Context Glucocorticoids (GC) prescribed for chronic pediatric illnesses are associated with osteoporotic fractures. Objective To determine the efficacy and safety of intravenous (IV) zoledronic acid (ZA) compared with placebo to treat pediatric GC-induced osteoporosis (GIO). Patients, Design and Setting Children 5-17 years of age with GIO were enrolled in this multi-national randomized, double-blind, placebo-controlled phase 3 trial (ClinicaTrials.gov NCT 00799266). Interventions and Main Outcome Measures Eligible children were randomized 1:1 to six monthly IV ZA 0.05 mg/kg or IV placebo. The primary endpoint was the change in lumbar spine bone mineral density Z-score (LSBMDZ) from baseline to month 12. Incident fractures and safety were assessed. Results Thirty-four children were enrolled (mean age 12.6 ± 3.4 years [18 on ZA, 16 on placebo]), all with low-trauma vertebral fractures. LSBMDZ increased from −2.13 ± 0.79 to −1.49 ± 1.05 on ZA, compared with −2.38 ± 0.90 to −2.27 ± 1.03 on placebo (least squares means difference 0.41 [95% confidence interval 0.02, 0.81; p=0.04]); when corrected for height Z-score, the least squares means difference in LBMDZ was 0.75 [0.27, 1.22; p=0.004]. Two children on placebo had new low-trauma VF versus none on ZA. Adverse events (AEs) were reported in 15/18 children (83%) on ZA, and in 12/16 (75%) on placebo, most frequently within 10 days after the first infusion. There were no deaths, nor treatment discontinuations due to treatment-emergent AEs. Conclusions LSBMDZ increased significantly on ZA compared with placebo over one year in children with GIO. Most AEs occurred after the first infusion.
SummaryFracture rates were compared in children of different ethnic backgrounds from Johannesburg, South Africa. More white children fracture than black and mixed ancestry children. Reasons for this may be due to greater sports participation by whites and genetic protective factors in blacks. This has to be further investigated.IntroductionFracture rates in childhood are as high as those in the elderly. Recent research has been undertaken to understand the reasons for this, but there is little information available on ethnic differences in childhood fracture rates.MethodsUsing the birth to twenty longitudinal cohort of children, we retrospectively obtained information on fractures and their sites from birth to 14.9 years of age on 2031 participants. The ethnic breakdown of the children was black (B) 78%, white (W) 9%, mixed ancestry (MA) 10.5% and Indian (I) 1.5%.ResultsFour hundred and forty-one (22%) children had sustained a fracture one or more times during their lifetime (males 27.5% and females 16.3%; p < 0.001). The percentage of children fracturing differed between the ethnic groups (W 41.5%, B 19%, MA 21%, I 30%; p < 0.001). Of the 441 children reporting fractures, 89(20%) sustained multiple fractures. The most common site of fracture was the upper limb (57%).ConclusionMore white children fracture than black and mixed ancestry children. This is the first study to show ethnic differences in fracture rates among children. The reasons for these differences have to be further elucidated. Greater sports participation by whites and genetic protective factors in blacks may be contributing factors.
Level III-retrospective study.
The etiology and pathogenesis of nutritional rickets are becoming progressively clearer. Vitamin D deficiency has generally been considered the major or only player in the pathogenesis of nutritional rickets. However, recent research into calcium deficiency has now provided clinicians with reasons to investigate and manage patients with nutritional rickets more appropriately.The important question when assessing cases of nutritional rickets is: “Is it calcium or vitamin D deficiency or both that play a major role in the pathogenesis of the disease?”The case presentation in this review highlights the risk factors, clinical presentation and pathophysiology of nutritional rickets in a young South African black child from a semi-urban area in Johannesburg, a city with abundant sunshine throughout the year.
The classification of the various forms of hypophosphatemic rickets has been rationalized by the discovery of the central role that fibroblast growth factor 23 (FGF23) plays in the pathogenesis of a number of genetic and acquired forms of the disease. Although the details of the interaction of FGF23 with other osteoblast/osteocyte-derived proteins remain unclear at present, the measurement of circulating levels of FGF23 appears to be a useful biochemical test in determining the various causes of hypophosphatemic rickets. Furthermore, animal studies suggest that agents interfering in the action of FGF23 might play important roles in the future management of the FGF23-mediated forms of rickets. Phase 1 and phase 2 trials in humans with X-linked hypophosphatemic rickets are currently under way.
South African black children fracture less than white children. Differences in bone mass, body composition, and physical activity may be contributing risk factors. This study aimed to investigate the association between fracture prevalence, bone mass, and physical activity in South African children. Using the Bone Health cohort of the Birth to Twenty longitudinal study, we retrospectively obtained information of lifetime fractures until age 15 years in 533 subjects. Whole-body bone mineral content (BMC), bone area (BA), fat mass (FM), and lean mass (LM) (measured by dual-energy X-ray absorptiometry [DXA]), anthropometric data, physical activity scores, and skeletal maturity were obtained at ages 10 and 15 years. Nonfracturing black females were used as the control group and comparisons were made between those who did and did not fracture within the same sex and ethnic groups. Of the 533 subjects, 130 (24%) reported a fracture (black, 15%; white, 41.5%; p < 0.001). White males who fractured were significantly taller (10 years, p < 0.01), more physically active (15 years, p < 0.05) and had higher LM (10 years, p ¼ 0.01; 15 years, p < 0.001), whereas white females who fractured were fatter (10 and 15 years, p ¼ 0.05 and p < 0.05, respectively), than their nonfracturing peers. White males who fractured had greater BA and BMC at all sites at 10 and 15 years compared to their nonfracturing peers after adjusting for differences in height and weight; BA and BMC were similar in each of the other sex and ethnic groups. No anthropometric or bone mass differences were found between black children with and without fractures. The factor associated with fractures in white males appears to be participation in sports activities, while in white females obesity appears to play a role. No contributing factors in black males and females were found, and needs further elucidation. ß
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