Primary Care Provider Management of Congenital Hypothyroidism Identified Through Newborn Screening.

OBJECTIVE: To assess Primary Congenital Hypothyroidism (CH) management patterns and feasibility of providing long-term care for patients with CH identified through newborn screening by Primary Care Providers (PCPs) in California and Hawaii. STUDY DESIGN: A survey was mailed to all physicians (N=823) listed as the referral doctor for confirmed patients with CH identified through newborn screening programs in both states between 01/01/2009-12/31/2013. Information was collected on CH management patterns, barriers to providing care, and knowledge on CH treatment. Descriptive statistics and bivariate logistic regression results were reported. RESULTS: 206 PCPs completed the survey. Among these, 78% currently have patients with CH and 91% indicated willingness to provide long-term care to new patients with CH. Among PCPs currently caring for patients with CH, 17% managed CH by themselves with limited assistance from endocrinologists; 63% were involved in managing CH but endocrinologists played a larger role than PCPs; 19% were not involved in CH care. Only 49% of PCPs correctly answered questions regarding recommended follow-up frequencies and 23% knew the correct age for a trial off levothyroxine for suspected transient CH. Top two perceived barriers to providing long-term care included "need guidance or support from endocrinologists" (61%) and "not familiar with CH treatment guidelines" (28%). CONCLUSION: The majority of PCPs surveyed are willing to provide long-term care to patients with CH, but need support from endocrinologists and increased knowledge about current treatment guidelines.

Patterns of bone mineral acquisition in children with epidermolysis bullosa: a longitudinal study.

BACKGROUND: Reduced bone mass and fractures are known complications of generalized forms of epidermolysis bullosa (EB). However, the aetiology - inadequate bone acquisition, premature bone loss, or a combination - is unclear. OBJECTIVES: To determine patterns of bone mineral acquisition in children with EB and to identify clinical and laboratory correlates of change in areal bone mineral density (aBMD). METHODS: Seventeen subjects ≥ 6 years of age with generalized EB were studied at two visits at least 12 months apart with clinical and laboratory evaluations and dual energy X-ray absorptiometry scans of the lumbar spine. Wilcoxon signed-rank tests were used to determine if changes from baseline to follow-up were significant. Wilcoxon rank-sum tests were used to compare subjects with gains in aBMD Z-score with those who experienced no change or decreases to determine if baseline laboratory or clinical characteristics differed between the two groups. RESULTS: Subjects gained height and weight at follow-up, but there was no significant improvement in mean Z-scores for height, weight or body mass index. Laboratory values did not change significantly. Mean bone mineral content and aBMD of the lumbar spine increased significantly at follow-up, but mean aBMD Z-scores remained static. No differences in clinical characteristics or laboratory values were seen between subjects with increased aBMD Z-scores vs. those whose scores decreased or did not change. CONCLUSIONS: Low bone mass in children with generalized EB is due primarily to inadequate gains in aBMD. Interventions to improve overall health and to help build bone mass in this patient population are warranted.

The relative contributions of lean tissue mass and fat mass to bone density in young women.

Although obesity is associated with increased risk of many chronic diseases including cardiovascular disease, diabetes, hypertension, and cancer, there is little evidence to suggest that obesity increases risk of osteoporosis. In fact, both weight and body mass index (BMI) are positive predictors of bone mass in adults, suggesting that those who are overweight or obese may be at lower risk of osteoporosis. However, recent evidence suggests that in children and adolescents, obesity may be associated with lower rather than higher bone mass. To understand the relation of fat mass to bone mass, we examined data gathered from an ethnically diverse group of 921 young women, aged 20-25 years (317 African Americans, 154 Asians, 322 Caucasians, and 128 Latinas) to determine how fat mass (FM) as well as lean tissue mass (LTM) is associated with bone mass. Bone mass, FM, and LTM were measured using dual energy X-ray absorptiometry (GE Lunar Corp, Madison, WI). Bone mass was expressed as bone mineral density (BMD; g/cm2) and bone mineral apparent density (BMAD; g/cm3) for the spine and femoral neck, and as BMD and bone mineral content (BMC; g) for the whole body. Regression techniques were used to examine the following: (1) in separate equations, the associations of LTM and FM with each bone mass parameter; and (2) in the same equation, the independent contributions of LTM and FM to bone mass. LTM and FM were positively correlated with BMD at all skeletal sites. When the contributions of FM and LTM were examined simultaneously, both FM and LTM continued to be positively associated with bone mass parameters but the effect of FM was noted to be smaller than that of LTM. We conclude that in young women, LTM has a greater effect than fat mass on bone density per kg of tissue mass.

Calcaneus ultrasound measurements in a convenience sample of healthy youth.

We examined age-related changes in quantitative ultrasound of the calcaneus in 311 healthy males and females ages 6.6-20 yr using the Lunar Achilles ultrasound device. This equipment has been adapted for pediatric use with the provision of shims designed to properly position smaller feet relative to the transducers. Broadband ultrasound attenuation (BUA) (decibels/megahertz), speed of sound (SOS) (meters/second), and stiffness index (SI) (percent) increased across the age range until a plateau was reached at 16-18 yr. BUA increased by 40%, SOS by 4%, and SI by 80% across this age range. There was no gender difference in age-related gains. Age, weight, height, and hours of weight-bearing physical activity were all significantly associated with BUA, SOS, and SI. After controlling for age and weight, hours of weight-bearing physical activity showed little to no additional effect on these parameters. Short-term in vivo precision using this device was similar in children to that observed in adults in our laboratory; coefficients of variation for between-day measurements were 1.8, 0.6, and 3.2% for BUA, SOS, and SI, respectively. These data support the feasibility of using the Lunar Achilles in evaluating pediatric bone mass. The ability of this technique to discriminate between osteopenic and normal children remains to be determined.

Acquisition of optimal bone mass in childhood and adolescence.

Peak bone mass (PBM), which is achieved by early adulthood, is a key determinant of the lifetime risk of osteoporosis. Because the foundation for skeletal health is established so early in life, osteoporosis prevention begins by optimizing gains in bone mineral throughout childhood and adolescence. Heritable factors account for an estimated 60-80% of the variability in PBM, with diet, physical activity and hormonal status serving as important modifiers of bone accrual. Recent pediatric studies have clarified the tempo and magnitude of gains in bone mineral and the modulating effects of diet, activity and sex steroids. The challenge lies in designing effective means to reverse trends of decreased calcium consumption, increased sodium intake and diminished physical activity among children and adolescents. Equally important is raising the awareness of health care providers to recognize children at risk for suboptimal acquisition of PBM.

Assessment of bone mineralization following renal transplantation in children: limitations of DXA and the confounding effects of delayed growth and development.

Pediatric renal transplantation recipients have numerous risk factors for decreased bone mass, including the underlying renal disease, nutritional deficits, decreased physical activity, inflammation and exposure to steroid therapy. The assessment of bone mineralization in children following renal transplantation is fraught with difficulty. Dual energy x-ray absorptiometry (DXA) is the most commonly employed tool to assess bone mineralization. However, DXA has important limitations in children and in individuals with renal disease. This brief review will examine the expected gains in bone size and bone mass during growth and the mechanisms by which renal failure and steroid therapy interrupt these process. In addition, the limitations of DXA for detecting impaired bone mineralization in children with renal disease are reviewed and alternative approaches explored.

Dual energy X-ray absorptiometry (DEXA) measurements of bone density and body composition: promise and pitfalls.

Dual energy X-ray absorptiometry (DEXA) is widely viewed as the preferred method to assess pediatric bone mineral content because of its speed, precision, and minimal radiation exposure, and the availability of pediatric reference data. DEXA can also be used to estimate body composition precisely with minimal patient cooperation. Accurate interpretation of DEXA data in children requires consideration of bone size, pubertal stage, skeletal maturation, ethnicity and body composition. Bone mineral content may be underestimated in smaller children and overestimated in larger ones. Corrections for skeletal age or sexual maturity may also be needed in children with advanced or delayed growth. Errors in body composition measurement occur because body fat and fat-free mass are not distributed uniformly. In addition, fat mass present adjacent to bone will influence the measurement of bone mineral content. In conclusion, DEXA is a valuable tool for assessing pediatric bone health, but accurate interpretation of densitometry results requires recognition of a myriad of pitfalls.

Mechanobiology of femoral neck structure during adolescence.

Understanding femoral neck structure may be critical to preventing fractures at this site. We examined the correlates of changes in the femoral neck during adolescence. Dual energy x-ray absorptiometry measurements of proximal femora were made in 101 Caucasian youths (ages 9 to 26 years). Relationships were examined between developmental parameters (age, pubertal stage, height, body mass, lean mass, and fat mass) and femoral structure (bone mineral content, bone mineral density, neck width, cross-sectional area, and cross-sectional strength). Lean body mass was the best predictor of femoral neck structure, explaining 53-87 percent of the variance, and was independent of gender. Body mass only explained 51-79 percent of the variance. Previously we found body mass to be the strongest predictor of femoral mid-diaphyseal cross-sectional properties. These findings suggest that trabecular bone of the femoral neck may be more responsive to its mechanical environment than the cortical diaphysis. In addition, lean body mass may be a more reliable predictor of muscle loading than body mass.

Use of hormone replacement therapy to reduce the risk of osteopenia in adolescent girls with anorexia nervosa.

PURPOSE: To assess how commonly hormone replacement therapy (HRT) and other measures are prescribed for the treatment of osteopenia in children and adolescents with anorexia nervosa (AN). METHODS: A self-administered questionnaire was distributed and completed by allopathic and osteopathic physician members of the Society for Adolescent Medicine at its 1998 annual meeting. The questionnaire was also mailed and E-mailed between March 1998 and February 1999. Descriptive statistics included percentages and measures of central tendency. RESULTS: The questionnaire was completed by 394 of the 1029 physicians surveyed (38.3%). Of the 268 respondents who treated patients with AN under the age of 18 years, 77.6% prescribed HRT. The decision to prescribe HRT was influenced by patient's age but not by bone mineral status. Among those who prescribed HRT, additional therapies included increased caloric intake (89.4%), weight gain (82.2%), increased calcium intake (84.1%), a change in exercise patterns (59.1%), and vitamin D supplementation (37.0%). Only 59 (22.0%) did not use HRT as a treatment modality. One-third of nonprescribers cited the lack of evidence of efficacy of HRT in preventing osteopenia. More recent medical graduates were less likely to prescribe HRT. CONCLUSIONS: This survey suggests that practitioners caring for adolescent females with AN commonly prescribe HRT for the treatment of osteopenia despite the paucity of evidence demonstrating that it effectively prevents or reverses bone loss associated with this disorder.

Bone mineral acquisition in healthy Asian, Hispanic, black, and Caucasian youth: a longitudinal study.

Ethnic and gender differences in bone mineral acquisition were examined in a longitudinal study of 423 healthy Asian, black, Hispanic, and white males and females (aged 9-25 yr). Bone mass of the spine, femoral neck, total hip, and whole body was measured annually for up to 4 yr by dual energy x-ray absorptiometry. Age-adjusted mean bone mineral curves for areal (BMD) and volumetric (BMAD) bone mineral density were compared for the 4 ethnic groups. Consistent differences in areal and volumetric bone density were observed only between black and nonblack subjects. Among females, blacks had greater mean levels of BMD and BMAD at all skeletal sites. Differences among Asians, Hispanics, and white females were significant for femoral neck BMD, whole body BMD, and whole body bone mineral content/height ratio, for which Asians had significantly lower values; femoral neck BMAD in Asian and white females was lower than that in Hispanics. Like the females, black males had consistently greater mean values than nonblacks for all BMD and BMAD measurements. A few differences were also observed among nonblack male subjects. Whites had greater mean total hip BMD, whole body BMD, and whole body bone mineral content/height ratio than Asian and Hispanic males; Hispanics had lower spine BMD than white and Asian males. The tempo of gains in BMD varied by gender and skeletal site. In females, total hip, spine, and whole body BMD reached a plateau at 14.1, 15.7, and 16.4 yr, respectively. For males, gains in BMD leveled off at 15.7 yr for total hip and at age 17.6 yr for spine and whole body. Black and Asian females and Asian males tended to reach a plateau in BMD earlier than the other ethnic groups. The use of gender- and ethnic-specific standards is recommended when interpreting pediatric bone densitometry data.

Natural history of growth hormone receptor deficiency.

This review discusses the natural history of growth hormone receptor deficiency (GHRD) in relation to epidemiology, mortality, growth, certain aspects of body composition, and intellectual development. The majority of affected individuals are of Semitic origin and 90% come from the Indian peninsula, the Middle East, or elsewhere in the Mediterranean. There is a twofold increased mortality before the age of 7 years for children with GHRD. Affected adults may have increased cardiovascular risk resulting from increased total cholesterol and low-density lipoprotein cholesterol, unrelated to adiposity or insulin resistance. Intrauterine growth is affected minimally, if at all. Within a genetically homogeneous population in Ecuador, postnatal growth effects are as variable as in a large genetically heterogeneous population. There is no influence of parental heights. Areal bone mineral density is reduced in adults with GHRD, but estimated volumetric bone density (bone mineral apparent density) is normal. Intellectual development is unaffected by GHRD.

Influence of pre-adolescent diet on quantitative ultrasound measurements of the calcaneus in young adult women.

Nongenetic determinants of quantitative ultrasound (QUS) properties of the bone remain to be identified. The purpose of this study was to determine relationships between early adolescent diet and QUS bone measurements taken in young adulthood. Subjects were participants in the 10-year longitudinal National Heart, Lung, and Blood Institute Growth and Health Study (NGHS). QUS parameters measured at the calcaneus in a convenience subsample of 63 18- to 19-year-old black and white women were correlated with dietary data collected when the subjects were aged 9-11 years. We hypothesized that pre-adolescent intake of calcium, magnesium, vitamin C and protein, nutrients known to be associated with bone development, would be associated with QUS measurements in young women. Stepwise multiple regression analysis, controlling for race, height and weight, demonstrated that pre-adolescent intake of calcium and magnesium were positively related to QUS parameters (calcium with broadband ultrasound attenuation, and magnesium with speed of sound and bone velocity). Our findings suggest that pre-adolescent diet may be associated with bone properties as measured by ultrasound. Further investigations of this relationship may yield a deeper understanding of the impact of diet on skeletal development. The small size of the convenience sample used for the analysis precludes stronger inferences at this time.

A comparison of calcaneus ultrasound and dual X-ray absorptiometry in healthy North American youths and young adults.

Quantitative ultrasound is the newest noninvasive method to be accepted for assessing bone mineral in adults. Heel ultrasound measurements correlate with bone density measurements by dual X-ray absorptiometry (DXA) and predict fracture risk in adults. Far less is known about the value of calcaneus ultrasound (CUS) in children. We determine spine, femoral neck, and whole-body bone mineral by DXA and heel bone mass by CUS in 125 youths (69 females, 56 males) ages 9-25 yr. CUS and DXA measurements of bone mass increased with age and pubertal development during adolescence in a parallel fashion. Among females, Tanner stage was a stronger predictor than age for all CUS and DXA measurements, and among males, pubertal stage was a stronger predictor for spine bone mineral apparent density (BMAD) and femoral bone mineral density (BMD). CUS measurements correlated moderately well with DXA measurements of the spine, femoral neck, and whole-body BMD and spine BMAD (r = 0.23-0.58, p < 0. 008). CUS warrants further study as a tool for assessing bone mineral acquisition in children.

Bone acquisition and loss in children and adults with cystic fibrosis: a longitudinal study.

OBJECTIVES: To determine patterns of bone mineral acquisition in children and young adults with cystic fibrosis (CF) and to identify clinical and laboratory correlates of change in bone mineral density (BMD). STUDY DESIGN: Bone mineral and clinical status were assessed in 41 patients with CF (26 female, aged 9 to 50 years) at baseline and 1.5 years later. Bone mineral content of the lumber spine, femoral neck, and whole body was determined by dual-energy x-ray absorptiometry and expressed as BMD and bone mineral apparent density (BMAD). Changes in weight, height, pubertal status, glucocorticoid use, physical activity, disease severity, and biochemical markers of bone turnover were examined for associations with changes BMD and BMAD. RESULTS: Mean BMD Z-scores (adjusted for age and sex) were reduced at the spine, hip, and whole body at baseline in both adults and youths, and decreased further at all sites among youths at follow-up (-0.4 at spine, p < 0.05; -0.3 at hip, p < 0.10; -0.5 for whole body, p < 0.0005). These data indicate failure to gain bone mineral at the expected rate. BMAD was also reduced at follow-up, suggesting that the observed osteopenia could not be explained by small bone size. Bone loss at multiple sites was observed in four youths and two adults. In general glucocorticoid use, change in body mass, physical activity, and disease severity were the most significant correlates for change in BMD and in BMD Z-score. CONCLUSIONS: Osteopenia in CF generally reflects inadequate gains in bone mineral, although bone loss may occur, particularly in patients requiring glucoc therapy. Late gains in bone mineral may accompany weight gain and pubertal development, but the catch-up appears to be incomplete.