Decreased bone mass has been frequently reported in children and adults with inflammatory bowel disease (IBD) (1–4). Because of significant differences in normal bone physiology in children and adults, IBD probably affects skeletal health differently in these 2 populations. During childhood, bones are sculpted through a process called modeling. Although the growth plate is responsible for longitudinal growth, modeling results in changes in bone shape, width and size until skeletal maturity is achieved. Modeling involves the simultaneous activities of osteoblasts and osteoclasts on bone surfaces, resulting in the generation of relatively large amounts of bone tissue. Bone remodeling occurs in both adults and children. The apparent function of remodeling is to replace fatigued or stressed bone, and quantum amounts of bone are removed and laid down again in discrete microscopic foci. Remodeling is characterized by an initial wave of resorptive osteoclasts followed by a second wave of bone-forming osteoblasts that fill the resorption lacuna with collagenous matrix that later becomes calcified. In adults, both total bone mass and structural integrity are maintained by bone remodeling (5). Remodeling also plays an important role in calcium homeostasis and acid-base equilibrium, by releasing stored calcium and phosphate into the circulation.
Bone mass is an important determinant of skeletal strength, but it is clearly not the only one. Connectivity and orientation of trabeculae in cancellous bone, as well as bone stiffness and resistance to deformation (eg, bone quality), also play important roles in resistance to mechanical failure. Bone thinning associated with postmenopausal or aging-related osteoporosis and other systemic diseases in adults has an impact on both bone mass and bone quality and is due to the subversion of normal bone remodeling. In these disorders, bone formation by osteoblasts can no longer keep up with osteoclastic bone resorption, resulting in bone loss and breakdown of the bone microarchitecture. Over time, this weakened bone is not able to sustain ordinary mechanical strain (eg, bending over) or minor trauma (eg, a fall from standing height) and will fracture. In adults with IBD, increase bone resorption may be the primary mechanism for bone loss, together with reduced osteoblast activity (6–9).
Because in the developing skeleton bone modeling (and not remodeling) is the dominant process, net bone formation will be susceptible to the effects of IBD. In pediatric patients it has been shown that active IBD markedly decreases bone metabolic activity, especially bone formation (10). It is likely that inflammatory (10–12), nutritional and hormonal mechanisms (13,14) are responsible. Therefore, IBD affects skeletal health differently in adults and in children. In children, the predominant disease phenotype appears to be one of growth arrest, with dormant bone metabolism, at least at diagnosis, whereas in adults increased bone dissolution appears to be the main mechanism. This fundamental difference needs to be considered when choosing therapies to improve skeletal mass in patients with IBD.
Do these alterations in bone cell function increase fracture risk in patients with IBD? Because clinically the only important clinical manifestation of decreased bone mass is fracture, this question is essential for our patients. In adults with IBD, fracture risk appears to be modestly increased (15–19). For children with IBD, the risk is unknown. Vertebral compression fractures have been reported (20), but no systematic studies of fracture risk have been performed. In this issue of the Journal of Pediatric Gastroenterology and Nutrition, Persad et al. have taken an important first step to examine this issue. The investigators distributed a questionnaire containing queries about fracture occurrence, general physical activity level, and dairy intake for the preceding year to 209 patients with IBD; 132 questionnaires were returned. The authors conclude that the prevalence of fracture is similar in healthy siblings, but it is not similar in children with IBD. This should be reassuring to our patients. Persad et al., however, noted a trend toward higher fracture prevalence in the unaffected control group, which, if confirmed in future studies, could be explained by “sheltering” of the child with IBD, or by more adventurous behavior by the unaffected sibling, perhaps to gain attention. This is an interesting possibility that the authors are pursuing. Moreover, there was no significance in the rate of fractures in those individuals with high activity levels and those with low activity levels, or individuals with high or low dairy intake, despite the fact that children with IBD tended to be less active and consume fewer dairy products. Bone mineral density as measured by dual-energy x-ray absorptiometry did not predict fracture risk.
Although this study is the first of its kind in children with IBD, it has limitations. Its major weakness is that it is retrospective and based on recall on a questionnaire. Families whose children had fractures (either in the child with IBD or his or her sibling) may have been more likely to return the questionnaire than families whose children never had fractures, which may explain why overall frequency of fractures in this cohort is higher than previously reported in healthy children (21). The selection of healthy siblings as controls has advantages because they share a similar environment with their siblings with IBD. However, because the frequency of traumatic fractures varies by age and sex (21), the controls would have to be closely matched to the cases to be comparable, and in this study gender frequency was unbalanced. Subsequent studies of this type should include a matched control group for age, sex and race. In addition, because genetic makeup is the most important determinant of bone mass, it will be important to include a study group of unrelated children in future work. Furthermore, asymptomatic vertebral fractures, which may not be uncommon in patients with IBD (22), were not studied. In the future, formal vertebral fracture assessment should be performed in children with IBD. The sample size in the Persad et al. study may have been inadequate to detect differences in fracture rates between the 2 study groups.
These limitations notwithstanding, the study by Persad et al. should spark interest in developing prospective multicenter collaborations to examine the prevalence of traumatic and pathological fractures in children with IBD at various skeletal sites (eg, long bones, spine). Because IBD could induce failure to produce a skeleton of optimal mass and strength during growth, which may increase fracture risk later in life, it would be of interest to study individuals who were diagnosed with IBD during childhood. These studies should be powered to show the influence of various therapies on bone mass and fracture risk over time and to separately analyze patients with Crohn disease and ulcerative colitis. In the meantime, attention to disease control, nutrition and physical activity will probably help to optimize skeletal health in children with IBD.
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