Reduced spinal bone mineral density in adolescents of an Ultra-Orthodox Jewish community in Brooklyn.

OBJECTIVES: Bone mass increases throughout childhood, with maximal bone mass accrual rate occurring in early to mid-puberty and slowing in late puberty. Prevention of osteoporosis and its morbidities depends primarily on the establishment of adequate peak bone mass. Physical activity, calcium intake, and vitamin D stores (from sunlight conversion of precursors of vitamin D and to a lesser degree from dietary intake) are vital determinants of bone mineral density (BMD). BMD is further controlled by genetic and environmental factors that are poorly understood. Observance of ultra-Orthodox Jewish customs may have a negative effect on the factors that promote bone health, and there have been anecdotal reports of higher fracture rates in this population. The ultra-Orthodox Jewish lifestyle encourages scholarly activity in preference to physical activity. Additionally, modest dress codes and inner-city dwelling reduce sunlight exposure. Orthodox Jews do not consume milk products for 6 hours after meat ingestion, leading to potentially fewer opportunities to consume calcium. Foods from the milk group are some of the best sources of dietary calcium. Our aims are to examine BMD in a group of healthy ultra-Orthodox Jewish adolescents in an urban community and to attempt to correlate it to physical activity and dietary factors. DESIGN AND METHODS: We recruited 50 healthy, ultra-Orthodox Jews, ages 15 to 19 years (30 males and 20 females). None were taking corticosteroids or had evidence of malabsorption. All girls were postmenarchal and nulliparous. Pubic hair Tanner stage for boys and breast Tanner stage for girls were determined. Weight and height standard deviation scores were calculated. Calcium, phosphorus, protein, vitamin D, and calorie intake were assessed using a comprehensive food questionnaire referring to what has been eaten over the last year. Hours per week of weight-bearing exercise and walking were determined. Serum levels of calcium, intact parathyroid hormone (PTH), 25 hydroxyvitamin D (25[OH]D) and 1,25 dihydroxyvitamin D (1,25[OH](2)D) were measured. Lumbar spine (L) BMD was assessed by dual energy radiograph absorptiometry. The pediatric software supplied by Lunar Radiation Corporation, which contains gender- and age-specific norms, provided a z score for the lumbar BMD for each participant. L2 to L4 bone mineral apparent density (BMAD) was calculated from L2 to L4 BMD. RESULTS: BMD of L2 to L4 was significantly decreased compared with age/sex-matched normative data: mean z score was -1.25 +/- 1.25 (n = 50). The mean L2 to L4 BMD z score +/- standard deviation was -1.71 +/- 1.18 for boys and -0.58 +/- 1.04 for girls. Eight boys (27%) had L2 to L4 BMD z scores <-2.5, which defines osteoporosis in adulthood. Twenty-seven adolescents (54%), 16 boys and 11 girls, had Tanner stage V. Two participants (4%) had delayed development of Tanner stage V. Mean consumption of calcium by participants under 19 years old was 908 +/- 506 mg/day (n = 46), which is lower than the adequate intake of 1300 mg/day for this age. The consumption of phosphorus was 1329 +/- 606 mg/day, and the consumption of vitamin D was 286 +/- 173 IU/day (n = 50). The mean serum 25(OH)D level was 18.4 +/- 7.6 ng/mL, and the mean serum 1,25(OH)(2)D level was 71.1 +/- 15.7 pg/mL (n = 50). Boys had significantly higher serum levels of 1,25(OH)(2)D than did girls (74.9 +/- 16.46 pg/mL vs 65.25 +/- 12.8 pg/mL, respectively). The serum levels of PTH, calcium, and protein were (mean +/- standard deviation): 33 +/- 16 pg/mL, 9.5 +/- 0.69 mg/dL, and 7.8 +/- 0.6 g/dL, respectively (n = 50). L2 to L4 BMD z score had positive correlation with walking hours (r = 0.4). L2 to L4 BMD z score had negative correlation with serum level of 1,25(OH)(2)D )r = -0.33; n = 50). We could not find significant correlation between L2 to L4 BMD z scores for the entire cohort and any of calcium, vitamin D, phosphorus, or protein intake. However, the L2 to L4 BMD z scores of boys had positive correlation with calcium, phosphorus, and protein intake (r = 42, r = 44, and r = 43, respectively). After adjustment for Tanner stage, boys who had Tanner stage V (n = 16) had stronger positive correlation between L2 to L4 BMD z scores and calcium and protein intake (r = 0.55 and r = 0.57, respectively), as was the correlation between L2 to L4 BMD z score and weight-bearing activity and walking hours (r = 0.77 and r = 0.72, respectively; n = 16). By multiple regression analysis with stepwise selection, sex, walking hours, weight-standard deviation scores, and serum PTH predicted 54% of the variability in L2 to L4 BMD z score. Sex, walking hours, and age predicted 65% of the variability in L2 to L4 BMAD. CONCLUSIONS: Lumbar BMD is significantly decreased in ultra-Orthodox Jewish adolescents living in an urban community. Boys had profoundly lower spinal BMD than did girls. Previous studies have introduced estrogen as a critical factor in bone mineralization. (ABSTRACT TRUNCATED)

Growth hormone use in pediatric growth hormone deficiency and other pediatric growth disorders.

The diagnosis and management of growth disorders in children, particularly disorders that respond to therapy with growth hormone (GH), raise challenging clinical and economic issues. Several such issues are presented in the following article in which Dr. Ron Rosenfeld examines the evaluation and diagnosis of the child with short stature; Dr. David B. Allen discusses the anabolic and metabolic indications for GH treatment in children; Dr. Margaret H. MacGillivray reviews GH dosing, height outcomes, and follow up; and Dr. Craig Alter presents the payer's perspective on the diagnosis and treatment of pediatric GH deficiency. In addressing the use of GH in other pediatric populations, Dr. Paul Saenger focuses on Turner syndrome, Dr. Henry Anhalt on chronic renal insufficiency of childhood, and Dr. Ray Hintz on idiopathic short stature. Dr. Harvey P. Katz presents one managed care organization's policy and implementation plan that is used to guide decisions regarding coverage for GH treatment.

Ambiguous genitalia.

The newborn whose genitalia are ambiguous presents a challenge to the pediatrician and the family. A clear understanding of the basis of sex differentiation and timely consultation with a pediatric endocrinologist is critical in the evaluation and determination of sex of rearing in a newborn who has ambiguous genitalia. Sex karyotype and a 17-OHP level may suffice in the initial evaluation of female pseudohermaphroditism because most patients will have virilizing CAH. If male pseudohermaphroditism is suspected on the basis of palpable gonads, we routinely obtain a karyotype, basal adrenal steroid levels, and levels of hCG-stimulated serum testosterone and DHT, then consider a testosterone treatment trial. Physicians who care for children who have ambiguous genitalia must appreciate the family's cultural, religious, and psychological needs and avoid determining sex of rearing before accurate diagnosis is reached.

A single-sample, subcutaneous gonadotropin-releasing hormone test for central precocious puberty.

OBJECTIVE: We compared a rapid, subcutaneous (SQ), single-sample gonadotropin-releasing hormone (GnRH) stimulation test with the standard multiple-sample, intravenous (IV) GnRH stimulation test used in the evaluation of central precocious puberty (CPP). METHODS: We evaluated 22 patients presenting with evidence of precocious puberty. GnRH (100 microg) was administered subcutaneously in the clinic setting with single serum luteinizing hormone (LH) measured 40 minutes after injection. A standard IV GnRH stimulation test was performed within 2 weeks, with serum LH obtained at 0, 20, 40, and 60 minutes. LH was assayed by immunochemiluminometric assay. RESULTS: The mean peak LH levels after IV and SQ testing were identical. A significant correlation (r = .88) was found between the LH determined by SQ stimulations and the peak LH determined by IV GnRH testing. CPP was diagnosed (LH, >/- 8 IU/L) by both SQ and IV testing in 7 of 22 patients and was excluded by both tests in 14 of 22 patients. A diagnostic discrepancy between peak IV and SQ results was seen in 1 patient. CONCLUSIONS: We conclude that mean GnRH-stimulated LH levels from rapid SQ and standard IV testing are indistinguishable and that individual LH levels by each method are strongly correlated. A rapid SQ GnRH test is a valid tool for laboratory confirmation of CPP.

A quantitative assay for IGF-I and IGF binding protein mRNAs: expression in malignant melanoma cells.

The quantification of messenger RNA is central in studies of gene expression. We describe a quantitative assay for specific mRNAs (QASM) that measures mRNAs for insulin-like growth factor-I, IGF binding proteins (IGFBPs) -2, -3, -4, and -5, and beta-actin. The assay utilizes reverse transcription and polymerase chain reaction, followed by an ELISA based DNA assay technique. The use of internal (competitive) quantification standards gave poorly linear results, while external standards gave linear and reproducible results. QASM results correlated with IGFBP protein concentrations in conditioned medium and with mRNA levels determined by Northern blotting. QASM was used to study IGFBP expression in human malignant melanoma cells. Messenger RNA for IGFBP-2, -3, and -5 were present, while IGF-I and IGFBP-4 mRNAs were not detected. IGFBP-2 and -3 expression was increased in a dose dependent manner by treatment with IGF-I. Protein concentrations in conditioned media paralleled mRNA levels. QASM is a sensitive, specific, and reproducible approach to determining mRNA levels.

Novel spinal dysplasia in two generations.

We report on a father and son with a previously undescribed skeletal abnormality and severe short stature. Antenatal sonographic evaluation of the propositus (son), obtained due to maternal pre-eclampsia, suggested an abnormal spine. At birth, no congenital anomalies were noted and transition to extra-uterine life was smooth. Radiographs performed five days after birth showed spina bifida, hemivertebrae in the mid-thoracic region, and widened lumbar interpedicular distances. MRI of the lower thoracic and lumbar vertebrae documented crescent-shaped appearance of the affected vertebrae and abnormally narrow A-P diameter of the vertebral bodies. Intervertebral discs were small, and the posterior elements, as well as the spinous processes of the affected vertebrae, were markedly hypoplastic. However, there was no narrowness of the spinal canal, and the limbs were unaffected. CT scan with three-dimensional reformatting of the thoracic and lumbar vertebrae documented unusual sagittal clefting of all of the vertebral bodies, which has previously been undescribed. The father had severe kyphoscoliosis and a height of 131.6 cm (-7.5 S.D.). Radiographically, he was found to have multiple segmentation anomalies and diminished A-P diameter of his affected vertebral bodies. The multiple vertebral anomalies are the probable cause for the father's severe kyphoscoliosis. The pattern of inheritance suggests that an autosomal dominant gene is responsible for this condition and that the father represents a de novo mutation. These radiographic abnormalities have not been described previously and represent a new form of vertebral spinal dysplasia.

Nursing bottle caries: characteristics of children at risk.

Nursing bottle carries is a pattern of extensive decay in newly erupted maxillary incisors. We examined nutritional, demographic, and behavioral characteristics of children with this condition and age/sex-matched controls, generating a profile of factors associated with increased risk for the development of this disease. Parents of 24 consecutive bottle caries patients seen in a private pediatric dental office completed a questionnaire. Controls were children receiving routine primary pediatric health services at a university based clinical office. Children with bottle caries were more likely to be living in a single parent household (p = 0.005). A higher incidence of sleep difficulties and strong temper also was reported (p = 0.05). Cases were more likely to take the bottle to bed and, to an older age than controls. They received less professional advice regarding weaning as well as less fluoride supplementation (p = 0.025). Clinical recognition of this profile may foster provision of specific anticipatory guidance resulting in primary prevention of this condition.

Double-blind comparison of ketazolam, diazepam and placebo in once-a-day vs t.i.d. dosing.

Comparison of ketazolam given once-a-day with diazepam given three times a day and placebo given either once or 3 times a day in 101 anxious outpatients showed ketazolam to be significantly better than placebo in alleviating the symptoms of anxiety and, on several measures of efficacy, better than diazepam as well. Significantly fewer patients on ketazolam dropped out of the study due to ineffective medication than on the other 3 treatments. The incidence of side effects was lowest in the ketazolam group. Of particular note, drowsiness was reported twice as often by diazepam patients as by ketazolam patients.

Drug abuse in junior high school populations.

Illegal drug use in a population of 3,807 junior high school students in a suburban area appeared strongly correlated with family instability, student personal problems, and low academic performance. Use of tranquilizers, amphetamines, and sedatives was often motivated by attempts at self-medication to reduce painful feelings. Over 14% of illegal users took an overdose with about half of them intentional. Illegal users and nonusers agreed that drug education programs and the threat of legal penalties had little influence in their decisions about drugs.