Clinical, cellular, microscopic, and ultrastructural studies of a case of fibrogenesis imperfecta ossium

Abstract

Fibrogenesis imperfecta ossium is a rare disorder of bone usually characterized by marked osteopenia and associated with variable osteoporosis and osteosclerosis, changing over time. Histological examination shows that newly formed collagen is abnormal, lacking birefringence when examined by polarized light. The case presented demonstrates these features and, in addition, a previously undocumented finding of a persistent marked reduction of the serum C3 and C4. Osteoblasts established in culture from a bone biopsy showed abnormal morphology on electron microscopy and increased proliferation when cultured with benzoylbenzoyl-ATP and 1,25-dihydroxyvitamin D, contrasting with findings in normal osteoblasts in culture. A gene microarray study showed marked upregulation of the messenger RNA (mRNA) for G-protein-coupled receptor 128 (GPR 128), an orphan receptor of unknown function and also of osteoprotegerin in the patient’s osteoblasts in culture. When normal osteoblasts were cultured with the patient’s serum, there was marked upregulation of the mRNA for aquaporin 1. A single pathogenetic factor to account for the features of this disorder has not been defined, but the unique findings described here may facilitate more definitive investigation of the abnormal bone cell function.

Bone disorders: Getting a better handle on collagen deficiency

The identification of biological anomalies in a patient may soon facilitate the diagnosis and treatment of fibrogenesis imperfecta ossium. In this rare but debilitating disorder, the dense fibrous collagen network, which imparts tensile strength to bone, progressively degrades, giving rise to brittle tissue. However, the mechanisms involved in this disorder remain unclear, which leads to misdiagnosis and inadequate therapeutic options. To close this knowledge gap, Phillip Clifton-Bligh and co-workers from the University of Sydney, Australia, evaluated the disorder at multiple stages. Blood tests of patients revealed reduced levels in serum C3 and C4, two proteins associated with the immune system. Moreover, osteoblasts extracted from affected bone exhibited unusual proliferation, protein production and gene expression. These findings lay the foundation for deeper studies of abnormal bone cell function.

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