Vitamin D status of White pregnant women and infants at birth and 4 months in North West England: A cohort study.

The prevalence of vitamin D deficiency in pregnant white-skinned women (WSW) and their infants has not been investigated at northern latitudes in a developed county. A 2-year observational cohort study was undertaken in the North West of England to determine 25-hydroxyvitamin D (25OHD) levels in WSW and their infants during pregnancy and 4 months postdelivery and to explore factors associated with these levels. Nutritional and lifestyle questionnaires were completed and 25OHD levels measured at 28 weeks and 4 months postdelivery. Twenty-seven percent and 7% of WSW had insufficient and deficient levels of 25OHD during pregnancy and 48% and 11% four months postdelivery. WSW with Fitzpatrick skin-type I (FST I) have significantly lower 25OHD than other skin types after controlling for time spent outside and vitamin D intake. Twenty-four percent and 13% of infants had insufficient and deficient 25OHD levels at 4 months. Unsupplemented breast-fed infants have the highest level of insufficiency (67%) compared with formula-fed infants (2%). Factors associated with infant serum 25OHD levels at 4 months included breast feeding, supplementation, and time outside. WSW have a high prevalence of insufficiency and deficiency during pregnancy which doubles 4 months after birth. Breast-fed infants of WSW are rarely considered at risk of vitamin D insufficiency but have high rates compared with formula-fed infants. This is the first study to show the finding that FST I WSW have significantly lower levels of 25OHD than those with FST II-IV (difference adjusted for diet and time outside 14 (95%CI 7-21) nmol/L).

CRTAP mutation in a patient with Cole-Carpenter syndrome.

In 1987, Cole and Carpenter reported two unrelated infants with multiple fractures and deformities of bone, with a skeletal phenotype similar to severe osteogenesis imperfecta. In addition, these patients also had proptosis, blue sclerae, hydrocephalus, and a distinct facial gestalt. They were reported to be of normal intelligence. Radiologically, these patients had characteristic skeletal manifestations including craniosynostosis and deformities similar to severe progressive osteogenesis imperfecta. Since the first description, there have only been a few other reports of patients with a similar phenotype. Collagen studies performed in reported patients have been normal. The molecular basis of this syndrome has not been elucidated and the inheritance pattern is still unknown. We report on a child with Cole-Carpenter syndrome phenotype who has a homozygous c.118G>T mutation in exon 1 of the CRTAP gene. We describe the clinical features and correlate this with her molecular results. This is the first report towards elucidating the molecular basis of Cole-Carpenter syndrome.

Sunlight exposure and photoprotection behaviour of white Caucasian adolescents in the UK.

BACKGROUND: Sun exposure has positive and negative effects on health, yet little is known about the sun exposure behaviour of UK adolescents, including those more prone or less prone to sunburn. OBJECTIVE: To examine sun exposure behaviour of UK white Caucasian adolescents including time spent outdoors, holiday behaviour, use of sunscreen and clothing, with assessment for differences between sun-reactive skin type groups. METHODS: White Caucasian adolescents (12-15 years) attending schools in Greater Manchester completed a two-page questionnaire to assess sun exposure and photoprotective behaviour. RESULTS: A total of 133 adolescents (median age 13.4 years; 39% skin type I/II, 61% skin type III/IV) completed the questionnaire. In summer, adolescents spent significantly longer outdoors at weekends (median 4 h/day, range 0.25-10) than on weekdays (2, 0.25-6; P < 0.0001). When at home in the UK during summer, 44% reported never wearing sunscreen compared to just 1% when on a sunny holiday. Sunscreen use was also greater (frequency/coverage) when on a sunny holiday than at home in the UK summer (P < 0.0001). Adolescents of skin types I/II (easy burning) spent significantly less time outdoors than skin types III/IV (easy tanning) on summer weekends (P < 0.001), summer weekdays (P < 0.05) and on a sunny holiday (P = 0.001). Furthermore, skin types I/II reported greater sunscreen use during summer in the UK and on sunny holiday (both P < 0.01), and wore clothing covering a greater skin area on a sunny holiday (P < 0.01) than skin types III/IV. There was no difference in sun exposure behaviour/protection between males and females. CONCLUSION: The greater sun-protective measures reported by adolescents of sun-reactive skin type group I/II than III/IV suggest those who burn more easily are aware of the greater need to protect their skin. However, use of sunscreen during the UK summer is low and may need more effective promotion in adolescents.

Adding intrathecal midazolam to local anesthetics improves sensory and motor block and reduces pain score without increasing side effects in lower limb surgeries: A meta-analysis and systematic review.

This meta-analysis was done to investigate the role of intrathecal midazolam in lower limb surgeries regarding prolongation of spinal block, postoperative pain control and associated side effects. The included studies reported onset and duration of sensory and motor block, time to first request analgesia, 24h opioid consumption, postoperative pain control, and associated side effects following use of intrathecal midazolam for lower limb surgeries. This review was performed following the PRISMA guidelines and using the online databases, Medline, Science Direct, Google scholar and Cochrane library. We registered this review with the PROSPERO database (ID-CRD42022346361) in August 2022. A total of 10 randomised controlled trials were included in this meta-analysis. Our results showed patients receiving 1mg intrathecal midazolam showed significantly faster onset of sensory block [P=.001 (CI: -0.98, -0.31)]. Duration of sensory and motor block were also significantly prolonged in intrathecal midazolam group [P<.00001 (CI: 18.08, 39.12), P=.002 (CI: 0.45, 2). Intrathecal midazolam also increased the time to first request analgesia [P=.0003, (CI: 1.22, 4.14)]. Pain scores at 4 and 12h postoperatively were significantly lower in patients receiving intrathecal midazolam [P=.00001 (CI: -1.20, -0.47) and P=.05 (CI: -0.52, -0.01) respectively]. In conclusion, the addition of intrathecal midazolam to local anesthetics in lower limb surgeries results in early onset of sensory and motor block. It also increases the duration of sensory and motor block. The time to first request analgesia is increased. VAS pain scores at 4 and 12h postoperatively were also lower without any increased side effects.

Vitamin D status and muscle function in children with neurofibromatosis type 1 (NF1).

OBJECTIVES: The aim of this cross-sectional study was to assess the vitamin D status and muscle function in children with NF1 compared with their unaffected siblings. METHODS: NF1 children between 5 and 18 years of age and who had at least one unaffected sibling were identified. Serum concentrations of 25-hydroxyvitamin D (25(OH)D), calcium, inorganic phosphate, alkaline phosphate, parathyroid hormone and 1,25-dihydroxyvitamin D were measured. The Leonardo Mechanography Ground Reaction Force Platform (GRFP) was used to measure EFI, jump power, force and height. RESULTS: There was no significant difference in 25(OH)D between NF1 subjects and unaffected siblings. Relative jump power and force were found to be significantly different. The adjusted means (95% confidence limits) of non-NF1 and NF1 children for relative jump power (W/kg), controlling for body mass and age, were 37.31 (34.14, 40.49) and 32.51 (29.34, 35.68), respectively (P=0.054); and force (N/kg), controlling for body mass, age and gender, were 25.79 (24.28, 27.30) and 21.12 (19.61, 22.63), respectively (P<0.0001). Jumping parameters were not related to serum 25(OH)D. CONCLUSIONS: There was no significant relationship between vitamin D status and NF1 status in children. NF1 children had significantly impaired jumping power and force, when compared to their unaffected siblings.

The muscle-bone unit of peripheral and central skeletal sites in children and young adults.

UNLABELLED: Changes and gender differences in the muscle bone unit at different skeletal sites were investigated during pubertal development. Females accrued greater BMC in relation to muscle compared to males; these gender differences were greater after adjustment for height and regional fat mass. PURPOSE: To describe changes and gender differences in the muscle-bone unit at different skeletal sites during pubertal development. METHODS: Four hundred forty-two children aged 5-18 years were studied. Measurements of bone mineral content (BMC), lean mass (LM) and fat mass of the whole body (WB), legs, arms and lumbar spine were obtained from dual-energy X-ray absorptiometry. Peripheral quantitative computed tomography was used to measure BMC of the radius diaphysis and cross-sectional muscle area (CSMA) of the mid-forearm. These measurements were used to describe differences between, and within, genders at each pubertal stage in BMC accrual relative to muscle, both before and after adjustment for height, regional fat and muscle at central and peripheral skeletal sites. RESULTS: In males, there were significant increases in adjusted WB and leg BMC at the end of pubertal development. Unadjusted and adjusted lumbar spine BMC increased at the onset of, and at the end, of puberty. Radius BMC increased at most pubertal stages. In females, there were increases in unadjusted and adjusted whole body BMC at late puberty, in leg BMC at the onset of puberty and at pubertal stage four. Unadjusted arm BMC increased at most pubertal stages; however, after adjustment, an increase occurred at pubertal stage four. Both adjusted and unadjusted lumbar spine BMC increased at pubertal stage four. Unadjusted radius BMC increased at most pubertal stages. Females had greater BMC at all skeletal sites, compared to males, except at the radius, where adjusted BMC was greater in males at pubertal stage four. CONCLUSIONS: Males and females accrue more BMC in relation to lean mass at multiple skeletal sites as puberty proceeds. Females accrue more BMC in relation to lean mass, in comparison to males, at most skeletal sites.

Monitoring response to conventional treatment in children with XLH: Value of ALP and Rickets Severity Score (RSS) in a real world setting.

INTRODUCTION: X-linked hypophosphataemia (XLH) is conventionally managed with oral phosphate and active vitamin D analogues. OBJECTIVES: To evaluate long term treatment response by assessing biochemical disease activity [serum alkaline phosphatase (ALP)], radiological rickets severity score (RSS), growth and morbidity in patients with XLH on conventional therapy and assess the correlation between serum ALP and RSS. METHODS: XLH patients from 3 UK tertiary centres with ≥3 radiographs one year apart were included. Data was collected retrospectively. The RSS was assessed from routine hand and knee radiographs and ALP z scores were calculated using age-specific reference data. RESULTS: Thirty-eight (male = 12) patients met the inclusion criteria. The mean ± SD knee, wrist and total RSS at baseline (median age 1.2 years) were 2.0 ± 1.2, 1.9 ± 1.2 and 3.6 ± 1.3 respectively; and at the most recent clinic visit (median age 9.0 years, range 3.3-18.9) were 1.6 ± 1.0, 1.0 ± 1.0 and 2.5 ± 1.5 respectively. The mean ± SD serum ALP z scores at baseline and the most recent visit were 4.2 ± 2.3 and 4.0 ± 3.3. Median height SDS at baseline and most recent visit were -1.2 and -2.1 (p = 0.05). Dental abscess, craniosynostosis, limb deformity requiring orthopaedic intervention and nephrocalcinosis were present in 31.5%, 7.9%, 31.6% and 42.1% of the cohort respectively. There was no statistically significant (p > 0.05) correlation between ALP z scores and knee (r = 0.07) or total (r = 0.12) RSS. CONCLUSIONS: Conventional therapy was not effective in significantly improving biochemical and radiological features of disease. The lack of association between serum ALP and rickets severity on radiographs limits the value of ALP as the sole indicator of rickets activity in patients receiving conventional therapy.

Bone status of adolescent girls in Pune (India) compared to age-matched South Asian and white Caucasian girls in the UK.

UNLABELLED: Underprivileged adolescent girls in Pune, India, were shorter and lighter, and had reduced lean body mass (LBM) compared with relatively 'well off' age-matched South Asian and white Caucasian girls in the UK. Pune girls had low bone mass for projected bone area (BA) in comparison to their UK counterparts, but they had the appropriate amount of bone mineral content (BMC) for their LBM. PURPOSE: To determine whether adolescent girls from a low socioeconomic group in Pune, India, who had low dietary calcium intake (449 mg/day; range 356-538 mg/day) and hypovitaminosis D (median serum 25-hydroxyvitamin D 23.4 nmol/l; range 13.5-31.9 nmol/l), would have lower lumbar spine (LS) bone mineral apparent density (BMAD), and total body (TB) BMC adjusted for LBM. METHODS: Dual energy X-ray absorptiometry was used to measure TB and LS BMC, BA and TB LBM in 50 postmenarcheal girls in Pune. These variables were compared with data from 34 South Asian and 82 white Caucasian age-matched girls in the UK. RESULTS: Pune girls were shorter and lighter, and had less LBM for height, compared to both UK groups, and they had later age of menarche than UK Asians. BA-adjusted TB BMC and LS BMAD were lower in Pune girls (mean+/-SE 1,778+/-17 g; 0.332+/-0.005 g/cm(3)), compared to the UK South Asians (mean+/-SE 1,864+/-18 g; 0.355+/-0.006 g/cm(3)) and UK white Caucasians (mean+/-SE 1,864+/-13 g; 0.345+/-0.004 g/cm(3)). In contrast both LS and TB BMC adjusted for TB LBM were not significantly different between the groups. CONCLUSION: Pune girls had low bone mass for projected BA relative to UK South Asian and white Caucasian girls, but had the appropriate amount of BMC for their LBM.

A reference database for the Stratec XCT-2000 peripheral quantitative computed tomography (pQCT) scanner in healthy children and young adults aged 6-19 years.

SUMMARY: We have produced paediatric reference data for forearm sites using the Stratec XCT-2000 peripheral quantitative computed tomography scanner. These data are intended for clinical and research use and will assist in the interpretation of bone mineral density and bone geometric parameters at the distal and mid-shaft radius in children and young adults aged between 6-19 years. INTRODUCTION: Peripheral quantitative computed tomography (pQCT) provides measurements of bone mineral content (BMC), density (BMD) and bone geometry. There is a lack of reference data available for the interpretation of pQCT measurements in children and young adults. The aim of this study was to provide reference data at the distal and mid-shaft radius. METHODS: pQCT was used to measure the 4% and 50% sites of the non-dominant radius in a cohort of healthy white Caucasian children and young adults aged between 5 and 25 years. The lambda, mu, sigma (LMS) technique was used to produce gender-specific reference centile curves and LMS tables for calculating individual standard deviations scores. RESULTS: The study population consisted of 629 participants (380 males). Reference centile curves were produced; total and trabecular BMD for age (distal radius) and for age and height, bone area (distal and mid-shaft radius), cortical area, cortical thickness, BMC, axial moment of inertia, stress-strain index and muscle area (mid-shaft radius). CONCLUSIONS: We present gender-specific databases for the assessment of the distal and mid-shaft radius by pQCT. These data can be used as control data for research studies and allow the clinical interpretation of pQCT measurements in children and young adults by age and height.

Growth, bone health & ambulatory status of boys with DMD treated with daily vs. intermittent oral glucocorticoid regimen.

Oral glucocorticoids (GC) preserve muscle strength and prolong walking in boys with Duchenne muscular dystrophy (DMD). Although vertebral fractures have been reported in boys taking GC, fracture rates for different GC regimes have not been investigated. The aim of this pragmatic longitudinal study was to compare growth, body mass, bone mineral density (BMD), vertebral fractures (VF) and ambulatory status in boys with DMD on daily (DAILY) or intermittent (INTERMITTENT), oral GC regimens. A convenience sample of 50 DMD boys from two centres was included in the study; 25 boys each were on the DAILY or INTERMITTENT regimen. Size adjusted lumbar spine BMD (LS BMAD), total body less head BMD (TBLH), by DXA and distal forearm bone densities by pQCT, GC exposure, VF assessment and ambulatory status were analysed at three time points; baseline, 1 and 2 years. At baseline, there were no differences in age, GC duration or any bone parameters. However, DAILY boys were shorter (height SDS DAILY = -1.4(0.9); INTERMITTENT = -0.8(1.0), p = 0.04) with higher BMI (BMI SDS DAILY = 1.5(0.9); INTERMITTENT = 0.8(1.0), p = 0.01). Over 2 years, DAILY boys got progressively shorter (delta height SDS DAILY = -0.9(1.1); INTERMITTENT = +0.1(0.6), p < 0.001). At their 2 year assessment, 5 DAILY and 10 INTERMITTENT boys were non-ambulant. DAILY boys had more VFs than INTERMITTENT boys (10 versus 2; χ2 p = 0.008). BMAD SDS remained unchanged between groups. TBLH and radius BMD declined significantly but the rate of loss was not different. In conclusion, there was a trend for more boys on daily GCs to remain ambulant but at the cost of more VFs, greater adiposity and markedly diminished growth. In contrast, boys on intermittent GCs had fewer vertebral fractures but there was a trend for more boys to loose independent ambulation.

Calcium supplementation and weight bearing physical activity--do they have a combined effect on the bone density of pre-pubertal children?

The adaptation of bone to exercise has been shown to be modified by dietary calcium intake. The aim of this randomised controlled trial was to investigate whether there was a differential response to calcium supplementation in elite gymnasts and school children controls. The primary hypothesis was that gymnasts who took calcium supplements would have greater increases in cortical and trabecular volumetric bone mineral density (vBMD) at the radius and tibia. Secondary outcomes studied were changes in bone geometry at the radius and tibia and lumbar spine and whole body measurements. Children were randomised to 12 months daily supplementation of 500 mg elemental calcium (1250 mg (in the form of calcium carbonate salt)) or placebo. Outcome measures were assessed using peripheral quantitative computed tomography (pQCT) (distal and diaphyseal radius and tibia) and dual energy X-ray absorptiometry (DXA) (lumbar spine and whole body). Eighty-six subjects participated in the trial (44 gymnasts, 42 controls) and 75 subjects completed the trial (39 gymnasts, 36 controls). Data were analysed by analysis of covariance adjusting for baseline value of bone parameters, age, height, gender and puberty, and delay between baseline measurement and start of intervention. The primary analysis was for a calcium-exercise interaction; a pooled calcium effect with no interaction was also tested. Results are presented as ratios (95% confidence intervals). At the distal tibia, trabecular vBMD showed a significant interaction (p=0.04), with controls (1.00: 0.99, 1.09) responding more than gymnasts (0.98: 0.94, 1.02) to supplementation. At the distal radius, change in trabecular vBMD was not significant (p=0.05). There were no differences in change in cortical vBMD at either site between the gymnasts and controls (tibia: p=0.82, radius: p=0.88). For all other secondary outcomes at radius, tibia, spine and whole body no significant interactions were found. In conclusion, there was no beneficial effect of additional calcium in gymnasts who already consume their recommended nutrient intake (888 mg/day; United Kingdom reference nutrient intake for 8- to 11-year-olds is 555-800 mg/day) for calcium. We speculate that gymnasts have already adapted their bones (geometry and vBMD) to the demands imposed upon them by the loading they are subjected to during gymnastics and do not benefit from additional calcium supplementation.

Relationship of tibial speed of sound and lower limb length to nutrient intake in preterm infants.

BACKGROUND: Metabolic bone disease of prematurity is characterised by impaired postnatal mineralisation of the rapidly growing infant skeleton. OBJECTIVE: To longitudinally evaluate postnatal changes in tibial speed of sound (tSOS; which reflects cortical thickness and bone mineral density) and lower limb length (LLL; a measure of tibial growth) in very low birthweight preterm infants receiving contemporary neonatal care. METHODS: tSOS and LLL were measured using a quantitative ultrasound device and an electronic neonatal knemometer, respectively, in the same limb, weekly, for a median period of four weeks (3-16 weeks) in 84 preterm infants (median gestation 26.8 weeks (range 23-35.2 weeks) and median birth weight 869.5 g (range 418-1481 g)). RESULTS: Initial tSOS and LLL were correlated with gestation (r = 0.42, p<0.001; r = 0.76, p<0.001, respectively) and birth weight (r = 0.23, p = 0.038; r = 0.93, p<0.001, respectively). Postnatally, tSOS decreased (r = -0.15, p = 0.011) whereas LLL increased (r = 0.96, p<0.001) with age. The rate of postnatal change in LLL, but not in tSOS, was positively influenced by intake of calcium (p = 0.03), phosphorus (p = 0.01) and vitamin D (p = 0.03). CONCLUSIONS: The postnatal decline in tSOS, which is probably due to cortical thinning secondary to endocortical bone loss, and increase in LLL provide new insight into the development of long bones in preterm infants.

Impact of intercurrent illness on calcium homeostasis in children with hypoparathyroidism: a case series.

BACKGROUND: Hypoparathyroidism is characterised by hypocalcaemia, and standard management is with an active vitamin D analogue and adequate oral calcium intake (dietary and/or supplements). Little is described in the literature about the impact of intercurrent illnesses on calcium homeostasis in children with hypoparathyroidism. METHODS: We describe three children with hypoparathyroidism in whom intercurrent illnesses led to hypocalcaemia and escalation of treatment with alfacalcidol (1-hydroxycholecalciferol) and calcium supplements. RESULTS: Three infants managed with standard treatment for hypoparathyroidism (two with homozygous mutations in GCMB2 gene and one with Sanjad-Sakati syndrome) developed symptomatic hypocalcaemia (two infants developed seizures) following respiratory or gastrointestinal illnesses. Substantial increases in alfacalcidol doses (up to three times their pre-illness doses) and calcium supplementation were required to achieve acceptable serum calcium concentrations. However, following resolution of illness, these children developed an increase in serum calcium and hypercalciuria, necessitating rapid reduction to pre-illness dosages of alfacalcidol and oral calcium supplementation. CONCLUSION: Intercurrent illness may precipitate symptomatic hypocalcaemia in children with hypoparathyroidism, necessitating increase in dosages of alfacalcidol and calcium supplements. Close monitoring is required on resolution of the intercurrent illness, with timely reduction of dosages of active analogues of vitamin D and calcium supplements to prevent hypercalcaemia, hypercalciuria and nephrocalcinosis.

A pilot interventional study to evaluate the impact of cholecalciferol treatment on HbA1c in type 1 diabetes (T1D).

BACKGROUND: Higher 25(OH)D3 levels are associated with lower HbA1c, but there are limited UK interventional trials assessing the effect of cholecalciferol on HbA1c. AIMS: (1) To assess the baseline 25(OH)D3 status in a Manchester cohort of children with type 1 diabetes (T1D). (2) To determine the effect of cholecalciferol administration on HbA1c. METHODS: Children with T1D attending routine clinic appointments over three months in late winter/early spring had blood samples taken with consent. Participants with a 25(OH)D3 level <50 nmol/L were treated with a one-off cholecalciferol dose of 100,000 (2-10 years) or 160,000 (>10 years) units. HbA1c levels before and after treatment were recorded. RESULTS: Vitamin D levels were obtained from 51 children. 35 were Caucasian, 11 South Asian and 5 from other ethnic groups. 42 were vitamin D deficient, but 2 were excluded from the analysis. All South Asian children were vitamin D deficient, with mean 25(OH)D3 of 28 nmol/L. In Caucasians, there was a negative relationship between baseline 25(OH)D3 level and HbA1c (r = -0.484, P < 0.01). In treated participants, there was no significant difference in mean HbA1c at 3 months (t = 1.010, P = 0.328) or at 1 year (t = -1.173, P = 0.248) before and after treatment. One-way ANCOVA, controlling for age, gender, ethnicity, BMI and diabetes duration showed no difference in Δ HbA1c level. CONCLUSION: We report important findings at baseline, but in children treated with a stat dose of cholecalciferol, there was no effect on HbA1c. Further studies with larger sample sizes and using maintenance therapy are required.

Perspective: cerebral palsy as a model of bone development in the absence of postnatal mechanical factors.

To ensure optimal skeletal development, mechanical loading is imperative. The consequences of the removal of, or complete absence of, mechanical loading are illustrated by the clinical condition of cerebral palsy (CP). Clinical and radiological evaluation of children with CP provides an insight into how the growing skeleton develops when mechanical loading is reduced due to non-physiological muscle function. The poor bone status or "physiologic osteopenia" that these children suffer is multifactorial compromised of both mechanical and non-mechanical effects; primarily it is the lack of normal loading from the musculature which causes the development of a bone incapable of withstanding daily activities. Fractures occur during daily activities such as dressing and handling. Increased bone resorption during periods of immobilisation after fracture or surgery, also increases bone fragility. Trials of physical, nutritional and pharmacological treatments in CP children result in increased bone mineral density. Trials that include fracture prevention as the primary end point are required in this vulnerable group of children.

Bone geometry and density in the skeleton of pre-pubertal gymnasts and school children.

We have studied the differences between the peripheral and axial skeleton of pre-pubertal gymnasts and controls. We hypothesised that compared to controls, gymnasts would have larger and stronger radius and tibia diaphyses with greater bone mineral content and larger cross-sectional muscle area. At the distal metaphyseal sites of the radius and tibia, gymnasts would have greater bone cross-sectional area and total and trabecular volumetric bone mineral density (vBMD). Differences between the lumbar spine, total body and body composition in gymnasts versus controls were also studied. Peripheral quantitative computed tomography (pQCT) was used to measure bone geometry, density and muscle of the peripheral skeleton; dual energy X-ray absorptiometry (DXA) for total body and axial measurements. Eighty-six pre-pubertal children, 44 gymnasts (mean age 9.0 years, range 5.4-11.9 years) and 42 controls (mean age 8.8 years, range 5.6-11.9 years) were studied. Eighty-four children were Caucasian, one child was mixed race, one Chinese. Data were adjusted for age, sex and height. Differences in the effect size between sexes were also tested. At the 50% radius diaphysis gymnasts had larger bones (9.2%, p = 0.0054) with greater cortical area (8.2%, p = 0.022) and stress strain index (surrogate measure of bone strength) than controls (13.6%, p = 0.015). The effect size was different between males and females for cortical thickness (p = 0.03). At the 65% tibia diaphysis, gymnasts had greater cortical area (5.3%, p = 0.057) and thickness (6.2%, p = 0.068) than controls; consequently, bone strength was 5.4% higher (p = 0.14). There were no significant differences in cortical volumetric bone mineral density (vBMD) at the radius or tibia diaphysis between the groups. There was a difference in effect size for tibia muscle cross-sectional area between the sexes (p = 0.035). At the distal radius and tibia total and trabecular vBMD was greater (Total: radius 17%, p < 0.0001, tibia: 5.7%, p = 0.0053; trabecular: radius 21%, p < 0.0001, tibia 4.5%, p = 0.11). Bone size was not different in gymnasts compared to controls Lumbar spine BMC (12.3%, p = 0.0007), areal bone mineral density (aBMD) (9.1%, p = 0.0006) and bone mineral apparent density (BMAD) (7.6%, p = 0.0047) were greater in gymnasts but vertebral size was not significantly different. Likewise, total body BMD (3.5%, p = 0.0057) and BMC (4.78%, p = 0.085) were greater in gymnasts but there were no differences in skeletal size. These data suggest site-specific differences in how the pre-pubertal skeleton develops in response to the repetitive loading it experiences when participating in regular gymnastics. At diaphyseal sites these differences are predominantly in the bone and muscle geometry and not density. Conversely, at trabecular sites, the differences are increased density rather than geometry. In conclusion, the present study has demonstrated skeletal differences between gymnasts and controls. These differences appear to be site and sex specific.

Intrauterine programming of urinary calcium and magnesium excretion in children born to mothers with insulin dependent diabetes mellitus.

BACKGROUND: Offspring of diabetic rats have reduced urinary calcium and magnesium excretion compared with offspring of controls; these differences persist up to 16 weeks after birth, a time equivalent to young adulthood in humans. OBJECTIVES: To test the hypothesis that urinary calcium and magnesium excretion would be lower in children born to mothers with insulin dependent diabetes mellitus (ChMIDDM) than those born to non-diabetic mothers. METHODS: Concentrations of calcium, magnesium, sodium, and creatinine were measured in first void spot urine samples collected from 45 (28 male; median age 9.6 years) ChMIDDM and 127 (58 male; median age 11.3 years) controls. Analysis of covariance was used to test for differences in urinary calcium to creatinine ratios (UCa/Cr), magnesium to creatinine ratios (UMg/Cr), and log sodium to creatinine ratios (logUNa/Cr) between controls and ChMIDDM after allowing for the effects of sex and age. RESULTS: UCa/Cr (difference -0.10, 95% confidence interval (CI) -0.19 to -0.01; p = 0.03) and UMg/Cr (difference -0.15, 95% CI -0.22 to -0.08; p<0.0001) were lower in ChMIDDM than controls. However, logUNa/Cr did not differ between ChMIDDM and controls (difference -0.14, 95% CI -0.33 to 0.05; p = 0.1). The daily estimated intake of magnesium, sodium, and protein were significantly higher and that of calcium non-significantly higher in ChMIDDM than controls. In ChMIDDM, UCa/Cr and UMg/Cr were not related to diabetic control of mothers. CONCLUSIONS: Results of this study provide the first evidence that in humans, as in rats, there is modification of renal Ca and Mg handling in ChMIDDM, which persists well into childhood.

Effects of two synthetic parathyroid hormone-related protein fragments on maternofetal transfer of calcium and magnesium and release of cyclic AMP by the in-situ perfused rat placenta.

Two human parathyroid hormone-related protein (hPTHrP) fragments were tested for effects on maternofetal transfer of 45Ca and Mg across the in-situ perfused rat placenta at 21 days of gestation (term = 23 days). The fetal placental circulation was perfused with a Mg-free Krebs-Ringer solution and the unidirectional maternofetal clearance (Kmf) of 45Ca and Mg compared with that of 51Cr-EDTA, the latter being employed as a paracellular diffusional marker. Placental perfusion with hPTHrP(1-34) (100 ng/ml) or hPTHrP(75-86)amide (50 ng/ml) did not significantly alter the Kmf of 45Ca or that of Mg. In separate rats, however, hPTHrP(1-34) but not hPTHrP(75-86)amide stimulated marked placental cyclic AMP (cAMP) release, the peak response of 63 +/- 7 pmol/min occurring 10 min after the beginning of the peptide perfusion. A lower dose of hPTHrP(1-34) (4 ng/ml) produced a similar peak release of cAMP, as did [Nle8,21, Tyr34]-rPTH(1-34)amide (4 ng/ml) and the adenylate cyclase agonist forskolin (17 mumol/l). Forskolin also rapidly increased the Kmf of 45Ca but not that of Mg or 51Cr-EDTA. The present study indicates that hPTHrP does not acutely affect maternofetal transfer of Ca or Mg across the perfused rat placenta. The data also question the role played by cAMP in the stimulatory actions of forskolin on placental Ca transport.

Effects of acute maternal hyperglycaemia and hyperosmolality on maternofetal transfer of calcium and magnesium across the in situ perfused rat placenta.

The effects of acute maternal hyperglycaemia and hyperosmolality on maternofetal placental transfer of Ca, Mg and 51Cr-EDTA were investigated in the rat. On day 21 of gestation (term = 23 d) the fetal circulation of the in situ placenta of anaesthetised rats was perfused with a Mg-free Krebs Ringer solution and the unidirectional maternofetal fluxes of Ca (CaJmf) and Mg (MgJmf), and the unidirectional maternofetal clearance of 51Cr-EDTA ((EDTA)Kmf) were determined before and during maternal hyperglycaemia, hyperosmolality and volume expansion, attained by infusing 30% D-glucose, 25% mannitol and 0.9% saline solutions, respectively, into the maternal circulation. MgJmf was significantly reduced during glucose infusion (23.9 +/- 1.2 v 28.2 +/- 1.4 nmol min(-1) g(-1) placenta during control perfusion (mean +/- SEM); p < 0.005) and during mannitol infusion (28.2 +/- 1.0 v 33.5 +/- 1.5 nmol min(-1) g(-1) placenta; p < 0.001). CaJmf and (EDTA)Kmf were not significantly altered by maternal hyperglycaemia or hyperosmolality. There was no significant change in MgJmf during infusion of saline into the maternal circulation. Maternal plasma Na concentration was significantly reduced in both glucose and mannitol infusion experiments, whereas maternal plasma Mg concentration was significantly reduced only during glucose infusion. We postulate that the reduced maternal plasma Na concentration in the glucose and mannitol experiments might decrease MgJmf via alteration of placental Na+/Mg2+ exchange activity.