8,31,32]. Crucially, traditional nutritional markers often fail to detect this decline. A study in pediatric autoimmune liver disease revealed a striking discordance: while only 3% of patients met BMI-based malnutrition criteria, 48% were sarcopenic [11]. This underscores that reliance on weight-based metrics risks underestimating nutritional risk [33]. Consequently, clinicians should assess nutritional status, muscle mass, and functional status separately to accurately capture the child’s risk profile [34,35].

4. Epidemiology of sarcopenia in pediatric gastroenterology and hepatology

The recognition of muscle wasting as a critical comorbidity in pediatric gastroenterology has lagged behind adult medicine. While sarcopenia is firmly established as a predictor of mortality in adult cirrhosis—with prevalence rates ranging from 30% to 60% [36-38]—pediatric data have historically been sparse. However, accumulating evidence now demonstrates that sarcopenia is highly prevalent across a spectrum of pediatric GI and liver diseases, affecting approximately one-quarter to one-half of patients depending on the population and diagnostic criteria used [11,13,15,19,39] Crucially, this deficit is often "hidden" in children who exhibit normal weight or obesity, and it serves as a potent, independent predictor of adverse clinical outcomes.

5. Prevalence and prognostic impact in chronic liver disease

Muscle wasting is ubiquitous in children with ESLD. A recent review by Chen et al. [8] summarized that across various cohorts of children with chronic liver disease or those awaiting transplantation, 24% to 70% met criteria for sarcopenia. The wide variability reflects differences in measurement techniques (computed tomography [CT], magnetic resonance imaging [MRI], DXA) and the heterogeneity of study populations, which range from infants with biliary atresia to adolescents with autoimmune conditions [11,39].

6. Pediatric liver transplant candidates

Cross-sectional imaging consistently reveals significant muscle deficits in children awaiting liver transplantation. Mangus et al. [40] found height-indexed psoas muscle area 23% lower than controls, and Lurz et al. [41] observed markedly reduced tPMA. Crucially, muscle mass does not correlate with Pediatric End-stage Liver Disease (PELD) scores [42]. Because PELD relies solely on biochemical markers, it fails to capture nutritional deterioration, meaning children with "low-risk" scores may harbor unrecognized frailty. Pretransplant sarcopenia is prevalent and clinically consequential. Woolfson et al. identified sarcopenia (tPMA z score < -2) in 40% of candidates [17], which correlated with concurrent malnutrition and longer posttransplant intensive care unit (ICU) stays. Furthermore, Jitwongwai et al. [43] observed that lower psoas index tracked with higher waitlist mortality in a cohort dominated by infants with biliary atresia, underscoring the severe burden of muscle loss in this population.

7. Sarcopenia in infants with biliary Atresia

Infants with biliary atresia are uniquely vulnerable to malnutrition due to cholestasis and hypermetabolism. Takeda et al. [39] identified sarcopenia (tPMA z score < -2) in 24% of 89 infants undergoing liver transplantation. Clinically, this deficit predicted significantly greater intraoperative blood loss, longer operative times, and severe postoperative complications, including portal vein stenosis and bloodstream infections. Reinforcing these findings, Verhagen et al. [44] reported 101 children (mostly biliary atresia) and found that in infants <1 year, lower skeletal muscle index correlated with longer hospital and ICU stays, while lower subcutaneous fat was associated with severe infections. These data demonstrate that even in the first year of life, sarcopenia is a major determinant of surgical resilience.

8. Autoimmune liver diseases: the "hidden" deficit

Sarcopenia is prevalent in noncirrhotic conditions like autoimmune hepatitis and primary sclerosing cholangitis, driven by systemic inflammation and corticosteroids rather than malabsorption. Amevor et al. [11] evaluated 58 children using MRI and found that 48% met sarcopenia criteria (tPMA ≤ 5th percentile). Strikingly, while nearly half were sarcopenic, only 3% were classified as underweight by BMI. This profound discordance highlights that reliance on weight-based metrics masks muscle wasting in this population. Furthermore, sarcopenic patients exhibited significantly higher visceral fat volumes, indicating a "sarcopenic obesity" phenotype [21]. Clinically, low muscle mass correlated with worse parent-reported general health scores, suggesting that "hidden" sarcopenia negatively impacts quality of life [11].

9. Sarcopenia in MASLD

MASLD represents a paradigm of sarcopenic obesity, where low muscle mass drives disease severity independent of BMI [45]. Mirroring adult data showing a >5-fold risk of steatosis with low muscle, Yodoshi et al. [19] demonstrated in over 300 children that lower skeletal muscle mass index (SMI) on MRI was independently associated with higher steatosis grades. Multivariate analysis revealed that each 1-unit increase in skeletal muscle index reduced the odds of severe steatosis by 27%, regardless of BMI z score [19]. Subsequent BIA studies confirmed that low muscle mass—rather than body fat percentage—was the stronger predictor of histologic severity [18,19]. This relationship extends to nonobese MASLD; Kwon and Jeong [46] found that 70% of children with fatty liver and BMI <23 kg/m² met sarcopenia criteria compared to 48% of controls. These findings indicate that relative muscle deficiency is as metabolically detrimental as excess fat, likely by exacerbating insulin resistance and reducing protective myokines [26,47].

10. Sarcopenia in pediatric IBD

Children with IBD are at high risk for sarcopenia, which is frequently present at diagnosis [48]. A systematic review by Aljilani et al. [48,49] confirmed lower lean mass in patients versus controls. MRI studies indicate that up to 80% of pediatric Crohn’s patients have reduced muscle area [16,50]. Pedersen et al. [51] similarly found that lower muscle area predicted complications and surgical risk. Prognostically, sarcopenia marks an aggressive phenotype independent of BMI [52]. Atlan et al. [53] demonstrated in 101 children that those in the lowest muscle quartile faced strikingly higher hazards of requiring biologic therapy (hazard ratio [HR], 12) and experiencing exacerbations (HR, 9). This deficit was more prevalent in Crohn disease (68%) than ulcerative colitis (32%). Fortunately, interventions like exclusive enteral nutrition can improve lean mass [54], underscoring the importance of monitoring muscle mass to predict risk and guide therapy.

11. Acute illness and sarcopenia

"Acute sarcopenia" can develop rapidly during severe illness [55]. López et al. [56] demonstrated in children with perforated appendicitis that psoas muscle area decreased by a mean of 0.9% per day over a 7- to 10-day hospitalization. This rapid catabolism occurred regardless of baseline BMI, affecting even well-nourished children [55]. Mirroring "ICU-acquired weakness," this specific muscle loss is often masked by minimal declines in BMI, yet can significantly delay recovery [57]. Because episodic acute losses can accumulate into chronic depletion, muscle preservation strategies must be initiated immediately upon admission rather than waiting for chronic signs to appear [55].

1. Liver disease and transplantation outcomes

Pediatric evidence mirrors adult hepatology, identifying sarcopenia as a critical determinant of survival and morbidity independent of PELD scores [17,42]. Boster et al. [42] demonstrated that reduced muscle area predicts significantly higher posttransplant mortality, capturing "biological frailty" often missed by standard labs. Regarding morbidity, sarcopenia in children with chronic liver disease and those undergoing liver transplantation is associated with longer intensive care and hospital stays, greater ventilator dependence, and higher rehospitalization rates [17,42,60]. In infants with biliary atresia, pretransplant sarcopenia correlates with increased intraoperative blood loss, a higher incidence of portal vein complications, prolonged hospitalization, and more frequent severe postoperative infections, underscoring its role as a marker of heightened perioperative vulnerability [60].

2. Prognostic significance in MASLD and metabolic disease

Although pediatric longitudinal data are limited, sarcopenia appears to accelerate metabolic dysregulation in youth with obesity and MASLD, consistent with adult data linking low muscle mass to MASLD progression, advanced fibrosis, and mortality [61-63]. In adolescents, lower baseline relative muscle mass is associated with a higher subsequent risk of type 2 diabetes and adverse cardiometabolic profiles, suggesting that skeletal muscle loss marks an early trajectory toward metabolic decompensation [63,64]. In adults, the coexistence of sarcopenia and obesity substantially increases the odds of MASLD and MASLDrelated fibrosis [62], thereby defining a “sarcopenic obese” phenotype that likely represents a high-risk subgroup in pediatrics as well, warranting aggressive insulin sensitization and targeted resistance-based exercise to halt disease progression [61,64].

3. Disease course and surgical risk in IBD and other conditions

In pediatric IBD, sarcopenia functions as a biomarker of more refractory disease, paralleling adult data in which low muscle mass predicts failure of steroid therapy, need for biologics or rescue therapy, and earlier progression to surgery [48,65,66]. It also signals heightened surgical vulnerability, being associated with higher rates of postoperative complications, infections, readmission, and prolonged hospitalization, thereby supporting a prehabilitation approach that leverages the preoperative window for intensive nutritional and functional optimization [48,65,66]. This coupling of low muscle mass with reduced physiological resilience appears consistent across pediatric conditions, with oncology and cardiac cohorts showing that pretreatment sarcopenia predicts treatment toxicity, postoperative complications, and inferior survival [34].

1. Chronic inflammation and hypermetabolism

The development of sarcopenia in children with chronic GI and liver diseases reflects a convergence of chronic inflammation with anabolic resistance, nutrient deficiency and accelerated starvation, and liver-muscle and endocrine dysregulation, all superimposed on the critical developmental window for muscle and pubertal growth (Fig. 2) [48,67] Chronic systemic inflammation is a central driver of muscle loss in conditions such as IBD and autoimmune liver diseases. Proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, and interleukin-6, directly promote skeletal muscle protein breakdown through activation of ubiquitin–proteasome and autophagy pathways [68]. In parallel, these cytokines exert central effects on appetite regulation, inducing anorexia and thereby compounding substrate deficiency at times when metabolic demands are increased [65,69]. Beyond direct catabolism, persistent inflammation induces a state of anabolic resistance. Proinflammatory signaling interferes with the growth hormone (GH)–insulin-like growth factor-1 (IGF-1) axis by inhibiting JAK/STAT signaling, blunting GH-mediated anabolic effects on skeletal muscle [70]. Clinically, this manifests as low circulating IGF-1 levels in children with active Crohn disease despite normal or elevated GH concentrations, resulting in impaired linear growth and failure of muscle accretion during a period when muscle mass should normally increase rapidly [69]. Severe inflammation and ESLD may further exacerbate muscle loss by increasing resting energy expenditure by approximately 10%–20%, such that failure to proportionally increase caloric intake leads to catabolism of both adipose tissue and skeletal muscle to meet energy requirements [69,70].

Fig. 2.

Proposed diagnostic and management algorithm for pediatric sarcopenia in gastrointestinal and liver diseases. At-risk children undergo screening, objective assessment of muscle mass, and ageappropriate functional testing. In cooperative children, diagnosis is based on low muscle mass plus low muscle function relative to pediatric reference data; when function cannot be assessed, low muscle mass supports an operational diagnosis that should prompt intervention and follow-up reassessment. Management includes protein-adequate nutrition, resistance-based activity or physical therapy, optimization of underlying disease, and longitudinal monitoring. 6MWT, 6-minute walk test; ALM, appendicular lean mass; BIA, bioelectrical impedance analysis; BMI, body mass index; CT, computed tomography; DXA, dual-energy x-ray absorptiometry; ESLD, end-stage liver disease; GH, growth hormone; GI, gastrointestinal; IBD, inflammatory bowel disease; MASLD, metabolic dysfunction-associated steatotic liver disease; MRI, magnetic resonance imaging; MUAC, mid-upper arm circumference; PELD, pediatric end-stage liver disease; PT, physical therapy; tPMA, total psoas muscle area.

2. Nutritional deficits and "accelerated starvation"

Inadequate substrate availability compromises muscle protein synthesis and accelerates catabolism, particularly in the background of cirrhosis-related anabolic resistance [67,71,72]. Reduced oral intake is common and multifactorial, driven by cytokine-mediated anorexia, organomegaly-related early satiety, and dysgeusia in chronic liver disease [72]. In cholestatic disorders, fat malabsorption further compounds nutritional compromise by leading to deficiencies in lipid-soluble vitamins. Among these, vitamin D deficiency is especially relevant, as impaired vitamin D signaling has been associated with muscle weakness and myopathy, potentially amplifying functional consequences of muscle mass loss [31]. In advanced liver disease, nutrient deficiency is compounded by a distinct metabolic phenomenon often referred to as “accelerated starvation.” Because the liver is the primary glycogen reservoir, reduced glycogen storage capacity in cirrhosis precipitates an early transition to fasting physiology, even after short periods without intake. Children therefore shift rapidly toward amino acid mobilization from skeletal muscle to support hepatic gluconeogenesis [73]. This pathophysiology provides a strong physiological rationale—supported by clinical trials in cirrhosis—for late-evening nutritional supplementation as a strategy to attenuate overnight muscle protein breakdown and preserve lean mass [67,74].

3. The liver-muscle axis and hormonal dysregulation

Chronic liver disease creates a biochemical and endocrine environment that actively suppresses muscle health. A prominent example is hyperammonemia. When hepatic ammonia clearance is impaired, skeletal muscle becomes an alternative site for ammonia disposal via conversion to glutamine; however, this adaptive mechanism carries metabolic costs, including consumption of branched-chain amino acids that would otherwise support muscle protein synthesis [75]. Hyperammonemia is also directly toxic to myocytes: it impairs mitochondrial function, reduces ATP production, and increases reactive oxygen species generation [75]. Concomitantly, hyperammonemia upregulates myostatin—an inhibitor of muscle growth—and inhibits mechanistic target of rapamycin (mTOR) signaling, a central regulator of muscle protein synthesis [75]. Endocrine perturbations further contribute to impaired muscle accrual. Cirrhosis can disrupt the gonadal axis, contributing to low testosterone in adolescent males via increased aromatization to estrogen [76]. Given the central role of sex steroids in pubertal gains in muscle mass, pubertal delay and hypogonadism can meaningfully worsen failure to accrue muscle. Metabolic dysregulation also plays a key role, particularly in MASLD and cirrhosis. Systemic insulin resistance reduces insulin’s anabolic suppression of proteolysis and impairs glucose uptake in skeletal muscle, contributing to metabolic inflexibility and promoting fat infiltration into muscle (myosteatosis), which further impairs muscle quality and physical function [77].

4. Iatrogenic and environmental factors

Iatrogenic exposures and reduced mechanical loading frequently amplify disease-driven muscle loss. Glucocorticoids are potently catabolic, suppressing muscle protein synthesis, increasing proteolysis, and worsening insulin resistance [78]. With prolonged exposure, type II fiber atrophy and proximal weakness become clinically relevant, particularly in steroid-dependent IBD and autoimmune hepatitis. In parallel, fatigue, pain, and hospitalization reduce habitual physical activity and mechanical loading. Because mechanical loading is required to stimulate muscle anabolism (“use it or lose it”), disuse accelerates atrophy and worsens insulin resistance [79]. Consistent with this framework, in pediatric liver transplant recipients, lower moderate-to-vigorous physical activity has been associated with sarcopenia [80], suggesting that physical inactivity is not merely a consequence but also a reinforcing driver of muscle depletion.

5. Pediatric specificity: impaired muscle accrual during growth

A defining pediatric vulnerability is that chronic disease blunts the normal trajectory of muscle gain, especially during puberty. Thus, a teenager with IBD and delayed puberty may not only lose muscle during catabolic episodes but also miss the developmental window for peak muscle acquisition [70,81]. Even after disease control, incomplete “catch-up” in muscle accrual can leave a persistent deficit—distinct from adult atrophy and tightly linked to growth failure and delayed sexual maturation [70].

1. Clinical assessment and screening

Assessment begins with a high index of suspicion. Physical signs such as temporal wasting, prominent interosseous muscles, or “flabby” skin folds may suggest muscle depletion, but examination is relatively insensitive for mild sarcopenia, particularly in children with overweight or obesity in whom muscle loss can be masked by adiposity [21]. Longitudinal growth trajectories remain essential: declines in weight-for-height or BMI percentiles may indicate loss of somatic tissue that often includes muscle. mid-upper arm circumference (MUAC), triceps skinfold, and mid-upper arm muscle area can serve as bedside adjuncts; however, their specificity for muscle depletion is limited. For example, in infants with ESLD, MUAC did not correlate with imaging-based psoas area index [41], indicating that a “normal” MUAC cannot reliably exclude sarcopenia. In addition, fluid-retaining states (edema/ascites) can confound anthropometric interpretation, further reinforcing the need for objective measures.

2. Objective muscle mass quantification

Laboratory markers are occasionally discussed as indirect surrogates of muscle mass, but their clinical utility remains limited [82]. Low serum creatinine in the setting of stable renal function may suggest reduced muscle mass, and the creatinine-to-cystatin C ratio has emerged as a promising pediatric adjunct associated with impaired physical performance. However, these markers remain nonspecific and are influenced by renal function, inflammation, and liver disease; therefore, they should be viewed as practical screening adjuncts rather than stand-alone diagnostic tests for pediatric sarcopenia. Mechanistically relevant markers such as IGF-1 or myostatin are also of interest, but they are not yet validated for routine clinical use [83].

3. Clinical application: a proposed diagnostic algorithm

Given the heterogeneity of current methods and the lack of a universal consensus, we propose a pragmatic, step-by-step diagnostic algorithm (Fig. 3) to standardize sarcopenia assessment in pediatric gastroenterology and hepatology.

Fig. 3.

Pathophysiologic mechanisms of pediatric sarcopenia in gastrointestinal and liver diseases. Panel A summarizes cytokine-driven anorexia, hypermetabolism, proteolysis, and anabolic resistance. Panel B illustrates the liver-muscle axis, including hyperammonemia, accelerated starvation, insulin resistance, endocrine dysregulation, glucocorticoid exposure, and physical inactivity, all of which impair muscle accretion and promote muscle loss during growth. TNF, tumor necrosis factor; IL, interleukin; GH, growth hormone; IGF-1, insulin-like growth factor-1.

4. The importance of reference data

A major barrier to standardized diagnosis has historically been the lack of robust pediatric normative data [7]. Recent advances, however, have provided clinically useful benchmarks. Notably, Lurz et al. [2] published sex-specific percentiles for tPMA derived from healthy children aged 1–16 years, allowing muscle measurements to be interpreted analogously to growth charts. More recently, BIA-derived age- and sex-specific reference curves and sarcopenia-related cutoffs have been reported in Asian youth, including SMI < -2 SD and MFR below the mean -2 SD of the age- and sex-stratified 3rd BMI quintile as practical interim cutoffs [22]. Because these thresholds are modality- and population-specific, they should complement rather than replace broader pediatric reference standards, but they represent an important step toward ethnicity-sensitive assessment [22]. Similarly, normative reference curves for handgrip strength have been established by the CDC and other cohorts [91,92]. The use of such population-specific references is essential; applying fixed adult cutoffs to growing children will inevitably result in misclassification and diagnostic error.

5. Differentiation from secondary causes

Clinicians must distinguish sarcopenia related to systemic GI/liver disease from "secondary" sarcopenia caused by primary neuromuscular disorders (e.g., cerebral palsy) or severe disuse (e.g., casting). The algorithm presented here focuses on metabolic and nutritional etiologies, where intervention can reverse the underlying deficit.

1. Nutritional rehabilitation

The foundation of management is ensuring sufficient substrate for muscle protein synthesis. Malnutrition and hypermetabolism frequently coexist in this population, necessitating aggressive support.

2. Exercise and physical activity: the anabolic stimulus

Exercise is the primary physiologic stimulus for muscle hypertrophy [99]. While nutritional support provides the amino acids, mechanical loading provides the signal (mTOR activation) required to build muscle [99,100]. Without this stimulus, nutritional supplementation alone may lead to fat gain rather than muscle accretion.

3. Evidence and safety in pediatric chronic disease

• Safety profile: Resistance training has demonstrated an excellent safety profile in vulnerable pediatric populations, including chronic kidney disease, cancer survivors, and solid organ transplant recipients [101-103].

• Efficacy: Even in posttransplant cohorts, home-based exercise programs have been shown to significantly improve functional capacity (e.g., 6-minute walk distance) and muscle circumference [103,104].

4. Strategy 1: In-hospital mobilization

The rapid muscle catabolism observed in pediatric acute appendicitis (~1% loss of psoas area per day) serves as a stark warning: muscle loss begins immediately upon immobilization [56].

• Goal: Mitigate "acute sarcopenia" during hospitalization for flares or surgery.

• Intervention: Mobilization should be viewed as a "vital sign." For bedbound patients (e.g., severe acute colitis), physical therapy (PT) should initiate low-intensity in-bed resistance exercises (e.g., bridging, straight leg raises) and assisted transfers [105,106]. Ambulation in the hallway should occur as soon as hemodynamic stability allows [106].

5. Strategy 2: Outpatient resistance training (rebuilding the reserve)

For the stable outpatient, the focus shifts to hypertrophy. The prescription follows the FITT(frequency, intensity, time, type) principle [107]:

• Type (modality): Resistance training is superior to aerobic exercise for reversing sarcopenia [107, 108]. Effective modalities include body-weight exercises (squats, lunges, push-ups), resistance bands (Therabands), or light free weights. These induce the mechanical tension necessary for muscle growth.

• Frequency & time: Aim for 2–3 sessions per week, with each session lasting 20–30 minutes [107,108]. Consistency is more critical than duration.

• Intensity: The target is moderate intensity [107-109]. Exercises should feel "somewhat hard" (rating of perceived exertion 5–7/10), allowing the child to complete 8–12 repetitions with good form before fatigue.

• Progression: "Start low and go slow." For a frail child with IBD, therapy might begin with sit-to-stand repetitions from a chair (functional squatting) [107-109]. As strength improves, resistance can be progressively increased to ensure continued adaptation.

6. Strategy 3: Developmental considerations

Management should be individualized to developmental stage. In infants and younger children, the priority is preservation of growth and muscle accrual through energy-and protein-adequate feeding, correction of micronutrient deficiencies, and play-based or PT-guided activity that promotes gross motor development. In school-aged prepubertal children, structured habit-building, supervised body-weight or resistance-band exercise, and close monitoring of growth velocity are central. In adolescents, pubertal muscle accretion, delayed puberty, autonomy, and body image become increasingly relevant; accordingly, higher absolute protein delivery, progressive resistance training, and evaluation for endocrine contributors such as delayed puberty or hypogonadism should be considered when recovery is suboptimal. Although pediatric sarcopenia-specific trials are limited, tailoring interventions to growth stage is physiologically justified and clinically pragmatic.

• Engaging Adolescents [110]: Teenagers are often motivated by functional goals (e.g., "returning to sports") or aesthetics ("looking fit") rather than "disease management." Framing resistance training as "sports conditioning" can improve adherence.

• School Reintegration [111]: Returning to physical education class is a key milestone. Clinicians should provide clear clearance letters that allow for "activity as tolerated" or adaptive physical education (e.g., shorter duration, no contact) to prevent social isolation while ensuring safety.

7. Emerging and adjunctive therapies

While standard care focuses on nutrition and exercise, several adjunctive therapies are under investigation or used in refractory cases:

• Hormonal agents: In adolescents with severe growth failure or delayed puberty, GH or low-dose anabolic steroids (e.g., oxandrolone) have been used off-label to promote anabolism (e.g., in burn victims or Turner syndrome) [112,113]. While effective for muscle gain, they carry risks of virilization and liver enzyme elevation. Their use is currently reserved for exceptional, refractory cases under expert endocrine guidance.

• Neuromuscular electrical stimulation (NMES): For critically ill children in the ICU who are too sedated or weak for active PT, NMES can passively stimulate muscle contraction. Small trials in adults suggest it may attenuate atrophy during prolonged immobilization; pediatric applications are exploring this as a bridge to active rehab [114,115].

8. Integrated management and monitoring

Successful treatment of pediatric sarcopenia requires a shift from a siloed "organ-specific" approach to a comprehensive "whole-body" strategy. This demands a coordinated multidisciplinary team to orchestrate the complex interplay between disease control, nutrition, and rehabilitation.