Christopher T. Cowell

Bone mineral density in adolescent female athletes: relationship to exercise type and muscle strength

PURPOSE This study investigated the influence of different exercise types and differences in anatomical distribution of mechanical loading patterns on bone mineral density (BMD) in elite female cyclists, runners, swimmers, triathletes, and controls (N = 15 per group). Associations between leg strength and BMD were also examined. METHODS Areal BMD (g x cm(-2)) was assessed by duel-energy x-ray absorptiometry (DXA) (total body (TB), lumbar spine (LS), femoral neck (FN), legs, and arms). Right knee flexion and extension strength was measured using a Cybex Norm isokinetic dynamometer at 60 degrees x s(-1). RESULTS Runners had significantly higher unadjusted TB, LS, FN, and leg BMD than controls (P < 0.05); higher TB, FN, and leg BMD than swimmers (P < 0.05); and greater leg BMD than cyclists (P < 0.05). Absolute knee extension strength was significantly (P < 0.01) correlated (0.33 < or = r < or = 0.44) with TB, FN, LS, and leg BMD for all groups combined. Weaker but still significant correlations (0.28 < or = r < or = 0.33) existed for normalized (per leg lean tissue mass) knee extension strength and all BMD sites, except FN BMD. There were no significant correlations between absolute or normalized knee flexion strength and any of the BMD variables. Absolute knee extension strength was entered as the second independent predictor for LS and leg BMD in stepwise multiple linear regression analysis (MLRA), accounting for increments of 4% and 12%, respectively, in total explained variation. CONCLUSION We conclude that running, a weight bearing exercise, is associated with larger site-specific BMD than swimming or cycling, that the generalized anatomical distribution of loads in triathlon appears not to significantly enhance total body BMD status, and that knee extension strength is only a weak correlate and independent predictor of BMD in adolescent females.

Importance of lean mass in the interpretation of total body densitometry in children and adolescents

OBJECTIVE Most studies that use total body dual energy x-ray absorptiometry (DEXA) in children rely on areal bone mineral density (BMD=bone mineral content [BMC]/bone area [BA]) and compare the output with age- and sex-specific normative data. Because this approach is prone to size-related misinterpretation, this study focuses on the interrelations among BMC, body size (height), and lean tissue mass (LTM). STUDY DESIGN This cross-sectional study presents normative total body LTM data in relation to height and BMC for 459 healthy white subjects (249 female), 3 to 30 years of age. Guidelines for DEXA interpretation in children are provided and illustrated for patients with growth hormone deficiency (n=5) and anorexia nervosa (n=5). RESULTS LTM/height tended to be greater in male than in girls. The BMC/LTM ratio was greater in female than in boys (P<.001), even after adjustment for age and height. Sex-specific reference curves were created for LTM/height, the BMC/LTM ratio, BA/height, and BMC/BA. CONCLUSIONS We recommend that total body DEXA in children should be interpreted in 4 steps: (1) BMD or BMC/age, (2) height/age, (3) LTM/height, and (4) BMC/LTM ratio for height. This allows differentiation of the origin of a low BMD or BMC/age, for example, short stature and primary, secondary, and mixed bone defects.

Normal or Early Development of Puberty despite Gonadal Damage in Children Treated for Acute Lymphoblastic Leukemia

To determine the timing of pubertal development and the frequency of gonadal dysfunction in children who survive acute lymphoblastic leukemia, we assessed pubertal status and the plasma levels of sex steroids, gonadotropin, and inhibin in 45 children (20 girls and 25 boys) who had received combination chemotherapy along with 24 Gy of irradiation to the cranium (modified LSA2L2 protocol). We also reexamined testicular biopsy specimens, obtained at the time of the cessation of chemotherapy, for the presence of germ cells. Germ-cell damage, indicated by marked elevations in the plasma level of follicle-stimulating hormone (P less than 0.001 for the comparison with normal children), was evident in both sexes and was confirmed in the boys by the absence of germ cells in the testicular biopsy specimens and by the small size of the testes for pubic-hair stage. Only 44 percent of the pubertal girls had measurable plasma inhibin levels, as compared with more than 93 percent of normal pubertal girls. Although plasma sex-steroid levels were normal, the secretion of luteinizing hormone in response to stimulation with gonadotropin-releasing hormone was elevated in the pubertal children (P less than 0.01 for the comparison with normal controls)--a finding that suggests compensation for decreased gonadal function. Despite clear evidence of gonadal damage, girls had early menarche at a mean age (+/- SD) of 11.95 +/- 0.91 years, as compared with the Australian standard of 12.98 +/- 1.11 years (P less than 0.01). Thus, in girls, puberty was early despite primary gonadal damage. Thirteen of 23 boys reached puberty at a mean age of 12.36 +/- 0.73 years. We conclude that treatment for acute lymphoblastic leukemia may lead to primary gonadal damage in both sexes, regardless of the age at treatment, but that the secondary characteristics of puberty develop at a normal age or, in girls, relatively early.

The re-emerging burden of rickets: a decade of experience from Sydney

Aim: To define the demographics and clinical characteristics of cases presenting with nutritional rickets to paediatric centres in Sydney, Australia. Methods: Retrospective descriptive study of 126 cases seen from 1993 to 2003 with a diagnosis of vitamin D deficiency and/or confirmed rickets defined by long bone x ray changes. Results: A steady increase was seen in the number of cases per year, with a doubling of cases from 2002 to 2003. Median age of presentation was 15.1 months, with 25% presenting at less than 6 months of age. The most common presenting features were hypocalcaemic seizures (33%) and bowed legs (22%). Males presented at a younger age, with a lower weight SDS, and more often with seizures. The caseload was almost exclusively from recently immigrated children or first generation offspring of immigrant parents, with the region of origin predominantly the Indian subcontinent (37%), Africa (33%), and the Middle East (11%). Seventy nine per cent of the cases were born in Australia. Eleven cases (all aged <7 months) presented atypically with hyperphosphataemia. Conclusions: This large case series shows that a significant and increasing caseload of vitamin D deficiency remains, even in a developed country with high sunlight hours. Cases mirror recent immigration trends. Since birth or residence in Australia does not appear to be protective, screening of at risk immigrant families should be implemented through public health policies.

Effects of Therapy in X-Linked Hypophosphatemic Rickets

BACKGROUND Patients with X-linked hypophosphatemic rickets, which is clinically manifested by growth failure and bowing of the legs, are usually treated with phosphate and a vitamin D preparation. However, the efficacy of this treatment has been disputed, and nephrocalcinosis is a recognized complication of therapy. METHODS We studied 24 patients with X-linked hypophosphatemic rickets (9 boys and 15 girls) ranging in age from 1 to 16 years (median, 5.3). The duration of combination therapy ranged from 0.3 to 11.8 years (median, 3.0). We measured height as a standard-deviation (SD) score (the number of SDs from the mean height for chronologic age). Measurements made before the age of two years or after the onset of puberty were excluded. We compared the results with those reported in 1971 for 16 untreated prepubertal Australian patients. We also determined the severity of nephrocalcinosis (on a scale of 0 to 4, with 0 indicating no abnormalities and 4 stone formation) with renal ultrasonography and whether it could be related to the dosage of phosphate or vitamin D or to other factors. RESULTS Patients treated for at least two years before the onset of puberty (n = 19) had a mean height SD score of -1.08, as compared with -2.05 in the untreated historical controls. The 13 patients who had been treated with calcitriol and phosphate for at least two years had an increase in the mean height SD score of 0.33, from -1.58 to -1.25 (95 percent confidence interval, 0 to 0.67; P = 0.05). Nineteen of the 24 patients (79 percent) had nephrocalcinosis detected on renal ultrasonography. The grade of nephrocalcinosis was significantly correlated with the mean phosphate dose (r = 0.60, P = 0.002), but not with the dose of vitamin D or the duration of therapy. All patients had normal serum creatinine concentrations. CONCLUSIONS Therapy with calcitriol and phosphate may increase the growth of children with X-linked hypophosphatemic rickets. Nephrocalcinosis in these children represents a complication of therapy and is associated with the dose of phosphate received.

Waist-to-height ratio: a simple option for determining excess central adiposity in young people

Waist circumference is recommended as a means of identifying people at risk of morbidity associated with central adiposity. Yet, there are no universally agreed cut-points to determine when a waist circumference is too large in young people. In this study we examined the relation between sex- and age-specific waist circumference cut-points, the waist-to-height ratio (WHtR) cut-point of <0.5 and cardiovascular disease (CVD) risk clustering in 164 young people, mean age 14.9±0.2 years (mean±s.d.). In total 19 (11.6%) of the sample were identified as having CVD risk clustering. These young people were significantly (P<0.001) heavier and had higher body mass index (BMI) and waist circumference z-scores compared to those without CVD risk clustering. The WHtR cut-point of 0.5 estimated CVD risk clustering to a similar extent to sex- and age-adjusted cut-points for waist circumference and BMI. Young people with excess central adiposity (WHtR⩾0.5) were 11 times (OR 11.4, P<0.001), more likely to have CVD risk clustering compared to those who did not have excess central adiposity. The WHtR has several advantages; it is easy to calculate, does not require sex- and age-specific centiles and as has been previously suggested, it is a simple message, easily understood by clinicians and families, to ‘keep your waist circumference to less than half your height’.

Abdominal fat and birth size in healthy prepubertal children

BACKGROUND: Studies examining the foetal origins hypothesis suggest that small birth size may be a marker of foetal adaptations that programme future propensity to adult disease. We explore the hypothesis that birth size may relate to fat distribution in childhood and that fat distribution may be a link between birth size and adult disease.OBJECTIVE: To investigate the relationship between birth size and abdominal fat, blood pressure, lipids, insulin and insulin:glucose ratio in prepubertal children.DESIGN: Cross-sectional study, based on a birth cohort of consecutive full-term births.SUBJECTS: Two hundred and fifty-five (137 females) healthy, 7- and 8-y-old children.MEASUREMENTS: Body composition and abdominal fat was measured by dual energy X-ray absorptiometry. Lipid, glucose and insulin profiles were measured after an overnight fast and an automated BP monitor was used for blood pressure measurements.RESULTS: There was a negative association between abdominal fat and birth weight s.d. score across a range of normal birth weights (β=−0.18; 95% CI=−0.31 to −0.04, P=0.009) and a positive association with weight s.d. score at 7/8 y (β=0.35; 95% CI=0.24 to 0.46, P<0.001). Children who were born with the lowest weight s.d. score and had the greatest weight s.d. score at 7/8 y had significantly more (P<0.001) abdominal fat, as a percentage of total fat (6.53±1.3%) than those who had the highest birth weight s.d. score and the lowest weight s.d. score at 7/8 y (4.14±0.5%). Similar results were seen if head circumference, but not ponderal index, was used as an indicator of birth size. Increased abdominal fat was associated with higher total cholesterol:HDL cholesterol, higher triglyceride concentration and increased diastolic blood pressure.CONCLUSIONS: Birth weight independently predicted abdominal fat. Children with the highest amount of abdominal fat were those who tended to be born lighter and gained weight centiles. Increased abdominal fat was associated with precursor risk factors for ischaemic heart disease.

Zoledronic Acid Prevents Osteopenia and Increases Bone Strength in a Rabbit Model of Distraction Osteogenesis

Prolonged healing times and stress‐shielding osteopenia remain problematic in distraction osteogenesis. In this study of 30 rabbits, zoledronic acid increased regenerate volume, mineralization, and tibial strength and prevented osteopenia over a 6‐week period. Translation to the clinical setting, if safe, could improve outcomes in distraction osteogenesis in children.

Slowing of growth in height and weight on stimulants: A characteristic pattern

Objective:  The aims of the present study were to describe the growth pattern of children starting stimulant medication and to analyse the changes over time in height, weight and height velocity in a cohort of treated patients.

Use of bisphosphonate therapy for osteoporosis in childhood and adolescence

Abstract:  Congenital and acquired forms of osteoporosis in childhood and adolescence can result in morbidity from fracture and pain in childhood, and place an individual at significant risk for problems in adult life. A range of therapies exist for the prevention and treatment of osteoporosis, including optimization of daily calcium intake, adequate vitamin D status, weight‐bearing exercise, treatment with sex steroids where delayed puberty is a problem and, more recently, use of bisphosphonate therapy. Intravenous pamidronate therapy (a bisphosphonate) has been shown to reduce fractures and improve bone density in children with osteogenesis imperfecta, and might prove to be of benefit in other osteoporotic conditions in childhood. However, a number of issues regarding the optimal use of bisphosphonate therapy in children and adolescents remain to be resolved, including total annual dose and frequency and duration of administration. Bisphosphonate therapy should, therefore, be used only in the context of a well‐run clinical programme with specialist knowledge in the management of osteopenic disorders in childhood.