Diana González

Risk of fractures in celiac disease patients: a cross-sectional, case-control study

OBJECTIVES:Although osteopenia and osteoporosis are well-recognized complications of celiac disease, no controlled studies have been done to assess the prevalence of fractures in a large cohort of patients. The objectives of this study were to determine the prevalence of bone fractures and vertebral deformities in celiacs and to analyze the relationship between fractures and clinical data of patients.METHODS:We studied 165 patients with a well-established diagnosis of celiac disease. A similar number of age- and gender-matched control subjects with functional GI disorders were evaluated. The design of the study was cross-sectional, with a retrospective historical review through a personal interview of all subjects. All patients underwent bone mineral density measurement by dual-energy, x-ray absorptiometry and spinal x-ray. Vertebral deformities were determined by visual inspection of spinal x-rays and by morphometric analysis.RESULTS:Among celiacs, 41 patients (25%) referred have had from one to five fractures in the peripheral skeleton. On the contrary, only 14 (8%) control subjects experienced fractures. This difference was highly significant (odds ratio, 3.5; 95% confidence interval [CI], 1.8–7.2; p < 0.0001). Although inspection of spinal x-rays showed evidence of vertebral deformities in the lumbar spine in only two patients, a more detailed examination of lateral x-rays using morphometric criteria detected lumbar spine vertebral deformities in nine (five also had fractures in the peripheral skeleton) and in four controls (odds ratio, 2.8; 95% CI, 0.7–11.5; p = NS). Eighty percent of fractures were detected before the diagnosis of celiac disease or in patients who were noncompliant with the gluten-free diet; only 7% of patients experienced fractures after starting treatment. Regression analysis adjusted for multiple comparisons showed that patients with fractures were diagnosed with celiac disease later (p < 0.06) and remained undiagnosed for more prolonged periods (p < 0.05). There was a trend, which did not reach statistical significance, for a lower bone mineral density in the lumbar spine and total skeleton among patients with fractures.CONCLUSIONS:This study has demonstrated that patients with celiac disease had a high prevalence of bone fractures in the peripheral skeleton. Most of these events occurred before diagnosis or while patients were noncompliant with gluten-containing diet. Our results suggest that early diagnosis and effective treatment of celiac disease were the most relevant measures to protect patients from the risk of fractures.

Pre- and post-treatment serum levels of cytokines IL-1β, IL-6, and IL-1 receptor antagonist in celiac disease. Are they related to the associated osteopenia?

Objective:Decreased bone mineral density is a common finding in untreated celiac disease patients. However, the precise pathophysiology of osteopenia remains incompletely understood. Pathological features of gluten sensitivity are associated with local release of proinflammatory and antiinflammatory cytokines. We investigated the serum levels of IL-1β, IL-6, and IL-1 receptor antagonist in celiac patients and correlated them with bone density measurements.Methods:We assessed serum samples of 16 female patients at the time of diagnosis (on an unrestricted diet) and after a mean time of 37 months on a gluten-free diet. At the same time, bone mineral density in the lumbar spine and total skeleton was determined by DEXA.Results:Untreated patients had high serum levels of IL-1β and IL-6 and normal IL-1-RA. Treatment produced a decrease in median IL-1β levels (p = NS) and a significant diminution of IL-6 (p < 0.05). On the contrary, IL-1-RA increased significantly after treatment (p < 0.05). Baseline lumbar spine Z-score and IL-6 levels exhibited a significant inverse correlation (r =–0.61; p < 0.01). Patients with more severe baseline osteopenia (< -2 Z-scores) had a significantly lower IL-1-RA than those with less bone compromise (> -2 Z-scores).Conclusions:Our data demonstrate that the inflammatory process observed in active celiac disease is associated with high serum levels of IL-1β and IL-6 and normal levels of IL-1-RA. Treatment significantly reduces both proinflammatory cytokines and significantly increases the antiinflammatory one. We also suggest that these cytokines might have a role in the osteopenia associated with celiac disease.

Long‐term effect of gluten restriction on bone mineral density of patients with coeliac disease

Aim: To assess the long‐term effect of a gluten‐free diet on bone mineral density of adults with untreated coeliac disease.

Body composition and bone mineral density in untreated and treated patients with celiac disease

Body composition and bone mineral density (BMD) were studied by X-ray absorptiometry in 20 untreated and 12 treated women with celiac disease, as well as in 85 age-matched control women. Untreated patients had a significantly lower body weight, fat mass, lean tissue mass and BMD at the lumbar spine and total skeleton compared to controls (p < 0.001 for all parameters). Treated patients had also a significantly lower body weight (p < 0.01) fat mass (p < 0.05) and bone mineral density at lumbar spine and total skeleton (p < 0.05) compared with controls, but lean tissue mass was not diminished. However, treated patients had a significantly higher body weight, fat mass and BMD of the total skeleton compared with untreated celiac patients (p < 0.01 for all parameters). Serum alkaline phosphatase levels were increased in untreated patients but serum 250HD was normal. In conclusion, celiac disease causes a global and almost universal reduction of fat mass and BMD. The results of this cross-sectional study suggest that osteopenia does not seem to be completely restored by adequate treatment. Alteration of vitamin D metabolism was not the cause of osteopenia in the majority of patients.

Is it necessary to screen for celiac disease in postmenopausal osteoporotic women

Decreased bone mass is a frequent finding in celiac patients, and subclinical celiac disease (CD) appears to be unusually overrepresented among patients with idiopathic osteoporosis. Since silent CD may be more common than previously believed, it has been suggested that all osteoporotic patients should be checked for occult CD. The aim of this study was to explore the prevalence of CD in a well-defined population of postmenopausal osteoporotic women. We evaluated 127 consecutive postmenopausal patients (mean age: 68 years; range: 50-82 years) with verified osteoporosis. The observed prevalence of CD in this group was compared to that observed in a group of 747 women recruited for a population-based study. The screening algorithm used to diagnose CD was based on a 3-level screening using type IgA and IgG antigliadin antibodies (AGA) in all the patients (1st level) followed by antiendomysial antibodies (EmA) and total IgA (2nd level) of samples testing positive, and intestinal biopsy of positive cases (3rd level). At the end of the serological screening, only 1 of 127 osteoporotic women was eligible for jejunal biopsy showing a characteristic celiac flat mucosa (prevalence 7.9 x 1,000; 95% CI 0.2-43.1). In addition, CD was diagnosed in 6 of 747 women of the population-based study (prevalence: 8.0 x 1,000; 95% CI 3.3-18.3). There was no significant difference between the two groups. Therefore, our study showed that the prevalence of CD in postmenopausal osteoporotic women was lower than that reported in previous studies and similar to that of the general population. In conclusion, although the relatively small size of the group tested does not allow us to be conclusive, the results suggest that a case finding policy in postmenopausal osteoporosis would have a high cost/benefit ratio except for patients not responding to conventional therapies, or presenting borderline laboratory results.

Efficacy of the bisphosphonate APD in the control of Paget's bone disease

Fifty-four patients with Pagets bone disease have been treated with the bisphosphonate APD. Twenty-six patients had not previously received treatment for Pagets disease; and 28 had been treated before with EHDP alone or in combination with calcitonin. APD was given orally in a mean dose of 500 mg daily (congruent to 6.8 mg/kg of body weight) for 4 to 12 months. Bone pain diminished or disappeared in 34 of 39 patients with symptoms. A very significant diminution of the biochemical indices of bone turnover was observed in all patients, but the responses were faster in patients who had not previously received treatment for Pagets disease. After 4 months of treatment the serum levels of alkaline phosphatase of previously untreated patients diminished from 58.8 +/- 8.0 to 20.0 +/- 3.9 KA units (P less than 0.001) and urinary excretion of hydroxyproline diminished from 108.6 +/- 16.9 to 42.4 +/- 8.3 mg/24 h (P less than 0.001). In 23 of 26 previously untreated patients the biochemical indices decreased to the normal range (complete response). A reduction of 50% or more without reaching the normal range was observed in the other 3 patients (partial response). Actuarial analysis of the duration of the effect 12 months after stopping APD disclosed that 63% of patients who had achieved a complete response but only 23% of those with a partial response were in biochemical remission. A second course of APD was administered to 11 patients. The results were as effective during the second as the first course in 9 patients, whereas 2 patients had no response to retreatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute antiosteoclastic effect of salmon calcitonin in osteoporotic women.

SummaryTwenty-one women with primary osteoporosis received an intramuscular injection of 100 IU of salmon calcitonin at 8am. Blood samples were collected up to 5 h postcalcitonin and urine was collected for 24 h in three periods of 8 h each. A significant fall of the total hydroxyproline excretion (THP) was observed in every period but the maximum effect took place 8–16 h postcalcitonin. The effect was more pronounced in those patients with a greater basal excretion of THP and in those with a more significant diminution of their bone mass. A significant diminution of the urinary excretion of calcium was found 8–24 h postcalcitonin, while phosphate excretion increased throughout the three 8 h periods. The effect of calcitonin in osteoporotic women was compared with the results obtained in 9 patients with Pagets disease. In absolute values the fall of THP excretion was significantly greater in the pagetic patients but the percentage diminution was not significantly different in osteoporotic women and in pagetic patients. Salmon calcitonin induced a significant acute diminution of bone turnover in patients with osteoporosis, as defined by decreases in total urinary hydroxyproline. The calcitonin-induced hypocalcemia does not seem to be an accurate index of the hormone action in osteoporosis.

Short‐Term Therapy with Oral Olpadronate in Active Paget's Disease of Bone

One of the aims of the treatment of Pagets disease with bisphosphonates should be the normalization of the activity of the disease with the shortest possible exposure to the drug. Olpadronate (OPD) is a new bisphosphonate characterized by the dimethylation of the amino group, its potency is near to alendronate, and more soluble in the digestive media than other aminobisphosphonates. We treated 46 patients (28 men and 18 women, mean age 70 years) with active Pagets disease with oral OPD, 200 mg/day for 12 ± 2 days, except 2 patients who received 400 mg/day. Eight patients had never been treated before, and 38 had previously received antiosteolytic drugs. The period without treatment prior to OPD was (X ± 1 SD) 14 ± 12 months. Baseline bone alkaline phosphatase (BALP) (levels fell from (X ± 1 SD) 54.0 ± 62.7 IU/ml (range 22–396) to a lowest mean value of 16.2 ± 6.4 IU/ml (range 8–45) (normal range 5–21 IU/ml). Forty patients normalized BALP values, in most of the cases within the first 3 months after OPD treatment. Two patients showed partial response (> 50% decrease from baseline), three patients presented poor response (< 50% decrease from baseline), and one patient did not respond at all. Two patients complained of gastric discomfort, and one patient had diarrhea, which disappeared after discontinuation of the drug. Follow‐up was carried out on 36 patients; 22 patients are still in remission, with an average length of 9.0 ± 2.6 months. Fourteen patients experienced relapse after 9 ± 2 months remission. In conclusion, a 12‐day treatment with 200 mg/day of OPD proved to be a very effective and well tolerated therapy of Pagets disease and induced biochemical remissions in the vast majority of patients, even in those with very active disease.

Acute effect of the intranasal administration of salmon calcitonin in osteoporotic women

Eleven women with primary osteoporosis (mean age, 63.1 years; range, 57-78) received in a random schema: placebo, 200 and 400 IU of salmon calcitonin nasal spray (sCT-NS) during 3 successive days. Total and ionized calcium and phosphate in serum were determined before and 5 h after calcitonin. Total hydroxyproline (THP) and creatinine excretion were measured in urine in three periods of 8 h each after calcitonin administration. The THP excretion after placebo administration showed a circadian rhythm with peak excretion during the night. This rhythm was not altered by sCT-NS administration at 8 a.m. but a sustained diminution of the THP/creatinine excretion was observed. The average decrease after 400 IU of sCT-NS was 9, 16 and 6% during the first, second and third periods of urine collection. Although the average effect of the 200 and 400 IU doses was similar, only the diminution induced by the latter dose on the 24-h period was statistically significant: placebo, 24.8 +/- 2.9; 200 IU, 20.8 +/- 2.9 (P n.s.); 400 IU, 20.1 +/- 2.2 mg/24 h (P less than 0.01). No significant changes were observed on serum except a fall provoked by the 400 IU dose upon ionized calcium (4.44 +/- 0.08 to 4.37 +/- 0.06 mg/dl; P less than 0.05). The administration of 200 or 400 IU of sCT-NS provoked a sustained but moderate decrease of bone resorption on osteoporotic females of a lesser degree than the one observed in a previous study after the parenteral administration of 100 IU.

Comparison of the acute effect of the intranasal and intramuscular administration of salmon calcitonin in paget's disease

SummaryOn 7 patients with mild-to-moderately active Pagets disease, 200 IU of salmon calcitonin (SCT) nasal spray (NS), induced a significant decrease of the total urinary hydroxyproline excretion (THP) during the 8–16 hour and the 0–24 hour (P<0.05) periods after treatment as compared to control day. However, the administration of 100 IU of SCT intramuscularly (i.m.) caused a significantly greater effect than 200 IU-NS during the second 8 hour period after its administration (P<0.01) and on the over-all 24 hour effect (P<0.05). On 3 patients with severe Pagets disease, SCT-NS was essentially ineffective whereas the injection of SCT induced a marked diminution of the THP excretion.