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CONTEXT Fibrogenesis imperfecta ossium (FIO) is a rare and progressive skeletal bone disorder of undetermined etiology. Given its FIO, the pathogenesis of FIO remains elusive and no effective treatment exists. Based on review of all published cases and our collective experience of FIO, we offer a comprehensive approach for the diagnosis and management of this complex and fatal disorder. EVIDENCE ACQUISITION A review of electronic and print medical literature comprising case reports and articles retrieved from PubMed database up to March 2018 was conducted using the search term "fibrogenesis imperfecta". In addition, references from retrieved case reports and articles were screened for articles containing information on FIO and differential diagnoses. EVIDENCE SYNTHESIS Twenty-six articles containing information concerning twenty-nine cases were identified. We reviewed the clinical and pathophysiologic features of all published cases. Comprehensive information on FIO is lacking in the literature. Diagnostic approach, in an attempt to gain insight into the disease, differed depending on the advancements in science and tools available at the time of patient identification. The response to various treatments used has been widely variable. CONCLUSION The dearth of information on FIO and low index of suspicion may lead to delayed or missed diagnoses and management. The fundamental skeletal defect appears to be an abnormality in organic matrix of bone characterized by defective mineralization of the abnormal collagen. Research focused on the identification of pathogenetic factors is needed. Albeit, long-term outcomes of growth hormone therapy are yet to be ascertained, short-term effectiveness appears promising.

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.