Risk factors for reduced bone mineral density measurements in milk-allergic patients.

BACKGROUND: Earlier studies noted that young adults with IgE-mediated cow's milk allergy (IgE-CMA) have significantly lower bone mineral density (BMD) than age- and gender-matched controls. We sought to identify additional risk factors contributing to the low BMD in IgE-CMA patients. METHODS: Postpubertal (defined by Tanner stage V) IgE-CMA patients (n = 78; 16- to 30-year-old females and 17.5- to 30-year-old males) were evaluated prospectively for BMD using a DXA scan, serum values of bone turnover factor, and dietary and lifestyle questionnaires. Patients receiving > 2 short courses of systemic steroid treatments were excluded. RESULTS: Abnormal BMD measurements (T- or Z-scores < -1.0) of the lumbar vertebrae, femoral neck, or hip were noted in 60 patients, while normal BMD values were present in 18 patients, despite similarly decreased calcium intakes between the groups (P = 0.92). Patients with abnormal BMD were more likely to be asthmatic (P = 0.014), have a lower weight z-score (P = 0.007), have a decreased percent caloric intake derived from fat (P = 0.01), and have an increased carbohydrate intake (P = 0.03), in comparison with the normal-BMD group. Serum values of bone turnover were similar between the groups. On multivariate regression analysis, only asthma significantly (P = 0.006) increased the risk for osteopenia and osteoporosis (OR 38.5, 95% CI 2.8-500). Fitting continuous z-scores into a regression model, both asthma and weight z-score were significant (adjusted r2  = 0.272). Asthma was significantly overrepresented in osteopenic and osteoporotic subpopulations while decreased weight only in patients with osteoporosis. CONCLUSIONS: In the context of a low calcium intake, asthma and weight are independent risk factors for decreased BMD in IgE-CMA patients.

Vitamin D insufficiency in a sunny environment: a demographic and seasonal analysis.

BACKGROUND: Hypovitaminosis D has been shown to be extremely common in various regions around the world, mostly at high latitudes. Israel is characterized by certain features--cultural (e.g., ethnic isolates) and geographic (e.g., sunny climate)--that have been identified for their possible association with vitamin D status. OBJECTIVES: To conduct an ecological study on a representative sample of the population of Israel, testing vitamin D status across age groups, genders, ethnic groups, and seasons. METHODS: We obtained serum samples from 195 heaIthy Israeli volunteers representing a broad demographic spectrum. Serum concentrations of 25(OH)D were measured with the commercial kit Liaison 25(OH)D Assay (DiaSorin, Italy). RESULTS: The mean vitamin D level for the entire cohort was surprisingly low (22.9 +/- 10.1 ng/ml), with 149 subjects (78%) suffering from vitamin D insufficiency (< 30 ng/lml). Vitamin D status was better in infants than in olderage groups. Differences by gender were significant only inthe infant age group (i.e., vitamin D status was worse among females) and were not prominent across older ages. Israelis of Ashkenazi origin had higher vitamin D mean levels than those of Sephardic origin, who, in turn, had higher vitamin D levels than Arab subjects (31.4 +/- 12, 24.1 +/- 10, and 17.6 +/- 9 ng/ml respectively). With regard to season, there were no differences between the samples collected in winter and the samples collected in summer. CONCLUSIONS: The results suggest that hypovitaminosis D is common across all ages, genders and seasons in Israel, a country characterized by a sunny Mediterranean climate. Specific ethnic groups may be at especially high risk.

Linking traits based on their shared molecular mechanisms.

There is growing recognition that co-morbidity and co-occurrence of disease traits are often determined by shared genetic and molecular mechanisms. In most cases, however, the specific mechanisms that lead to such trait-trait relationships are yet unknown. Here we present an analysis of a broad spectrum of behavioral and physiological traits together with gene-expression measurements across genetically diverse mouse strains. We develop an unbiased methodology that constructs potentially overlapping groups of traits and resolves their underlying combination of genetic loci and molecular mechanisms. For example, our method predicts that genetic variation in the Klf7 gene may influence gene transcripts in bone marrow-derived myeloid cells, which in turn affect 17 behavioral traits following morphine injection; this predicted effect of Klf7 is consistent with an in vitro perturbation of Klf7 in bone marrow cells. Our analysis demonstrates the utility of studying hidden causative mechanisms that lead to relationships between complex traits.