Bisphosphonate therapy is the mainstay of pharmacological intervention in young people with skeletal fragility. The evidence of its use in a variety of conditions remains limited despite over three ...decades of clinical experience. On behalf of the Australasian Paediatric Endocrine Group, this evidence‐based consensus guideline presents recommendations and discusses the graded evidence (using the GRADE system) for these recommendations. Primary bone fragility disorders such as osteogenesis imperfecta are considered separately from osteoporosis secondary to other clinical conditions (such as cerebral palsy, Duchenne muscular dystrophy). The use of bisphosphonates in non‐fragility conditions, such as fibrous dysplasia, avascular necrosis, bone cysts and hypercalcaemia, is also discussed. While these guidelines provide an evidence‐based approach where possible, further research is required in all clinical applications in order to strengthen the recommendations made.
To examine outcomes of pamidronate treatment on fibrous dysplasia of bone in three children with McCune-Albright syndrome (MAS).
Radiological evidence of fibrous dysplasia progress was reviewed for ...three children with MAS who were treated with pamidronate from age 2.5-5 years, for 8-10.5 years.
Despite minimal pain and a low fracture rate in long bones, except where gross deformity exists, all dysplastic lesions present in long bones continued to undergo uncontrolled expansion. In contrast, there were no major new changes in facial configuration, no clinically obvious expansion of sphenoid wing lesions and no encroachment on optic foramina or visual field restriction in any patient.
Despite previous reports of limitation or reduction in size of fibrous dysplasia lesions in adults and children, it is our experience that bisphosphonate treatment of polyostotic fibrous dysplasia in children with MAS does not arrest the expanding nature of these lesions.
IntroductionPerthes disease (PD) is an idiopathic disorder presenting with avascular necrosis to the femoral head, which frequently results in flattening. Long-term function is directly related to ...the subsequent femoral head sphericity. Current treatment includes mechanical modalities and surgical procedures, which are therapeutic but are not uniformly able to prevent collapse. The use of the nitrogen-containing bisphosphonate zoledronic acid (ZA) to inhibit osteoclastic bone resorption is aimed at preserving femoral head strength, reducing collapse and thus maintaining shape. The proposed multicentre, prospective, randomised controlled trial intends to evaluate the efficacy of ZA treatment in PD.Methods and analysisAn open-label randomised control trial recruiting 100 children (50 each treatment arm) 5 to 16 years old with unilateral PD. Subjects are randomly assigned to either (a) ZA and standard care or (b) Standard care. The primary outcome measure is deformity index (DI), a radiographic parameter of femoral head roundness assessed at 24 months, following 12 months of ZA treatment (3-monthly doses of ZA 0.025 mg/kg at baseline, 3, 6, 9 and 12 months) plus 12 months observation (group A) or 24 months of observation (group B). Secondary outcome measures are femoral head subluxation, Faces Pain scale, Harris hip score and quality of life. Assessments are made at baseline, 3 monthly during the first year of follow-up and then 6 monthly, until the 24th month.Ethics and disseminationThe study commenced following the written approval from the Human Research Ethics Committee. Safety considerations regarding the effects of ZA are monitored which include the subject’s symptomatology, mineral status, bone mass and turnover activity, and metaphyseal modelling. Data handling plan requires that all documents, clinical information, biological samples and investigation results will be held in strict confidence by study investigators to preserve its safety and confidentiality.Trial registration numberAustralian and New Zealand Clinical Trials ACTRN12610000407099, pre-results.
Summary
objective Germline mutations in succinate dehydrogenase (SDH)B, SDHC and SDHD, encoding three of the four subunits of mitochondrial complex II, have been implicated in the tumourigenesis of ...familial paragangliomas and phaeochromocytomas. Twenty‐three SDHB mutations have been identified to date.
patients We present a novel missense SDHB exon 2 mutation (c.118 A > G; K40E) identified in an Australian family. The proband was diagnosed with phaeochromocytoma at an early age following an unexpected hypertensive crisis and was found to be SDHB mutation‐positive. Subsequent genetic screening of 26 family members has identified 17 mutation‐positive relatives. In addition to the proband, four mutation positive relatives were found to have clinical symptoms or a lesion and/or catecholamine excess after the identification of the mutation led to further evaluation. Both the proband and an uncle have required surgical removal of a tumour.
conclusions This family indicates the importance of germline screening of first‐degree relatives when a patient presents with an apparently sporadic extra adrenal phaeochromocytoma at a young age or whenever a patient with a nonsecretory paraganglioma is found.
The symptoms, auxological characteristics, and stimulated 17-hydroxyprogesterone (17-OHP) concentrations in a group of patients with non-classical 21-hydroxylase deficiency (NCCAH) were compared with ...those of their siblings. Ten index cases consisting of nine females and one male patient aged 3-33 years and 16 siblings were studied. In the sibling group five subjects were slightly virilised and of these, two females were found to have NCCAH according to their stimulated 17-OHP concentrations. The remaining nine siblings, who were not virilised, all had normal stimulated 17-OHP concentrations. Among the total NCCAH group (index cases and affected siblings) eight patients had the diagnosis made within two years of the onset of symptoms. In four patients diagnosis was delayed until adulthood. In seven patients investigated, bone age was significantly increased before treatment. The mean height and body mass index Z scores of the affected patients as a total group or when divided according to skeletal maturity were not significantly different from either the normal mean or from their unaffected siblings. Virilised siblings of patients with NCCAH should have stimulated 17-OHP levels measured to exclude the disease. Patients with NCCAH do not appear to be at risk of short adult stature despite increased bone age in childhood.
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