Longitudinal Study of Cortical Bone Loss in Patients with Inflammatory Bowel Disease

Bone mineral density of the radius was measured by single-photon absorptiometry in 50 patients with inflammatory bowel disease. Thirty-three had Crohn's disease and 17 ulcerative colitis; 25 were women. The mean age was 45 years (range, 18–70 years). Measurements were repeated in 39 of them after a mean follow-up period of 7.9 years (range, 7.1–8.2 years). In female patients the mean (95% confidence interval) annual change in radial bone mineral density was -0.74% (-1.34% to -0.14%) (P = 0.022), the greatest bone loss occurring in postmenopausal women (mean, -1.16% (-2.01% to -0.30%)). In male patients the mean annual rate of bone loss was -0.07% (-0.41% to 0.28%) (P = NS). Patients with abnormally low values at the first measurement remained osteopenic at the second measurement, whilst some others with normal values initially showed increased rates of bone loss and had a subnormal bone mineral density after the follow-up period. These results show increased rates of cortical bone loss in some patients with inflammatory bowel disease and emphasize the need to monitor bone mass in these patients so that prophylactic measures can be instituted.     

Hormone replacement therapy prevents bone loss in patients with inflammatory bowel disease.

Patients with inflammatory bowel disease have an increased prevalence of osteoporosis, and suffer high rates of spinal bone loss. Hormone replacement therapy (HRT) is effective in the treatment and prevention of osteoporosis but has not been studied in patients with inflammatory bowel disease. A two year prospective study of HRT in inflammatory bowel disease was performed in 47 postmenopausal women aged 44 to 67 years with ulcerative colitis (25) or Crohn's disease (22). Patients had radial and spinal bone density measured annually by single photon absorptiometry and quantitative computed tomography respectively. The mean (95% confidence intervals) annual change in radial bone density was +1.42%/yr (+0.58 to +2.26; P < 0.005) and for spinal bone +2.60%/yr (+1.06 to +4.15; p < 0.005). There was no significant correlation between rates of change of bone density at the two sites, or between the rates of change and the initial bone density either in the radius or spine. Twelve patients were given prednisolone during the study, and their rates of change for spinal bone density were lower, but values were not statistically significantly different from those who did not receive corticosteroids. Changes in bone density for patients with ulcerative colitis and Crohn's disease were not significantly different. The change in bone density did not correlate with the patients' age or number of years after the menopause. It is concluded that HRT is effective in prevention of bone loss in postmenopausal women with inflammatory bowel disease.     

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.     

Bone loss associated with gastrointestinal disease: prevalence and pathogenesis

Decreased bone mineral density is a frequent finding in gastrointestinal disease. Factors contributing to this are (1) malabsorption of vitamin D, calcium and possibly vitamin K and other nutrients; (2) treatment with glucocorticoids; (3) inflammatory cytokines in inflammatory bowel disease; and (4) hypogonadism induced by gastrointestinal disease. A low bone mineral density has been reported in (1) patients who have undergone gastrectomy (27-44% with Z-scores of < -1); (2) pernicious anaemia; (3) coeliac disease (8-22% with Z-scores of < -2); (4) Crohn's disease (mean 32-38% with Z-scores of < -1); and (5) ulcerative colitis (mean 23-25% with Z-scores of < -1). Reduced bone mineral density is thus prevalent in these individuals and is compounded by age related bone loss, leading to the development of severe bone disease in some patients.     

Bone loss in patients with inflammatory bowel disease is less than expected: a follow-up study.

BACKGROUND: In spite of the accumulating evidence of an increased prevalence of osteopenia and osteoporosis in patients with inflammatory bowel diseases (IBD), the time course of bone loss is not well described, and there is little knowledge about factors indicating an increased risk of rapid bone loss. METHODS: We conducted a follow-up study in 80 IBD patients (45 men and 25 premenopausal and 10 postmenopausal women), 19 with ulcerative colitis and 61 with Crohn disease, with a mean follow-up time of 568 +/- 60 days, to assess bone loss, risk factors of rapid bone loss, and value of bone markers to predict bone loss. Bone mineral density was measured by dual-energy X-ray absorptiometry, bone formation by bone alkaline phosphatase (BAP), and bone resorption by N-terminal telopeptide of type-I collagen (NTX) and free deoxypyridinoline (DPD). RESULTS: Bone density changes per year were 0.46% +/- 3% at the spine, 0.06% +/- 5.1% at the femoral neck, -1.1% +/- 7.7% at the triangle of Ward, and -0.52% +/- 1.86% at total body level. Type and duration of disease, sex, age, and level of NTX, DPD, and BAP at base line did not show significant differences between patients who lost and those who did not lose bone mass. Bone loss was significantly higher in patients with (n = 28) than in those without steroids (n = 52) at the femoral neck and Ward triangle but not at the spine and total body. CONCLUSIONS: Change in bone mass in IBD patients during short-term follow-up is low on average, but there is great heterogeneity within the population, which cannot be explained by the use of steroids alone. Bone loss cannot be predicted by analysis of bone markers.     

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.     

Increased rate of spinal trabecular bone loss in patients with inflammatory bowel disease.

The rate of spinal trabecular bone loss during one year was measured in 54 patients with inflammatory bowel disease. The mean change in spinal bone mineral content was -5.1 mg/ml K2HPO4, representing 3% of the initial bone mineral content. The rate of bone loss showed a significant negative correlation with body mass index (r = -0.276, p less than 0.05) but no other significant correlations were found with other clinical or biochemical indices, including the total amount of prednisolone taken during the course of the study. Eleven patients had bone loss greater than 15 mg/ml/year; these included four non-steroid treated patients, two of whom had disease confined to the large bowel. The results indicate rapid rates of bone loss in some patients with inflammatory bowel disease over the course of one year. Although steroid therapy and malnutrition are likely to be contributory factors in some patients, other, as yet unidentified, risk factors also operate. The rapid bone loss observed in some patients emphasises the need for effective prophylactic regimes.     

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.     

Change in bone mineral density in patients with rheumatoid arthritis during the first decade of the disease.

OBJECTIVE: Rheumatoid arthritis (RA) has been reported to be associated with bone loss during the first years of the disease. The magnitude of this problem after the initial years has not yet been evaluated. In the present study, the change in bone mineral density (BMD) in patients with recent-onset RA as well as the effects of inflammation, mobility, and the use of prednisone on this change were studied in the first decade of the disease. METHODS: BMD was measured twice in 76 RA patients with mean disease durations of 2.35 years at the first BMD measurement and 8.90 years at the second BMD measurement. BMD was measured in both hips using dual x-ray absorptiometry. Results were expressed as mean +/- SEM Z scores (using age- and sex-matched reference values) and as mean +/- SEM percent change in BMD (in gm/cm2) per year. The effects of inflammation, mobility, and the use of prednisone on change in BMD were evaluated using multiple linear regression analyses. RESULTS: At the first BMD measurement, RA patients had lower BMD compared with the reference values (Z score -0.42+/-0.11, 95% confidence interval [95% CI] -0.64, -0.20). Between the 2 measurements, we observed a small decrease in BMD of -0.28+/-0.11%/year (95% CI -0.07 to -0.49). However, the rate of bone loss was smaller than expected. The Z score increased by 0.13+/-0.05 between the 2 BMD measurements (95% CI 0.02, 0.23). Only the use of prednisone was significantly associated with increased bone loss. In a separate analysis that included only postmenopausal women, increased physical activity and longer time since menopause were both associated with decreased bone loss. In this subgroup of patients, the use of prednisone was significantly associated with increased bone loss as well. A high erythrocyte sedimentation rate was associated with increased bone loss, but this did not reach statistical significance. CONCLUSION: After the initial years of the disease, bone loss in RA patients is lower than expected compared with age- and sex-matched reference values. Postmenopausal RA patients with low levels of physical activity are at increased risk of losing bone. Use of prednisone was the only variable consistently associated with reduction in BMD in RA patients.     

Evolution of osteopenia in inflammatory bowel disease

OBJECTIVE: Our aim was the assessment of frequency and evolution of osteopenia in patients with inflammatory bowel disease and identification of related factors. METHODS: Bone mineral density (BMD) of the lumbar spine was measured in 54 patients with Crohn's disease (CD) and in 49 patients with ulcerative colitis (UC) and was repeated after a mean observation period of 21 (range, 8-50) months in 30 CD and 14 UC patients. Eighteen age-matched healthy subjects served as controls. Serum biochemistry (parathyroid hormone, osteocalcin, alkaline phosphatase, insulin-like growth factor 1, minerals, and markers of inflammation) was assessed at the time of the second BMD measurement. RESULTS: Reduced BMD values were found in 48% of CD, and in 38% of UC patients. Compared with control subjects, the mean BMD was significantly lower in CD (p < 0.003) and UC (p < 0.0001) patients. BMD was positively correlated with the body mass index (p < 0.05) and inversely correlated with the lifetime steroid dose (p < 0.03). After 21 months the BMD of CD patients was virtually unchanged, with an annual variation (%deltaBMD/yr) of -0.31 +/- 0.49, whether treated with steroids or not, whereas in UC patients the BMD decreased significantly (p < 0.02) with a %deltaBMD/yr of -2.47 +/- 0.82 (p < 0.02 vis CD). This decrease can be attributed to steroid treatment. No biochemical alterations were detected in patients with rapid bone loss, compared with those with stable BMD. CONCLUSIONS: Low bone density is frequent in both CD and UC, but apparently stable in CD. The evolution of BMD suggests that low bone density is associated with the pathogenesis of CD, whereas in UC it seems to be correlated with the side effects of corticosteroid treatment.     

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.     

Prospective 10-year study of the determinants of bone density and bone loss in normal postmenopausal women,including the effect of hormone replacement therapy

OBJECTIVE: To prospectively assess bone density and the factors determining the rate of bone loss over a 10-year period of postmenopausal life. DESIGN: Prospective, observational study. METHODS: One hundred and four normal White postmenopausal women, baseline mean age 59 years (range 47-71 years) completed the study (mean duration of follow-up 10.2 years, range 9.4-10.6 years). None had diseases or were taking medications affecting bone metabolism at entry to the study. Information was collected on medical, fracture and smoking history, alcohol use, dietary calcium intake and physical activity. Body composition and bone density were measured by dual-energy X-ray absorptiometry at baseline and at 10 years. Biochemical, haematological and hormonal analyses were performed. RESULTS: Twenty-four percent of the women started hormone replacement therapy (HRT) during the study period; most of these remained on therapy at follow-up. The mean duration of therapy was 6.6 years (range 2.8-10.4 years). The use of HRT was associated with significant gains in bone density (total body + 3.0%, trochanter + 4.2%, Ward's triangle + 4.4%, spine + 10.5%) and a significant reduction in vertebral fracture risk [standardized risk ratio compared with non-HRT users 0.42 (confidence interval 0.18-0.83)]. HRT use was not associated with greater weight gain than that occurring in other members of the cohort. The baseline and follow-up bone densities in the non-HRT users were highly correlated (0.82 < or = r < or = 0.91, P < or = 0.0001) and baseline bone density accounted for the majority of the variance in the 10-year results. Multivariate analyses showed that the independent correlates of rate of change of bone density were weight and fat mass (both baseline values and changes during follow-up), time after menopause, sex hormone concentrations, urinary calcium loss, PTH levels and haemoglobin concentration (which may reflect nutrition and health). CONCLUSIONS: Bone density is highly predictable over an extended period of time in normal postmenopausal women. Maintenance of body weight and good health reduce bone loss. HRT is effective for treating osteoporosis, with improvement in bone density and reduction in vertebral fractures. Good compliance with HRT long-term is achievable. These findings are relevant to deciding the frequency of bone density measurement, and in advising women regarding prevention and treatment of postmenopausal bone loss.     

Biochemical markers and bone densitometry in inflammatory bowel disease.

AIMS: Bone mineral density is reduced in patients with inflammatory bowel disease. The possible causes of this situation are delayed puberty, malabsorption, and corticosteroid use, among others. No published data exist regarding the use of biochemical markers and bone densitometry to assess osteopenia in these patients in Spain. METHODS: We studied 54 patients (24 men and 30 women), 22 with Crohn's disease and 32 with ulcerative colitis. Age, type of disease and average daily dose of prednisone-equivalent corticosteroids were evaluated. Lumbar bone mineral density was assessed quantitative digital radiography densitometry. The bone resorption marker urine D-pyridinoline and the bone formation marker serum osteocalcin were also assessed. RESULTS: Mean age was 36.61 +/- 13.37 years. Daily corticosteroid dose was correlated with D-pyridinoline (r = 0.413; p < 0.01), and D-pyridinoline was inversely correlated with osteocalcin (r = -0.304; p < 0.01). There was a negative correlation between bone mineral density and corticosteroid dose. There was no relationship between biochemical markers and bone densitometry findings in these patients. There were no differences in terms of bone densitometry findings or biochemical markers between the two types of inflammatory bowel disease. CONCLUSIONS: D-pyridinoline correlated inversely with osteocalcin. Daily corticosteroid dose correlated directly with D-pyridinoline, and inversely with bone mineral density.     

Can biochemical markers be used to screen patients with inflammatory bowel disease for osteoporosis?

Reduced bone mineral density has been reported in patients with inflammatory bowel disease and recent studies indicate that there is also an increase in the relative risk of fracture. Absolute risk of fracture is, however, generally low and thus measurement of bone mineral density as a screening procedure for all patients with inflammatory bowel disease may be inappropriate. In one study, urinary excretion of N-telopeptides, which reflects whole body bone resorption, was shown to be negatively related to bone mineral density, raising the possibility that this measurement could be used to select those in whom bone densitometry is required. However, the value of this approach in predicting fracture risk remains unproven and the relative contributions of clinical risk factors, biochemical markers of bone turnover and bone mineral density measurements to fracture risk in patients with inflammatory bowel disease require further study.     

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.     

Spinal and peripheral bone mineral densities in acromegaly: the effects of excess growth hormone and hypogonadism

STUDY OBJECTIVE: To measure spinal and peripheral bone mineral densities in patients with acromegaly. DESIGN: Retrospective study. SETTING: Tertiary care center. SUBJECTS: Twenty-four patients with acromegaly and 24 case controls. Seventeen patients (12 eugonadal and 5 hypogonadal) had "active" disease as indicated by elevated plasma concentrations of growth hormone or somatomedin C or both at the time of the study. Seven patients (all hypogonadal) had inactive disease by these criteria. MEASUREMENTS AND MAIN RESULTS: Bone mineral was measured by single photon absorptiometry of the forearm and dual photon absorptiometry of the spine. The forearm bone mineral content of patients with active disease, regardless of gonadal status, was significantly higher than that of normal subjects (P less than 0.001) or of patients with inactive disease (P less than 0.001). The disease "activity" (17.2 +/- 3.7; CI, 9.5 to 24.9) and the sex of the patient (female, -16.6 +/- 3.4; CI, -23.7 to -9.5) were the only independent predictors of forearm measurements. Vertebral bone densities were lower in acromegalic patients than in normal subjects (P less than 0.001). Vertebral values were correlated with the gonadal status of the patients (hypogonadism, -0.126 +/- 0.056; CI, -0.244 to -0.009) and with serum calcium concentrations (0.592 +/- 0.274; CI, 0.032 to 1.153) but not with acromegalic activity. In 13 patients, forearm bone was measured before and after treatment (mean duration of follow-up, 3.4 years). Patients with persistently elevated, plasma somatomedin C concentrations at the end of the study period showed a mean annual increase of 1.5% in forearm measurements during the period of observation, whereas patients with normal concentrations showed a mean annual decrease of 1.0% (P less than 0.01 for the difference between the groups). The percent change in forearm bone mineral content per year (y) was highly correlated with residual somatomedin C activity (x): y = 2.023x - 2.75; r = 0.665. CONCLUSIONS: Forearm and vertebral bone mineral measurements change in opposite directions in acromegaly. The high forearm values are attributable to the growth-promoting action of growth hormone and somatomedin C, whereas low vertebral values are associated with hypogonadism.     

Bone mineral density in patients with inflammatory bowel disease: a population-based prospective two-year follow-up study

BACKGROUND: Bone loss and osteoporosis are commonly reported in inflammatory bowel disease (IBD), especially Crohn disease (CD). The aims of the present study were to evaluate changes in bone mineral density (BMD) in IBD patients during a 2-year follow-up period, and to investigate the role played by possible contributing factors in bone loss. METHODS: Sixty patients with CD and 60 with ulcerative colitis (UC) were studied initially. Fifty-five CD and 43 UC patients were re-examined after 1 year, and 50 CD and 44 UC patients after 2 years. Lumbar spine, femoral neck and total body BMD were measured by dual X-ray absorptiometry (DXA), and Z scores were obtained by comparison with age-matched and sex-matched healthy subjects. Biochemical variables were assessed at inclusion and at the 1-year follow-up visit. RESULTS: Mean BMD values were unchanged in both CD and UC patients. In patients with repeated measurements, significant differences in Z scores (delta Z score) were found for femoral neck and total body in CD and for total body in UC. Significant bone loss occurred in 11 CD (22%) and 12 UC (27%) patients. A significant increase in BMD was found in 21 CD (42%) and 20 UC (46%) patients. In CD patients the initial BMD values for lumbar spine and femoral neck were inversely correlated to BMD changes at the same sites and the change in body mass index (BMI) was positively correlated to change in the total body BMD. C-reactive protein was significantly higher in CD patients with bone loss. Biochemical markers of bone metabolism could not be used to predict BMD changes. Although it was not significant, there was a relationship between corticosteroid therapy and bone loss in CD. CONCLUSIONS: Only minor changes in BMD were observed in both CD and UC patients during a 2-year period. The multifactorial pathogenesis of bone loss in IBD makes it difficult to assess the importance of each single contributing factor. However, our results indicate that disease activity and corticosteriod therapy are involved in bone loss in CD patients.     

Longitudinal study of changes in hip bone mineral density in Caucasian and African-American women

OBJECTIVES: To determine whether changes in hip bone mineral density (BMD) differ in Caucasian and African American women. DESIGN: Longitudinal study of changes in hip BMD. SETTING: Four U.S. clinical centers. PARTICIPANTS: Six thousand seven Caucasian (mean age 73) and 482 African-American (mean age 75) women enrolled in the Study of Osteoporotic Fractures. MEASUREMENTS: Total hip and femoral neck BMD were measured an average of 3.5 years apart (Caucasian) and 2.0 years apart (African American). Annual absolute and percentage changes in BMD and bone mineral apparent density (BMAD) were calculated. RESULTS: The multivariate adjusted annual percentage change in BMD was greater in Caucasian than African-American women at the total hip (-0.574%/y vs -0.334%/y) and femoral neck (-0.515%/y vs -0.203%/y) (both, P<.001). Similar findings were observed for BMAD. The average annualized rate of BMD loss was twice as high in women aged 75 and older as in women younger than 75 in both ethnic groups. The annual percentage loss in femoral neck BMD in nonusers versus hormone therapy users was (-0.57% vs -0.22%) in Caucasians and (-0.35% vs 0.64%) in African Americans (interaction P=.03). CONCLUSION: The average rate of hip BMD loss is approximately twice as great in Caucasian as African-American women and increases with age in both groups. The hormonal and biochemical factors that contribute to ethnic differences and the increase in bone loss with advancing age need to be identified.     

Osteoporosis in patients with inflammatory bowel disease.

Bone mineral content in spinal trabecular and peripheral cortical bone was measured in 75 unselected patients with small and/or large intestinal inflammatory bowel disease. Osteoporosis, defined as a bone mineral content greater than 2 SD below the age and sex matched normal mean value was present in 23 patients (30.6%). Three amenorrhoeic females aged 34, 38, and 42 years had severe clinical osteoporosis and a further three patients had one or more vertebral crush fractures. Eighteen of the 23 patients with osteoporosis had small intestinal disease with one or more resections and the mean lifetime steroid dose in those with osteoporosis was significantly higher than in those with normal bone mineral content. Bone mineral content in spinal trabecular bone showed significant negative correlations with lifetime steroid dose and serum alkaline phosphatase and a significant positive correlation with serum albumin. Peripheral cortical bone mineral content was positively correlated with body weight, height and body mass index. We conclude that the prevalence of osteoporosis is increased in patients with inflammatory bowel disease, severe clinical osteoporosis developing in some relatively young patients. The pathogenesis of this bone loss is probably multifactorial; steroid therapy is likely to be an important contributory factor.     

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.