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

Vitamin D deficiency is frequently observed in patients with Crohn's disease and may be associated with an increased risk of development of metabolic bone disease. To estimate the incidence of metabolic bone disease by noninvasive methods, 31 patients (17–75 years old) with Crohn's disease and low 25-hydroxy vitamin D (25-OHD) levels in winter were investigated in the following summer by measuring the bone mineral content (BMC) of the distal radius by single photon absorptiometry and the cortical area ratio (CAR) calculated from radiographs of the right hand and by x-ray of the lumbar spine. Forty-five percent of the patients showed signs of metabolic bone disease. BMC and CAR correlated with 25-OHD serum levels (P<0.05), especially in men. Furthermore, the amount of sun exposure has an influence not only on 25-OHD serum levels both in summer and in winter (P=0.0006), but also on the BMC (P=0.07). Consequently, vitamin D deficiency is of major importance for the development of metabolic bone disease in patients with Crohn's disease. Vitamin D deficiency can be prevented by increasing sun exposure and long-term vitamin D supplementation.     

Longitudinal study of bone mineral density in patients with Crohn's disease

Osteoporosis is frequent in Crohn's disease. The aim of the study was to assess the rate of bone loss over time retrospectively and the influence of disease-related factors on bone loss. Twenty-nine patients (8 male), admitted for repeated bone mineral density assessments (BMD) were enrolled. BMD measured by dual energy x-ray absoptiometry was expressed in grams per square centimeter, and as sex- and age-matched Z score. The mean interval between BMD assessments was 41 months, during which period 27 patients used corticosteroids (mean dose 8.6 g) and 21 patients some form of bone protective medication. Initial Z scores at a mean age of 41 years were significantly below zero (spine –1.6 ± 1.4; femur –1.4 ± 1.4). Over time, no change in absolute BMD was observed accompanied by an improvement in Z scores. At the same time, an increase in body weight and a decrease in erythrocyte sedimentation rate (ESR) was observed. Multilinear regression analysis demonstrated change in ESR as independent predictor for change in femoral Z score. In conclusion, low BMD is frequent in Crohn's disease, but decline of BMD over time was not found, despite ongoing use of corticosteroids.     

Mutifactorial analysis of risk factors for reduced bone mineral density in patients with Crohn＇s disease

AIM: To determine the prevalence of osteoporosis in a cohort of patients with Crohn's disease (CD) and to identify the relative significance of risk factors for osteoporosis. METHODS: Two hundred and fifty-eight unselected patients (92 M, 166 F) with CD were studied. Bone mineral density (BMD) was measured at the lumbar spine and hip by dual X-ray absorptiometry. Bone formation was assessed by measuring bone specific alkaline phosphatase (BSAP) and bone resorption by measuring urinary excretion of deoxypyridinoline (DPD) and N-telopeptide (NTX). RESULTS: Between 11.6%-13.6% patients were osteoporotic (T score < -2.5) at the lumbar spine and/or hip. NTX levels were significantly higher in the patients with osteoporosis (P < 0.05) but BSAP and DPD levels were not significantly different. Independent risk factors for osteoporosis at either the lumbar spine or hip were a low body mass index (P < 0.001), increasing corticosteroid use (P < 0.005), and male sex (P < 0.01). These factors combined accounted for 23% and 37% of the reduction in BMD at the lumbar spine and hip respectively. CONCLUSION: Our results confirm that osteoporosis is common in patients with CD and suggest that increased bone resorption is the mechanism responsible for the bone loss. However, less than half of the reduction in BMD can be attributed to risk factors such as corticosteroid use and low BMI and therefore remains unexplained.     

Diagnostic value of calcaneal quantitative ultrasound in the evaluation of osteoporosis in middle-aged and elderly patients

To study the correlation between calcaneal quantitative ultrasound (QUS) and dual-energy X-ray absorptiometry (DXA), and analyze the diagnostic value of calcaneal QUS in the evaluation of middle-aged and elderly osteoporosis.We assessed bone mineral density (BMD) at the femoral neck and intertrochanteric of left hip and lumbar spine (L1–L4) sites with DXA and QUS parameters of the right and left calcanei in a cohort of 82 patients over the age of 50 years. Using DXA parameters as the gold standard for the diagnosis of osteoporosis, the correlation coefficient between BMD and QUS parameters was calculated. Receiver operating characteristic curve was generated and areas under the curves were evaluated. Cut-off values for QUS were defined.In men, there was a moderate correlation between calcaneal QUS and proximal femoral BMD (P < .05), but no significant correlation between calcaneal QUS and lumbar BMD (P > .05). In women, calcaneal QUS were moderately correlated with lumbar spine and proximal femoral BMD (P < .05). Using DXA as the gold standard, the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of calcaneal QUS in the diagnosis of osteoporosis were 90.2%, 89.2%, 100%, 100%, and 50.0%, respectively. According to the receiver operating characteristic curve, when the QUS T-score of calcaneum was –1.8, the area under the curve was 0.888, the sensitivity was 73.21%, and the specificity was 92.31% (P < .05). When the QUS T-score of calcaneum was –2.35, the sensitivity was 37.2% and the specificity was 100%.Calcaneal QUS can be used to predict proximal femoral BMD in middle-aged and elderly people, as well as lumbar BMD in women. As a screening method for osteoporosis, calcaneal QUS has good specificity, so it can be recommended to use it as a pre-screening tool to reduce the number of DXA screening. When the QUS T-score of calcaneum is –1.8, it has the greatest diagnostic efficiency for osteoporosis; when the QUS T-score of calcaneum is ≤–2.35, it can be diagnosed as osteoporosis.     

Poor correlations between measurements of bone quality by quantitative ultrasound sonography and dual energy X-ray absorptiometry in patients with beta-thalassaemia major

Objectives: Osteopenia/osteoporosis is a major component of morbidity even in young patients with β‐thalassaemia major. Dual energy X‐ray absorptiometry (DXA) is the reference method for determining bone mineral density (BMD). Quantitative ultrasound sonography (QUS) for bone measurement is a relatively new, inexpensive and radiation‐free method that could serve as an alternative to DXA. Our aim was to assess bone status in thalassaemic patients both with QUS and DXA and, consequently, to investigate the degree of correlation between the two methods. Methods: Thirty‐three patients (15 male and 18 female) with β‐thalassaemia major, regularly transfused and systematically iron‐chelated, participated in the study. Mean age was 22.0 ± 8.0 yr (range: 6.5–41.0 yr). All patients were evaluated with QUS at radius and tibia and had DXA scan at lumbar spine vertebrae (L2–L4), whereas 20 patients were additionally assessed with DXA at the left hip (femoral neck, trochanter region and Ward’s triangle). Results: Results were expressed as Z‐scores compared with sex‐ and age‐matched population. Lowest mean Z‐scores measured with DXA were recorded at lumbar spine and Ward’s triangle (?1.1 ± 1.13 and ?0.95 ± 1.07, respectively). Lowest mean QUS‐derived Z‐scores were measured at radius, statistically significant compared with Z‐scores measured at tibia (?0.6 ± 1.1 vs. 0.4 ± 1.1, P < 0.001). QUS measurements at radius were significantly correlated to QUS measurements at tibia (r = 0.51, P = 0.002). The latter were correlated to BMD measured at lumbar spine (r = 0.516, P = 0.002) and at trochanter region (r = 0.646, P = 0.003). All BMD measurements at hip were significantly correlated to each other. Lumbar spine BMD was correlated to BMD at femoral neck (r = 0.607, P = 0.003) and to BMD at Ward’s triangle (r = 0.438, P = 0.027). Finally, no agreement was recorded between the two methods in identifying thalassaemic patients at risk for osteoporosis (κ = 0.203, P = 0.04). Conclusion: Quantitative ultrasound sonography could not serve as an alternate to DXA.     

Dietary calcium intake and its relation to bone mineral density in patients with inflammatory bowel disease

Objectives. To investigate calcium intake and its association with bone mineral density (BMD) and the type and extent of the disease in patients with inflammatory bowel disease (IBD).
Setting. University hospital clinic.
Subjects. A total of 152 unselected IBD patients and 73 healthy controls.
Measurements. Dietary calcium intake was assessed with a food frequency questionnaire and BMD of the lumbar spina and proximal femur was measured.
Results. The IBD patients had lower dietary calcium intake (1034 [SD 493] mg) than the controls (1334 [514] mg, P <0.001). The difference was significant in the males (1047 [552] mg and 1575 [586] mg, respectively, P <0.001), but not in the females (1020 [422] mg and 1112 [303] mg). The dietary daily calcium intake was below 1000 mg in 53% of the patients and 27% of the controls ( P = 0.0004) and below 400 mg in 9.2% of the patients and none of the controls ( P =0.007). The calcium intake was not associated with the severity or the type of IBD. Seventy-one (47%) patients and eight (11%) controls avoided lactose in their diet ( P < 0.001). In the IBD patients, no association between the calcium intake and BMD was detected, whereas in the controls a positive correlation between the calcium intake and the BMD of the proximal femur was found.
Conclusions. Calcium intakes below the recommendations are seen more often in the IBD patients than in the healthy controls, but in the IBD patients the calcium intake is not associated with BMD in a cross-sectional study. A low-lactose diet is common among IBD patients. To reduce the risk of inadequate calcium intake, unnecessary dietary restrictions concerning, e.g. milk products, should be avoided for these patients.     

Altered bone metabolism in inflammatory bowel disease: there is a difference between Crohn's disease and ulcerative colitis

OBJECTIVES: The aims of this study were to assess bone metabolism in inflammatory bowel disease (IBD) patients and to evaluate potential differences between Crohn's disease (CD) and ulcerative colitis (UC) with respect to the mechanisms underlying bone loss in this group of diseases. DESIGN AND SETTING: This was a cross-sectional study which started in 1992. Patients were randomly selected for invitation to participate and were examined during the years 1992-95 in one research clinic in Milan. SUBJECTS AND METHODS: Fifty-one patients suffering from CD (30 women and 21 men, mean age 38.7 +/- 13.2 years) and 40 with UC (15 women and 25 men, mean age 34.4. +/- 12.5 years) entered the study. Thirty healthy subjects were selected as sex- and age-matched controls (C). Spine and femoral neck bone mineral density (expressed as T score), calciotropic hormones (parathyroid hormone, PTH; 25-hydroxycholecalciferol, 25(OH)D3; 1,25-hydroxycholecalciferol, 1, 25(OH)D3) and biochemical markers of bone turnover (ostecalcin, OC; total alkaline phosphatase, ALP; type I collagen C-terminal telopeptide, ICTP) were evaluated. RESULTS: Spine and femur T scores were similar in the two groups (spine: CD = -1.49 +/- 1.46; UC = -1. 67 +/- 1.13; femur: CD = -1.80 +/- 1.36; UC = -1.60 +/- 1.03). Based upon the WHO guidelines, only 8% of CD patients and 15% of UC patients had a normal bone mineral density (BMD), 55% (CD) and 67% (UC) were osteopenic, and 37% (CD) and 18% (UC) were osteoporotic. The distribution amongst the three different diagnostic groups was not significantly different between CD and UC groups (P = 0.11). PTH and 25(OH)D3 concentrations were not significantly different between CD and UC patients and controls, whilst 1,25(OH)D3 concentrations were significantly lower in both CD and UC patients compared with controls (P < 0.05). Bone turnover was increased in UC but not in CD patients, as shown by significantly increased concentrations in UC patients of both OC (CD = 7.77 +/- 5.06, UC = 10.03 +/- 6.24, C = 6. 58 +/- 2.87, P < 0.05 vs. C) and ICTP (CD = 5.74 +/- 3.94, UC = 10.2 +/- 8.47, C = 3.48 +/- 0.95, P < 0.05 vs. CD and C). In a stepwise regression that included age, sex, disease duration and cumulative prednisolone dose as independent variables, the femur T score was significantly inversely related to disease duration (r2 = 0.125, F = 6.06) in CD patients. In UC patients, the spine T score was inversely related to age (r2 = 0.107, F = 5.49) and significantly related to sex (more negative in males: r2 = 0.3, F = 16.1); the femur T score was significantly related to sex (more negative in males) and inversely related to the cumulative prednisolone dose (r2 = 0.283, F = 7.3). CONCLUSIONS: These data show that IBD patients have a diffuse osteopenia, the degree of which is not different in CD and UC; however, bone turnover is significantly higher in UC. Finally, osteopenia is related to disease duration in CD, whilst it is related to the male sex and glucocorticoid treatment in UC.     

Low bone mineral density in patients with inflammatory bowel disease

To assess the prevalence and risk factors for low bone mineral density in inflammatory bowel disease, we studied 61 consecutive patients, mean age 36±11 years. Twenty-seven had a Crohn's disease and 34 ulcerative colitis (including 13 with ileoanal anatomosis). Three patients, two women and one man (32, 70, and 45 years old, respectively) had vertebral crush fractures. Bone mineral density measured by dual energy x-ray absorptiometry at spine and femoral level was more than 2sd below normal values in 23% of the patients, all of them having received steroid therapy. Eighteen patients (29%) had never received steroid therapy; their bone mineral density was not different than those who had. Univariate analysis showed a positive correlation between bone mineral density and body weight or oral calcium intakes, and a negative correlation with steroid daily dose. After ileoanal anastomosis, bone mineral density was not different from other groups and showed a positive correlation with time elapsed since coloproctectomy. We concluded that bone mineral density is low in patients with inflammatory bowel disease and exposes them to the risk of bone fracture. Bone mineral density after ileoanal anastomosis may increase with time after surgery.     

The role of quantitative ultrasound in predicting osteoporosis defined by dual X-ray absorptiometry

The aim of this study was to establish whether quantitative ultrasound (QUS) parameters could identify patients classified as osteoporotic and osteopenic on the basis of dual energy X-ray absorptiometry (DEXA). One hundred and twenty-three patients (39 male, 84 female) with osteoporosis and suspected of having osteoporosis were included in this study. Broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured and bone mineral densities (BMD) of the lumbar spine and left hip was measured by DEXA. Subjects were classified into three groups (normal, osteopenic and osteoporotic) on the basis of BMD T-scores measured by DEXA. QUS parameters of the osteoporotic group were significantly lower than those of osteopenic and normal groups; there was no difference in QUS parameters between the normal and osteopenic groups. Correlations of both right and left SOS and BUA with the spine and femoral neck BMD were moderate (r = 0.343-0.539, P < 0.001). There was also reasonable correlation between DEXA and QUS T-scores (r = 0.364-0.510, P < 0.001). QUS had a sensitivity of 21% and a specificity of 95% for diagnosing osteoporosis. We concluded that, although DEXA and QUS parameters were significantly correlated, QUS parameters can not predict osteopenia as defined by DEXA, and sensitivities and specificities of QUS parameters were not sufficiently high for QUS to be used as an alternative to DEXA.     

Prevalence and predictors of osteopenia and osteoporosis in adults with Type 1 diabetes

Aims To determine the prevalence and biochemical/hormonal determinants of osteopenia and osteoporosis in adults with Type 1 diabetes. Methods One hundred and two patients (52 female, 50 male) with Type 1 diabetes aged 20–71 years underwent cross‐sectional assessment of biochemical/hormonal markers of bone metabolism, and bone mineral density (BMD) measurement at forearm, hip and spine using dual energy x‐ray absorptiometry. BMD data were available for 102 age‐ and gender‐matched population‐based control subjects. Results After adjusting for age and body mass index (BMI), osteopenia and osteoporosis were more common at the spine in males with Type 1 diabetes than in control subjects (P = 0.030). In Type 1 males, after adjustment for age and BMI, BMD, T‐ and Z‐scores at the hip, femoral neck and spine were lower compared with age‐matched control subjects (P ≤ 0.048). Female Type 1 patients and control subjects had similar BMDs and T‐ and Z‐scores at all sites. On multiple linear regression analysis, which adjusted for the natural logarithm of the sex hormone binding globulin concentration, smoking status and alcohol consumption, and (for women) menopausal status, each of BMI, serum ionized calcium and serum alkaline phosphatase (negatively) were independently associated with BMD at the hip and femoral neck in Type 1 diabetic subjects. Conclusions Adult males with Type 1 diabetes have reduced bone density at the hip, femoral neck and spine when compared with age‐matched control subjects. Impaired bone formation may occur in Type 1 diabetes.     

Immune status in healthy relatives of patients with familial Crohn's disease

Immune-mediated mechanisms and genetic factors are believed to be involved in the pathogenesis of Crohn's disease. We studied T- and B-cell subpopulation proportions and various functionnal assays, including proliferative responses to PHA and Con A, Con A-induced suppressive activity, and natural killer cell assay toward the K562 cell line, in the peripheral blood of 22 patients with inactive familial Crohn's disease and their 35 healthy relatives including nine families. HLA-A, -B, and -DR antigens were determined in all the subjects. With the exception of minor abnormalities of suppressor cell activity present in some relatives of two families, neither significant impairments of immunological parameters in patients or their relatives nor concordant segregation of HLA haplotypes and disease were observed. These data indicate that peripheral immune abnormalities previously described in patients with Crohn's disease do not constitute primary factors involved in the disease itself and that familial incidence in Crohn's disease cannot be linked to immunological markers presently studied.     

Bone status assessed by quantitative ultrasound in children with inflammatory bowel disease: a comparison with DXA

Background: To determine the bone status in children with inflammatory bowel diseases (IBD) using quantitative ultrasound (QUS) measurement at hand phalanges and compare the obtained results with dual-energy X-ray absorptiometry (DXA).

Methods: Fifty-one children with IBD underwent DXA and QUS measurements at hand phalanges in the year 2013. The control group for the QUS consisted of 460 children. Reference data for DXA comes from Hologic Explorer.

Results: QUS measurements did not differ significantly between IBD patients and healthy controls. There was no difference between UC and CD subjects. DXA measurements in patients with IBD were lower than in the healthy population. Tanner stage and nutritional status correlated with bone status contrary to steroids therapy.

Conclusion: Low bone mineral density often complicates IBD in children. QUS is not an appropriate method for the assessment of bone status in children. Nutritional status seems to have a greater impact on bone status than corticosteroids therapy.     

Bone mineral density in patients with Crohn's disease during long-term treatment with azathioprine

Florén C-H, Ahrén B, Bengtsson M, Bartosik J, Obrant K (Lund University, Malmö, Sweden). Bone mineral density in patients with Crohn's disease during long-term treatment with azathioprine. J Intern Med 1998; 243 : 123–26.

Objectives

To ascertain whether patients with Crohn's disease treated with azathioprine maintained bone mineral mass better than patients treated with steroids alone.

Design

Retrospective study.

Setting

University Hospital of Malmö, Sweden.

Subjects

A total of 59 patients with ileocolonic, ileocaecal or colonic Crohn's disease.

Methods

Bone mass was assessed by dual photon X-ray absorptiometry at the level of L2 – L4.

Results

Patients treated with a high lifetime dose of steroids (> 5 g prednisolone) had significantly (P= 0.011) lower Z-score of L₂–L₄ (?0.87 ± 1.11; 11 SD) than steroid-treated patients, who had received a low dose of prednisolone (< 5 g) (0.08 ± 1.16 SD). Azathioprine did not negatively influence the steroid effect on bone mineral density.

Conclusions

Azathioprine does not seem to affect bone mineral density by itself. However, by being steroid-saving, it seems to conserve bone mineral mass in patients with Crohn's disease.

     

Crohn's disease associated with gastric cancer

Received: May 15, 2000 / Accepted: November 10, 2000     

老年男性骨量减少的相关因素初探

目的通过定量超声测定法（QUS）测得骨密度T值,同时调查各种危险因素,探讨与老年男性骨质疏松相关的危险因素。方法老年科体检的60岁以上男性217例,采用QUS对其进行骨密度的测定,根据检测结果将其分为骨量正常组、骨量低下组和骨质疏松组,并对所有患者进行问卷调查,包括年龄、饮茶、吸烟、体重、血脂、疾病史、用药史等以及血糖、血脂、肌酐清除率等生化指标测定,比较各因素和骨密度T值之间的关系。结果年龄、饮茶、高血压、甘油三酯、低密度脂蛋白胆固醇与骨密度呈相关关系（P值分别为0.007,0.027,0.049,0.027,0.033）;进一步的多因素分析显示,饮茶与高血压和老年男性骨量减少呈独立相关（P=0.027,P=0.088）结论饮茶对骨密度呈显著正相关,高血压等心血管疾病危险因素和老年男性骨量减少存在相关性,考虑到后一类人群发生骨密度降低的风险,应定期进行骨密度测定。     

Experience with perirectal fistulas in patients with Crohn's disease

The experience of the senior author has been reviewed in dealing with perianal fistulas in patients with Crohn's disease. Early surgical therapy was advocated, the theory being, that perianal fistulas start as intersphincteric fistulas. This fistula is easily controlled surgically by fistulotomy with partial internal anal sphincterotomy. Delay in surgical treatment, especially in Crohn's patients, results in more complicated fistulas that may require colostomy or proctectomy. The presence of Crohn's disease did not affect the healing of fistulotomy. In our series fistulotomy was the treatment of choice in patients with 26 fistulas; 18 of 19 went on to full healing. We conclude that early fistulotomy, before an intersphincteric fistula has time to blossom fistulotomy, before an intersphincteric fistula has time to blossom into a more difficult management problem, is the treatment of choice in patients with Crohn's disease who have perianal fistulas Read at the XIIth, Biennial Congress of the International Society of University Colon and Rectal Surgeons, Glasgow, Scotland, July 10 to 14, 1988. Work performed at the Orlando Regional Medical Center, Orlando, Florida.     

High prevalence and correlates of low bone mineral density in young adults with sickle cell disease

Sickle cell disease (SCD) is a prevalent genetic disorder in which sickle hemoglobin leads to tissue hypoxia and adverse effects on bone. Published studies suggest that children with SCD often have undiagnosed osteopenia or osteoporosis. Minimal data exist on the prevalence of low bone mineral density (BMD) in adults. Our objective was to describe the prevalence of osteopenia and osteoporosis in adults with SCD and to identify patient or disease characteristics associated with low BMD. We conducted a cross-sectional study of adults with SCD. Through questionnaires, we collected data about disease course and osteoporosis risk factors. Patients underwent dual X-ray absorptiometry (DXA) measurement of BMD at the hip, spine, and forearm and sampling of blood and urine for markers of bone turnover, sickle cell disease severity, and secondary causes of osteoporosis. Our main outcome measure was prevalence of osteopenia and osteoporosis as defined by WHO criteria. Of 32 adults with SCD (14 men and 18 women) with a mean age of 34 years, 72% (95% confidence interval 53-86%) had low BMD at one or more anatomic sites. Thirteen patients were classified as osteoporotic and 10 as osteopenic. The prevalence of low BMD was greatest in the lumbar spine (66% of patients). Significant correlates of decreased BMD included low BMI (P < 0.01), male sex (P = 0.02), and low serum zinc concentrations (P < 0.01). The prevalence of osteopenia and osteoporosis in young adults with SCD is extremely high. Further research is needed to address fracture risk and therapeutic interventions.