The association of inflammatory bowel disease (IBD) with decreased bone mineral density has been well established in both the pediatric and adult populations (1,2). Osteopenia, defined as <1 standard deviation (SD) from the mean on dual-energy x-ray absorptiometry (DXA) scans, is reported to affect up to 50% of adult IBD patients (3). This is correlated with a significant difference in the incidence of fractures between a Canadian adult IBD population and a control group as reported by Bernstein et al. (4). Furthermore, a Dutch study noted an increase in the incidence of fractures in adult patients with Crohn disease as compared with those with ulcerative colitis (5). Several studies, including data from our institution (6), have noted lower bone mineral density measures, as determined by DXA studies, in up to 41% of children with IBD (7–9). Gokhale et al. showed a decrease in bone mineral density (BMD) between a pediatric IBD cohort and their siblings (10). The literature identifies few pediatric case reports describing vertebral fractures in patients with Crohn disease (11,12). However, to date, no study has assessed the clinical significance of decreased BMD finding in the pediatric IBD population. We therefore asked whether those patients with IBD have an increased prevalence of fractures compared with their siblings.
The primary aim of this study was to determine the prevalence of fractures in a pediatric population with IBD as compared with their healthy siblings who served as controls (SC). Secondary outcomes included identification of risk factors for fractures and to assess whether there was an association between fracture occurrence and the presence of decreased bone density within the IBD patient population. The questionnaire also examined daily dairy intake and levels of physical activity in the proceeding year.
PATIENTS AND METHODS
The study population consisted of patients followed at a pediatric IBD clinic; the controls were their siblings. Families of 209 patients with IBD followed at a tertiary pediatric care center were invited to participate in a study. Families were sent a questionnaire asking them to compare their children with IBD to a healthy SC (non-IBD). In the event of multiple children, the sibling closest in age and gender was selected for study. The surveys were mailed with an accompanying letter explaining the purpose of the study and requesting consent to participate. A reminder card was mailed to all nonresponders after 4 weeks. Additional telephone support for completing the survey was required by some families. Bone mineral density was measured by DXA scan. Lumbar spine BMD was measured using a Hologic 4500A densitometer (Hologic Inc, Bedford, MA). Uncorrected z scores for age were derived from the Hologic database (13). Interclass values ≥ 0.989 for total body, or ≥ 0.976 for legs and arms, and ≥ 0.875 for trunk and spine. Coefficient values ranged from 0.18% to 1.97% for total body, and from 0.96% to 6.91% for regional measures. The Hamilton Health Sciences research ethics board approved this project.
The survey consisted of 26 questions presented in checkbox format (see Appendix). In addition to history of fractures sustained, demographic data, type of IBD, specific information about, for example, activity level in the preceding year, dairy intake, and use of supplements was obtained.
Results were analyzed for significance using χ2 and Student t test. The prevalence rate of fractures in IBD versus non-IBD population was calculated.
Of the 209 surveys, 132 (63%) were returned. The characteristics of this sample closely resembled the overall clinic population at the time as compared for age (mean, 14.3 vs 14.7 years), gender (53% vs 59% male) and diagnosis (58.1% vs 57.8% Crohn disease). Questionnaires were obtained from 263 children, 132 IBD, and 131 non-IBD (Table 1). Fifty-five percent (n = 73) had Crohn disease, 39% (n = 52) had ulcerative colitis and 6% (n = 7) had indeterminate colitis. There were 76 males and 56 females with IBD with a mean age of 14.3 ± 3 years (range, 4–18 years). The sibling control group was almost equally matched, with 64 males and 62 females with an age range of 1 to 18 years (1 sibling was 26) with a mean age of 13.9 ± 1 years.
Of 263 children involved in the survey, 73 (28%) reported ever having a fracture. Forty-four (60%) were siblings (non-IBD) and 29 (40%) were children with IBD. Of the 29 children with IBD, 17 (59%) reported having a fracture after diagnosis, including 2 who had fractures both before and after IBD diagnosis. Although there was no statistical significance between the prevalence of fracture in the IBD (22%) versus non-IBD SC (33.6%), there were significantly more fractures in the control group compared with patients with IBD postdiagnosis (44 SC:17 IBD [postdiagnosis], P < 0.001). The total number of fractures reported was 96 (55 SC:41 IBD [NS]). There were 16 respondents with multiple fractures over the course of their lifetime, 8 with IBD and 8 SC. The number of fractured long bones as compared with all of the other bones was 68:28 (P < 0.001).
Parents were asked to characterize their children's activity levels at the time of the survey. There was no correlation between the occurrence of fracture and sporting activities. There was no significance in the rate of fractures in those with high activity levels and those with low activity levels (Table 2). However, a leading cause of fractures in both the IBD and SC populations was accidents (44 accidents:28 sports:12 unknown cause [NS]). No significant difference was identified when fractures were compared in 13 sibling controls (8 contact vs 6 noncontact sport [1 child had multiple fractures from the same activity] and in the 10 IBD patients [6 contact vs 4 noncontact]). Moreover, there proved to be no significance with respect to fracture occurrence when comparing those with high and low dairy intake (Table 2).
The questionnaire examined daily dairy intake and level of physical activity as secondary objectives (Table 2 and 3). A greater number of children with IBD with suboptimal dairy intake was identified compared with controls (55 IBD vs 33 SC). Moreover, as a group, the overall dairy intake of the IBD children was significantly lower than the overall dairy intake of their siblings using the χ2 distribution (P < 0.025). Furthermore, on analysis of their levels of physical activity, a similar trend as that observed in dairy intake was again noticed. The IBD group had many more children in the lower activity bracket than the sibling group (37 IBD:14 SC) with the overall physical activity of the IBD group being significantly lower than that of their siblings (P < 0.01).
Bone mineral density is performed yearly on most children followed for IBD. Records determined that 113 of 132 patients with IBD had DXA scans. Of the 70 patients with bone density reduced more than –1 SD, 17 had fractures and 53 were without fractures. The rate of fractures in patients with bone density reduced by >2 SD as compared with normal bone density was 24.3% vs 27.9% (NS). Bone density measures were not available for SCs.
The pathology of bone disease in IBD is complex and was recently reviewed by Sylvester (14). Many centers incorporate routine use of bone densitometry in the monitoring of their patients with IBD. However, the clinical relevance of routine bone densitometry in pediatric IBD patients has not been determined to date. In this survey, we found no statistically significant difference in the prevalence of fracture in patients with IBD compared with their normal siblings. Moreover, there were fewer total fractures in the IBD group compared with the non-IBD SC group. This is in contrast to the increased fracture incidence of approximately 40% in adult IBD patients as reported by Bernstein et al. (4). Several other adult studies in the IBD population have produced similar results (15–17), with only Stockbrugger et al. reporting on the discordance between the degree of osteopenia in adults and development of spontaneous vertebral fractures (18).
There are obvious weaknesses associated with the retrospective reporting of fractures in children by their caregivers. The relatively high rate of fractures described argues against fractures being forgotten by parents. Adult studies suggest that recall of past fractures can be reasonably accurate (19–21). The slightly greater recollection of fractures in the healthy SC argues against the concept that parents may recall fractures more frequently in “the vulnerable child” with IBD. There were no vertebral or hip fractures reported among our patients, as has been reported in adult patients (15,16) and isolated pediatric case reports (11,12).
Several studies have demonstrated decreased BMD in pediatric patients with IBD (1,8,10), with up to 50% having <2 SD from the mean on a DXA scan (8). This is similar to that seen in adult IBD patients, and thus a parallel increase in the fracture rate to the adult IBD population was anticipated. Our result, which does not identify a difference in the prevalence of fractures in IBD and controls, was unexpected. Our group has previously shown that use of industry-supplied normal values rather than local controls may overestimate the severity of bone deficit accounting for up to one half of the deficit reported in pediatric patients with IBD (13). Leonard et al. suggest this is particularly true for males (22). Furthermore, children with Crohn disease as a population are shorter and smaller than other children of the same age. Accordingly, the bone deficit may be more apparent than real for most patients, a factor partially corrected by using the patient's height age rather than chronological age for the purposes of z score determination (23). Moreover, DXA as presently performed measures total bone mineral, more of a risk factor for vertebral compression fracture than skeletal fracture. This survey failed to identify any patient reporting compression fracture, which, if asymptomatic, may only be found with vertebral radiographs. Lastly, the lighter weight of patients with Crohn disease may reduce the effect of body mass–producing injury in sports and other accidents. A population-based case-controlled study in a population of healthy Australian children found that decreased BMD was significant only in wrist and forearm fractures but not upper limb fractures at other sites (24). Thus, abnormal BMD reported as a z score from industry-supplied standards may not be as significant a predictor of fractures in children with IBD as it is in adults.
There appears to be limited data in the literature on the prevalence rate of fractures among healthy children (25) making it difficult to compare data and understand the true significance of the results. Although the study population is dissimilar, the prevalence rate of fractures reported by Wyshak in a cross-sectional study of high school girls (26) is similar to that noted in our study on the pediatric IBD population. However, the rate of fractures in the non-IBD SC appears to be higher. This interesting finding is not well explained and may reflect a higher survey response rate from families with a history of bone fracture (a potential bias would affect both IBD and SCs).
Although our group has previously reported that pediatric patients with IBD appear to be well adjusted between exacerbations (27), there appear to be lower physical activity levels in this group in the previous year. These results should be interpreted with caution because they represent a “snapshot” activity profile. However, if true, lower activity by patients with IBD may represent the phenomenon of “sheltering.” This speculation is being addressed in follow-up studies. Furthermore, our findings indicate that there is no significant difference in the occurrence of fractures between those who participate in contact (or high impact) and non-contact (low impact) sports. Most fractures reported were as a result of accidents (mainly falls); this may have skewed the results in favor of more fractures in healthy siblings. A recent review supports an association of injury and high-risk behavior (28) and an associated increase in the rate of fractures in children with high-risk behavior (29). The relatively high prevalence of fractures among SC raises the possibility that siblings of children with IBD may participate in more high-risk activities. Studies in other chronic diseases of childhood suggest the existence of such a phenomenon (30). Although much has been published on the quality of life for the pediatric patient with IBD (31,32), there is no similar data on their siblings.
Finally, our patients with IBD are observed on a regular basis and the families enjoy the benefit of counseling by a registered dietitian. It was notable that there was decreased dairy intake in this patient group. Perceived fears of lactose intolerance symptoms may influence dairy intakes in this patient population. Although calcium and vitamin D intake may play a role in the etiology of bone disease in the IBD population, this decreased intake needs to be interpreted with caution because the SC had an increased fracture rate despite an increased dairy intake considered adequate by the Health Canada food guide (33).
Our study is unique in the pediatric age group; however, there are several limitations. This is a retrospective study and is subject to recall biases. The control group is not age matched and the radiological diagnosis of the fracture was not verified. Despite a reasonable response rate, the number of participants is relatively small, and the study lacks power for subgroup analysis. However, this study opens the door to several intriguing questions, foremost being the clinical relevance of decreased BMD reports in the pediatric IBD population. These findings need to be confirmed because, if consistent, they would have implications in the treatment of BMD in pediatric IBD. Existing guidelines presently recommend the use of bisphosphonates in some adult patients with IBD requiring treatment with corticosteroids (34). Moreover, bisphosphonates are also used in the treatment of certain pediatric metabolic bone disease (35,36), including children with cancer (37). This report suggests that the clinical significance of apparent bone deficit in children with IBD needs to be clarified before considering bisphosphonate treatment in this population. Further studies defining the fracture risk in the pediatric IBD population are necessary before embarking on protocolized bone densitometry screening and treatment of bone deficit in this patient population.
Bone Fracture Questionnaire for IBD Patients and Healthy Siblings
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