Abstract
Background
The aim of our study was to investigate the impact of a structured exercise program on bone mineral density (BMD) and body composition parameters in children and adolescents with IBD in remission.
Methods
Patients were recruited to participate in a 6-month exercise program. Total body less head (TLBH) dual energy X-ray absorptiometry (DXA) was used to measure BMD. The same method was used to assess fat mass (FM) and lean body mass (LBM) at baseline and at the completion of the program.
Results
Based on the baseline and endpoint TBLH DXA measurements, a total of 42 study participants (25 boys; aged 15.3 ± 2.08 years) experienced an increase in BMD (from 0.959 ± 0.023 g/cm2 to 0.988 ± 0.025 g/cm2, p < 0.001) and LBM (from 37.12 ± 1.43 kg to 38.75 ± 1.61 kg, p = 0.012). Age- and sex-based BMD Z-score increased significantly (from −0.35 ± 0.15 to −0.28 ± 0.17, p = 0.020), whilst LBM Z-score did not significantly change (from −1.78 ± 0.23 to −1.71 ± 1.49, p = 0.908).
Conclusions
There was a significant improvement in BMD, age- and sex-based BMD Z-score, and LBM amongst study participants. Subgroup analysis showed that patients with CD and male study participants experienced significant improvement in all parameters, whilst patients with UC and IBD-U and female patients experienced improvement solely in BMD.
Impact statement:
Children and adolescents with IBD, regardless of disease activity, are under increased risk of secondary osteoporosis and lean body mass deficits.
A 6-month home-based structured exercise program leads to a significant improvement in bone mineral density and lean body mass.
Exercise therapy should be explored as a potentially adjacent to standard treatment modalities.
Introduction
Inflammatory bowel disease (IBD) is a group of chronic, relapsing and remitting inflammatory disorders of the alimentary tract, comprising of Crohn’s disease (CD), ulcerative colitis (UC) and IBD-unclassified (IBD-U). The incidence of pediatric IBD around the world has been steadily rising for the last two decades1.
The affected children and adolescents are at an increased risk of developing secondary osteoporosis, a systemic disorder characterized by low bone mass and deterioration of bone microarchitecture, with consequent increased risk of fractures throughout their lifetime2. Currently, the prevalence of low bone mineral density (BMD) in children and adolescents with IBD is estimated between 8% and 65%3–5. Moreover, a recent systematic review and meta-analysis demonstrated that 93.6% of patients with CD and 47.7% of patients with UC have deficits in lean body mass (LBM) compared to healthy controls, regardless of disease activity6. The impaired digestive and absorptive function of the gastrointestinal tract, chronic systemic inflammation, glucocorticoids used to treat relapses, poor dietary intake, as well as, the lack of physical activity, are all thought to play a role in the impairment of bone health and body composition7,8. Physical activity (PA), defined as any bodily movement produced by the skeletal muscle that results in energy expenditure9, improves physical fitness through an increase in cardiorespiratory efficiency, muscle mass accrual, increased muscular strength and endurance, thus leading to improved bone strength8.
We have previously described, in cross-sectional study, a strong positive correlation between the time spent in moderate-to-vigorous PA (MVPA) and BMD and LBM; with an increase in time spent in MVPA associated with an increase in BMD10. Puberty is generally deemed as a critical period of muscle and bone growth, with 90% of peak bone mass attained by late adolescence11. No studies have yet evaluated the effects of an exercise intervention on musculoskeletal outcomes in pediatric IBD. The aim of the study was to evaluate the impact of a home-based, structured exercise program on BMD and body composition in children and adolescents with IBD in clinical remission.
Materials and Methods
Participants and study design
A single-center pre-post interventional study was conducted from March 2019 to December 2020. Pediatric patients with IBD in stable clinical remission, aged 10 to 18 years old, were invited to participate in the study. The IBD diagnosis was made according to the Porto criteria12 and disease localization was determined based on the Paris classification13 at the time of study enrollment. Stable remission was defined as weighted pediatric CD activity index (wPCDAI) < 12.5 or pediatric UC activity index (PUCAI) < 10 14,15 and lasting for a minimum of one month prior to enrollment. Exclusion criteria were any acute or other chronic disease associated with a decrease in PA and a recent (within 1 month) and/or scheduled (within upcoming 6 months) surgical procedure. Patients who were already physically active, engaging in competitive sports for more than 180 minutes per week, and those receiving glucocorticosteroid therapy at the time of potential inclusion were not invited into the study.
The study was approved by the Institutional Review Board at the Children’s Hospital Zagreb. Written consent was obtained from both the patient and one of their parents or caregivers.
Baseline and endpoint measurements
Clinical and laboratory assessment, anthropometry and body composition measurements, dietary intake analysis, physical activity assessment (previously described in detail elsewhere10), as well as muscular strength and endurance assessment were done in all included patients at the time of enrollment and following the completion of the exercise program.
Clinical and laboratory assessment
Type and localization of the disease, current and earlier medical treatment of each patient was recorded, and cumulative glucocorticoid dose calculated (expressed as mg of prednisone received/body weight (BW)/year). Patients underwent a medical exam during which their pubertal status was assessed according to Tanner and Whitehouse16. Complete blood count (CBC), C-reactive protein (CRP), albumin and fecal calprotectin were determined with the aim to further evaluate disease activity. Serum levels of 25-hydroxyvitamin D (25(OH)D) were measured.
Anthropometry and body composition
The anthropometric assessment included measurements of BW, body height (BH), as well as the calculation of body mass index (BMI). Total body less head (TBLH) dual energy X-ray absorptiometry (DXA) (GE Lunar iDXA; enCore Software v17, GE Healthcare, Chicago, Illinois) was used to measure BMD and determine body composition. Patients were scanned in the supine position at high resolution and BMD, fat mass (FM) and fat free mass (FFM) were determined, whilst LBM was calculated as FFM minus bone mineral content (BMC). BMD measurements were expressed in g/cm2, as age- and sex-based Z-scores and as height-adjusted Z-scores17. Similarly, FM and LBM were expressed in kilograms and as age-, sex- and height-based Z-scores18.
Dietary intake
Dietary intake was assessed using three-day food diaries. Prodi 6.1 expert software package (Nutri-Science GmbH, Freiburg, Germany) was used to analyze collected data. Daily energy, macronutrient, vitamin D, calcium and phosphorus intake were expressed as a percentage of the daily recommended intake for healthy children of same age and sex19. Resting energy expenditure was defined using the Schofield equation and multiplied by an appropriate activity factor for observed physical activity level to determine estimated energy requirements (EER)20.
Physical activity
Fitbit Charge 2 (Fitbit Inc., San Francisco, California), a consumer-marketed triaxial accelerometer, was used to measure PA in free-living conditions. Subjects were asked to wear it on the non-dominant wrist, for 5 consecutive days before and after the intervention period. The device was initialized using complementary software with the subject’s characteristics in mind and synchronized daily with the mobile phone application. At the end of the wear period, data were downloaded from a secure website (Fitbit.com) and examined. Valid wear time was defined as ≥22 hours/day for 5 days. Total PA was analyzed as light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA).
Muscular strength and endurance
The five-task battery was designed to provide a swift and comprehensive assessment of muscle strength and endurance of the six large skeletal muscle groups. Prior to testing, each participant was instructed on the correct technique and form to ensure optimal task execution and to minimize the risk of injury. During a series of 30-second intervals, participants were asked to do the maximum possible number of repetitions of sit-ups, push-ups, back extensions and squats. The last, fifth exercise, was a plank hold, during which the participants were asked to remain in the standard plank position for as long as possible whilst maintaining the correct form.
Intervention
Following the initial multifaceted assessment, the patient and their parent or caregiver were introduced to a personalized, home-based structured exercise program lasting for a total of six months. The kinesiologist provided each participant with video materials demonstrating each exercise and its possible modifications based on the individual’s fitness level. Participants were also provided with a weekly exercise schedule and a diary to log in each training session. The exercises were divided into six 4-week-long sections and the intensity of exercises was gradually increased throughout the program. Adherence was assessed using the activity logs and via weekly telephone calls conducted with participants and their parents. Appropriate adherence to the program was defined as the performance of default exercises (for the predetermined number of repetitions) at least three times a week, with a minimum of 12 sessions per month, during the 26-week-long intervention period.
Outcomes
The primary outcome was to assess the changes in whole-body BMD, LBM and FM, expressed as absolute values and as age-, sex-, and height-based Z-scores at baseline and after the intervention. The primary outcome was also to compare changes among patients with CD, UC and IBD-U, male and female study participants, and prepubertal and early pubertal children (defined as stages I to III according to Tanner and Whitehouse16) with those with more advanced pubertal status (defined as stages IV and V). Secondary outcomes were to assess the changes in laboratory parameters pertaining to disease activity status, dietary intake, muscular strength,endurance and PA engagement at the baseline and following the intervention period. Lastly, the study aimed to explore the relationship between improvement of BMD and LBM and variables such as age at diagnosis, duration of the disease and different treatment modalities and to record possible adverse events during the intervention period.
Statistical analysis
The differences between categorical variables were assessed by chi-square test, whilst the differences for non-categorical variables were assessed by ANCOVA analysis and corrected for age and sex or disease. Binary logistic regression was performed; dependent values were increased in BMD and LBM Z score (expressed as binary values) and proposed predicted factors included age at diagnosis, disease duration, pubertal stage, use of biological therapy, exclusive enteral nutrition, glucocorticosteroid dose, surgical treatment. All statistical tests were done at the two-tailed α level of 0.05. Statistical analysis was performed using SPSS 24.0 (IBM Corporation, Chicago, Illinois) statistical software.
Results
Patient characteristics
Overall, 42 children (25 boys, 56%) with IBD in stable clinical remission were included. Of those, 22 (52%) were affected by CD, 18 (43%) with UC and 2 (1%) with IBD-U. Their baseline characteristics are summarized in Table 1. Amongst patients with CD, 17 (77%) had non-stricturing non-penetrating disease, whilst 5 (23%) had stricturing disease. Perianal disease was recorded in 11 (50%) patients with CD. On average, patients were recruited into the study 45 months after their diagnosis, and disease duration Did not different significantly between patients with CD and patients with UC and IBD-U. Same can be said for age and sex corrected values for BW Z-score, BH Z-score and BMI Z-score at baseline. Laboratory findings were normal, except for elevated fecal calprotectin levels.
Table 1.
Baseline characteristics of included patients based on the inflammatory bowel disease (IBD) subtype.
| CD (n = 22) | UC and IBD-U (n = 20) | p-value | |
|---|---|---|---|
| Age (years) | 15.36 ± 1.75 | 15.30 ± 2.44 | 0.546 |
| Male | 14 (64%) | 11 (55%) | 0.569 |
| Pubertal status° | I: 3 (14%) | I: 4 (20%) | 0.267 |
| II: 2 (9%) | II: 2 (10%) | ||
| III: 8 (36.5%) | III: 3 (15%) | ||
| IV: 8 (36.5%) | IV: 7 (35%) | ||
| V: 1 (4%) | V: 4 (20%) | ||
| Duration of the disease (months) | 43.38 ± 7.50 | 47.45 ± 9.34 | 0.706 |
| Localization of disease* | L1 (ileal): 6 (27%) | E1 (proctitis): 1 (5%) | – |
| L2 (colonic): 2 (9%) | E2 (left-sided): 3 (15 %) | ||
| L3 (ileocolonic): 14 (64%) | E3 (extensive): 2 (10 %) | ||
| L4 (additional upper gastrointestinal disease): 10 (45%) | E4 (pancolitis): 14 (70 %) | ||
| Receiving biological (anti TNFα) therapy | 9 (41%) | 3 (15%) | 0.116 |
| Previous surgical treatment of underlying condition | 8 (37%) | – | 0.006 |
| Cumulative oral corticosteroid dose (mg prednisone received/ BW/year) | 3.18 ± 1.05 | 15.06 ± 4.58 | 0.050 |
| C-reactive protein (mg/L) | 2.2 ± 2.3 | 1.3 ± 1.4 | 0.175 |
| Hemoglobin (g/L) | 134.5 ± 13.8 | 131.2 ± 14.8 | 0.900 |
| Thrombocytes (109/L) | 285.5 ± 60.9 | 289.1 ± 80.5 | 0.524 |
| Leukocytes (106/L) | 6.4 ± 2.1 | 6.6 ± 2.0 | 0.797 |
| Albumin (g/L) | 44.4 ± 2.5 | 43.8 ± 2.2 | 0.486 |
| Serum levels of vitamin D (nmol/L) | 52.9 ± 21.6 | 49.7 ± 18.7 | 0.610 |
| Fecal calprotectin (μg/L) | 354.6 ± 534.5 | 532.5 ± 699.6 | 0.362 |
| Caloric intake (% EER met) | 94.16 ± 6.89 | 93.30 ± 6.77 | 0.940 |
| Protein intake (% daily needs met) | 178.14 ± 11.14 | 155.31 ± 7.52 | 0.182 |
| Calcium intake (% daily needs met˟) | 72.02 ± 6.97 | 49.43 ± 3.93 | 0.017 |
| Phosphorus intake (% daily needs met˟) | 105.93 ± 8.66 | 81.08 ± 2.99 | 0.016 |
| Vitamin D intake (% daily needs met˟) | 147.38 ± 34.87 | 68.65 ± 23.34 | 0.051 |
| Total PA (min/day) | 216.87 ± 24.65 | 271.11 ± 19.68 | 0.059 |
| Sedentary time (min/day) | 885.47 ± 44.76 | 739.02 ± 41.11 | 0.031 |
| LPA (min/day) | 180.02 ± 15.37 | 228.11 ± 16.43 | 0.039 |
| MVPA (min/day) | 46.98 ± 13.56 | 43.00 ± 5.61 | 0.281 |
Values are expressed as count (percentage) and mean ± SD, corrected for age and sex. *Paris classification of the inflammatory bowel disease;13 ° Pubertal status according to Tanner and Whitehouse;16 ˟ Daily nutrient needs according to the D-A-CH reference values for nutrient intake19.
BW body weight, CD Crohn’s disease, EER estimated energy requirements, IBD-U inflammatory bowel disease unclassified, LPA light physical activity, MVPA moderate-to-vigorous physical activity, PA physical activity, SD standard deviation, UC ulcerative colitis.
Primary outcomes
As shown in Table 2, a significant increase in both BW Z-score (p = 0.017) and BH Z-score (p = 0.049) has been observed throughout the duration of the study, without a statistically significant increase in BMI Z-score (p = 0.120). Moreover, based on the baseline and endpoint TBLH DXA measurements, study participants experienced an increase in total body mass from 53.21 ± 11.13 kg to 56.24 ± 12.27 kg (p < 0.001), with an increase in BMD (from 0.959 ± 0.023 g/cm2 to 0.988 ± 0.025 g/cm2, p < 0.001), FM (from 16.05 ± 1.18 kg to 17.25 ± 1.19 kg, p < 0.001) and LBM (from 37.12 ± 1.43 kg to 38.75 ± 1.61 kg, p = 0.012). BMD Z-score and FM Z-score increased significantly (from −0.35 ± 0.15 to −0.28 ± 0.17, p = 0.020 and from −0.44 ± 0.18 to −0.29 ± 0.16, p = 0.044), whilst LBM Z-score did not significantly change (from −1.78 ± 0.23 to −1.71 ± 1.49, p = 0.908). However, when BMD Z-score was corrected for height, the difference was not significant anymore.
Table 2.
Comparison of anthropometry, bone mineral density, body composition and fitness parameters at baseline and after the completion of the high-impact bodyweight exercise program.
| Baseline | Endpoint | p-value | |
|---|---|---|---|
| Body weight Z-score | 0.29 ± 0.15 | 0.40 ± 0.15 | 0.017 |
| Body height Z-score | 0.67 ± 0.16 | 0.73 ± 0.16 | 0.049 |
| Body mass index Z-score | −0.11 ± 0.18 | −0.01 ± 0.19 | 0.120 |
| Bone mineral density (g/cm2) | 0.959 ± 0.023 | 0.988 ± 0.025 | <0.001 |
| Bone mineral density Z-score | −0.35 ± 0.15 | −0.28 ± 0.17 | 0.020 |
| Height-adjusted bone mineral density Z-score | −2.43 ± 0.5 | −2.51 ± 0.9 | 0.075 |
| Lean body mass (kg) | 37.12 ± 1.43 | 38.75 ± 1.61 | 0.012 |
| Lean body mass Z-score | −1.78 ± 0.23 | −1.71 ± 1.49 | 0.908 |
| Fat mass (kg) | 16.05 ± 1.18 | 17.25 ± 1.19 | <0.001 |
| Relative fat mass (%) | 29.94 ± 1.65 | 30.75 ± 1.61 | 0.504 |
| Fat mass Z-score | −0.44 ± 0.18 | −0.29 ± 0.16 | 0.044 |
| Sit-ups (repetitions/30 s) | 19.32 ± 5.82 | 21.0 ± 6.53 | 0.024 |
| Back extensions (repetitions/30 s) | 27.39 ± 12.09 | 38.27 ± 16.1 | <0.001 |
| Push-ups (repetitions/30 s) | 17.37 ± 6.67 | 24.59 ± 7.58 | <0.001 |
| Squats (repetitions/30 s) | 22.10 ± 4.87 | 24.88 ± 6.23 | <0.001 |
| Plank position (s) | 81.0 ± 46.26 | 114.34 ± 74.06 | <0.001 |
Values are expressed as percentage and as mean ± SD, corrected for age and sex. P-values were calculated from the paired sample t-test.
Subgroup analysis of observed BMD and body composition changes is detailed in Table 3. Patients with CD experienced a significant increase in BMD (p < 0.001), BMD Z-score (p = 0.017), LBM (p < 0.001), FM (p = 0.002) and FM Z-score (p = 0.030), but not in height-adjusted BMD Z-score (p = 0.103). Patients with UC and IBD-U significantly improved only their BMD (p = 0.001). Similarly, male patients experienced an improvement in BMD (p < 0.001), BMD Z-score (p = 0.043), LBM (p < 0.001) and FM (p = 0.006), without a statistically significant change in height-adjusted BMD Z-score (0.192), LBM Z-score (p = 0.126) and FM Z-score (p = 0.079). Female patients improved only in the BMD (p = 0.046) and FM (p = 0.026), while the increase in BMD Z-score, height-adjusted BMD Z-score, LBM, LBM Z-score and FM Z-score was not statistically significant (p = 0.269, p = 0.185, p = 0.708, p = 0.225 and p = 0.317, respectively). BMD and body composition were also compared amongst prepubertal and early pubertal children and those with more advanced pubertal status. The first group experienced a statistically significant increase in BMD, BMD Z-score and LBM (p < 0.001, p = 0.020 and p < 0.001 respectively), but not height-adjusted BMD Z-score (p = 0.286), whilst the later group experienced a statistically significant increase in BMD, FM and FM Z-score (p = 0.001, p = 0.002 and p = 0.019 respectively), without a significant increase in BMD Z-score, height-adjusted Z-score, LBM and LBM Z-score (p = 0.096, p = 0.092, p = 0.667 and p = 0.519 respectively).
Table 3.
Subgroup analysis of the impact of the high-impact bodyweight exercise program on bone mineral density and body composition.
| CD (n = 22)* ° | UC and IBD-U (n = 20)* ° | |||||
|---|---|---|---|---|---|---|
| Baseline | Endpoint | p-value | Baseline | Endpoint | p-value | |
| BMD (g/cm2) | 0.945 ± 0.114 | 1.028 ± 0.124 | <0.001 | 0.950 ± 0.158 | 0.967 ± 0.165 | 0.001 |
| BMD Z-score | −0.35 ± 0.91 | 0.50 ± 1.04 | 0.017 | −0.32 ± 0.86 | −0.31 ± 0.94 | 0.641 |
| Height-adjusted BMD Z-score | −0.58 ± 0.85 | −0.4 ± 1.04 | 0.103 | −0.64 ± 0.20 | −0.60 ± 0.19 | 0.613 |
| LBM (kg) | 38.35 ± 7.09 | 43.48 ± 8.16 | <0.001 | 35.30 ± 9.80 | 35.52 ± 11.39 | 0.801 |
| LBM Z-score | −1.45 ± 1.23 | −0.44 ± 1.26 | 0.083 | −1.98 ± 1.26 | −2.12 ± 1.63 | 0.199 |
| FM (kg) | 17.37 ± 7.43 | 19.03 ± 7.49 | 0.002 | 15.11 ± 6.66 | 15.71 ± 6.73 | 0.072 |
| FM Z-score | −0.21 ± 1.10 | −0.12 ± 0.98 | 0.030 | −0.55 ± 0.97 | −0.50 ± 0.95 | 0.570 |
| Boys (n = 25)* | Girls (n = 17)** | |||||
| Baseline | Endpoint | p-value | Baseline | Endpoint | p-value | |
| BMD (g/cm2) | 0.968 ± 0.141 | 1.016 ± 0.140 | <0.001 | 0.917 ± 0.123 | 0.935 ± 0.141 | 0.046 |
| BMD Z-score | −0.28 ± 0.75 | −0.17 ± 0.86 | 0.043 | −0.42 ± 1.05 | −0.39 ± 1.14 | 0.269 |
| Height-adjusted BMD Z-score | −0.46 ± 0.13 | −0.32 ± 0.15 | 0.192 | −0.83 ± 0.26 | −0.73 ± 0.28 | 0.185 |
| LBM (kg) | 39.71 ± 9.07 | 42.76 ± 9.53 | <0.001 | 32.77 ± 5.70 | 32.39 ± 7.82 | 0.708 |
| LBM Z-score | −1.63 ± 0.96 | −1.54 ± 0.96 | 0.126 | −1.80 ± 1.64 | −1.96 ± 2.04 | 0.225 |
| FM (kg) | 14.66 ± 7.79 | 15.93 ± 7.87 | 0.006 | 18.54 ± 5.30 | 19.49 ± 5.83 | 0.026 |
| FM Z-score | −0.42 ± 1.17 | −0.24 ± 1.08 | 0.079 | −0.32 ± 0.86 | −0.27 ± 0.87 | 0.317 |
Values are expressed as mean ± SD, corrected for age* and sex°. P-values were calculated from the paired sample t-test.
BMD bone mineral density, CD Crohn’s disease, IBD-U inflammatory bowel disease-unclassified, LBM lean body mass, UC ulcerative colitis.
Secondary outcomes
All study participants remained in stable clinical remission throughout their participation in the study and no significant changes in laboratory findings were detected. Furthermore, participants consumed on average 1993 ± 704 kcal/day at the time of enrollment and 1946 ± 503 kcal/day at the end of intervention period, without any statistical change in daily caloric intake detected (p = 0.995). Similarly, daily protein, calcium and phosphorus intake did not change significantly during the study period (p = 0.309, p = 0.851 and p = 0.206 respectively). On the contrary, whilst serum levels of vitamin D increased slightly, from 51.9 ± 20.2 nmol/L to 55.6 ± 18.1 nmol/L (p = 0.096), daily vitamin D intake significantly decreased from 22.5 ± 28.7 μg/day to 15.2 ± 21.7 μg/day (p = 0.02). Patients significantly increased their fitness level by the end of the study (Table 2). We have not observed any significant changes in the daily PA patterns of study participants before and after the completion of the structured exercise program; no statistically significant changes in total time spent in PA, time spent in LPA and time spent in MVPA were detected (p = 0.402, p = 0.437 and p = 0.866 respectively).
Regression models found that none of the proposed predicted factors (age at diagnosis, disease duration, pubertal stage, use of biological therapy, EEN, glucocorticosteroid dose and surgical treatment) was associated with an increase in BMD and LBM Z-scores.
Adherence to the program was defined as exercising at least three times a week during the 26-week-long intervention period and 36 (86%) study participants completed more than 75% of the expected training sessions. Only one participant withdrew from the study, citing increased stress levels due to the COVID-19 pandemic and the Zagreb earthquake in March 2020 as the reason for withdrawal. No adverse events were noted.
Discussion
To the best of our knowledge, this is the first interventional study evaluating the impact of a personalized, home-based structured exercise program on BMD and bone composition in children and adolescents with IBD in clinical remission. Study participants experienced significant improvements in BMD and age- and sex-based BMD Z-score, as well as in LBM. Subgroup analysis showed that only patients with CD and male study participants experienced significant improvement in all parameters, whilst patients with UC and IBD-U and female patients experienced solely improvement in BMD.
Only a handful of clinical trials regarding the impact of structuralized exercise programs on BMD and body composition have been conducted in adults with IBD, the first one dating back to 199721. A total of 117 patients with CD were included in a year-long study evaluating the effects of a low-impact exercise program. Although the intervention group experienced a greater increase in BMD compared to the control group, the difference did not reach a statistical significance21. More recently, 20 adult patients with IBD in clinical remission were randomized in a cross-over trial involving eight weeks of moderate intensity aerobic and resistance training. Significant improvement in body composition was noted in the intervention group compared to the control group, with a median decrease of 2.1% body fat and a median increase of 1.59 kg of LBM, as estimated by DXA22. Finally, a study conducted amongst 47 adults with stable CD assessing the effects of 6 months of combined impact and resistance training on BMD and muscle function, concluded that the intervention led to a significantly improved BMD and muscle function amongst study subjects23.
Our earlier findings show that children and adolescents with IBD in remission spent on average 45 minutes daily engaging in MVPA, with multivariate analysis showing positive correlation between time spent in MVPA and BMD10. During resistance training, repeated muscle contractions provide effective strain on bone, leading to bone remodeling and an increased bone mass and strength24. In children and adolescents, accrual of LBM precedes the accumulation of bone calcium, also suggesting that muscle development drives bone development25. Moreover, muscle mass contributes more to bone health when compared to fat mass26. Participants in our study who experienced significant improvements in BMD also gained on average 1.6 kg of LBM and 1.2 kg of FM.
Among study participants, those with CD and male study participants benefited the most from the intervention, with significant improvements observed in BMD, age- and sex-based BMD Z-score, and LBM, whilst patients with UC and IBD-U experienced an only improvement in BMD. Female study participants experienced significant increase in BMD and FM. Since patients with UC and IBD-U received higher cumulative glucocorticosteroid doses prior to study enrollment, it is worth noting that chronic glucocorticoid exposure has been known to lead to muscle atrophy and inadequate bone accrual11. The group in question also had a higher proportion of female participants. Special consideration should be paid to the fact that during normal growth and development, FM and LBM physiologically increase in both sexes.
However, during puberty, considerable sexual dimorphism occurs; the proportion of FM increases more slowly in boys because of a simultaneous rapid increase in FFM when compared to girls27. Observed positive changes in FM and LBM Z-scores bear great importance in interpreting the results of our study. Observed positive changes in BMD Z-scores cease to be statistically significant when corrected for height. We deem it important to specify that said height adjustments were based on measurements of healthy children and adolescents whilst children with chronic illness, delayed puberty and short stature were excluded from the dataset28. The results of our study point to potential added benefits of early introduction of structured exercise program, with prepubertal and early pubertal children experiencing greater improvements not only in BMD, but also in total LBM. These findings are in line with those published in a systematic review and support the notion of prepuberty and peripuberty as key times to intervene with exercise29. Age at diagnosis, disease duration, different treatment modalities such as the use of biological therapy and pubertal stage were not found to be associated with an increase in BMD and LBM Z-score, thus indicating that the observed improvements in bone health and body composition can be attributed to the resistance training. Our personalized, home-based, structured exercise program proved to be safe, with no adverse events noted during the study. Activity logs and weekly telephone calls were employed to maximize adherence and the program proved to be feasible with 86% of study participants completing more than 75% of expected training sessions. Endpoint assessment of muscular strength and endurance clearly showed a significant increase in physical fitness among study participants. Unfortunately, it did not induce positive long-term behavioral changes and no significant difference was observed amongst participants in daily PA prior and after the completion of the program.
The most prominent limitation of the study is the lack of a control group and relatively small sample size, rendering possible that the obtained results may not be representative of the pediatric IBD population in its entirety. Furthermore, the use of a consumer-marketed accelerometer instead of a research-grade accelerometer may be interpreted as a potential limitation. However, Fitbit Charge shows similar validity for assessing MVPA compared to the research-grade monitor30. The major strength of our study is the use of DXA, widely recognized as the gold standard in estimating BMD and body composition. We have considered an extensive range of potential confounding factors including duration of the disease, treatment, age, pubertal status and dietary intake. Lastly, the structured exercise program was designed specifically for improving bone health, simultaneously allowing individual adjustments of exercise intensity based on the initial muscular strength and endurance of each child.
To conclude, a six-month-long home-based resistance training significantly improved BMD and LBM in children and adolescents with IBD in clinical remission. No adverse events were noted, confirming once again that PA does not aggravate IBD symptoms, nor does it pose other health-related risks. The role of non-pharmacological approaches like exercise therapy as an adjunct to current treatment strategies should be further explored in clinical trials. Future studies should focus on exploring the effects of different exercise modalities, with contrasting exercise types, variable training duration and frequency, on BMD and body composition in children and adolescents with IBD, in order to improve future guidelines on the topic.
Author contributions
All authors made substantial contributions to conception and design, acquisition of data, analysis and interpretation of data; drafting and revising the manuscript and have approved the final version of the manuscript.
Funding
This study was part of a research project IP-2014-09-3788 and IP-2019-04-3028 funded by the Croatian Science Foundation.
Competing interests
The authors declare no competing interests.
Consent statement
Written consent was obtained from both the patient and one of their parents or caregivers in the case of all 42 study participants.
Footnotes
The original online version of this article was revised: there were two corrections in table 1, in the row ‘Age’. The CD value was corrected from 11.75 ± 0.75 to 15.36 ± 1.75 and the UC and IBD-U has been corrected from 11.35 ± 0.83 to 15.30 ± 2.44.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
These authors contributed equally: Iva Hojsak, Sanja Kolaček.
Change history
7/21/2023
A Correction to this paper has been published: 10.1038/s41390-023-02738-4
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