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.     

Lack of deleterious effect on bone mineral density of long-term thyroxine suppressive therapy for differentiated thyroid carcinoma

The effect of subclinical hyperthyroidism on bone mineral density is controversial and could be significant in patients with differentiated thyroid carcinoma who receive suppressive doses of levothyroxine (LT4). To ascertain whether prolonged treatment with LT4 to suppress thyrotropin had a deleterious effect on bone mineral density and/or calcium metabolism in patients thyroidectomized for differentiated thyroid cancer we have performed a cross-sectional study in a group of 88 women (mean +/- SD age: 51 +/- 12 years) treated with LT4 after near-total thyroidectomy and in a control group of 88 healthy women (51 +/- 11 years) matched for body mass index and menopausal status. We determined calcium metabolism parameters, bone turnover marker N-telopeptide and bone mass density by dual-energy X-ray absorptiometry. No differences were found between patients and controls in calcium metabolism parameters or N-telopeptide except for PTH, which was significantly increased in controls. No differences were found between groups in bone mineral density in femoral neck (0.971 +/- 0.148 gr/cm(2) vs 0.956 +/- 0.130 gr/cm(2) in patients and controls respectively, P = 0.5). In lumbar spine, bone mineral density values were lower in controls than in patients (1.058 +/- 0.329 gr/cm(2) vs 1.155 +/- 0.224 gr/cm(2) respectively, P < 0.05). When premenopausal (n = 44) and postmenopausal (n = 44) patients were compared with their respective controls, bone mineral density was similar both in femoral neck and lumbar spine. The proportion of women with normal bone mass density, osteopenia and osteoporosis in patient and control groups was similar in pre- and postmenopausal women. In conclusion, long-term suppressive LT4 treatment does not appear to affect skeletal integrity in women with differentiated thyroid carcinoma.     

Osteopenia and osteoporosis in Crohn's disease: prevalence in a Dutch population-based cohort

Reduced bone mineral density (BMD) has been reported in 3-77% of patients with inflammatory bowel disease (IBD). The majority of these studies are cross-sectional and from tertiary referral centres. The aim of our study was to estimate the prevalence of metabolic bone disease and of symptomatic fractures in a population of patients with Crohn's disease (CD) living in a well-defined geographic area. Patients with CD living in three adjacent municipalities within the IBD South-Limburg study area were investigated. BMD was measured by dual X-ray absorptiometry (DXA) of the femoral neck, lumbar spine and total body. The population comprised of 181 CD patients, 23 of whom were excluded. One-hundred-and-nineteen (75%) of the 158 eligible patients (37 males, 82 females with a mean age of 42 years (17-78)) were investigated. Osteopenia of lumbar spine and/or femoral neck was found in 45% of patients. Osteoporosis was found in another 13% of patients. Mean BMD (T-score) of femoral neck was significantly lower than of lumbar spine (P < 0.001). Male CD patients and patients aged under 18 at diagnosis are more at risk of having a low bone mass at the lumbar spine (P < 0.001) and total body (P = 0.018). The prevalence of osteoporosis in postmenopausal CD patients (29%) was significantly higher than in premenopausal patients (3%) (odds ratio: 12). Twenty-nine of 119 (24%) patients had a history of symptomatic fractures. Osteopenia and osteoporosis are frequent in CD and should have the full attention of the treating physician.     

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.     

Bone metabolism in ochronotic patients

We investigated skeletal involvement in five male and two female patients with ochronosis, aged 26-82 years. The main parameters of mineral metabolism, together with biochemical markers of bone resorption (urinary N-telopeptides of type I collagen) and formation (serum bone isoenzyme of alkaline phosphatase and serum osteocalcin) were evaluated. In the same subjects lumbar spine and femoral bone mineral density (BMD) were also measured by dual energy X-ray absorptiometry. All patients but the younger 26-year-old patient had lower than normal bone mass at femoral neck and total hip, showing marked osteopenia in three cases and osteoporosis in the remaining three cases. However, at lumbar spine BMD measurement provided spuriously overestimated results, because of intervertebral disc calcification and osteophyte formation. As far as biochemical markers of bone turnover are concerned, the most relevant finding was the increased N-telopeptides of type I collagen urinary excretion. Our results suggest that ochronosis may be associated with increased bone resorption rate leading to an accelerated bone loss. A role of the homogentisic acid polymer deposit in bone matrix and cells, possibly with osteocyte damage and interference in collagen metabolism, might be hypothesized.     

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.     

Comparison of alendronate and intranasal calcitonin for treatment of osteoporosis in postmenopausal women

This study compared the effects of oral alendronate and intranasal calcitonin for treatment of osteoporosis in postmenopausal women. Women at least 5 yr postmenopause (n = 299) were randomized to either 10 mg alendronate, matching alendronate placebo, or open-label intranasal calcitonin 200 IU daily for 12 months. Hip and spine bone mineral density (BMD) and markers of bone turnover were measured, and safety and tolerability were assessed. Alendronate produced greater increases in BMD than calcitonin at 12 months at the lumbar spine (5.16% vs. 1.18%; P < 0.001), trochanter (4.73% vs. 0.47%; P < 0.001), and femoral neck (2.78% vs. 0.58%; P < 0.001). Changes in BMD with calcitonin were greater than with placebo at the femoral neck, but were not different from placebo at either the trochanter or lumbar spine. Greater decreases in bone turnover were seen with alendronate than with calcitonin (serum bone-specific alkaline phosphatase, 43% vs. 9%, P < 0.001; urinary N-telopeptide, 62% vs. 11%, P < 0.001). Similar percentages of patients in each group reported an adverse experience during the study. We conclude that, in postmenopausal women with osteoporosis, 12 months of therapy with alendronate produced significantly greater increases in BMD of the hip and spine and greater decreases in bone turnover than intranasal calcitonin.     

Femoral neck osteopenia in patients with inflammatory bowel disease

Objective: The mechanism of bone loss in patients with inflammatory bowel disease (IBD) is not completely understood. The aim of this study was to assess indices of bone turnover and bone mineral density (BMD) in the lumbar spine and femoral neck in IBD patients.
Methods: Sixty-three patients with Crohn's disease and 41 with ulcerative colitis were studied. Serum bone-specific alkaline phosphatase (B-ALP), osteocalcin, parathyroid hormone (PTH), 25 hydroxyvitamin D, interleukin-6 (IL-6), and urinary N-telopeptide cross linked type 1 collagen (NTX) were determined. BMD of the lumbar spine and femoral neck was determined by dual x-ray absorptiometry in 59 patients.
Results: In the femoral neck 42% of the patients had osteopenia (−2.5 SD < BMD T score < −1 SD) and another 41% had osteoporosis (BMD T score < −2.5). In the spine 34% of the patients had osteopenia and additional 42% had osteoporosis. BMD T scores were lower in the femoral neck compared to the spine. Reduced BMD was unrelated to gender, disease type, lifetime corticosteroid dose, but inversely correlated with disease duration ( r =−0.36 , p < 0.05 ). Serum IL-6 was higher in IBD patients compared to controls. A reduced level of osteocalcin, a marker of bone formation, was present in 7% of patients and an increase in NTX, a marker of bone resorption, in 25% of them. Osteoporotic IBD patients (spine or hip BMD T score < −2.5) had increased serum IL-6, osteocalcin and PTH level compared to nonosteoporotic patients.
Conclusions: There is a high prevalence of reduced BMD at the spine and femoral neck in IBD patients, which is more severe in the hip. Bone turnover in osteoporotic IBD patients is associated with an increase in osteocalcin, PTH and IL-6. IL-6 may play a role in the pathogenesis of bone loss in IBD.     

Enhancement of bone mass in osteoporotic women with parathyroid hormone followed by alendronate

Treatment of osteoporosis with PTH causes a marked increase in vertebral bone mineral density (BMD). However, this effect is rapidly reversed when the treatment is stopped. The purpose of the present study was to determine whether the bisphosphonate alendronate could preserve or enhance bone density in patients previously treated with PTH. Sixty-six postmenopausal osteoporotic women were treated for 1 yr with 50, 75, or 100 microg recombinant human PTH-(1-84) or placebo, and then were given 10 mg alendronate daily for an additional year. BMD was measured in the femoral neck, lumbar spine, and whole body. Markers of bone turnover included skeletal alkaline phosphatase, osteocalcin, and N-telopeptide. During the first year, changes in BMD (mean +/- SD) in women receiving PTH (all doses combined) were 7.1 +/- 5.6% (spine), 0.3 +/- 6.2% (femoral neck), and -2.3 +/- 3.3% (total body). After switching to alendronate for 1 yr in women who previously had received PTH, mean changes in BMD were 13.4 +/- 6.4% (spine), 4.4 +/- 7.2% (femoral neck), and 2.6 +/- 3.1% (whole body). In the subgroup of patients who had received the highest dose of PTH, the mean increase in vertebral BMD was 14.6 +/- 7.9%. All markers of bone turnover increased during treatment with PTH and decreased to below baseline after 1 yr of alendronate. In conclusion, sequential treatment of osteoporosis with PTH and alendronate results in an increase in vertebral bone density that is considerably more than has been reported with alendronate or estrogens alone. This combination of drugs may be a useful approach to maximizing bone density in women with vertebral osteoporosis.     

Development and validation of the osteoporosis prescreening risk assessment (OPERA) tool to facilitate identification of women likely to have low bone density

Osteoporosis and its consequent increase in fracture risk is a major health concern for postmenopausal women and older men and has the potential to reach epidemic proportions. The "gold standard" for osteoporosis diagnosis is bone densitometry. However, economic issues or availability of the technology may prevent the possibility of mass screening. The goal of this study was to develop and validate a clinical scoring index designed as a prescreening tool to help clinicians identify which women are at increased risk of osteoporosis [bone mineral density (BMD) T-score -2.5 or less] and should therefore undergo further testing with bone densitometry. Records were analyzed for 1522 postmenopausal females over 50 years of age who had undergone testing with dual-energy X-ray absorptiometry (DXA). Osteoporosis risk index scores were compared to bone density T-scores. Hologic QDR 4500 technology was used to measure BMD at the femoral neck and lumbar spine (L1-L4). Participants who had a previous diagnosis of osteoporosis or were taking bone-active medication were excluded. Receiver-operating characteristic (ROC) analysis was used to identify the specific cutpoint value that would identify women at increased risk of low BMD. A simple algorithm based on age, weight, history of previous low impact fracture, early menopause, and corticosteroid therapy was developed. Validation of this five-item osteoporosis prescreening risk assessment (OPERA) index showed that the tool, at the recommended threshold (or cutoff value) of two, had a sensitivity that ranged from 88.1 [95% confidence interval (CI) for the mean: 86.2-91.9%] at the femoral neck to 90% (95% CI for the mean: 86.1-93.1%) at the lumbar spine area. Corresponding specificity values were 60.6 (95% CI for the mean: 57.9-63.3%) and 64.2% (95% CI for the mean: 61.4-66.9%), respectively. The positive predictive value (PPV) ranged from 29 at the femoral neck to 39.2% at the lumbar spine, while the corresponding negative predictive values (NPVs) reached 96.5 and 96.2%, respectively. Based on this cutoff value, the area under the ROC curve was 0.866 (95% CI for the mean: 0.847-0.882) for the lumbar spine and 0.814 (95% CI for the mean: 0.793-0.833) for the femoral neck. We conclude that the OPERA is a free and effective method for identifying Italian postmenopausal women at increased risk of osteoporosis. Its use could facilitate the appropriate and more cost-effective use of bone densitometry in developing countries.     

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.     

Coeliac disease and bone mineral density in adult female patients.

A cross sectional study was undertaken to examine the relationship between coeliac disease and bone mineral density. The 135 female coeliac patients registered on the database of the Department of Gastroenterology at Hull Royal Infirmary were approached by letter, advising them of a potential risk of osteoporosis and inviting them to undergo bone densitometry. A total of 81 registered women (60%) attended the Osteoporosis Laboratory, Princess Royal Hospital and underwent dual energy x ray absorptiometry at the lumbar spine (L2-L4) and femoral neck. Historical data relating to the time of diagnosis and adherence to a gluten free diet were obtained. A control group was selected from the local normal population and was first matched for height, weight, and menopausal status. Postmenopausal patients were then further matched to controls of equivalent menopausal age. In coeliac patients, bone mineral density expressed in g/cm2 as mean (SD) was significantly lower at the lumbar spine (1.076 (0.186)) than in the control group (1.155 (0.143), p < 0.001). This was also the case at the femoral neck (0.887 (0.142) versus 0.965 (0.127), p < 0.001). When the coeliac patients were stratified by menopausal status, it was found that femoral neck bone mineral density was significantly below control values in both premenopausal and postmenopausal women. Spinal bone mineral density exhibited a significant decrement only in the postmenopausal group. The age at diagnosis of coeliac disease and adherence to a gluten free diet did not influence bone mineral density at either hip or spine. These results confirm coeliac patients' higher risk of osteopenia. Coeliac disease should be added to the list of medical conditions which constitute an indication for bone densitometry in order that the individual risk of osteoporosis related fracture may be determined.     

Bone mineral density in Iranian patients with inflammatory bowel disease

Patients with inflammatory bowel disease (IBD) are at increased risk of developing osteopenia and osteoporosis. The aim of the study was to investigate the prevalence of decreased bone density and related risk factors in Iranian IBD patients. A total of 126 ulcerative colitis (UC) and 39 Crohn’s disease (CD) patients were enrolled. Dual-energy x-ray absorptiometry technique was used to measure bone density, and blood samples were obtained to measure biochemical markers. To find predictive variables for bone mineral density (BMD), stepwise regression analysis was carried out. A total of 53 IBD patients (32.1%) had diminished bone mineral density at either lumbar spine (L1–L4) or femoral neck. Of these, 9 (5.4%) had osteoporosis; however, 44 (26.7%) were osteopenic. Femoral neck bone density was significantly decreased among CD patients (p<0.04). There was no significant difference in BMD between men and women. We have found significant differences in BMD T scores at lumbar L1–L4, L2–L4, and femoral neck in corticosteroid ever-users (p<0.002, p<0.001, p<0.003, respectively). There was no significant difference in biochemical markers between UC and CD patients, except that more CD patients were hypocalcemic (p<0.001). Stepwise regression analysis has revealed lumbar spine T score was predicted by age (p<0.0001), corticosteroid use (p<0.002), and body mass index (BMI) (p<0.005); however, femoral neck was predicted by age (p<0.0001), BMI (p<0.0001), smoking (p<0.009), and corticosteroid use (p<0.028). Low bone density in Iranian UC and CD patients is in accordance with Western societies. Treatment with corticosteroid has increased this possibility in both groups. Corticosteroid use, age, smoking, and BMI are predictive factors for low bone density.     

Usefulness of bone densitometry in postmenopausal women with clinically diagnosed vertebral fractures

OBJECTIVE: To analyse whether bone mineral density (BMD) assessment is required in postmenopausal women presenting with low trauma vertebral fracture. METHODS: Women with vertebral fracture diagnosed over a 10 year period were recruited from our database. The following were excluded: (a) patients with high energy trauma; (b) patients with malignancies; (c) patients with a metabolic bone disease other than osteoporosis. All postmenopausal women were included in whom BMD had been evaluated at both the lumbar spine and femoral neck by dual energy x ray absorptiometry during the six months after the diagnosis. Patients with a potential cause of osteoporosis other than age and menopause were not considered. A total of 215 patients were identified. RESULTS: The mean (SD) age of the patients was 65.9 (6.9) years. BMD at the lumbar spine was 0.725 (0.128) g/cm(2) and the T score was -2.94 (1.22); BMD at the femoral neck was 0.598 (0.095) g/cm(2) and the T score was -2.22 (0.89). The BMD of the patients was significantly lower than that of the general population at both the lumbar spine and femoral neck. When the lowest value of the two analysed zones was considered, six patients (3%) showed a normal BMD, 51 (23.5%) osteopenia, and 158 (73.5%) osteoporosis. The prevalence of osteoporosis at the femoral neck increased with age; it was 25% in patients under 60, 35% in patients aged 60-70, and 60% in patients over 70. CONCLUSION: These results indicate that bone densitometry is not required in postmenopausal women with clinically diagnosed vertebral fractures if it is performed only to confirm the existence of a low BMD.     

The threshold of bone mineral density for vertebral fractures in female patients with primary hyperparathyroidism

BACKGROUND AND OBJECTIVE: Primary hyperparathyroidism (pHPT) is one of the causal diseases that induce secondary osteoporosis. Although patients with pHPT have reduced bone mineral density (BMD) especially at the cortical bone, there have been controversies about risk of fracture. Moreover, no reports have been available about the threshold of BMD for fractures in pHPT patients. METHODS: BMD values were measured by dual-energy x-ray absorptiometry at lumbar spine, femoral neck and distal one third of radius. Various indices were compared in 116 female pHPT patients and 716 control subjects. Moreover, we analyzed relationship between the cut-off values of BMD and the prevalence of vertebral fractures in pHPT and control subjects. RESULTS: The prevalence of subjects with vertebral fractures was lower in pHPT patients, compared with that of control subjects. Age and body height were significantly higher and lower in pHPT women with vertebral fractures, respectively. Lumbar spine BMD was significantly lower in pHPT women with vertebral fractures, presumably due to their increased age. There were no differences in femoral neck and radius BMD or in bone metabolic indices between pHPT women with and without vertebral fractures. On the other hand, age-matched BMD was not significantly different between both groups at any measured site. Cut-off values of BMD at lumbar spine and femoral neck were lower in postmenopausal pHPT patients, compared with those of the postmenopausal control group. Moreover, cut-off values of BMD at radius was much lower in postmenopausal pHPT patients, compared with those of the postmenopausal control group (pHPT vs control (g/cm(2)): 0.670 vs 0.706 at lumbar spine; 0.549 vs 0.570 at femoral; 0.394 vs 0.474 at radius). Sensitivity and specificity of vertebral fractures was lower in pHPT patients, compared with those in control group. CONCLUSIONS: The present cross-sectional study demonstrated that thresholds of BMD for vertebral fractures were lower especially at radial bone in female patients with pHPT, compared with those in the control group.     

Regional bone mineral density after orthotopic liver transplantation

OBJECTIVES: Although there is a fall in lumbar spine bone mineral density (BMD) after liver transplantation, little is known about femoral neck or total body BMD. Therefore we determined: (a) the proportion of patients with preexisting hepatic osteopenia before transplantation and (b) the effects of transplantation on global and regional BMD. DESIGN: Retrospective analysis of BMD measurements of patients before and up to 2 years after liver transplantation. METHODS: BMD was assessed by dual energy X-ray absorptiometry in 56 patients, before and at regular intervals after liver transplantation, for up to 24 months, to measure total body, lumbar spine (L2-L4) and femoral neck BMDs. RESULTS: Pre-transplant, 23% of patients had osteoporosis (a negative Z score > 2). Paired data before and after transplantation revealed no change in total body BMD. However, there was a fall in lumbar spine BMD (1.04+/-0.03 to 1.02+/-0.03 g/cm2; P < 0.04) at 1 month after transplantation. The reduction in lumbar spine BMD was seen up to 12 months, BMD at 18-24 months being similar to pre-transplant values. Femoral neck BMD also fell (0.96+/-0.06 to 0.83+/-0.04 g/cm2; P < 0.03), but only after 6-9 months, thereafter remaining below pre-transplant values until the end of the follow-up period. CONCLUSIONS: Although osteopenia is common in patients with liver disease, total bone density does not fall after transplantation. Nonetheless regional lumbar spine and femoral neck bone density does fall after transplantation with a risk period for femoral neck fracture which may extend for up to 2 years.     

Bones and Crohn's: risk factors associated with low bone mineral density in patients with Crohn's disease

Previous studies have confirmed that the prevalence of decreased bone mineral density is elevated in patients with inflammatory bowel disease. The objective of the current study was to determine the prevalence of osteopenia and osteoporosis in a cross-sectional outpatient population of 242 adult patients with Crohn's disease and to determine which clinical characteristics and serum and urine biochemical factors might be predictive of bone loss. Thirty-seven percent had normal bone density, 50.0% were osteopenic, and 12.9% were osteoporotic. Among the sites used to diagnose low bone mineral density, the femoral neck demonstrated the highest prevalence of osteopenia and the ultra-distal radius the highest prevalence of osteoporosis. However, low bone mineral density at one site was always predictive of low bone mineral density at the other. Corticosteroid use during the year before assessment was found to be consistently predictive of low bone mineral density in males but not in females. In contrast, low body mass index and high platelet counts were consistently predictive of low bone mineral density in females but not in males. Disease location, smoking, and age were not predictive of changes in bone mineral density.     

Prolactinomas in adolescents: persistent bone loss after 2 years of prolactin normalization

OBJECTIVE: To evaluate the effect of hyperprolactinaemia and its treatment with dopamine-agonists on bone mass and turnover in adolescent patients compared to adults. PATIENTS: Forty patients with hyperprolactinaemia (20 with disease onset during adolescence and 20 during adulthood) and 40 healthy control subjects. DESIGN: Open transverse (in patients and controls) and open longitudinal (in the patients). MEASUREMENTS: Bone mineral density (BMD) at lumbar spine and femoral neck, serum osteocalcin (OC) and urinary cross-linked N-telopeptides of type-1 collagen (Ntx) levels were evaluated in patients and controls. In the 40 patients, bone mass and turnover were re-evaluated after 12 and 24 months of treatment with bromocriptine (BRC, dose 2.5-10 mg daily), quinagolide (CV, dose 0.075-0.3 mg daily) or cabergoline (CAB, dose 0.5-1.5 mg weekly). RESULTS: Transverse study: BMD values were significantly lower in hyperprolactinaemic patients than in controls, both at lumbar spine (0.81 +/- 0.01 vs. 1.010 +/- 0.01 g/cm2; P < 0.001) and femoral neck (0.71 +/- 0.01 vs. 0.873 +/- 0.03 g/cm2; P < 0.001). Thirty-two patients (80%) had osteoporosis and/or osteopenia at one or both skeletal sites. A significant inverse correlation was found between T score values measured at lumbar spine and femoral neck and the estimated disease duration. BMD was significantly lower in young than adult patients both at lumbar spine (T score, -2.4 +/- 0.1 vs. -1.4 +/- 0.3, P < 0.01) and at femoral neck (T score, -2.1 +/- 0.05 vs. -1.5 +/- 0.2, P < 0.05). Similarly, serum OC levels were significantly lower (2.0 +/- 0.11 vs. 9.1 +/- 2.4 micrograms/l, P < 0. 01) while Ntx levels were significantly higher in patients than in controls (129.2 +/- 1.7 vs. 80.7 +/- 2.9 nmol Bone collagen equivalent (BCE)/mmol creatinine; P < 0.001). A significant inverse correlation was found between prolactin (PRL) levels and OC levels, lumbar and femoral T score values, as well as between disease duration and OC levels, lumbar and femoral T score values. A significant direct correlation was also found between Ntx levels and PRL levels and disease duration. Longitudinal study: Normalization of serum PRL levels was obtained in all patients after 6-12 months of treatment. A significant increase of serum OC levels together with a significant decrease of Ntx levels was observed after 12 and 24 months of treatment (P < 0.01). Urinary and serum calcium, phosphorus, creatinine, and serum alkaline phosphatase and parathyroid hormone levels did not change during the study period in all patients. After 12 months of therapy OC and Ntx concentrations were restored to normal. A slight but not significant increase of BMD values was recorded after 12 and 24 months of treatment. After 12 months of treatment the percent increment of BMD values in the whole group of patients was 1.13 +/- 0.6% at lumbar spine and 1.2 +/- 0.4% at femoral neck level, whereas after 24 months, it was 2.8 +/- 0.7% at lumbar spine and 3.5 +/- 0.7% at femoral neck level. After 12 months of treatment, the percent increment of BMD values was 0.7 +/- 0.2% and 1.6 +/- 1.1% at lumbar spine and 0.9 +/- 0.5% and 1.6 +/- 0.5% at femoral neck level in the young and adult patients, respectively, whereas after 24 months, it was 2.1 +/- 0.8% and 3.4 +/- 1.3% at lumbar spine and 2.6 +/- 0.8% and 4.4 +/- 1.0% at femoral neck level in the young and adult patients, respectively. CONCLUSIONS: Adolescents with prolactinoma have osteopenia or osteoporosis, a finding that strengthens the need for a prompt diagnosis. Since normalization of PRL concentrations by dopamine agonist therapy is unable to restore the bone mass, other therapeutic approaches should be considered in order to prevent further long-term problems.     

Risk assessment for osteoporosis by quantitative ultrasound of the heel in ankylosing spondylitis

OBJECTIVE: The aim of this cross-sectional cohort study is to assess the potential of quantitative ultrasound (QUS) of the calcaneus in pre-screening for vertebral/non-vertebral fractures, and in discriminating osteoporotic from normal bone density in patients with ankylosing spondylitis (AS); a second objective is to determine the prevalence of osteoporosis using dual-energy X-ray absorptiometry (DEXA) in this patient group. RESULTS: Included are 50 consecutive AS patients with no history of osteoporosis: mean (SD) age 52 (12) yrs, range 26-75 yr; female/male ratio 15/35. The mean (SD) DEXA T score in the lumbar spine (AP view) was -0.82 (1.73), mean (SD) DEXA T score in femoral neck -1.46 (1.12). The mean (SD) calcaneal QUS T score was -0.73 (0.95). In our population of AS patients the prevalence of femoral neck osteoporosis according to the WHO definition (DEXA T < -2.5) was 20%. Osteoporosis criteria were met at the femoral neck in 10 (20%) patients, and 7 of them (70%) were correctly diagnosed using QUS, with T < -1.0 as cut-off value; normal bone density at the femoral neck was found in 15 AS patients (30%), yet in 2 of them the calcaneal QUS T was < -1.0. In AS the 20% pretest probability of having femoral neck osteoporosis increased using calcaneal QUS, with a cut-off level T < -1.0 (70% sensitivity, 68% specificity), and then rose to 35% as the predictive value of a positive test, yielding a net result of QUS testing of +15%. The predictive value of a negative QUS test result was 90%, which makes QUS applicable to exclude severe osteoporosis. Vertebral and/or non-vertebral fractures occurred in 12 out of 50 AS patients (24%); 5 of them (10%) were associated with osteoporosis as defined by WHO criteria measured via DEXA. CONCLUSION: The performance of QUS is similar to DEXA in finding patients with osteoporosis-associated fractures: the sensitivity of QUS T < -1.0 in finding the fracture is 80%, and the sensitivity of femoral neck DEXA T < -2.5 in finding fractured patients is 60%. We conclude that both osteoporosis and fractures are common sequelae in AS. Calcaneal QUS offers a promising approach to screen for osteoporosis, and may be applied to exclude osteoporosis-associated high fracture risk in AS.