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There are limited data on the use of bisphosphonate therapy for secondary osteoporoses in childhood, and no previous reports of the use of zoledronic acid in this group. We report 20 children with a variety of underlying primary diagnoses with associated secondary osteoporosis, who were treated with 3 monthly zoledronic acid for 2 years (annualised dose 0.1mg/kg/year). There was a significant improvement in lumbar spine (by 1.88 SD±1.24 over first 12 months, p<0.001) and total bone mineral density as assessed by dual energy absorptiometry (DXA) scans, with a similar increase in bone mineral content for lean tissue mass (mean increase 1.34 SD in first 12 months, p<0.001). Bone turnover was reduced with a suppression of both osteocalcin and alkaline phosphatase in the first 12 months of treatment. Skeletal architecture was improved, with increased second metacarpal cortical thickness from 2.44mm to 2.72mm (p<0.001) and improved vertebral morphometry, with 7 patients who had vertebral wedging at baseline showing improved anterior (p=0.017) and middle (p=0.001) vertebral height ratios. Aside from well reported transient side effects with the first dose, there were no adverse effects reported. No adverse effects on anthropometric parameters were seen over the course of the study. Despite all patients having sustained fragility fractures prior to treatment, no fractures were reported during the study period. Further evidence is required to confirm efficacy, with long term follow up required to assess the impact of treatment on fracture risk., (Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.)

Background: Intravenous bisphosphonate therapy is associated with preservation of femoral head sphericity and congruence in 77% of children with traumatic avascular necrosis. The aim was to describe the systemic effects of intravenous zoledronic acid (ZA) on bone and mineral metabolism in otherwise normal children and adolescents with femoral head AVN., Material and Methods: 37 children (age 10.8+/-2.76 years) diagnosed with avascular necrosis AVN (Slipped Capital Femoral Epiphysis (SCFE), N=20 or Legg-Calve-Perthes disease (LCPD), N=17) were treated with at least 12 months of ZA. Bone mineral density (BMD) by DXA, bone morphometry and mineral homeostasis were evaluated at baseline, 6, 12 and 18 months. Data was retrieved retrospectively., Results: All children maintained height SD during treatment. BMI SD increased in the SCFE subgroup during the first 12 month period. Bone age increased appropriately. Age adjusted total body BMD, lumbar spine BMD and lean tissue mass adjusted bone mineral content (BMC) Z-scores increased significantly over the 18 months of treatment. The LS.BMD increase was greater in LCPD than in SCFE leading to more individuals with LCPD having a LS.BMD((age))Z-score over 2 SD at 12 months follow-up. Biochemical markers of bone turnover were decreased and PTH increased during the first 12 months of treatment and bone modeling was reduced. All markers stabilised over the next 6 months. There were no incidences of fracture, spondylolisthesis or osteonecrosis of the jaw., Conclusion: We here report that ZA in otherwise healthy children with femoral head AVN increases BMD - most pronounced in the LCPD group - and reduces bone modeling and turnover. Further efficacy and safety data are required before this therapy can be widely recommended.

Introduction: When expressed as a percentage of the average result in young adults, bone mineral content lags behind bone length before puberty. Even though this observation has led to speculation about bone fragility in children, such relationships could simply be due to scaling effects when measures with different geometrical dimensions are compared., Methods: The study population comprised 145 healthy subjects (6-25 years, 94 females). Magnetic resonance imaging and dual-energy X-ray absorptiometry were used to determine femur length, bone mineral content, cortical bone mineral density, cross-sectional bone geometry (bone diameter; cortical thickness; total, cortical and medullary areas; cross-sectional and polar moments of area; bone strength index) and muscle area at the proximal one-third site of the femur. Results were dimensionally scaled by raising two-, three- and four-dimensional variables to the power of 1/2, 1/3 and 1/4, respectively. Sex-differences were also assessed before and after functionally adjusting variables for femur length and weight or muscle size., Results: In prepubertal children, unscaled results expressed as percentages of adult values were lowest for variables with the highest dimensions (e.g., moments of area

Introduction: Previous reports have shown a high frequency of hypocalcaemia and flu-like symptoms following an initial first zoledronic acid dose of 0.02-0.025 mg/kg in children., Methods: We systematically evaluated the mineral status and symptomatology of 63 children with a variety of bone disorders treated with an initial zoledronic acid dose of 0.0125 mg/kg. The Mann-Whitney U test, chi-squared test and Fisher's exact test were used as appropriate., Results: 0.0125 mg/kg zoledronic acid reduced the incidence and intensity of hypocalcaemia but not the incidence of the flu-like symptoms compared to higher doses. Within the low dose cohort, flu-like symptoms were associated with an acute inflammatory response. Children who became hypocalcaemic received a higher dose in relation to their body mass index and body surface area., Conclusion: Reducing the initial zoledronic acid dose in children decreased the incidence of hypocalcaemia and thus improved safety. Dosing on the basis of body mass index or body surface area instead of body weight may further reduce the incidence of hypocalcaemia.

The state of bone health and the effect of growth hormone (GH) therapy on bone and body composition in children with idiopathic short stature (ISS) are largely unknown. A direct role of GH deficiency (GHD) on bone density is controversial. Using dual-energy X-ray absorptiometry, this study measured total body bone mineral content (TB BMC), body composition, and volumetric bone mineral density (vBMD) at the lumbar spine (LS) and femoral neck (FN) in 77 children (aged 3-17 years) with ISS (n = 57) and GHD (n = 20). Fifty-five children (GHD = 13) receiving GH were followed over 24 months including measurement of bone turnover. At diagnosis, size-corrected TB BMC SDS was greater (P

There has been recent concern in the literature that the treatment with bisphosphonates in children can have an adverse effect on metaphyseal modeling leading to "drug-induced osteopetrosis". We created a normal database called metaphyseal index in the distal femur so that we could quantify the inwasting modeling process in children on bisphosphonates. Radiographs of the distal femur of 468 normal children who had presented to our institution for orthopedic trauma were examined. A measurement of the distal femoral growth plate width (GPW) was recorded. The femoral width at an interval of 0.5 GPW proximal to the distal femoral growth plate was also recorded (0.5 W). The metaphyseal index was defined as a ratio of 0.5 W/GPW. A graph of the means, one and two standard deviations from the mean, was constructed using the data obtained from this cohort. We found this ratio to be constant with minimal variability regardless of the age or sex of the child. We plotted 20 patients at our institution given bisphosphonates for localized orthopedic complaints. Z scores for girls averaged 0.68 and boys 0.13. Three patients had Z scores >2.0, with values of 2.2, 2.9, and 3.2. Metaphyseal modeling in the distal femur is constant, with slight variation between sexes, resulting in a similar shape of the distal femur throughout childhood. Clinically relevant doses of bisphosphonates given for appropriate indications do not necessarily disturb this process, while the beneficial clinical effect is maintained.

In upper extremity bones, a sexual dimorphism exists in the development of periosteal and endocortical bone surfaces during growth. Little is known about developmental patterns of bone geometry at weight-bearing bones like the femur. Using MRI and dual energy X-ray absorptiometry (DXA), this study assessed the differences in mid-femoral total (TA), cortical (CA) and medullary areas (MA), cortical thickness, and cortical density (BMD(compartment)) between prepuberty and young adulthood in 145 healthy subjects (94 females) 6 to 25 years old. Additionally, agreement between mid-femoral total bone volume (TV) measurements by DXA and MRI were investigated. In both sexes, TA, CA, MA, and cortical thickness were significantly larger in adults compared to prepubertal subjects (P < 0.001), and males had greater values than females. This sex difference persisted for TA, CA, and cortical thickness (P < 0.05), but not MA, after adjusting for femur length and weight. Mean (SD) cortical BMD increased from 1.05 (0.07) and 1.09 (0.10) g/cm(3) in prepubertal children to 1.46 (0.14) and 1.42 (0.1) g/cm(3) in young adults, females and males, respectively (P < 0.001). TV measurements by DXA were significantly greater than by MRI (P < 0.001) in young adults. In conclusion, periosteal and endocortical expansion and increasing cortical BMD are the growth processes found at the mid-femur in both sexes. Our findings contrast to that in upper extremity bones, where MA is constant in females during growth. The difference in femoral bone development may be due to higher strains caused by weight bearing and genetic factors. DXA, in contrast to MRI, is inaccurate in the determination of mid-femoral TV measures.

The present study evaluated the use of a small animal total body software of dual energy x-ray absorptiometry (DXA) in the assessment of total body and regional bone mineral content (BMC) and bone mineral density (BMD) in small rats. Twenty-three rats, with weights ranging from 146 to 246 g, were included in the study. All were scanned using the same software version and same scan procedure (speed and scanned area). Total body BMD, BMC, and body weight were measured by DXA in each rat. Femoral BMC and BMD were analyzed by using regional analysis facilities. The repeatability (precision) of this software version was assessed prior to the study and the coefficients of variation (CV) were 2.9% for total body BMC, 0.8% for total body BMD, 1.2% for body weight, and 2.2% for mean femoral BMD. DXA measurements were compared with the measurements obtained by using established standards, namely weight and bone ash content. Total body ash content and femoral ash content were measured separately in all rats. There was a strong linear correlation between BMC and ash content in total body (r2 = 0.98, p = 0.0001) and in femur (r2 = 0.94, p = 0.0001). There was also an excellent linear association between body weight measured by DXA and scale weight (r2 = 0.99, p = 0.0001). We conclude that this software version is suitable for study on small animals and is a useful tool for assessment of regional as well as total body bone mineral status.