Assessment of Bone and Mineral Metabolism in Inflammatory Bowel Disease: Case Series and Review

doi:10.4158/EP.12.6.622

Endocrine Practice

Volume 12, Issue 6, November–December 2006, Pages 622-629

https://doi.org/10.4158/EP.12.6.622 Get rights and content

ABSTRACT

Objective

To determine the prevalence of low bone mass, fractures, and vitamin D deficiency and the levels of biochemical markers of mineral metabolism in patients with inflammatory bowel disease (IBD).

Methods

Our retrospective study consisted of 30 patients with Crohn’s disease (CD) and 18 patients with ulcerative colitis (UC). Dual-energy x-ray absorptiometry was performed to determine bone mineral density at the lumbar spine and hip. Serum calcium, phosphorus, parathyroid hormone, 25-hydroxyvitamin D (25-OHD), and 1,25-dihydroxyvitamin D, urinary N-telopeptide cross-linked collagen type I, and 24-hour urinary calcium levels were evaluated.

Results

On the basis of Z-score definitions of low bone mass in the IBD group as a whole, 13 patients (27%) had low bone mass at the lumbar spine. Similarly, at the femoral neck, 13 patients (27%) had low bone mass. There was a higher prevalence of low bone mass in the UC group than in the CD group, consistent with a high prevalence of fractures in that group. Of all patients with IBD, 65% had a history of fractures, of which 23% were atraumatic. Deficiency of 25-OHD was high, with a prevalence of 55% in patients with UC and 83% in patients with CD. Secondary hyperparathyroidism, defined as a parathyroid hormone level > 55 pg/mL in conjunction with a low or normal serum calcium and a low 25-OHD level, was present in 50% of patients with CD and only 7% of patients with UC.

Conclusion

Metabolic bone disease and fractures are common in IBD. The mean bone mineral density of the spine or femoral neck did not differ significantly between patients with CD and those with UC. Patients with UC had a higher prevalence of low bone mass, as defined by a Z-score of less than -2, than did patients with CD, consistent with a high prevalence of fractures in the UC group. In contrast, hyperparathyroidism attributable to vitamin D deficiency was more prevalent in patients with CD than in those with UC. This finding suggests a different etiologic mechanism of low bone mass in patients with CD. (Endocr Pract. 2006;12:622-629)

Section snippets

INTRODUCTION

Inflammatory bowel disease (IBD) is a common disorder, affecting up to 1 million Americans (1). Low bone mass is a common extraintestinal feature of IBD. In cross-sectional studies, the prevalence of low bone mass in patients with IBD ranges from 11% to 78% (2). The incidence of fractures among patients with IBD is 40% higher than in the general population (3). Despite these facts, few patients with IBD receive prophylactic treatment.

The skeletal manifestations of IBD include osteoporosis and

Study Cohort

This study was approved by the institutional review board of the Cleveland Clinic Foundation. Patient data were obtained from the metabolic bone clinic database from 1995 to 2002. Men and women between 15 and 78 years old, with mean and median ages of 48 and 45 years, respectively, who had a diagnosis of CD (N = 30) or UC (N = 18) were selected for analysis. Exclusion criteria eliminated all patients with IBD who had primary or tertiary hyperparathyroidism, renal failure, transplantation, or

RESULTS

Forty-eight patients with IBD fulfilled the criteria for inclusion. Thirty patients with CD (14 female and 16 male subjects; mean age, 48.0 ± 12.0 years) and 18 patients with UC (9 female and 9 male subjects; mean age, 48.9 ± 15.7 years) were studied.

DISCUSSION

In this retrospective study, we found a high prevalence of low bone mass, fractures, and vitamin D deficiency in patients with IBD. Patients with UC had a higher prevalence of low bone mass at the spine and hip than did patients with CD, consistent with high fracture rates in that group. Bone turnover and resorption as reflected by PTH and NTX levels, respectively, were higher in the CD group in comparison with the UC group. Fifty percent of our patients with CD had secondary

CONCLUSION

Our study demonstrates the high prevalence of low bone mass and fractures in patients with IBD. Our data highlight the multifactorial etiology of bone loss in IBD, with emphasis on malabsorption, vitamin D deficiency, and secondary hyperparathyroidism as a pathophysiologic mechanism, especially in patients with CD. Although mean BMD values were comparable between CD and UC groups, markers of bone metabolism differed significantly between these groups. This finding suggests differing mechanisms

DISCLOSURE

The authors have no conflicts of interest to disclose.

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Cited by (29)

Prevalence and Predictors of Reduced Bone Density in Child and Adolescent Patients With Crohn's Disease
2021, Journal of Clinical Densitometry
Reduced bone mineral density (BMD) has broadly been found to be associated with inflammatory bowel disease across a number of geographical locations and cultures. We aimed to estimate the prevalence of reduced BMD and identify clinical predictors in a cohort of Crohn's disease patients (CD) in Saudi Arabia. We conducted a retrospective study involving children and adolescents with CD between 2013 and 2018. BMD was evaluated using dual-energy X-ray absorptiometry scans of the spine and body. A multivariate analysis was performed for the detection of predictors of low BMD. Sixty-four patients were enrolled. The median age was 16 years (range, 8–19 years) and 55% of patients were males. Total body BMD scanning identified 25 patients (39%) with osteoporosis. Twenty patients (31.3%) were found to have z scores consistent with osteopenia. A multivariate regression analysis identified a low weight-for-age z score (B coefficient = 0.347, 95% confidence interval [CI] = 0.211–0.482, p < 0.001 for Spine BMD and B coefficient = 0.321, 95% CI = 0.170–0.472, p < 0.001 for total body BMD), a low height-for-age z score (B coefficient = 0.187, 95% CI = 0.035–0.338, p = 0.017 for spine BMD and B coefficient = 0.0.258, 95% CI = 0.089–0.427, p = 0.004 for total body BMD), a low 25-hyroxyvitamin D level (B coefficient = 0.026, 95% CI = 0.013–0.038, p < 0.001 for spine BMD and B coefficient = 0.016, 95% CI = 0.002–0.031, p = 0.026 for total body BMD), and a higher number of corticosteroid induction courses (B coefficient = −0.567, 95% CI = −0.923 to −0.212, p = 0.003 for spine BMD and B coefficient = −0.566, 95% CI = 0.963–0.169, p = 0.007 for total body BMD) as predictors of low BMD. In the spine BMD analysis, older age at the time of presentation was identified as a significant predictor for low bone density (B coefficient = 0.254, 95% CI = 0.141–0.368, p < 0.001). In conclusion, Saudi Arabian children and adolescents with CD have a high prevalence rate of low bone density compared to Western populations. Several clinical characteristics are identified as significant predictors for low BMD.
Vitamin D status in relation to Crohn's disease: Meta-analysis of observational studies
2016, Nutrition
Inconsistent findings have been published regarding vitamin D status among patients with Crohn's disease (CD) and the association with disease severity. We aimed to perform a meta-analysis evaluating serum 25-hydroxy vitamin D and 1,25 dehydroxyvitamin D among CD patients compared with healthy and non-healthy controls, the prevalence of vitamin D deficiency, and the association with disease.
We searched MEDLINE, SCOPUS, EMBASE, and Google Scholar up to March 2015 for observational studies assessing serum vitamin D levels in CD patients. A total of 63 studies were included in the following four meta-analyses: 1) a meta-analysis on the mean difference of 25(OH)D levels in CD patients compared with healthy (number of studies = 27) and non-healthy (n = 25) controls; 2) a meta-analysis on the mean difference of 1,25(OH)₂ D₃ levels in CD patients compared with healthy (n = 7) and non-healthy (n = 8) controls; 3) a meta-analysis on the prevalence of vitamin D deficiency (n = 34); 4) a meta-analysis on the correlation coefficients between vitamin D status severity of CD (n = 6). Subgroup analysis and meta-regression were used to discover possible sources of between-study heterogeneity.
It was found that CD patients had lower levels of 25(OH)D compared with healthy (−3.99 ng/mL; 95% confidence interval [CI]: −5.91 to −2.08) but not non-healthy controls (−1.07 ng/mL; 95% CI: −2.84 to 0.70). There was also no significant mean difference for 1,25(OH)₂ D₃ for both healthy and non-healthy controls. Meta-analysis on the prevalence of vitamin D deficiency showed an overall prevalence of 57.7% (95% CI: 0.502–0.649). An inverse association was observed between serum vitamin D and severity of CD (−0.36; 95% CI: −0.48 to −0.24). Meta-regression showed that mean levels of 25(OH)D were decreased 0.09 for each unit change of latitude among CD patients compared with healthy controls (B = −0.09, P = 0.004, I² _residual = 86.08%).
We found that patients with Crohn's disease had lower serum 25(OH)D concentrations compared with their healthy counterparts, and more than half of them have hypovitaminosis D. Moreover, there was an inverse correlation between circulating 25(OH)D concentrations and severity of Crohn's disease.
Critical roles of intestinal epithelial vitamin D receptor signaling in controlling gut mucosal inflammation
2015, Journal of Steroid Biochemistry and Molecular Biology
Although vitamin D receptor (VDR) is highly expressed in the intestine, the role of VDR signaling in the gut is not fully understood. Our recent studies unveil a regulatory circuit that centers gut epithelial VDR as a key molecule in the control of mucosal inflammation and colitis development. On the one hand, intestinal epithelial VDR signaling protects the integrity of the mucosal barrier by inhibiting inflammation-induced epithelial cell apoptosis. This barrier-protecting, anti-colitic activity is independent of the non-epithelial immune VDR actions. A healthy and intact mucosal barrier prevents bacterial invasion and thus reduces mucosal inflammation. On the other hand, inflammation in turn down-regulates epithelial VDR expression by inducing VDR-targeting microRNA-346, thus compromising mucosal barrier functions. Consistently, colonic epithelial VDR levels are markedly reduced in patients with inflammatory bowel diseases or in experimental colitis models, whereas vitamin D analog therapy that ameliorates colitis up-regulates epithelial VDR. Thus, gut epithelial VDR signaling appears to play an essential role in controlling mucosal inflammation and thus could be a useful therapeutic target in the management of inflammatory bowel diseases.
This article is part of a special issue entitled ‘17th Vitamin D Workshop’ .
How Activity of Inflammatory Bowel Disease Influences Bone Loss
2010, Journal of Clinical Densitometry
Bone loss is a common problem for individuals with inflammatory bowel disease (IBD). The aim of our study was to assess bone mineral density (BMD) in patients with IBD and to investigate the role of corticosteroid (CS) use and duration and activity of disease on BMD. Ninety-two patients (56 men and 36 women) with IBD, of whom 32 had ulcerative colitis (UC) and 60 had Crohn's disease (CD), underwent clinical assessment. Lumbar and femoral neck BMDs were measured by dual-energy X-ray absorptiometry. Osteopenia was observed in 14 patients (43%) with UC and in 24 patients (40%) with CD (p = 0.187). Four patients (12%) with UC and 7 patients (11%) with CD had osteoporosis (p = 0.308). Femoral BMD decreased in patients with long duration of CS use and correlated inversely with disease activity. Multiple regression analysis of BMD showed that statistically significant risk factors were duration of active disease and body mass index as well. Based on our results, it is necessary to take into account the risk of decreased BMD in patients with IBD. It is most important to achieve disease remission as soon as possible in addition to nutritional support.
High prevalence of low bone mineral density in patients with Inflammatory Bowel Disease in the setting of a peripheral Dutch hospital
2008, Journal of Crohn's and Colitis
Osteopenia and osteoporosis are frequently encountered in patients with Inflammatory Bowel Disease (IBD). Our aims were to evaluate the actual practice of screening for low bone mineral density (BMD) by dual energy X-ray absorptiometry (DEXA), to determine the prevalence of low BMD and to investigate the risk factors associated with a low BMD in the IBD population of a regional Dutch hospital.
A retrospective chart review was performed in 474 patients (259 with ulcerative colitis, 210 with Crohn's disease and 5 with indeterminate colitis). DEXA results and potential predictive factors of low BMD were documented. Predictive factors of low BMD were assessed by logistic regression.
DEXA was performed in 168 IBD patients (35.4%). A low BMD (T-score < − 1) was present in 64.3%. Osteoporosis (T-score < − 2.5) was found in 23.8%. Low BMI, older age at the moment of diagnosis and male gender were found to be predictive factors of low BMD. For patients with osteoporosis, disease duration was an additional predictive factor. After subgroup analysis predictive factors were found to be the same in patients with Crohn's disease.
The prevalence of osteopenia and osteoporosis in IBD patients in a regional centre is as high as the prevalence rates reported from tertiary referral centres. A low BMI, an older age at the moment of diagnosis and male gender were predictive factors of low BMD. Prediction of osteoporosis and osteopenia using risk factors identified in this and previous studies is presently not feasible.
Active Crohn disease and hypercalcemia treated with infliximab: Case report and literature review
2008, Endocrine Practice
To report a case of 1,25-dihydroxyvitamin D–mediated hypercalcemia caused by active Crohn disease that improved with infliximab therapy.
We present the clinical and laboratory findings and describe the clinical course of a patient who had hypercalcemia during Crohn disease exacerbations. The literature is reviewed regarding 1,25-dihydroxyvitamin D production in Crohn disease, and the 3 cases of hypercalcemia in individuals with Crohn disease reported in the literature are described.
A 50-year-old man with long-standing Crohn disease treated with multiple bowel resections presented for take-down ileostomy. He was hypercalcemic and had suppressed parathyroid hormone and parathyroid hormone–related peptide levels. Histopathology of the resected ileostomy site and adjacent small bowel indicated active Crohn disease. Hypercalcemia promptly resolved after a few days of treatment with intravenous glucocorticoids. One month later, hypercalcemia recurred in the presence of an inappropriately high 1,25-dihydroxyvitamin D level and increased urinary calcium and serum angiotensin-converting enzyme levels. The serum and urinary calcium levels became normal with infliximab therapy. Three previous reports of hypercalcemia caused by active Crohn disease describe effective treatment with glucocorticoids. This is the first report of successful response to infliximab in this setting.
Hypercalcemia mediated by 1,25-dihydroxyvitamin D in the setting of Crohn disease may respond to glucocorticoid-sparing immunomodulators. (Endocr Pract. 2008;14:87-92)

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Original ArticleAssessment of Bone and Mineral Metabolism in Inflammatory Bowel Disease: Case Series and Review

ABSTRACT

Objective

Methods

Results

Conclusion

Section snippets

INTRODUCTION

Study Cohort

RESULTS

DISCUSSION

CONCLUSION

DISCLOSURE

Am J Gastroenterol.

Gastroenterology.

Gastroenterology.

Gastroenterology.

Clin Gastroenterol Hepatol.

Clin Gastroenterol Hepatol.

Management of bone loss in inflammatory bowel disease

Semin Gastrointest Dis.

Inflammatory bowel disease and osteoporosis

Scand J Gastroenterol.

The incidence of fracture among patients with inflammatory bowel disease: a population-based cohort study

Ann Intern Med.

Vitamin D status, parathyroid hormone and bone mineral density in patients with inflammatory bowel disease

Scand J Gastroenterol.

Bone disease in vitamin D-deficient patients with Crohn’s disease

Dig Dis Sci.

Reduced bone density in patients with inflammatory bowel disease

Gut.

Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures

SMJ.

Efficacy of risedronate administration in osteoporotic postmenopausal women affected by inflammatory bowel disease

Osteoporos Int.

Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D

J Am Coll Nutr.

Original Article
Assessment of Bone and Mineral Metabolism in Inflammatory Bowel Disease: Case Series and Review