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Osteogenesis Imperfecta

By

Frank Pessler

, MD, PhD, Helmholtz Centre for Infection Research

Reviewed/Revised Dec 2022
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Topic Resources

Osteogenesis imperfecta is a hereditary collagen disorder causing diffuse abnormal fragility of bone and is sometimes accompanied by sensorineural hearing loss, blue sclerae, dentinogenesis imperfecta, and joint hypermobility. Diagnosis is usually clinical. Treatment includes growth hormone for some types, bisphosphonates, and denosumab.

  • I: Mild, blue sclerae

  • II: Neonatal lethal, blue sclerae

  • III: Progressive, variable scleral hue

  • IV: Variable and deforming, normal scleral hue

Their mode of inheritance is usually autosomal dominant Autosomal Dominant Genetic disorders determined by a single gene (Mendelian disorders) are easiest to analyze and the most well understood. If expression of a trait requires only one copy of a gene (one allele)... read more . Ninety percent of people who have one of these main types have mutations in the genes encoding the pro-alpha chains of type I procollagen (a structural component of bones, ligaments, and tendons), COL1A1 or COL1A2.

There are a number of other, rarer types (types V to XXI), which are caused by mutations in different genes.

Reference

Symptoms and Signs of Osteogenesis Imperfecta

Hearing loss is present in 50 to 65% of all patients with osteogenesis imperfecta and may occur in any of the 4 main types.

Type I 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 (neonatal lethal type 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.

Type III is progressive and 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.

Type IV is intermediate 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.

Diagnosis of Osteogenesis Imperfecta

  • Clinical evaluation

  • Sometimes analysis of type I procollagen or genetic testing

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) or sequence analysis of the COL1A1 and COL1A2 genes can be used when clinical diagnosis is unclear.

Severe osteogenesis imperfecta can be detected in utero by level II ultrasonography.

Treatment of Osteogenesis Imperfecta

  • Growth hormone

  • Bisphosphonates

  • Sometimes denosumab

  • Sometimes vitamin D

Growth hormone helps growth-responsive children (types I and IV).

Treatment with bisphosphonates is aimed at increasing bone density and decreasing bone pain and fracture risk (1 Treatment references Osteogenesis imperfecta is a hereditary collagen disorder causing diffuse abnormal fragility of bone and is sometimes accompanied by sensorineural hearing loss, blue sclerae, dentinogenesis... read more Treatment references ). IV pamidronate (0.5 to 3 mg/kg once a day for 3 days, repeated as needed every 4 to 6 months) or oral alendronate (1 mg/kg, 20 mg maximum, once a day) is used.

Denosumab is a potent inhibitor of osteoclastic bone resorption and is typically given as an injection. Studies have shown that this drug is beneficial in some patients with OI (2 Treatment references Osteogenesis imperfecta is a hereditary collagen disorder causing diffuse abnormal fragility of bone and is sometimes accompanied by sensorineural hearing loss, blue sclerae, dentinogenesis... read more Treatment references ).

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

Orthopedic surgery, physical therapy, and occupational therapy help prevent fractures and improve function.

Cochlear implantation is indicated in selected cases of hearing loss.

Treatment references

  • 1. Dwan K, Phillipi CA, Steiner RD, Basel D: Bisphosphonate therapy for osteogenesis imperfecta. Cochrane Database Syst Rev CD005088, 2016. doi: 10.1002/14651858.CD005088.pub4

  • 2. Li G, Jin Y, Levine MAH, et al: Systematic review of the effect of denosumab on children with osteogenesis imperfecta showed inconsistent findings. Acta Paediatr 107(3):534–537, 2018. doi: 10.1111/apa.14154

More Information

The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.

Drugs Mentioned In This Article

Drug Name Select Trade
Calcidol, Calciferol, D3 Vitamin, DECARA, Deltalin, Dialyvite Vitamin D, Dialyvite Vitamin D3, Drisdol, D-Vita, Enfamil D-Vi-Sol, Ergo D, Fiber with Vitamin D3 Gummies Gluten-Free, Happy Sunshine Vitamin D3, MAXIMUM D3, PureMark Naturals Vitamin D, Replesta, Replesta Children's, Super Happy SUNSHINE Vitamin D3, Thera-D 2000, Thera-D 4000, Thera-D Rapid Repletion, THERA-D SPORT, UpSpring Baby Vitamin D, UpSpring Baby Vitamin D3, YumVs, YumVs Kids ZERO, YumVs ZERO
Aredia
Binosto, Fosamax
Prolia, XGEVA
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