La adición de midazolam intratecal al anestésico local mejora los bloqueos sensorial y motor y reduce la puntuación del dolor sin incrementar los efectos secundarios en la cirugía de miembros inferiores. Metaanálisis y revisión sistemática / 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

Este metaanálisis investiga el impacto de midazolam intratecal en la anestesia espinal, el control del dolor postoperatorio y los efectos secundarios relacionados con la anestesia en la cirugía de miembros inferiores. Realizamos una búsqueda en Medline, Science Direct, Google Scholar y Cochrane Library de los estudios que reportaron el inicio y la duración de los bloqueos sensorial y motor, el tiempo transcurrido hasta la primera solicitud de analgesia, el consumo de opioides durante 24h, el control del dolor postoperatorio y los efectos secundarios tras la administración de midazolam intratecal en pacientes sometidos a cirugía de miembros inferiores. Se identificaron 10 estudios, que se incluyeron en el metaanálisis. La revisión fue realizada siguiendo las directrices PRISMA, registrándose en la base de datos PROSPERO (ID-CRD42022346361) en agosto de 2022. Nuestros resultados muestran que los pacientes que reciben 1mg de midazolam intratecal reflejaron un tiempo de inicio de bloqueo significativamente más alto (p=0,001 [IC: −0,98, −0,31]), mayor duración de los bloqueos sensorial y motor (p<0,00001 [IC: 18,08, 39,12]; p=0,002 [IC: 0,45, 2]), y mayor tiempo transcurrido hasta la primera solicitud de analgesia de rescate (p=0,0003 [IC: 1,22, 4,14]). Las puntuaciones de dolor a las 4 y 12h postoperatorias fueron significativamente inferiores en los pacientes que recibieron midazolam intratecal (p=0,00001 [: −1,20, −0,47] y p=0,05 [IC: −0,52, −0,01] respectivamente). En conclusión, la adición de midazolam intratecal al anestésico local en la cirugía de miembros inferiores acorta el tiempo de inicio de los bloqueos sensorial y motor, incrementa la duración del bloqueo y prolonga el tiempo transcurrido hasta la primera solicitud de analgesia. Las puntuaciones del dolor a las 4 y 12horas postoperatorias fueron menores, no observándose efectos secundarios adicionales.(AU)

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, 24hours 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 12hours postoperatively were significantly lower in patients receiving intrathecal midazolam (P=.00001[CI: −1.20, −0.47] and P=0.05 [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 12hours postoperatively were also lower without any increased side effects.(AU)

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.

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.

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.

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).

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.

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.

Molecular and clinical analysis of a neonatal severe hyperparathyroidism case caused by a stop mutation in the calcium-sensing receptor extracellular domain representing in effect a human 'knockout'.

OBJECTIVE: Loss-of-function calcium-sensing receptor (CAR) mutations cause elevated parathyroid hormone (PTH) secretion and hypercalcaemia. Although full Car deletion is possible in mice, most human CAR mutations result from a single amino acid substitution that maintains partial function. However, here, we report a case of neonatal severe hyperparathyroidism (NSHPT) in which the truncated CaR lacks any transmembrane domain (CaR(R392X)), in effect a full CAR 'knockout'. CASE REPORT: The infant (daughter of distant cousins) presented with hypercalcaemia (5.5-6  mmol/l corrected calcium (2.15-2.65)) and elevated PTH concentrations (650-950  pmol/l (12-81)) together with skeletal demineralisation. NSHPT was confirmed by CAR gene sequencing (homozygous c.1174C-to-T mutation) requiring total parathyroidectomy during which only two glands were located and removed, resulting in normalisation of her serum PTH/calcium levels. DESIGN AND METHODS: The R392X stop codon was inserted into human CAR and the resulting mutant (CaR(R392X)) expressed transiently in HEK-293 cells. RESULTS: CaR(R392X) expressed as a 54  kDa dimeric glycoprotein that was undetectable in conditioned medium or in the patient's urine. The membrane localisation observed for wild-type CaR in parathyroid gland and transfected HEK-293 cells was absent from the proband's parathyroid gland and from CaR(R392X)-transfected cells. Expression of the mutant was localised to endoplasmic reticulum consistent with its lack of functional activity. CONCLUSIONS: Intriguingly, the patient remained normocalcaemic throughout childhood (2.5 mM corrected calcium, 11 pg/ml PTH (10-71), age 8 years) but exhibited mild asymptomatic hypocalcaemia at age 10 years, now treated with 1-hydroxycholecalciferol and Ca2+ supplementation. Despite representing a virtual CAR knockout, the patient displays no obvious pathologies beyond her calcium homeostatic dysfunction.

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.

Pseudohypoparathyroidism type 1b due to paternal uniparental disomy of chromosome 20q.

CONTEXT: Pseudohypoparathyroidism type 1b (PHP1b) is the result of end-organ resistance to PTH and other hormones such as TSH in the absence of any features of Albright's hereditary osteodystrophy. Patients with PHP1b show imprinting abnormalities at the complex GNAS locus. The molecular cause of autosomal dominant familial PHP1b has been well-defined with identification of microdeletions within the GNAS locus or the nearby STX16, but the molecular mechanism of the GNAS imprinting defects in sporadic PHP1b cases remains elusive. OBJECTIVE: We investigated the underlying molecular mechanism of GNAS imprinting defects in two patients with sporadic PHP1b. RESULTS: We identified paternal uniparental disomy of the long arm of chromosome 20 (patUPD20) in two unrelated patients with sporadic PHP1b. This provides an explanation for the patients' GNAS methylation abnormalities and hormone resistance. Our data and a review of the six published cases of patUPD20 suggest that high birth weight and/or early-onset obesity and macrocephaly may also represent features of patUPD20. CONCLUSION: We suggest that patUPD20 should be considered in the evaluation of patients with sporadic PHP1b.

A pilot randomized controlled trial of oral calcium and vitamin D supplementation using fortified laddoos in underprivileged Indian toddlers.

BACKGROUND/OBJECTIVES: Low habitual dietary calcium intake and vitamin D deficiency are common among Indian children. Using 'laddoo', an Indian snack, as a vehicle for administering calcium and vitamin D supplements, a randomized double-blind controlled trial was conducted for 12 months to assess its efficacy on total body less head (TBLH) bone mineral content (BMC) in underprivileged toddlers. SUBJECTS/METHODS: A total of 60 toddlers (mean age 2.7±0.52 years, boys=31) were randomized to two groups, (i) study group receiving one calcium fortified laddoo (cereal-legume snack) containing 405 mg calcium per day and (ii) control receiving a non-fortified laddoo, containing 156 mg of indigenous calcium. Both groups also received a laddoo fortified with 30,000 IU of vitamin D(3) per month. Outcome measures included TBLH bone area (BA) and TBLH BMC by GE-Lunar DPX Pro Pencil Beam Dual-Energy X-ray absorptiometry. RESULTS: At baseline, mean energy, protein and calcium intakes were 71, 72 and 47% of Indian Recommended Dietary allowances. In all, 87 and 83% toddlers were hypocalcaemia and vitamin D deficient, respectively. Mean TBLH BMC was 289.5±45.8 g. Post supplementation, mean TBLH BMC of study group showed a significantly greater (P<0.01) increase of 35% as against 28% in controls and the difference remained significant after adjusting for vitamin D status, calcium intake, height and TBLH BA. CONCLUSIONS: Daily supplementation with calcium fortified laddoo, and monthly vitamin D supplement resulted in a significant increase in TBLH BMC of underprivileged toddlers. We believe that such strategies have the potential of addressing nutritional problems in developing countries.

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.

A randomized, controlled trial of vitamin D supplementation upon musculoskeletal health in postmenarchal females.

CONTEXT: There has been a resurgence of vitamin D deficiency rickets throughout the developed world, with infants and adolescents being primarily affected. Adolescence is a crucial period for muscle and bone mineral accumulation. OBJECTIVE: The aim was to determine the effect of vitamin D supplementation on the adolescent musculoskeletal system. DESIGN AND SETTING: We conducted a community-based, double-blind, randomized controlled trial in a secondary school. PARTICIPANTS: Postmenarchal 12- to 14-yr-old females participated in the trial. Ninety-nine were screened, 73 were included in randomized controlled trial, and 69 completed the trial. There were no adverse events. INTERVENTION: Four doses of 150,000 IU vitamin D(2) (ergocalciferol) were given over 1 yr. MAIN OUTCOME MEASURES: Dual-energy x-ray absorptiometry, peripheral quantitative computed tomography, and jumping mechanography were used. RESULTS: At follow-up, 25-hydroxyvitamin D [25(OH)D] status was 56.0 ± 8.9 nmol/liter in the intervention group and 15.8 ± 6.6 nmol/liter in controls. There were no effects of supplementation on bone; however, for muscle function, efficiency of movement improved in the vitamin D-treated group. There was an interaction between baseline 25(OH)D concentration and response to vitamin D supplementation for muscle jump velocity. CONCLUSIONS: Despite improvements in 25(OH)D status, treatment with vitamin D(2) was not shown to increase mineral accretion, bone geometry or strength, muscle force, or power. There were greater increases in jump velocity in girls with the lowest baseline 25(OH)D concentrations. Lack of effect of intervention after the period of peak mineral and muscle mass accretion suggests that earlier action is required.

Body composition and bone status of children born to mothers with type 1 diabetes mellitus.

BACKGROUND: Altered growth, body composition and abnormalities of skeletal mineralisation have been reported in offspring of mothers with type 1 and type 2 diabetes mellitus. AIMS: The authors hypothesised that children born to mothers with type 1 diabetes mellitus (CDM) would be taller, have higher body mass index (BMI), greater fat mass, thicker diaphyseal bone cortices and reduced trabecular bone mineral density (BMD), as compared to those born to non-diabetic mothers. METHODS: Anthropometric, body composition and bone parameters were assessed using dual-energy x-ray absorptiometry (DXA) and peripheral quantitative CT in 67 white Caucasian CDM (35 boys; age 5-18 years) and in 246 (121 boys) age-matched controls. RESULTS: CDM were taller (p<0.0001), heavier (p<0.0001) and had higher BMI (p=0.02), and had 32% more total body fat mass and 7.5% more total body lean mass than controls. At the total body and lumbar spine (L1-L4) sites, CDM had significantly higher bone area and bone mineral content compared with controls. However, areal BMD at both these sites and lumbar spine bone mineral apparent density were not significantly different in the two groups, indicating that CDM have bigger bones compared with controls but their mineral content per unit area or volume is not substantially different. The distal radial trabecular and total volumetric BMD in CDM was not demonstrably different from controls. At the mid-radius, both periosteal (2.4%; p=0.03) and endosteal circumferences (5.7%; p=0.02) were bigger in CDM compared with controls. CONCLUSION: The authors speculate that the intrauterine diabetic environment is associated with an increase in linear growth, adiposity and larger bone dimensions during childhood and adolescence.