Fibrogenesis Imperfecta Ossium and Response to Human Growth Hormone: A Potential Therapy

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The Journal of clinical endocrinology and metabolism


Context: Fibrogenesis imperfecta ossium (FIO) is a rare bone disease manifested by generalized bone pain, fragility fractures, progressive disability, and extensive mineralization defect seen in bone biopsy specimens. The pathogenesis of the disease is unknown and currently there is no effective treatment.

Objective: To report on the effect of recombinant human growth hormone (rhGH) therapy in FIO.

Design: An observational study in two patients.

Setting: Endocrinology clinic in an academic institution.

Patients or Other Participants: Two siblings with FIO.

Intervention(s): rhGH was administered subcutaneously at a dose of 1 U daily for 1 year.

Main Outcome Measures: Changes in clinical, biochemical, radiological, and bone histological (i.e., light and transmission electron microscopy, and histomorphometry) investigations.

Results: Except for an elevated serum alkaline phosphatase level, results of routine biochemical, hematological, and hormonal investigations were normal in both patients. Radiographs showed pseudofractures and bone scans revealed a "beheaded" tracer activity pattern (i.e., superscan without uptake in the skull). Bone biopsy specimens showed severe mineralization defect simulating osteomalacia with disorganized collagen fibril alignment. Treatment with rhGH was followed by clinical, biochemical, and radiological improvement in both the patients, with substantial improvement in the mineralization defect, most likely due to rhGH-induced improvement in collagen fibril arrangement.

Conclusion: We report on two brothers with FIO and demonstrate clinical improvement and restoration of normal bone pathology with rhGH therapy. We suggest that rhGH is a potential therapy for FIO for which no effective therapy currently exists.

Medical Subject Headings

Adult; Alkaline Phosphatase; Bone Diseases, Metabolic; Bone and Bones; Calcification, Physiologic; Fractures, Bone; Fractures, Spontaneous; Human Growth Hormone; Humans; Male; Microscopy, Electron, Transmission; Middle Aged; Musculoskeletal Pain; Osteomalacia; Recombinant Proteins; Siblings; Treatment Outcome

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