A prospective, longitudinal study of the long-term effect of treatment on bone density in children with celiac disease.

OBJECTIVE: Because osteopenia is a frequent complication of celiac disease, we evaluated the impact of a long-term gluten-free diet (GFD), initiated during childhood, on bone density. study design: Patients with celiac disease (n = 19; mean age, 14.2 +/- 2.6 years) were studied after 4.3 +/- 0.6 years of GFD. Bone density had been measured at diagnosis and after 1 year of GFD. We also studied 211 healthy children as a control group. Bone mineral density was measured by dual-energy x-ray absorptiometry. Intact parathyroid hormone (PTH) and bone-specific alkaline phosphatase (BALP) levels were measured in serum, and N-terminal telopeptide of type I collagen (NTx) was measured in urine. RESULTS: Although at diagnosis bone mineral content, bone area, and bone mineral density were significantly lower than in control subjects, the 3 measurements were normal after GFD. None of the patients on a GFD showed elevated values of PTH. Patients on a GFD had BALP (110.2 +/- 67.2 U/L) and NTx levels (261.9 +/- 187.8 nmol bone collagen equivalents/mmol creatinine) that were significantly higher than those of control subjects. The levels of BALP and NTx were significantly higher in patients with good compliance with the GFD, compared with patients with poorer compliance. CONCLUSIONS: This study shows that bone mineral content, bone area, and bone mineral density improve significantly with a GFD.

Mutational analysis of GNAS1 in patients with pseudohypoparathyroidism: identification of two novel mutations.

Pseudohypoparathyroidism (PHP) refers to two major variants that generally coexist in the same family, PHP type Ia (PHP Ia), in which both PTH resistance and a constellation of physical features, termed Albright's hereditary osteodystrophy (AHO), are present, and pseudopseudohypoparathyroidism (PPHP), in which AHO occurs without PTH resistance. Most patients with PHP Ia show a partial deficiency (50%) of Gs activity, due to loss of function mutations in Gsalpha gene (GNAS1). The present study reports clinical, biochemical, and molecular data of 8 unrelated families with PHP Ia and PPHP. The 13 exons of GNAS1 were screened for mutations by PCR and direct sequencing of the amplified products. We detected heterozygous mutations in the affected members of the 4 families in which PHP Ia was present. In 2 families 2 previously reported deletions in exons 5 and 7 were found, whereas in the other 2 families, 2 novel frameshift deletions were identified in exons 1 and 11, causing a premature stop codon in the mutant allele. No mutation was detected in the families in which PPHP was the only clinical manifestation. In conclusion, we report the first mutational analysis of Italian patients with PHP Ia and PPHP, and we describe two novel deletions in GNAS1. Furthermore, we confirm that these mutations cannot be detected in families with isolated PPHP, suggesting that these forms of AHO are genetically distinct from PHP Ia.

Body composition in children with celiac disease and the effects of a gluten-free diet: a prospective case-control study.

BACKGROUND: Celiac disease is the most common cause of malnutrition in children of Western countries. OBJECTIVE: The objective was to measure body composition in children at the time celiac disease was diagnosed and after consumption of a gluten-free diet (GFD). DESIGN: We assessed body composition by dual-energy X-ray absorptiometry in 29 children and adolescents with a mean (+/-SD) age of 9.5 +/- 3.4 y at the time celiac disease was diagnosed and in a subset of 20 patients after 1.2 +/- 0.2 y of a GFD. We also studied 23 patients aged 21.2 +/- 4.6 y who consumed a GFD for 10.6 +/- 4.5 y. Each patient was matched with a healthy control subject of the same age and sex. RESULTS: Untreated patients weighed less than control subjects (P = 0.04). Fat mass and bone mineral content were lower in the patients than in the control subjects (P < 0.01), as was lean mass of the limbs (P = 0.0013). After approximately 1 y of the GFD, there were no significant differences in body-composition values between patients and control subjects. Similarly, body-composition values of celiac disease patients who consumed the GFD long term were comparable with those of healthy subjects. CONCLUSIONS: Remarkable abnormalities in body composition were found in children at the time of diagnosis of celiac disease. Appropriate dietary treatment reverses body-composition abnormalities quickly and the beneficial effects of gluten withdrawal are persistent. Because these results are harder to achieve if celiac disease is first diagnosed in adulthood, efforts to encourage early diagnosis of celiac disease should be made.

Bone density and bone metabolism are normal after long-term gluten-free diet in young celiac patients.

OBJECTIVES: Osteoporosis and alterations of bone metabolism are frequent complications of celiac disease. We evaluated the impact of long-term gluten-free diet (GFD) initiated during childhood and adolescence on bone mineralization and bone metabolism. METHODS: We studied 30 celiac patients on GFD for > or = 5 yr. The mean age at diagnosis was 11.4+/-5.0 yr, and the mean duration of GFD was 10.7+/-4.3 yr. Results were compared with those obtained in 240 healthy controls. Bone mineral density (BMD) was measured in the lumbar spine and in the whole skeleton by dual-energy x-ray absorptiometry. Serum levels of bone-specific alkaline phosphatase (BALP) and N-terminal propeptide of type I procollagen (PINP) were measured as bone formation indices, and urine levels of N-telopeptide of type I collagen (NTx) as bone resorption index. RESULTS: BMD measurements of celiac patients (lumbar spine: 1.131+/-0.121 g/cm2; total body: 1.145+/-0.184 g/cm2) did not differ from those of control subjects (lumbar spine: 1.131+/-0.184 g/cm2; total body: 1.159+/-0.118 g/cm2). The levels of BALP, PINP, and NTx of celiac patients did not differ from those of controls. Patients who started GFD before puberty had BMD and bone metabolism measurements comparable to those of patients who started GFD during puberty. CONCLUSIONS: Our data show that long-term dietary treatment ensures normal mineralization and bone turnover.