Endocrine Abstracts

Familial expansile osteolysis is a rare autosomal dominant disorder of bone, first described in a kindred from Northern Ireland in 1988. There are histological similarities to Paget's disease but the disorder typically presents in the young.

Case report: Our patient presented at 15 years of age with sensorineural hearing loss, skeletal pain, gingival hypertrophy and mobile teeth. Neither parent was similarly affected. Radiographs demonstrated tooth root resorption and there were areas of increased Tc-99m uptake in the shafts of humeri, tibia and dentition. Bone mineral density was low at lumbar spine (T score -4 at L-spine and -2 at hip). Alkaline phosphatase level was elevated at 650 units per litre, with normal calcium, phosphate and PTH levels. Urinary N-telopeptide and urinary deoxypyridine per creatinine ratio were elevated at 1802 nanomole BCE per millimole creatinine and 37 nanomillilitre per millimole creatinine respectively. Alveolar and iliac crest bone biopsy showed features of high bone turnover abnormality consistent with familial expansile osteolysis. Genetic studies showed a duplication within the TNFRSF11A gene predicting an abnormal signal peptide within the encoded RANK protein.

Our patient underwent dental clearance and was treated with 4 courses of pamidronate infusions coupled with calcium and vitamin D supplements, which markedly improved bone mineral density (T score -2.35 at L-spine and -0.34 at hip). Alkaline phosphatase normalised and urinary N-telopeptide and urinary deoxypyridine per creatinine ratio decreased to 113 nanomole BCE per millimole creatinine and 8.7 nanomillilitre per millimole creatinine, respectively. Repeat skeletal survey showed hyperostosis affecting metatarsals, phalanges, left tibia, left humerus, radius and ulna.

Summary: FEO is a disorder of bone remodelling due to mutations in the TNFRSF11A gene encoding RANK protein. Mutations increase signalling and abnormal osteoclast activity. Long term risk of skeletal deformity, recurrent fractures and osteosarcoma exists and require long term surveillance.