Osteogenesis Imperfecta

Hearing loss affects up to 70% of all patients with osteogenesis imperfecta and may occur in any of the 5 clinical types.

Type I (nondeforming with persistently blue sclera) is the mildest. Symptoms and signs in some patients are limited to blue sclerae (due to a deficiency in connective tissue allowing the underlying vessels to show through) and musculoskeletal pain due to joint hypermobility. Recurrent fractures in childhood are possible.

Type II (perinatal lethal or osteogenesis imperfecta congenita) is the most severe and is lethal. Multiple congenital fractures result in shortened extremities. Sclerae are blue. The skull is soft and, when palpated, feels like a bag of bones. Because the skull is soft, trauma during delivery may cause intracranial hemorrhage and stillbirth, or neonates may die suddenly during the first few days or weeks of life.

Osteogenesis Imperfecta (Blue Sclerae)

Hide Details

This photo shows a close-up of the eye showing a blue sclera (normally white).

JAMES STEVENSON/SCIENCE PHOTO LIBRARY

Type III (progressively deforming) is the most severe nonlethal form of osteogenesis imperfecta. Patients with type III have short stature, spinal curvature, and multiple, recurrent fractures. Macrocephaly with triangular facies and pectal deformities are common. Scleral hue varies.

Cardiopulmonary abnormalities, including valvular disease, heart failure, and restrictive lung disease (both parenchymal and due to chest and spinal abnormalities), can be seen in types II and III.

Osteogenesis Imperfecta (Skeletal Findings)

Hide Details

This photo shows a patient with severe osteogenesis imperfecta who has a barrel chest, spinal curvature, severe bone deformities, loose joints, and poor muscle development.

R M.A. ANSARY/SCIENCE PHOTO LIBRARY

Type IV (moderate) is intermediate/moderate in severity. Survival rate is high. This type is variable and deforming. Bones fracture easily in childhood before adolescence. Sclera are typically normal in color. Height is moderate-short stature. Accurate diagnosis is important because these patients may benefit from treatment.

Type V manifests with calcification of the interosseous membranes and/or hypertrophic callus and with radial head dislocation. Sclera are blue to bluish-gray. This type can be mild to moderate in severity and individuals with mild symptoms can lead relatively normal lives.

• Clinical evaluation

• Analysis of type I procollagen and/or genetic testing

• Sometimes prenatally with ultrasound, chorionic villus sampling, or amniocentesis

Diagnosis of osteogenesis imperfecta is usually clinical, but there are no standardized criteria.

Analysis of type I procollagen from cultured fibroblasts (from a skin biopsy) and/or sequencing of the COL1A1, COL1A2, and other causative genes is used to confirm the diagnosis.

Prenatally, osteogenesis imperfecta can be detected by detailed ultrasound; the optimal timing and likelihood of diagnosis depends on the type and severity (1). If a parental mutation is known, chorionic villus cells or amniocytes can be analyzed for that specific mutation. Chorionic villus cells (but not amniocytes) can also be cultured for analysis of the type I procollagen produced and for comparison with the procollagen test results of an affected family member.

• Bisphosphonates

• Growth hormone

• Sometimes denosumab or teriparatide

• Sometimes vitamin D

• Sometimes surgery

Treatment with bisphosphonates (eg, pamidronate 0.5 to 3 mg/kg IV once a day for 3 days, repeated as needed every 4 to 6 months; zoledronic acid 0.0125 to 0.025 mg/kg IV repeated every 3 to 6 months; alendronate 1 mg/kg [20 mg maximum] orally once a day) is aimed at increasing bone density and decreasing bone pain, and risk of fracture and scoliosis (Treatment with bisphosphonates (eg, pamidronate 0.5 to 3 mg/kg IV once a day for 3 days, repeated as needed every 4 to 6 months; zoledronic acid 0.0125 to 0.025 mg/kg IV repeated every 3 to 6 months; alendronate 1 mg/kg [20 mg maximum] orally once a day) is aimed at increasing bone density and decreasing bone pain, and risk of fracture and scoliosis (1, 2).

Growth hormone in conjunction with bisphosphonate therapy can improve growth and bone mineral density in some patients (2, 3).

Denosumab, a receptor activator of nuclear factor kappa-B ligand (RANKL), is a potent inhibitor of osteoclastic bone resorption and is typically given as an injection. Studies have shown that this medication is beneficial in some patients with osteogenesis imperfecta (Denosumab, a receptor activator of nuclear factor kappa-B ligand (RANKL), is a potent inhibitor of osteoclastic bone resorption and is typically given as an injection. Studies have shown that this medication is beneficial in some patients with osteogenesis imperfecta (2, 4).

Teriparatide, a recombinant parathyroid hormone, is used for 24 months and is given subcutaneously. It is not for use in children (Teriparatide, a recombinant parathyroid hormone, is used for 24 months and is given subcutaneously. It is not for use in children (5). Romosozumab, a sclerostin antibody, and fresolimumab, a transforming growth factor (TGF)-beta inhibitory antibody, are still in clinical trials (). Romosozumab, a sclerostin antibody, and fresolimumab, a transforming growth factor (TGF)-beta inhibitory antibody, are still in clinical trials (6).

Vitamin D supplementation should be provided to people who are deficient in this hormone.Vitamin D supplementation should be provided to people who are deficient in this hormone.

Orthopedic surgery, including implantation of rods into long bones, can stabilize growth and prevent fractures (2). Physical therapy and occupational therapy with a focus on sustainable muscle strength maintenance help improve function.

Cochlear implantation is indicated in selected cases of hearing loss.