Childhood acute lymphoblastic leukemia (cALL) survivors are at increased risk for bone comorbidities, but accurate screening tools for such comorbidities are limited. Polygenic scores (PGS) could ...stratify cALL survivors for risk of long-term adverse bone outcomes. We evaluated 214 (51% female) cALL survivors from the Prévenir les Effets TArdifs de la LEucémie study (median age 21 yr). Bone mineral density (BMD) measurements were obtained using dual X-ray absorptiometry at the lumbar spine (LS-BMD), femoral neck (FN-BMD), and total body (TB-BMD), and vertebral fractures (VF) were documented using the vertebral deformity criterion. We computed a PGS for adult heel quantitative ultrasound speed of sound (gSOS), known to be associated with the risk of osteoporotic fracture, using imputed genotype data of the participants, and tested it for association with BMD Z-scores and VF risk, adjusting for clinical risk factors, and in sex and prognostic risk-stratified analyses. We found that a gSOS below the mean was associated with lower BMD in all three sites in univariate and multivariate models. In univariate analyses, 1 SD increase in gSOS conferred a 0.16 SD increase in LS-BMD (95% CI 0.005-0.31), whereas a gSOS above the mean was associated with a 0.31 SD higher LS-BMD (95% CI 0.008-0.61), a 0.36 SD higher TB-BMD (95% CI 0.06-0.67), and a 0.43 SD higher FN-BMD (95% CI 0.13-0.72). Models combining gSOS with clinical risk factors explained up to 16% of the variance of BMD phenotypes and obtained an area under the receiver operating characteristic curve for VF of 0.77 in subgroup analyses. Cranial radiation, high cumulative glucocorticoid doses, high risk group, and male sex were significant risk factors for lower BMD Z-scores. In conclusion, a PGS, in combination with clinical risk factors, could be used as a tool to risk stratify cALL survivors for treatment-related bone morbidity.
Recent data suggest that cow's milk allergy (CMA) has become more persistent, prolonging treatment via strict elimination of cow's milk products into a period of skeletal growth. The objectives of ...this study were to compare bone mineral density (BMD), vitamin D status, and dietary intakes of calcium and vitamin D between prepubertal children with persistent CMA and those with non-cow's milk food allergies (NCMA) as control subjects and to assess the use of and compliance to calcium and vitamin D supplementation among children with persistent CMA.
Fifty-two children with persistent CMA and 29 with NCMA were recruited. BMD was measured by using dual energy radiograph absorptiometry, and vitamin D status was assessed by using plasma 25-hydroxyvitamin D concentrations. Calcium and vitamin D intakes, as well as compliance to calcium and vitamin D supplementation, were recorded.
Lumbar spine BMD z scores were significantly lower in children with CMA. Low bone mass was detected in 6% of the CMA group compared with none in the NCMA group. Children with CMA displayed significantly lower calcium intakes than control subjects. Vitamin D status was not reduced in children with CMA compared with control subjects. Fewer than one-half of children with CMA reported the use of calcium and vitamin D supplements. However, adherence was high among supplement users, with a mean compliance rate of 5.5 days per week.
These prepubertal children with persistent CMA had lower lumbar spine BMD z scores than children with NCMA, which likely resulted from lower calcium intake.
Children who did not have a history of allergies but who had recurrent wheezing with colds were given high-dose inhaled fluticasone or placebo by their parents at the first signs of an upper ...respiratory tract infection. Practitioners prescribed fewer treatments with oral corticosteroids for children treated with inhaled fluticasone than for those given placebo, but those treated with fluticasone had smaller gains in height and weight. This preemptive use of inhaled corticosteroids cannot be recommended.
Practitioners prescribed fewer treatments with oral corticosteroids for children treated with inhaled fluticasone than for those given placebo, but those treated with fluticasone had smaller gains in height and weight. This preemptive use of inhaled corticosteroids cannot be recommended.
Upper respiratory tract infections account for more than 80% of wheezing episodes in children.
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With more than 30 acute care visits per 1000 population, preschool-age children have a rate of acute care visits for asthma that is higher by a factor of three than that for school-age children and adults.
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Most children wheeze only when they have upper respiratory tract infections, are usually nonatopic, and outgrow symptoms by 6 years of age.
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Yet, since preschool-age children have 6 to 10 upper respiratory tract infections each year,
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recurrent virus-induced wheezing is associated with considerable distress and use of . . .
Background New evidence supports the use of supplemental vitamin D in the prevention of exacerbation of asthma; however, the optimal posology to sufficiently raise serum levels while maximising ...adherence is unclear. The objective was to ascertain the efficacy of high-dose vitamin D.sub.3 in increasing serum vitamin D in preschoolers with asthma and provide preliminary data on safety and efficacy outcomes. Methods We conducted a 7-month, triple-blind, randomised, placebo-controlled, pilot trial of children aged 1-5 years with viral-induced asthma. Participants were allocated to receive two oral doses of 100,000 IU vitamin D.sub.3 (intervention) or identical placebo (control) 3.5 months apart, once in the fall and once in the winter. Serum 25-hydroxyvitamin D (25OHD) was measured by tandem mass spectrometry at baseline, 10 days, 3.5 months, 3.5 months + 10 days, and 7 months. The main outcome was the change in serum 25OHD from baseline (DELA25OHD) over time and at 3.5 and 7 months; other outcomes included the proportion of children with 25OHD greater than or equai to 75 nmol/L, safety, and adverse event rates. Results Children (N = 47) were randomised (intervention, 23; control, 24) in the fall. There was a significant adjusted group difference in the DELA25OHD (95% confidence interval) of 57.8 (47.3, 68.4) nmol/L, p < 0.0001), with a time (p < 0.0001) and group*time interaction effect (p < 0.0001), in favour of the intervention. A significant group difference in the DELA25OHD was observed 10 days after the first (119.3 105.8, 132.9 nmol/L) and second (100.1 85.7, 114.6 nmol/L) bolus; it did not reach statistical significance at 3.5 and 7 months. At 3.5 and 7 months, respectively, 63% and 56% of the intervention group were vitamin D sufficient (greater than or equai to 75 nmol/L) compared to 39% and 36% of the control group. Hypercalciuria, all without hypercalcaemia, was observed in 8.7% of intervention and 10.3% of control samples at any time point. Exacerbations requiring rescue oral corticosteroids, which appear as a promising primary outcome, occurred at a rate of 0.87/child. Conclusion Two oral boluses of 100,000 IU vitamin D.sub.3,once in the fall and once in the winter, rapidly, safely, and significantly raises overall serum vitamin D metabolites. However, it is sufficient to maintain 25OHD greater than or equai to 75 nmol/L throughout 7 months in only slightly more than half of participants. Trial registration ClinicalTrials.gov, NCT02197702 (23 072014). Registered on 23 July 2014. Keywords: Asthma, Child, Vitamin D, Cholecalciferol, Paediatric, Randomised controlled trial, Viral-induced, Pilot study
Vertebral fractures due to osteoporosis are a potential complication of childhood acute lymphoblastic leukemia (ALL). To date, the incidence of vertebral fractures during ALL treatment has not been ...reported.
We prospectively evaluated 155 children with ALL during the first 12 months of leukemia therapy. Lateral thoracolumbar spine radiographs were obtained at baseline and 12 months. Vertebral bodies were assessed for incident vertebral fractures using the Genant semiquantitative method, and relevant clinical indices such as spine bone mineral density (BMD), back pain, and the presence of vertebral fractures at baseline were analyzed for association with incident vertebral fractures.
Of the 155 children, 25 (16%; 95% CI, 11% to 23%) had a total of 61 incident vertebral fractures, of which 32 (52%) were moderate or severe. Thirteen (52%) of the 25 children with incident vertebral fractures also had fractures at baseline. Vertebral fractures at baseline increased the odds of an incident fracture at 12 months by an odds ratio of 7.3 (95% CI, 2.3 to 23.1; P = .001). In addition, for every one standard deviation reduction in spine BMD Z-score at baseline, there was 1.8-fold increased odds of incident vertebral fracture at 12 months (95% CI, 1.2 to 2.7; P = .006).
Children with ALL have a high incidence of vertebral fractures after 12 months of chemotherapy, and the presence of vertebral fractures and reductions in spine BMD Z-scores at baseline are highly associated clinical features.
Adolescent idiopathic scoliosis (AIS) is a three-dimensional malformation of the spine of unknown cause that develops between 10 and 18 years old and affects 2–3% of adolescents, mostly girls. It has ...been reported that girls with AIS have a taller stature, lower body mass index (BMI), and bone mineral density (BMD) than their peers, but the causes remain unexplained. Energy metabolism discrepancies, including alterations in adipokine and incretin circulatory levels, could influence these parameters and contribute to disease pathophysiology. This pilot study aims to compare the anthropometry, BMD, and metabolic profile of 19 AIS girls to 19 age-matched healthy controls. Collected data include participants’ fasting metabolic profile, anthropometry (measurements and DXA scan), nutritional intake, and physical activity level. AIS girls (14.8 ± 1.7 years, Cobb angle 27 ± 10°), compared to controls (14.8 ± 2.1 years), were leaner (BMI-for-age z-score ± SD: −0.59 ± 0.81 vs. 0.09 ± 1.11, p = 0.016; fat percentage: 24.4 ± 5.9 vs. 29.2 ± 7.2%, p = 0.036), had lower BMD (total body without head z-score ± SD: −0.6 ± 0.83 vs. 0.23 ± 0.98, p = 0.038; femoral neck z-score: −0.54 ± 1.20 vs. 0.59 ± 1.59, p = 0.043), but their height was similar. AIS girls had higher adiponectin levels 56 (9–287) vs. 32 (7–74) μg/mL, p = 0.005 and lower leptin/adiponectin ratio 0.042 (0.005–0.320) vs. 0.258 (0.024–1.053), p = 0.005. AIS participants with a Cobb angle superior to 25° had higher resistin levels compared to controls 98.2 (12.8–287.2) vs. 32.1 (6.6–73.8), p = 0.0013. This pilot study suggests that adipokines are implicated in AIS development and/or progression, but more work is needed to confirm their role in the disease.
Preterm infants are at increased risk of osteopenia of prematurity due to insufficient bone mineral accretion. Data on long term effects of prematurity on bone health are conflicting. This study ...aimed to compare bone mineral density (BMD) in young adults born very preterm and full-term controls and to examine factors associated with long-term bone health.
This observational cross-sectional study enrolled 101 young adults (18-29 years) born <29 weeks of gestation and 95 sex- and age-matched full-term controls. Participants underwent dual-energy X-ray absorptiometry to measure areal BMD and body composition. Generalized estimated equations were used to compare groups adjusting for height
-score, lean body mass and fat mass.
Adults born preterm were shorter and lighter than full-term controls. Areal BMD was reduced at the lumbar spine, the femoral neck and whole body in the preterm versus full-term group, but after adjustment, areal BMD
-score was only significantly lower at the femoral neck by -0.3 unit (95% confidence interval -0.6 to -0.0). Low BMD (
-score ≤ -1 standard deviation) at any site was observed in 53% of adults born preterm versus 28% of full-term controls, but this was not statistically significantly different. We did not identify any neonatal factors associated with lower BMD within the preterm group.
Very preterm birth is associated with lower areal BMD at the femoral neck in young adulthood, even after accounting for body size. Whether this will translate into higher risk of osteoporotic fractures later in life remains unknown.
Introduction Rickets is not an unusual diagnosis for pediatricians even currently in developed countries. Children typically present with leg bowing, enlargement of wrists, rachitic rosary (swelling ...of costochondral junctions) and/or waddling gait. But not every child with growth delay and enlarged metaphyses is diagnosed with rickets. Metaphyseal anadysplasia (MAD) is a disorder of variable severity with metaphyseal flaring and irregularities, without vertebral abnormalities. MAD is characterized by an early onset and a regressive course in late childhood without treatment, despite persistent short stature. Autosomal dominant or recessive variants in the matrix metalloproteinase 13 gene (MMP13) are responsible for these transient metaphyseal changes. Case presentation We report a new pathogenic heterozygous variant in MMP13 (NM_002427.4: c.216G>C, p.Gln72His) in a toddler, initially thought to have rickets, and his father, with MAD phenotypes. Additionally, we review the seven reported MMP13 variants. Conclusion One should keep a wide differential diagnosis in cases of suspected rickets, including skeletal dysplasias which might have a regressive course. Keywords: Metaphyseal anadysplasia, Regressive course, Rickets mimicking presentation disease , Autosomal dominant variant
Background
Acute lymphoblastic leukemia is the most common type of pediatric cancer. Acute lymphoblastic leukemia causes an altered bone mineral homeostasis state, which can contribute to osteopenia, ...and bone fractures, most commonly vertebral fractures. With the increasing number of childhood cancer survivors, late adverse effects such as musculoskeletal comorbidities are often reported and are further influenced by inactive lifestyle habits. Physical activity has been shown to increase the mechanical workload of the bone, mitigating bone impairment in other cancer-specific populations.
Objective
This interventional pilot study aims to investigate the use of telehealth to deliver a home-based exercise intervention for early-on survivors of bone marrow–related hematological malignancies and to assess its impact on survivors’ musculoskeletal and functional health.
Methods
We aimed to recruit a group of 12 early-on survivors of acute lymphoblastic leukemia, within 6 months to 5 years of treatment, to participate in and complete the proposed telehealth intervention with a parent. The 16-week intervention included 40 potential home-based physical activity interventions supervised by a kinesiologist through a telehealth internet platform, with monthly progression. Patients were recruited to the cohort if they were able to participate in the intervention during the first month (minimum 12 weeks of intervention). Evaluation before and after the intervention protocol highlighted differences in functional capacities and musculoskeletal health of patients using mechanography, peripheral quantitative computed tomography, 6-minute walk test, and grip force test.
Results
The recruitment rate for the intervention was low (12/57, 21% of contacted patients). Of 12 patients, 3 were excluded (1=relapse, 1=failure to meet technical requirements, and 1=abandoned). The 9 patients who completed the intervention (6 girls; mean age 10.93, SD 2.83 years; mean BMI 21.58, SD 6.55 kg/m2; mean time since treatment completion 36.67, SD 16.37 months) had a mean adherence of 89% and a completion rate of 75%. In addition, these patients showed functional improvements in lower limb muscle force and power as well as in the 6-minute walk test distance. Participants also showed improved bone health after the intervention on the following parameters: bone mineral content, stress-strain index, total and cortical cross-sectional area at the 14% site (P=.03, P=.01, P=.01, and P=.001, respectively) and 38% site of the tibia (P=.003, P=.04, P=.001, and P=.003, respectively).
Conclusions
High adherence and participation rates suggest that telehealth is a feasible method to deliver exercise interventions to young early-on survivors of acute lymphoblastic leukemia. The proposed intervention seems promising in providing benefits to patients’ functional performance and bone health, but a large-scale study is needed to confirm this assumption.
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