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



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



An observational study in two patients.



Endocrinology clinic in an academic institution.



Two siblings with FIO.



rhGH was administered subcutaneously at a dose of 1 U daily for 1 year.



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



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.



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.
Department of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
Sanjay Kumar
SK
Bhadada
Department of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
Vandana
V
Dhiman
Department of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
Soham
S
Mukherjee
Department of Orthopedics, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
Sameer
S
Aggarwal
Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
Amanjit
A
Bal
Department of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
Suja P
SP
Sukumar
Department of Nuclear Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
Ashwani
A
Sood
Department of Medicine, RNT Medical College, Udaipur, Rajasthan 313001, India.
Dinesh Chandra
DC
Sharma
Department of Radiodiagnosis, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
Niranjan
N
Khandelwal
Department of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
Anil
A
Bhansali
Medical Genetics, University of Antwerp, Antwerp 2650, Belgium.
Wim
W
Van Hul
Bone and Mineral Research Laboratory, Henry Ford Health System, Detroit, Michigan 48202.
Sudhaker D
SD
Rao
D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D001851:Bone Diseases, Metabolic / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D002113:Calcification, Physiologic; D050723:Fractures, Bone / Q000209:etiology; D005598:Fractures, Spontaneous / Q000209:etiology; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D059352:Musculoskeletal Pain / Q000209:etiology; D010018:Osteomalacia / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D011994:Recombinant Proteins / Q000627:therapeutic use*; D035781:Siblings; D016896:Treatment Outcome
D011994:Recombinant Proteins; D019382:Human Growth Hormone; D000469:Alkaline Phosphatase