Clinical, cellular, microscopic, and ultrastructural studies of a case of fibrogenesis imperfecta ossium.
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.
Department of Physiology, School of Medical Sciences, Bosch Institute, University of Sydney , Sydney 2006, New South Wales, Australia.
Melissa L
ML
Barron
Department of Physiology, School of Medical Sciences, Bosch Institute, University of Sydney , Sydney 2006, New South Wales, Australia.
Mark S
MS
Rybchyn
Department of Physiology, School of Medical Sciences, Bosch Institute, University of Sydney , Sydney 2006, New South Wales, Australia.
Sutharshani
S
Ramesh
Department of Physiology, School of Medical Sciences, Bosch Institute, University of Sydney , Sydney 2006, New South Wales, Australia.
Rebecca S
RS
Mason
Douglas HanlyMoir Pathology , Macquarie Park 2113, New South Wales, Australia.
S
S
Fiona Bonar
Department of Orthopaedics, Royal Prince Alfred Hospital , Camperdown 2050, New South Wales, Australia.
Paul
P
Stalley
Department of Endocrinology, Mayo Clinic , Rochester 55905, MN, USA.
Sundeep
S
Khosla
Department of Microbiology, Royal North Shore Hospital , St Leonards 2065, New South Wales, Australia.
Bernie
B
Hudson
Department of Haematology, Royal North Shore Hospital , St Leonards 2065, New South Wales, Australia.
Christopher
C
Arthur
Department of Endocrinology, Royal North Shore Hospital , St Leonards 2065, New South Wales, Australia.
Edward
E
Kim
Department of Endocrinology, Royal North Shore Hospital, St Leonards 2065, New South Wales, Australia; Faculty of Medicine, University of Sydney, Sydney 2006, New South Wales, Australia.
Roderick J
RJ
Clifton-Bligh
Department of Endocrinology, Royal North Shore Hospital, St Leonards 2065, New South Wales, Australia; Faculty of Medicine, University of Sydney, Sydney 2006, New South Wales, Australia.
Phillip B
PB
Clifton-Bligh