A novel disorder of osteoporosis, osteonecrosis, and metaphyseal fracture

We describe two unrelated women who in theirfifth decade developed a severe disorder characterized by large joint osteonecrosisand multiple minimal trauma fractures in both the axial and appendicular skeleton, including unusual metaphyseal fractures of theproximal tibia. Bone density testing showed borderline osteoporosis of the spine and osteopenia of the femur. Therapy with bispho-sphonates and teriparatide failed to prevent further fractures. To our knowledge, this disorder has not been described previously.Investigations to date, including a genetic screen, have not revealed its cause

Juvenile Paget’s disease with compound heterozygous mutations in TNFRSF11B presenting with recurrent clavicular fractures and a mild skeletal phenotype

Juvenile Paget’s disease (JPD) is a rare recessively-inherited bone dysplasia. The great majority of cases described to date have had homozygous mutations in TNFRSF11B, the gene encoding osteoprotegerin. We describe a boy who presented with recurrent clavicular fractures following minor trauma (8 fractures from age 2 to 11). He was of normal height and despite mild lateral bowing of the thighs and anterior bowing of the shins he remained physically active. Abnormal modelling was noted in ribs and humeri on clavicular radiographs, and a skeletal survey at the age of 7 showed generalised diaphyseal expansion of the long bones with thickening of the periosteal and endosteal surfaces of the cortices. On biochemical evaluation, serum alkaline phosphatase was noted to be persistently elevated. The diagnosis of JPD was confirmed by the finding of compound heterozygous mutations in TNFRSF11B: a maternally-inherited A > G missense mutation at position 1 of the first amino acid codon (previously reported) and a paternally-inherited splice acceptor site mutation in intron 3 at a highly conserved position (not previously reported). Bioinformatics analysis suggested both mutations were disease-causing. Compound heterozygote mutations in TNFRSF11B causing JPD have been previously reported only once – in a boy who also had a relatively mild skeletal phenotype. The milder features may lead to delay in diagnosis and diagnostic confusion with other entities, but the extraskeletal features of JPD may nonetheless develop

SERUM ALUMINIUM MEASUREMENTS IN RENAL BONE DISEASE

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