Craig Munns

Fracture prediction and the definition of osteoporosis in children and adolescents: the ISCD 2007 Pediatric Official Positions.

Osteoporosis in adults has been defined on the basis of densitometric criteria, but at present the term osteoporosis does not have a widely recognized definition in pediatrics. Consequently, the International Society for Clinical Densitometry (ISCD) 2007 Position Development Conference reviewed the literature describing the relationship between bone densitometric studies and fractures in apparently healthy children and adolescents, and prepared Official Positions regarding the definition of osteoporosis in children and adolescents. The ISCD Official Positions with respect to the above issues, as well as the rationale and evidence used to derive these positions, are presented here.

Delayed osteotomy but not fracture healing in pediatric osteogenesis imperfecta patients receiving pamidronate.

This study evaluated factors influencing fracture (n = 197) and osteotomy (n = 200) healing in children with moderate to severe OI. Pamidronate treatment was associated with delayed healing after osteotomy, but not after fracture. The data suggest that both pamidronate and mechanical factors influence bone healing in this cohort.

Consensus Statement: Global Consensus Recommendations on Prevention and Management of Nutritional Rickets

BACKGROUND Vitamin D and calcium deficiencies are common worldwide, causing nutritional rickets and osteomalacia, which have a major impact on health, growth, and development of infants, children, and adolescents; the consequences can be lethal or can last into adulthood. The goals of this evidence-based consensus document are to provide health care professionals with guidance for prevention, diagnosis, and management of nutritional rickets and to provide policy makers with a framework to work toward its eradication. EVIDENCE A systematic literature search examining the definition, diagnosis, treatment, and prevention of nutritional rickets in children was conducted. Evidence-based recommendations were developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system that describe the strength of the recommendation and the quality of supporting evidence. PROCESS Thirty-three nominated experts in pediatric endocrinology, pediatrics, nutrition, epidemiology, public health, and health economics evaluated the evidence on specific questions within five working groups. The consensus group, representing 11 international scientific organizations, participated in a multiday conference in May 2014 to reach a global evidence-based consensus. RESULTS This consensus document defines nutritional rickets and its diagnostic criteria and describes the clinical management of rickets and osteomalacia. Risk factors, particularly in mothers and infants, are ranked, and specific prevention recommendations including food fortification and supplementation are offered for both the clinical and public health contexts. CONCLUSION Rickets, osteomalacia, and vitamin D and calcium deficiencies are preventable global public health problems in infants, children, and adolescents. Implementation of international rickets prevention programs, including supplementation and food fortification, is urgently required.

Global Consensus Recommendations on Prevention and Management of Nutritional Rickets

Background: Vitamin D and calcium deficiencies are common worldwide, causing nutritional rickets and osteomalacia, which have a major impact on health, growth, and development of infants, children, and adolescents; the consequences can be lethal or can last into adulthood. The goals of this evidence-based consensus document are to provide health care professionals with guidance for prevention, diagnosis, and management of nutritional rickets and to provide policy makers with a framework to work toward its eradication. Evidence: A systematic literature search examining the definition, diagnosis, treatment, and prevention of nutritional rickets in children was conducted. Evidence-based recommendations were developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system that describes the strength of the recommendation and the quality of supporting evidence. Process: Thirty-three nominated experts in pediatric endocrinology, pediatrics, nutrition, epidemiology, public health, and health economics evaluated the evidence on specific questions within five working groups. The consensus group, representing 11 international scientific organizations, participated in a multiday conference in May 2014 to reach a global evidence-based consensus. Results: This consensus document defines nutritional rickets and its diagnostic criteria and describes the clinical management of rickets and osteomalacia. Risk factors, particularly in mothers and infants, are ranked, and specific prevention recommendations including food fortification and supplementation are offered for both the clinical and public health contexts. Conclusion: Rickets, osteomalacia, and vitamin D and calcium deficiencies are preventable global public health problems in infants, children, and adolescents. Implementation of international rickets prevention programs, including supplementation and food fortification, is urgently required.

Effects of Intravenous Pamidronate Treatment in Infants With Osteogenesis Imperfecta: Clinical and Histomorphometric Outcome

Clinical and histomorphometric outcome was compared between children with OI who had received pamidronate since infancy and age‐matched patients who had never received pamidronate. Pamidronate was associated with improved vertebral shape and mass, higher cortical width, increased cancellous bone volume, and suppressed bone turnover.

Risedronate in children with osteogenesis imperfecta: a randomised, double-blind, placebo-controlled trial

BACKGROUND Children with osteogenesis imperfecta are often treated with intravenous bisphosphonates. We aimed to assess the safety and efficacy of risedronate, an orally administered third-generation bisphosphonate, in children with the disease. METHODS In this multicentre, randomised, parallel, double-blind, placebo-controlled trial, children aged 4-15 years with osteogenesis imperfecta and increased fracture risk were randomly assigned by telephone randomisation system in a 2:1 ratio to receive either daily risedronate (2·5 or 5 mg) or placebo for 1 year. Study treatment was masked from patients, investigators, and study centre personnel. Thereafter, all children received risedronate for 2 additional years in an open-label extension. The primary efficacy endpoint was percentage change in lumbar spine areal bone mineral density (BMD) at 1 year. The primary efficacy analysis was done by ANCOVA, with treatment, age group, and pooled centre as fixed effects, and baseline as covariate. Analyses were based on the intention-to-treat population, which included all patients who were randomly assigned and took at least one dose of assigned study treatment. The trial is registered with ClinicalTrials.gov, number NCT00106028. FINDINGS Of 147 patients, 97 were randomly assigned to the risedronate group and 50 to the placebo group. Three patients from the risedronate group and one from the placebo group did not receive study treatment, leaving 94 and 49 in the intention-to-treat population, respectively. The mean increase in lumbar spine areal BMD after 1 year was 16·3% in the risedronate group and 7·6% in the placebo group (difference 8·7%, 95% CI 5·7-11·7; p<0·0001). After 1 year, clinical fractures had occurred in 29 (31%) of 94 patients in the risedronate group and 24 (49%) of 49 patients in the placebo group (p=0·0446). During years 2 and 3 (open-label phase), clinical fractures were reported in 46 (53%) of 87 patients in the group that had received risedronate since the start of the study, and 32 (65%) of 49 patients in the group that had been given placebo during the first year. Adverse event profiles were otherwise similar between the two groups, including frequencies of reported upper-gastrointestinal and selected musculoskeletal adverse events. INTERPRETATION Oral risedronate increased areal BMD and reduced the risk of first and recurrent clinical fractures in children with osteogenesis imperfecta, and the drug was generally well tolerated. Risedronate should be regarded as a treatment option for children with osteogenesis imperfecta. FUNDING Alliance for Better Bone Health (Warner Chilcott and Sanofi).

Vitamin D and health in pregnancy, infants, children and adolescents in Australia and New Zealand: a position statement.

The recommended level for serum 25‐hydroxyvitamin D (25(OH)D) in infants, children, adolescents and during pregnancy and lactation is ≥ 50 nmol/L. This level may need to be 10–20 nmol/L higher at the end of summer to maintain levels ≥ 50 nmol/L over winter and spring. Sunlight is the most important source of vitamin D. The US recommended dietary allowance for vitamin D is 600 IU daily in children aged over 12 months and during pregnancy and lactation, assuming minimal sun exposure. Risk factors for low vitamin D are: lack of skin exposure to sunlight, dark skin, southerly latitude, conditions affecting vitamin D metabolism and storage (including obesity) and, for infants, being born to a mother with low vitamin D and exclusive breastfeeding combined with at least one other risk factor. Targeted measurement of 25(OH)D levels is recommended for infants, children and adolescents with at least one risk factor for low vitamin D and for pregnant women with at least one risk factor for low vitamin D at the first antenatal visit. Vitamin D deficiency can be treated with daily low‐dose vitamin D supplements, although barriers to adherence have been identified. High‐dose intermittent vitamin D can be used in children and adolescents. Treatment should be paired with health education and advice about sensible sun exposure. Infants at risk of low vitamin D should be supplemented with 400 IU vitamin D3 daily for at least the first year of life. There is increasing evidence of an association between low vitamin D and a range of non‐bone health outcomes, however there is a lack of data from robust randomised controlled trials of vitamin D supplementation.

Intravenous Bisphosphonate Therapy for Traumatic Osteonecrosis of the Femoral Head in Adolescents

BACKGROUND Femoral head osteonecrosis as a result of trauma in adolescents has a poor prognosis as a result of femoral head collapse and subsequent degenerative change of the hip. There are currently no satisfactory treatments for adolescents with this condition, although bisphosphonate therapy has improved the outcome in animal models of osteonecrosis. We evaluated bisphosphonate therapy for femoral head osteonecrosis following trauma in adolescents. METHODS We established a protocol for identifying adolescents with osteonecrosis of the femoral head with use of bone scans immediately after surgical treatment of hips at risk for the development of osteonecrosis following trauma. In a consecutive group of twenty-eight patients with an unstable slipped capital femoral epiphysis (twenty-two patients), femoral neck fracture (four), or traumatic hip dislocation (two), seventeen patients with osteonecrosis were identified. These patients (thirteen boys and four girls with a mean age of 12.7 years) and their families gave consent for the patients to receive treatment with intravenous bisphosphonates. The average duration of the bisphosphonate treatment was 20.3 months (range, seven to thirty-nine months). All patients were followed clinically and radiographically for a minimum of two years. RESULTS After a mean duration of follow-up of 38.7 months, fourteen patients were pain-free. Clinically, all seventeen patients had a good or excellent outcome. On the average, the Harris hip score was 91.2 points, the Iowa Hip Rating was 92.1 points, and the Global Pediatric Outcomes Data Collection Instrument (PODCI) score was 91.5 points. According to the radiographic classification system of Stulberg et al., nine hips were rated as Class I or II; six, as Class III; and two, as Class IV. CONCLUSIONS Bisphosphonate therapy may play an adjunctive role in the treatment of adolescents with osteonecrosis of the femoral head following trauma.

Generalized Joint Hypermobility and Risk of Lower Limb Joint Injury During Sport A Systematic Review With Meta-Analysis

Background: Generalized joint hypermobility is a highly prevalent condition commonly associated with joint injuries. The current literature has conflicting reports of the risk of joint injury in hypermobile sporting participants compared with their nonhypermobile peers. Systematic reviews have not been conclusive and no meta-analysis has been performed. Purpose: This review was undertaken to determine whether individuals with generalized joint hypermobility have an increased risk of lower limb joint injury when undertaking sporting activities. Study Design: Systematic review with meta-analysis. Methods: Studies were identified through a search without language restrictions of PubMed, CINAHL, Embase, and SportDiscus databases from the earliest date through February 2009 with subsequent handsearching of reference lists. Inclusion criteria for studies were determined before searching and all included studies underwent methodological quality assessment by 2 independent reviewers. Meta-analyses for joint injury of the lower limb, knee, and ankle were performed using a random effects model. The difference in injury proportions between hypermobility categories was tested with the z statistic. Results: Of 4841 identified studies, 18 met all inclusion criteria with methodological quality ranging from 1 of 6 to 5 of 6. A variety of tests of hypermobility and varied cutoff points to define the presence of generalized joint hypermobility were used, so the authors determined a standardized cutoff to indicate generalized joint hypermobility. Using this criterion, a significantly increased risk of knee joint injury for hypermobile and extremely hypermobile participants compared with their nonhypermobile peers was demonstrated (P < .001), whereas no increased risk was found for ankle joint injury. For knee joint injury, a combined odds ratio of 4.69 (95% confidence interval, 1.33-16.52; P = .02) was calculated, indicating a significantly increased risk for hypermobile participants playing contact sports. Conclusion: Sport participants with generalized joint hypermobility have an increased risk of knee joint injury during contact activities but have no altered risk of ankle joint injury.

Consensus statement on standard of care for congenital myopathies.

Recent progress in scientific research has facilitated accurate genetic and neuropathological diagnosis of congenital myopathies. However, given their relatively low incidence, congenital myopathies remain unfamiliar to the majority of care providers, and the levels of patient care are extremely variable. This consensus statement aims to provide care guidelines for congenital myopathies. The International Standard of Care Committee for Congenital Myopathies worked through frequent e-mail correspondences, periodic conference calls, 2 rounds of online surveys, and a 3-day workshop to achieve a consensus for diagnostic and clinical care recommendations. The committee includes 59 members from 10 medical disciplines. They are organized into 5 working groups: genetics/diagnosis, neurology, pulmonology, gastroenterology/nutrition/speech/oral care, and orthopedics/rehabilitation. In each care area the authors summarize the committee’s recommendations for symptom assessments and therapeutic interventions. It is the committee’s goal that through these recommendations, patients with congenital myopathies will receive optimal care and improve their disease outcome.