Tumor necrosis factor-alpha haplotype is strongly associated with bone mineral density in patients with Crohn's disease

BACKGROUND AND AIM: There is limited consensus on the major variables that determine bone integrity and bone loss in patients with Crohn's disease. Twin and family studies in the general population indicate that up to 85% of variance in bone mineral density is inherited. The aim was to determine the prevalence of bone loss and both molecular and clinical risk factors for bone loss in a large Crohn's disease population. METHODS: This was a cross-sectional study of 304 patients with Crohn's disease attending the Inflammatory Bowel Disease unit at Royal Brisbane and Women's Hospital, Queensland. The results of bone density testing were ascertained directly and by a mailed questionnaire. Bone mineral density data were combined with clinical information and correlated with single nucleotide polymorphisms within the tumor necrosis factor-alpha (TNF-alpha), interleukin-10, and NOD2/CARD15 genes. RESULTS: Of 304 Crohn's disease patients, 101 had undergone previous bone density testing. Forty-five patients (45%) had been diagnosed with osteopenia and 18 (18%) were osteoporotic. After multivariate analysis, both the TNF-alpha GT haplotype and the -857 CC genotype showed strong associations with bone mineral density overall (P = 0.003 and P = 0.002, respectively). Body mass index (P = 0.01) and previous bowel resection in female patients (P = 0.03) were predictive of a higher spine bone density, while body mass index (P = 0.003) and the effect of years since first bowel resection (P = 0.02) remained independent predictors of proximal femur bone mineral density. There were no other significant associations observed. CONCLUSIONS: This study has identified a novel protective association between a TNF-alpha haplotype and bone mineral density in Crohn's disease. It confirms the important influence of body mass index and intestinal resection on bone loss in this population.     

Bone mineral density is reduced in patients with Crohn''s disease but not in patients with ulcerative colitis: a population based study.

BACKGROUND: Patients with inflammatory bowel disease are at risk of developing metabolic bone disease. AIMS: To compare bone mineral density in patients with Crohn's disease with patients with ulcerative colitis and healthy subjects, and to evaluate possible risk factors for bone loss in inflammatory bowel disease. PATIENTS: 60 patients with Crohn's disease, 60 with ulcerative colitis, and 60 healthy subjects were investigated. Each group consisted of 24 men and 36 women. METHODS: Lumbar spine, femoral neck, and total body bone mineral density were measured by dual x ray absorptiometry (DXA), and Z scores were obtained by comparison with age and sex matched normal values. RESULTS: Mean Z scores were significantly lower in patients with Crohn's disease compared with patients with ulcerative colitis and healthy subjects. Patients with ulcerative colitis had bone mineral densities similar to healthy subjects. Use of corticosteroids, body mass index (BMI), and sex were significant predictor variables for bone mineral density in Crohn's disease. In ulcerative colitis only body mass index and sex were of significant importance. Disease localisation and small bowel resections had no influence on bone mineral density in patients with Crohn's disease. CONCLUSIONS: Patients with Crohn's disease have reduced bone mineral density. Several factors are probably involved, but the reduction is associated with corticosteroid therapy. When studying skeletal effects of inflammatory bowel disease, patients with Crohn's disease and those with ulcerative colitis should be evaluated separately.     

Risk Factors for Low Bone Mineral Density in Children and Adolescents with Inflammatory Bowel Disease

Objective To evaluate bone mineral density of the lumbar spine in children and adolescents with inflammatory bowel disease, and to identify the clinical risk factors associated with low bone mineral density. Methods Bone mineral density of the lumbar spine was evaluated using dual-energy X-ray absorptiometry (DXA) in 40 patients with inflammatory bowel disease. Patients were 11.8 (SD = 4.1) years old and most of them were male (52.5%). Multiple linear regression analysis was performed to identify potential associations between bone mineral density Z-score and age, height-for-age Z-score, BMI Z-score, cumulative corticosteroid dose in milligrams and in milligrams per kilogram, disease duration, number of relapses, and calcium intake according to the dietary reference intake. Results Low bone mineral density (Z-score bellow -2) was observed in 25% of patients. Patients with Crohn's disease and ulcerative colitis had equivalent prevalence of low bone mineral density. Multiple linear regression models demonstrated that height-for-age Z-score, BMI Z-score, and cumulative corticosteroid dose in mg had independent effects on BMD, respectively, beta = 0.492 (P = 0.000), beta = 0.460 (P = 0.001), beta = -0.014 (P = 0.000), and these effects remained significant after adjustments for disease duration, respectively, beta = 0.489 (P = 0.013), beta = 0.467 (P = 0.001), and beta = -0.005 (P = 0.015). The model accounted for 54.6% of the variability of the BMD Z-score (adjusted R (2) = 0.546). Conclusions The prevalence of low bone mineral density in children and adolescents with inflammatory bowel disease is considerably high and independent risk factors associated with bone mineral density are corticosteroid cumulative dose in milligrams, height-for-age Z-score, and BMI Z-score.     

Screening for osteoporosis in patients with inflammatory bowel disease by using urinary N-telopeptides

BACKGROUND: Patients with inflammatory bowel disease are at increased risk of osteoporosis. DESIGN AND METHODS: We carried out a prospective study of bone mineral density and biochemical markers of bone metabolism like osteocalcin and urinary N-telopeptides in 72 patients with inflammatory bowel disease and evaluated if one of these markers detects osteoporosis. In addition, bone mineral density and N-telopeptides were analysed retrospectively in a second series of 93 patients with inflammatory bowel disease in order to assess predictive values found in the first patient group in an independent sample. RESULTS: Multiple linear regression showed that N-telopeptides (P < 0.0001) and total white blood cell count (P = 0.006) correlated negatively with the bone mineral density of the lumbar spine and only N-telopeptides (P = 0.005) correlated negatively with the bone mineral density of the femoral neck. Using receiver operator characteristic curves N-telopeptide concentrations of > 40 (30) nmol N-telopeptides/mmol creatinine were chosen as best cut-off values to exclude osteoporosis at the lumbar spine (femoral neck). Using these cut-off values a negative predictive value of 100% (100%) and a positive predictive value of 37.5% (27.9%) were found in the first group, and a negative predictive value of 95.2% (96%) and a positive predictive value of 15.6% (23.3%) in the second, independent group of patients. CONCLUSION: Our data suggest that N-telopeptide levels could be used as a tool for the screening of osteoporosis and for selecting those inflammatory bowel disease patients where bone mineral density measurement is indicated.     

Corticosteroid-induced osteoporosis: does it occur in patients with Crohn's disease?

OBJECTIVE: In Crohn's disease, osteoporosis is frequently found. However, the etiology of osteoporosis remains unclear. The aim of this study was to determine disease-related variables predictive for impaired bone mineral density (BMD). METHODS: A total of 91 patients with Crohn's disease who were admitted for BMD assessment were enrolled in the study. BMD was measured at the femoral neck and lumbar spine by dual energy x-ray absorptiometry (DXA). Results were expressed as T-score and as age- and sex-matched Z-score. Data were obtained by a questionnaire and from patients' medical records. Stepwise linear regression analysis was used to determine independent variables predictive for BMD. RESULTS: Mean age at BMD assessment was 41 +/- 12 yr, duration of disease 11.6 +/- 8.5 yr, and body mass index (BMI) 23.0 +/- 4.1 kg/m2. The cumulative dose of steroids used was 18.7 +/- 19.2 g. Mean Z-scores were less than zero (spine, -1.1 +/- 1.3 SD; femur, -1.1 +/- 1.2 SD; p < 0.0001). A total of 27 patients (30%) fulfilled the World Health Organization criteria for osteoporosis and 46 patients (50%) for osteopenia. Osteoporotic patients used more corticosteroids and had longer duration of disease, lower BMI, and more bowel resections than patients with normal BMD. However, in the linear regression analysis, the only significant independent predictors for BMD of the lumbar spine and femoral neck were BMI and history of bowel resections. BMI and history of resections together accounted for 28% of BMD Z-scores. CONCLUSIONS: BMI and a history of bowel resections were significant predictive variables for BMD. Despite the high dose of steroids used in this study, no detrimental effect could be demonstrated as independent predictor for osteoporosis.     

Lack of correlation between the vitamin D receptor Fokl start codon polymorphism and bone mineral density in patients with Crohn's disease.

INTRODUCTION: We have examined the association of bone mineral density of patients with inflammatory bowel disease with a polymorphism in the gene encoding the vitamin D receptor. The thymine/cytosine (T/C) polymorphism in the first of two start codons can be defined by a restriction fragment length polymorphism using the restriction endonuclease FokI. Vitamin D receptor alleles containing the polymorphism have been denoted by f and alleles lacking the site by F. METHODS: We report on an association analysis of a basic population of 244 caucasian patients with Crohn's disease. We have genotyped the FokI polymorphism of the VDR in these patients and associated the genotype with the bone mineral density of the lumbar spine and the femoral neck. RESULTS: In the cohort 42% of the patients were scored FF homozygous, 43.7% Ff heterozygous, and 14.3% ff homozygous. 14.4% of the FF patients, 18.8% of the Ff patients, and 9.7% of the ff patients had osteoporosis of the lumbar spine and 21.25% of the FF patients, 25.3% of the Ff patients, and 18.5% of the ff patients had osteoporosis of the femoral neck. In this cohort no association between the genotype and the bone mineral density in the group as a whole nor when separated according to sex or age was found. CONCLUSIONS: In summary in our cohort no association of the FokI polymorphism and the BMD of the lumbar spine and femoral neck in patients with inflammatory bowel disease was found.     

Analysis of risk factors for low bone mineral density in inflammatory bowel disease

BACKGROUND/AIM: Several risk factors have been suggested for osteoporosis which frequently occurs in inflammatory bowel disease (IBD) patients. We studied prevalence and risk factors for reduced bone mineral density (BMD) in IBD patients at the University Hospital of Zurich, Switzerland. METHODS: The BMD was determined by dual-energy X-ray absorptiometry at the lumbar spine and femoral neck in 88 IBD patients (55 with Crohn's disease, 30 with ulcerative colitis, and 3 with indeterminate colitis). Z scores were obtained by comparison with age- and sex-matched normal values, and T scores by comparison with sex-matched healthy young adults. Osteopenia and osteoporosis were defined according to the WHO guidelines. Predictive factors for BMD were analyzed by group comparison and stepwise regression analysis. RESULTS: Osteopenia was present in 43% of the patients at the lumbar spine and in 42% of them at the femoral neck. Osteoporosis was present in 14% of the patients at the lumbar spine and in 5% of them at the femoral neck. At the lumbar spine, stepwise regression analysis showed that body mass index, age, number of bowel resections, topic steroids, and azathioprine correlated with the Z scores. Cumulative steroid dose, topic steroids, age and bowel resection were found to be predictors for a pathological T score. At the femoral neck, regression analysis showed that body mass index, age, topic steroids, and azathioprine correlated with the Z scores. Only a low body mass index was a significant predictor for pathological femoral T scores. CONCLUSIONS: Osteopenia and osteoporosis are commonly found in IBD patients. Steroid treatment and bowel resection were significant risk factors for osteoporosis of the lumbar spine. However, disease-inherent factors also appear to confer a major risk, indicating that the BMD should be determined in all IBD patients, irrespective of steroid treatment.     

A controlled study of bone mineral density in patients with inflammatory bowel disease.

To assess the prevalence of and risk factors for low bone mineral density in inflammatory bowel disease (IBD), 152 IBD patients and 73 healthy controls were studied. Sixty seven patients had ulcerative colitis, 78 had Crohn's disease (52 of them (66.7%) had ileal disease), and seven had indeterminate colitis. Bone mineral density values (g/cm2) measured by dual energy x ray absorbtiometry at the spine (L2-L4), the femoral neck, Ward's triangle, and the trochanter were 1.177, 0.948, 0.850, and 0.838 in the patients and 1.228 (p = 0.034), 1.001 (p = 0.009), 0.889 (NS), and 0.888 (p = 0.012) in the control group, respectively. The type or extent of the disease or previous small bowel resection did not have any significant effect on the bone mineral density values. There was a weak, but statistically significant negative correlation between bone mineral density and the total lifetime corticosteroid dose (in the lumbar spine r = -0.164, p = 0.04, the femoral neck r = -0.185, p = 0.02, Ward's triangle r = -0.167, p = 0.04, and the trochanter r = -0.237, p = 0.003). The patients whose lifetime corticosteroid dose (prednisone/prednisolone) was more than 10 g had especially low bone mineral density (p < 0.05 compared with the groups with no or less than 5 g of corticosteroid). The patients who had never taken peroral corticosteroids did not have decreased bone mineral density. In conclusion, IBD patients have significantly lower bone mineral density values than healthy controls, but the difference is not so great as has been reported previously. Low bone mineral density values in these patients are related to high lifetime corticosteroid doses.     

Decreased trabecular bone mineral density in newly diagnosed inflammatory bowel disease patients in Korea

BACKGROUND: Decreased bone mineral density (BMD) is common in Western patients with inflammatory bowel disease (IBD). However, BMD has never been studied in Asia where the demographic and socio-economic status are different from the West. The aim of this study was to investigate the prevalence and mechanisms of osteopenia in newly diagnosed Korean patients with IBD. METHODS: We studied 14 patients with Crohn's disease (CD) and 25 patients with ulcerative colitis (UC), all of whom had never been treated with corticosteroids. Bone mineral density was measured in the lumbar spine and the femoral neck by dual energy X-ray absorptiometry. Biochemical parameters including serum osteocalcin, parathyroid hormone, plasma inactive and active vitamin D, and urinary deoxypyridinoline were measured. RESULTS: The BMD Z score at the lumbar spine was lower both in CD and in UC patients, but there was no significant difference between the two groups. There was no significant difference in nutritional status or biochemical parameters of bone metabolism between patients with a normal BMD and those with a decreased BMD. CONCLUSIONS: Low BMD at the lumbar spine is common in newly diagnosed Korean patients with IBD, a result which is similar to Western studies. The mechanism for low bone mass remains undetermined; however, nutritional status and hormonal parameters of bone metabolism, and ethnic differences are not likely to be an important factor in the pathogenesis of this bone loss.     

Relationship of bone mineral density with disease activity and functional ability in patients with ankylosing spondylitis: a cross-sectional study

In ankylosing spondylitis, inflammatory activity probably plays a key role in the pathophysiology of bone loss. The aim of the study was to investigate the relationship of bone mineral density (BMD) at the lumbar spine and hip region with some measures of disease activity and functional ability in patients with ankylosing spondylitis. In 80 patients with established ankylosing spondylitis, disease activity and functional ability were determined by C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI). Spinal pain and patient global health were assessed using horizontal visual analog scale. BMD was measured by dual-energy X-ray absorptiometry. There was a significant negative correlation of bone density T scores with acute-phase reactants (i.e., patients with lower T scores had higher level of CRP and ESR). That relationship was reflected more reliably at proximal femur sites than at the lumbar spine. There were also significant differences in ESR, BASDAI, BASFI, spinal pain and global health between three groups of patients according to WHO classification of osteoporosis (normal, osteopenic and osteoporotic). Significantly, more patients with osteopenia at the lumbar spine had lower BASDAI index than those with normal BMD (P?=?0.030). Our results indicate an association of low BMD with high disease activity in patients with AS. Femoral BMD seems to be more associated with disease activity and functional ability than lumbar spine BMD.     

Bone mineral density in patients with Behçet’s disease

Behçets disease is a complex, multisystemic, inflammatory disorder characterized clinically by recurrent oral and genital ulcerations as well as uveitis, sometimes leading to blindness. The etiology and pathogenesis of this syndrome remain obscure. However, various factors are suspected, including genetic propensity, infectious precipitants, and immunological abnormalities. Considering the chronicity and unclear etiology of the disease, we conducted a prospective investigation of a possible alteration in the bone mineral density of affected persons. Thirty-five patients (18 males and 17 females, mean age 38.02±7.93 years) diagnosed with Behçets disease and 33 sex- and age-matched healthy controls (14 males and 19 females, mean age 40.06±7.66 years) were seen on an outpatient basis, and bone densitometry measurements were done from June 2000 to December 2002 at the Mersin University Hospital in Turkey. Postmenopausal women with Behçets disease and patients receiving oral corticosteroid therapy were excluded from the study. The mean disease duration was 6.68±7.05 years. Bone mineral density was measured with dual X-ray absorptiometry at the lumbar spine and right femur. The mean Z scores of the patient and control groups were –0.50±1.06 and –0.13±0.92 at the lumbar spine, respectively, and 0.38±1.07 and 0.45±1.20 at the right femur, respectively. No significant differences in bone mineral density values were detected in the groups at either the lumbar (P=0.15) or right femur (P=0.82) site. Body mass index and disease duration did not influence bone mineral density, and age had a positive correlation with bone mineral density in patients with Behçets disease. In conclusion, although it is difficult to draw definite conclusions due to the relatively small sample size, our study confirms that bone mineral density in Behçets disease was not lower than in healthy subjects.     

Bone density improves with disease remission in patients with inflammatory bowel disease

BACKGROUND AND AIMS: Patients with inflammatory bowel disease (IBD) are at risk of low bone mineral density (BMD). The aim of this cross-sectional study was to investigate (i) whether patients with IBD in long-term remission have greater bone density relative to patients with active disease, (ii) the effect of remission on BMD in ulcerative colitis and Crohn's disease, and (iii) the effect of azathioprine treatment, used to induce remission, on BMD. PATIENTS AND METHODS: BMD relative to the age-standardised mean (Z-score) was measured by dual-energy X-ray absorptiometry at the left femoral neck and lumbar spine in consecutive patients with IBD. Patients were divided into the following groups: (i) active disease, (ii) remission of less than one year, (iii) remission of one to three years, and (iv) remission of more than three years. Active disease was defined as three or more bowel motions per day, treatment with oral or rectal corticosteroids, and/or presence of a fistula. The subgroups with ulcerative colitis and Crohn's disease and the effect of taking azathioprine were compared. All results were controlled for confounding variables.RESULTS A total of 137 (64 ulcerative colitis, 73 Crohn's disease) patients were evaluated. Patients in remission for more than three years had a normal mean Z-score that was significantly higher than those with active disease at both the femoral neck and the lumbar spine for both ulcerative colitis and Crohn's disease. Patients taking azathioprine and in remission had significantly higher mean Z-scores at the lumbar spine than patients with active disease and who were not taking azathioprine. CONCLUSION: In patients with ulcerative colitis and Crohn's disease, age-matched BMD is higher with increasing duration of disease remission and induction of remission by azathioprine.     

Vitamin D deficiency, bone mineral density and weight in patients with advanced pulmonary disease

OBJECTIVE: To study the influence of underweight, body composition and vitamin D deficiency on bone mineral density in patients with advanced pulmonary disease. DESIGN: Cross-sectional study with time span for inclusion set at 5 years. SETTING: The clinical work and biochemical analyses were carried out at Rikshospitalet University Hospital, Norway. Analyses for vitamin D metabolites and bone markers were carried out at Aker University Hospital, and bone measurements at Clinic of Osteoporosis. SUBJECTS: Seventy-one candidates for lung transplantation (63% chronic obstructive pulmonary disease, 42 underweight and 29 normal weight) were included. MAIN OUTCOME MEASURES: Body composition, bone mineral density at lumbar spine and femur neck, serum concentration of calcidiol and vitamin D intake. RESULTS: Subnormal calcidiol levels were present in 52% of the underweight patients and 69% of the normal-weight patients. The resulting models of linear regression showed that for the lumbar spine T scores model, the total variation of 16.7% was explained by group (underweight/normal weight), sex and age. For the femur neck T scores model, the total variation of 20.4% was explained by the interaction of underweight and vitamin D deficiency (with borderline significance) and by arm muscle circumference percentage of standard. In patients with normal calcidiol levels, the median intake of vitamin D was 17 microg in the underweight patients and 11 microg in the normal-weight patients. CONCLUSIONS: Vitamin D deficiency was common in both underweight and normal-weight patients, but only in the underweight patients, an association between vitamin D deficiency and reduced femur neck T scores was indicated.     

Bone mineral density in patients with Parkinson's Disease

BACKGROUND AND AIMS: This study assesses bone mineral density (BMD) in the lumbar spine, proximal femur and hand, and examines the relationship between BMD and disease duration, Hoehn and Yahr staging in Turkish elderly patients with Parkinson's disease (PD). DESIGN: Twenty-four PD patients and 31 age- and sex-matched controls took part in the study. The BMD in the lumbar spine (L2-L4), femoral neck, Ward's triangle, trochanter and bilateral hands were evaluated by dual X-ray absorptiometry (DXA). RESULTS: There was no significant difference in right hand BMD (rHBMD), L2-L4 spinal BMD, and right proximal femur BMD between patients and controls. However, in female patients hand BMD and right femoral neck BMD were significantly lower than in female controls (p<0.05). Male patients had no significant difference in BMD measurements in any sites compared with controls. Patients' Hoehn and Yahr index and disease duration were negatively correlated with BMD in all sites except L2-L4. CONCLUSIONS: We emphasize the increased risk for osteoporosis in elderly female patients with PD, which is more prominent in proximal femur and hand measurements. Elderly female patients should be carefully examined and screened for osteoporosis to prevent bone loss and associated disability.     

Association of dehydroepiandrosterone sulfate and testosterone deficiency with bone turnover in men with inflammatory bowel disease

BACKGROUND AND AIMS: We investigated the coexistence of dehydroepiandrosterone sulfate (DHEAS) and testosterone deficiency in men with inflammatory bowel disease (IBD) and their relationship with bone homeostasis. PATIENT AND METHODS: In 45 men with IBD (25 with ulcerative colitis, 20 with Crohn's disease) the testosterone and DHEAS levels were examined in relationship to bone mineral density, osteocalcin levels, and urinary deoxypyridinoline excretions. RESULTS: We detected osteoporosis in 10 and osteopenia in 22 patients at the lumbar spine and/or femoral neck. Lower testosterone levels were measured in 20. Lower DHEAS levels were present in 23 patients; these had higher deoxypyridinoline excretion and lower lumbar spine and femoral neck BMD T scores than patients with normal DHEAS. DHEAS and BMD were correlated at the lumbar spine and the femoral neck. Associations remained significant after adjustment for age, weight, steroid use, and inflammatory activity. No independent effect of testosterone deficiency was detected on bone parameters. CONCLUSION: DHEAS deficiency may contribute to the bone loss of men with IBD. This putative action of DHEAS on bone turnover is contrary to the common effect of testosterone deficiency and steroid therapy.     

Influence of Disease Activity and Chronicity on Ankylosing Spondylitis Bone Mass Loss

We investigated 30 consecutive Brazilian patients with definite ankylosing spondylitis (AS) fulfilling the New York and the European spondyloarthropathy study group classification criteria. The mean age at study was 37 years old and the mean disease duration was 17 years. Bone densitometry employed the dual-energy X-ray absorptiometry (DEXA) technique, using a Hologic QDR-1000/W densitometer. Axial bone mineral density (BMD) was measured in the lumbar spine (L1–L4) and appendicular BMD was measured in the total proximal femur and sub-regions (neck, greater trochanter, intertrochanter and Ward’s triangle). Based on World Health Organisation criteria, the lumbar spine showed osteopenia or osteoporosis in 50% of the patients, while 86% had osteopenia or osteoporosis in the total proximal femur. When compared with the normal population, the patients showed a significant BMD decrease in the lumbar spine and total proximal femur with sub-regions, except for the femoral neck. A comparison of BMD between patients with active and inactive disease did not reveal a significant effect of clinical disease activity on the lumbar spine and total proximal femur with sub-regions, except for Ward’s triangle. Concerning disease chronicity, there were significant positive correlations between disease duration and lumbar spine, total proximal femur, greater trochanter and intertrochanteric regional BMD. This false increase in lumbar spine BMD found mostly in patients with long standing AS was due to the presence of paravertebral calcification and ossification. We conclude that the bone mass loss in AS is better evaluated in the proximal femur, because of the greater sensitivity of bone densitometry in this region, which is almost free of artefacts. Received: 1 September 1998 / Accepted: 24 February 1999     

Etidronate for osteoporosis in primary biliary cirrhosis: a randomized trial

BACKGROUND/AIM: Osteoporosis is a common complication of primary biliary cirrhosis but there is no accepted therapy for the osteoporosis. In this randomized controlled trial, we compared the effects of etidronate to placebo on the treatment of osteoporosis associated with primary biliary cirrhosis. METHODS: Sixty-seven patients with primary biliary cirrhosis and osteopenia, defined by bone mineral density criteria (T-score < -2.0) were enrolled. Measurements of the lumbar spine and proximal femur, as well as x-rays of the lumbar spine, were obtained. Patients received cyclical etidronate 400 mg/day for 14 days every 3 months for at least 1 year. Supplemental calcium was administered on the days patients did not receive etidronate. RESULTS: Of the 67 patients entered, 60 completed at least 1 year of therapy. There was no significant difference in changes in bone density at either the lumbar spine or femur in patients receiving etidronate when compared to placebo. Fractures occurred in eight patients, four receiving etidronate. Etidronate therapy was associated with a significant reduction in markers of bone turnover compared to placebo. These changes did not correlate with changes in bone density. CONCLUSIONS: Cyclical etidronate administered with supplemental calcium did not significantly improve bone density in patients with primary biliary cirrhosis.     

Effect of the long-term use of inhaled corticosteroids on bone mineral density in asthmatic women

OBJECTIVE: Inhaled corticosteroids have become a key element in the maintenance treatment of bronchial asthma. Recent studies have shown that administration of inhaled corticosteroids is associated with evidence of derangement in bone turnover. Therefore, we studied the bone mineral density (BMD) of asthmatic women receiving long-term inhaled corticosteroids and compared them with healthy individuals matched for age, sex, menopausal status and body mass index. METHODOLOGY: Thirty-two female patients with bronchial asthma, who had been using inhaled corticosteroids (beclomethasone dipropionate 750-1500 microg/day) regularly for at least 3 months, were included in the study. Bone mineral density measurements were done with dual X-ray absorptiometry in the lumbar area of the spine and the hip. Detailed laboratory examination was also done for the patients and 26 controls. RESULTS: There was a significant decrease in BMD of the patient group at the lumbar region and femur as compared with normal controls. In the patients there was a significant negative correlation between the duration of therapy, daily and cumulative doses, and BMD at the lumbar region but not BMD at the femur. CONCLUSIONS: These results indicate that long-term use of inhaled corticosteroids is associated with significant bone loss in asthmatic women and is especially related to the duration of therapy. Therefore, it is necessary to appropriately screen and give prophylactic treatment to those who are likely to develop osteoporosis from inhaled corticosteroid treatment.     

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.     

Reduced bone density in patients with inflammatory bowel disease.

BACKGROUND: Reduced bone mineral density in patients with inflammatory bowel disease is thought to be due to disturbances in calcium homeostasis or the effects of corticosteroid treatment. AIMS: To assess the prevalence and mechanism of reduced bone mineral density in 79 patients with inflammatory bowel disease (44 with Crohn's disease, 35 with ulcerative colitis) who did not have significant risk factors for low bone densities. METHODS: Dual x ray absorptiometry was used to measure bone mineral density and serum and urinary markers of osteoblast (alkaline phosphatase, procollagen 1 carboxy terminal peptide and osteocalcin) and osteoclast (pyridinoline, deoxypyridinoline, and type 1 collagen carboxy terminal peptide) activities to assess bone turnover. RESULTS: There was a high prevalence of low bone mineral density (prevalence of T scores < -1.0 from 51%-77%; T scores < -2.5 (osteoporosis) from 17%-28%) with hips being more often affected than vertebrae (p < 0.001). Reduced bone mineral density did not relate to concurrent or past corticosteroid intake, or type, site, or severity of disease. Whereas calcium homeostasis was normal, bone markers showed increased bone resorption without a compensatory increase in bone formation. CONCLUSIONS: The greater prevalence of reduced hip bone mineral density, as opposed to vertebral, mineral density and the pattern of a selective increase in bone resorption contrasts with that found in other known causes of metabolic bone disease.