Growth, stool consistency and bone mineral content in healthy term infants fed sn-2-palmitate-enriched starter infant formula: A randomized, double-blind, multicentre clinical trial.

BACKGROUND: Palmitate in breast milk is predominantly located in the triacylglycerol sn-2 position, while infant formulae contain palmitate predominantly in the sn-1 and sn-3 positions. During digestion, palmitate in the sn-1 and sn-3 positions is hydrolyzed to free palmitic acid that can subsequently complex with calcium to form insoluble soaps; this may partially explain why formula-fed infants have harder stools than breast-fed infants. METHODS: This large (n = 488) randomized, double-blind, multicentre trial investigated whether increasing the sn-2 palmitate content of infant formula improves stool consistency and bone mineral content (measured by dual-energy x-ray absorptiometry), without affecting growth or health. From ∼1 week to 4 months of age, infants were exclusively fed one of three formulae: i) control formula (CF; 16% of total palmitate at sn-2; n = 162), (ii) experimental formula 1 (EF1; 43% of total palmitate at sn-2; n = 166) or (iii) experimental formula 2 (EF2; 51% of total palmitate at sn-2; n = 160). RESULTS: Intention-to-treat analysis showed softer stools in both EF groups (vs. CF) at ages 2 weeks and 1 and 2 months (p ≤ 0.01), but not 3 and 4 months. At 4 months, all groups had similar growth outcomes while bone mineral content was significantly higher in EF1 (p = 0.0012) and EF2 (p = 0.0002) compared with CF. Comparison of reported adverse events up to 12 months revealed no differences among groups. All 3 infant formulae exhibited equally good digestive tolerance. CONCLUSIONS: Formulae enriched in sn-2 palmitate fed in early infancy are safe, improve stool consistency (from 2 weeks to 2 months) and increase bone mineral content (at 4 months).

Precocious hypothyroidism mechanisms after radioiodine treatment in Graves' disease.

OBJECTIVE: Hypothyroidism can occur after radioiodine treatment for Graves' disease. It may happen precociously and transiently in the first year after treatment. The purpose of this study was to understand the mechanisms responsible for precocious hypothyroidism. METHODS: 36 patients treated for Graves disease by radiodiodine were prospectively studied; The following variables were included in the analysis: age, gender, attendance for Graves' orbitopathy (GO), delay before radioiodine treatment, number of recurrences, previous treatments, corticosteroid therapy, thyroid mass, and (131)I dose. The titres of free T4 (FT4), thyroid-stimulating hormone (TSH), anti-TSH receptor antibodies (TRAb), anti-thyroid peroxydase antibodies (TPOAb) and anti-thyroglobulin antibodies (TGAb) were monitored. Thyroid stimulating (TSAb) and blocking (TBAb) antibodies were determined and (123)I uptake was measured when hypothyroidism occurred. RESULTS: 23 patients became precociously hypothyroid (group A) while 13 patients did not (group B). The initial TGAb titre was higher in group A (p=0.0024), and corticosteroid therapy was used more frequently to avoid aggravating GO in group B (p=0.0276). TPOAb and TGAb titres increased significantly only in group A (p=0.0112 and p=0.0202, respectively). When hypothyroidism occurred, TBAb was present in 13 patients. Transient hypothyroidism due to TBAb was observed in 1 patient. No iodide organification impairment was disclosed by the perchlorate test. CONCLUSION: Radioinduced thyroiditis appears to be the main mechanism involved in the pathogenesis of precocious hypothyroidism. A higher TGAb titre before treatment is associated with precocious hypothyroidism, suggesting the prognostic value of TGAb. Transient hypothyroidism directly due to TBAb remains rare.

Evaluation of bone loss and its mechanisms in anorexia nervosa.

The purpose of this cross-sectional study was to assess the extent of and mechanisms involved in bone loss in anorexia nervosa patients. We compared 113 anorexia nervosa patients (mean age 25 +/- 8 years, mean duration of disease 5.7 +/- 6.1 years) with 21 age-matched controls. Mean duration of amenorrhea was 3.2 +/- 4.7 years. We measured serum calcium and phosphate; bone remodeling markers (osteocalcin, bone-specific alkaline phosphatase [BSAP], serum crosslaps [CTX], and carboxyl-terminal telopeptide of type I collagen [ICTP]); follicle-stimulating hormone and luteinizing hormone levels; and estradiol (ultrasensitive assay), cortisol, urinary free cortisol, thyroid function, prolactin, and nutritional factors (insulin-like growth factor I [IGF-I], IGF binding protein 3 [IGFBP3]). In controls, only bone remodeling markers and nutritional factors were measured. Osteodensitometry was also performed on both patients and controls. Weight and body mass index (BMI) were significantly lower in anorexia nervosa patients than in controls (P < 0.0001). No significant differences were observed in biological indicators except for IGF-I, which was lower in anorexia nervosa patients (0.9 +/- 0.4 UI/mL) than in controls (1.5 +/- 0.4 UI/mL) (P < 0.0001). Densitometric measurements at three sites were significantly lower in anorexia nervosa patients and correlated with duration of disease and amenorrhea and with IGF-I at the hip only (P < 0.01). In the study population, osteoporosis was observed in 24 patients (21%) and osteopenia in 54 patients (48%). Patients with osteoporosis were significantly older and had longer disease and amenorrhea durations; lower weight and BMI; higher alkaline phosphatase, BSAP, and osteocalcin; and lower serum ICTP, IGF-I, and IGFBP3. All of these differences were significant and remained so even after multiple adjustments were made, except for IGF-I (P = 0.21). When multivariate analysis was performed, we found that age at onset of amenorrhea, weight, alkaline phosphatase, urinary free cortisol, and serum estradiol concentration accounted for 54% of the variance in spinal bone mineral density (BMD). Duration of amenorrhea, alkaline phosphatase, and weight explained 46.6% of the variance in femoral neck BMD. Duration of amenorrhea, IGF-I, and ICTP levels accounted for 38.6% of the variance observed in total hip BMD. The etiology of bone loss in patients with anorexia nervosa is multifactorial. Hypoestrogenia alone cannot account for this loss, and nutritional factors, IGF-I concentrations in particular, seem to play an important role.

Bone structure of the calcaneus: analysis with magnetic resonance imaging and correlation with histomorphometric study.

The purpose of this study was to compare structural measurements obtained from MR images of the calcaneus with those obtained from conventional histomorphometry. Sagittal magnetic resonance (MR) images of the calcaneus of 24 fresh human cadaveric feet were obtained at a spatial resolution achievable in vivo. A three-dimensional gradient echo-sequence was used with a slice thickness of 700 microm and in plane resolution of 172 x 172 microm. Structural analysis (four histomorphometric parameters; seven connectivity parameters) was performed in the superior region of the calcaneus. Bone biopsy specimens were obtained in the same area and were sectioned for histomorphometric study. Most of the MR histomorphometric parameters were overestimated (by a factor ranging from 0.8 to 3), as compared with histomorphometry. However, significant ( P<0.05) correlations were found between MR imaging and histomorphometric measurements for bone volume/tissue volume, trabecular separation, trabecular number, star volume of the marrow space, node count and terminus count. MR histomorphometric parameters correlated much better with histomorphometry than connectivity parameters. This study suggests that structural parameters characterizing cancellous bone in the calcaneus can be derived from MR images in the limited spatial resolution regime applicable in vivo.

Bone mineral density changes in hypercalciuretic osteoporotic men treated with thiazide diuretics.

UNLABELLED: A few studies suggest that thiazide diuretic agents may have modest beneficial effects on bone. Few data are available on the effects of these medications in patients with osteoporosis and hypercalciuria. OBJECTIVE: To evaluate the effects of thiazide diuretic therapy on bone mass and urinary calcium excretion in hypercalciuretic osteoporotic male patients. PATIENTS AND METHODS: Osteoporosis was defined as a greater than 2.5 standard deviation (S.D.) decrease in bone mineral density (BMD) at the lumbar spine or hip (T-score). We used an open-label prospective design to compare 14 patients with hypercalciuretic osteoporosis treated with a thiazide diuretic for 18 months and 13 patients with primary osteoporosis treated with calcium and vitamin D supplementation. Mean age was 53.5 +/- 9.6 years in the thiazide group and 48.7 +/- 8.4 years in the calcium-vitamin D supplementation group. The following serum parameters were assayed at baseline: 25OH-D3, 1,25OH-D3, parathyroid hormone (PTH), and bone turnover markers. Urinary calcium excretion and BMD by dual-energy X-ray absorptiometry at the spine and hip were determined at baseline and after 18 months of treatment. RESULTS: Annual BMD increases were similar in the two groups during the 18-month treatment period: lumbar spine, 0.6 +/- 2.5% (P = 0.47) in the thiazide group and 0.004 +/- 3% (P = 0.78) in the supplementation group; femoral neck, 0.47 +/- 2.6% (P = 0.89) and 1.1 +/- 3.2% (P = 0.22); total hip, 0.65 +/- 2.5% (P = 0.37) and 0.12 +/- 2.1% (P = 0.51). Urinary calcium excretion fell by 45.9% in the thiazide group from baseline to study completion (P = 0.0015). CONCLUSION: We found no evidence that thiazide therapy increased bone mass in patients with hypercalciuria and osteoporosis as compared to calcium-vitamin D supplementation in patients with osteoporosis but no hypercalciuria. In contrast, our results establish the efficacy of thiazide diuretics in reducing urinary calcium excretion, an effect that may decrease the risk of urinary lithiasis. Studies in larger patient cohorts treated for longer periods are needed to confirm or refute our findings.

Trabecular bone structure of the calcaneus: preliminary in vivo MR imaging assessment in men with osteoporosis.

PURPOSE: To use magnetic resonance (MR) imaging to evaluate potential differences in bone structure between men with and men without osteoporosis. MATERIALS AND METHODS: Sagittal MR images of the calcaneus were obtained in 50 men (26 patients with osteoporosis and 24 age-matched healthy control subjects). Osteoporosis was defined as a low bone mineral density (at least 2.5 SDs below the normal value for young adults at either the lumbar spine or proximal femur) as measured with dual-energy x-ray absorptiometry. Seventeen patients had a history of osteoporotic fractures. For each participant, 10 consecutive sagittal three-dimensional gradient-echo MR sections were analyzed by using a rectangular region of interest. Twenty structural measurements were obtained from these images. Additionally, density measurements at the calcaneus were obtained in 46 participants. The significance of differences between the two groups was calculated by using the unpaired Student t test. The odds ratios for fracture per 1 SD decrease in the control group were calculated with logistic regression analysis. Adjustment for participant weight and height was performed if necessary. RESULTS: Thirteen of 20 structural parameters, especially connectivity parameters, showed significant differences between control subjects and patients (P <.05). Differences between the two groups were more significant (P <.001) for apparent bone marrow skeleton length, apparent node count, apparent node-to-node strut count, and apparent terminus-to-terminus strut count. Odds ratios for 11 of 13 structural parameters but not for calcaneus density were significant (P <.05). After adjustment for calcaneus density, these parameters were still significant predictors of osteoporotic fracture. CONCLUSION: Structural measurements derived from MR images of the calcaneus may be used in vivo to characterize trabecular bone architecture in men with osteoporosis.