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Osteogenesis Imperfecta

The literal meaning of osteogenesis imperfecta is “imperfect bone formation”. This genetic defect in osteogenesis imperfect makes it impossible for the body to manufacture strong and sturdy bones. Patients suffering from osteogenesis imperfecta can have hundreds of bone fractures in a given lifetime.


All people suffering from osteogenesis imperfecta have relatively softer bones which are perennially susceptible to fractures. Afflicted patients usually appear with a short stature compared to their normal counterparts. The bluish tint found in the sclera of patients is classically seen in the majority of patients. A certain degree of auditory defect is also observable among the afflicted individuals. The defect in collagen type synthesis will sometimes present with hypermobile joints or “loose joints” and they usually have pes planus (flat foot). The defective dentin results in poor dentition in most cases. These patients may also present with bowed legs and arms. Scoliosis and kyphosis are common spinal finding in osteogenesis imperfecta.

  • What is Known: • Acute and chronic musculoskeletal pain remains a major issue in OI. • Pain has a negative impact on quality of life.[ncbi.nlm.nih.gov]
Mitral Valve Prolapse
  • In a 48-year-old man with osteogenesis imperfecta and mitral valve prolapse, we performed the first successful mitral valve repair by right anterior mini-thoracotomy.[ncbi.nlm.nih.gov]
  • Common problems also include the development of bowing of the legs, curvature of the spine ( scoliosis and kyphosis ), umbilical and inguinal hernias and mild mitral valve prolapse (flopping down of the leaflets of the mitral heart valve).[medicinenet.com]
  • Cardiac effects are important; they include aortic incompetence, aortic root widening and mitral valve prolapse. Often there is hypermobility of joints, with flat feet, hyper-extensible large joints and dislocations.[patient.info]
  • valve prolapse 0001634 Osteopenia 0000938 Otosclerosis 0000362 Recurrent fractures Increased fracture rate Increased fractures Multiple fractures Multiple spontaneous fractures Varying degree of multiple fractures [ more ] 0002757 Thin skin 0000963 Wormian[rarediseases.info.nih.gov]
Blue Sclera
  • CONCLUSIONS: Osteogenesis imperfecta is a genetic disorder with distinctive clinical features such as bone fragility, recurrent fractures, blue sclerae, and dentinogenesis imperfecta.[ncbi.nlm.nih.gov]
  • sclerae, Adair-Dighton syndrome, Mild osteogenesis imperfecta, Non-deforming osteogenesis imperfecta, Van der Hoeve syndrome, Classic non-deforming OI with blue sclerae Osteogenesis imperfecta type III Synonyms: OI type 3, Osteogenesis imperfecta, progressively[rarediseases.info.nih.gov]
  • […] fibrous dysplasia (see these terms), non-accidental injury (multiple fractures without osteoporosis), and osteoporosis due to medication, nutritional deficiency, metabolic disease, or leukemia.[orpha.net]
  • Bachrach, Osteoporosis in Childhood and Adolescence, Osteoporosis, 10.1016/B978-0-12-415853-5.00043-1, (1037-1086), (2013). Alphonsus K. S. Chong, Rosalyn P.[doi.org]
  • The fourth group of patients showed dominant inheritance of osteoporosis leading to fractures, with variable deformity of long bones, but normal sclerae.[ncbi.nlm.nih.gov]
  • Transient Osteoporosis A rapidly developing, painful local osteoporosis of unknown cause. The hip joint and ankle are often affected. Unlike osteoporosis, transient osteoporosis is reversible.[web.archive.org]
Bone Pain
  • Bone pain ameliorated just after the first cycle of pamidronate, while the activity and mobility increased quickly.[ncbi.nlm.nih.gov]
  • No difference in bone pain. No difference in mobility.[doi.org]
  • Chronic osteomyelitis causes intermittent (months to many years) bone pain, tenderness, and draining sinuses.[msdmanuals.com]
  • Bisphosphonates have been used for a variety of conditions in childhood where there is bone pain and immobility in association with osteoporosis and/or abnormal bone formation.[gosh.nhs.uk]
Skeletal Dysplasia
  • When a skeletal dysplasia is detected during the antenatal period, especially early in the pregnancy, it can be associated with a poor prognosis.[ncbi.nlm.nih.gov]
  • Skeletal dysplasias: A radiographic approach and review of common non-lethal skeletal dysplasias. World J Radiol 2014;6:808-25. [ PUBMED ] 20. Trejo P, Rauch F.[doi.org]
Narrow Pelvis
  • pelvis, compression fractures, protrusio acetabuli, [20] and shepherd’s-crook deformities of the femurs Newborn has bilateral femoral fractures.[emedicine.medscape.com]
  • pelvis, compression fractures, protrusio acetabuli, and shepherd’s- crook deformities of the femurs 27.  Mild OI (type I) : thinning of the long bones with thin cortices,wormian bones,no deformity of long bones Extremely severe OI (type II) : beaded[de.slideshare.net]
  • pelvis, compression fractures, protrusio acetabuli, and shepherd's crook deformities of the femurs Densitometry - DEXA can be used to assess bone mineral density (BMD) in children with milder forms of OI.[doi.org]
Joint Dislocation
  • dislocation; - hearing: - hearing defects 2nd to inner and middle ear abnormalities may develop, & affected children require regular audiologic examinations; - pelvis: - protrusio acetabuli may occur in type III and may narrow pelvic outlet, and can[wheelessonline.com]
  • […] the Osteogenesis Imperfecta Panel and their clinical significance Gene Associated phenotypes Inheritance ClinVar HGMD ALPL Odontohypophosphatasia, Hypophosphatasia perinatal lethal, infantile, juvenile and adult forms AD/AR 78 291 B3GAT3 * Multiple joint[blueprintgenetics.com]
  • The skeletal manifestations include spontaneous fractures, joint dislocations, and growth retardation. [38], [39] Figure 6: (a-h) Osteogenesis imperfecta.[doi.org]
  • Both subgroups have a similar frequency of joint hypermobility, bruising, deafness, and joint dislocations [Paterson et al., 1983 ].[onlinelibrary.wiley.com]


The diagnosis of osteogenesis imperfecta is easily clenched with a thorough clinical history and physical examination. A positive history of a bone fracture caused by a little force is very suspicious of the disease. The following diagnostic modalities and tests are further implored for the work up of patients with osteogenesis imperfecta:

  • X-ray studies: The radiograph of the child will show multiple fractures and bone deformities characteristic of the bone disease.
  • Ultrasound: Sonograms can detect severe osteogenesis imperfecta while the baby is still in the uterus.
  • Genetic testing: These tests will identify the mutations of the gene that expresses as osteogenesis imperfecta.
  • Skin punch biopsy: Definitive diagnosis can be achieved by a biopsy by the histologic demonstration of defective collagen structures and fibroblasts in the skin and ligaments [7]. 
  • Amniocentesis: A chorionic villi sampling through genetic analysis procedures can be done to diagnose the disease even before birth.


There is no cure available yet for osteogenesis imperfecta. However, there are well-established therapies known to allay the symptoms of pain and reduce its complications. The following therapies are available for patients suffering from osteogenesis imperfecta:

  • Biphosphonates: This drug are actively given to patients suffering from osteoporosis to foster better bone formation and repair. This will significantly reduce bone pain in osteogenesis imperfecta.
  • Regular exercises: Frequent low impact exercises can strengthen the muscles and support the brittle bones from crumbling. 
  • Bracing: The use of sturdy or metal bracing in the spine and long bones can help prevent the occurrence of fractures among patients.
  • Reconstructive surgery: Complications of osteogenesis imperfecta found in the legs and spine will benefit from reconstructive surgery to restore the ambulation in patients [8]. 
  • Plaster casting: Patients presenting with long bone fractures are routinely placed in cast to assist bone healing. However, patients with osteogenesis imperfecta may require a shortened time for casting to avoid the development of osteoporosis of disuse. 
  • Psychological support: Children and young adults will need adequate psychological support and therapies to overcome the many challenges associated with the bone disease
  • Physiotherapy: Patients with severe disability associated with the disease will benefit greatly from physiotherapy and the use of appliances like wheelchairs and canes [9].


There is a wide variation in the outcome of patients suffering from osteogenesis imperfecta in terms of morbidity. The genotypic combination influences directly the severity of disability expressed in each patient [6]. Severe perinatal cases can result to fetal death in utero or death of the infant during the perinatal period. These cases present with several pathologic fractures in the body during autopsies. The life expectancy of patients suffering from osteogenesis imperfecta is comparable to the normal population except for those cases with enduring neurologic and respiratory complications.


Studies have revealed that osteogenesis imperfecta is genetically transmitted from parents to children. The mode of transmission for this bone disease is by means of autosomal dominance. The defective gene has been transmitted from one of the parent or carrier parent to a susceptible offspring, thus, symptoms may vary from parent to child in terms of disability and severity in most cases. The missing gene in the defect codes for collagen type 1 needed for the structural integrity of most long bones in the body [1]. The defective collagen synthesis also gives rise to defective teeth, ligaments and eye sclera.


In general, osteogenesis imperfecta has an incidence rating of 1 case per 20,000 live births. The prevalence of the milder forms of osteogenesis imperfecta is observably higher and often times underdiagnosed in the clinics. In the United States, there are approximately 20,000 to 50,000 people afflicted by this bone defect [2]. The incidence rate is fairly equivalent worldwide but with a slightly higher incidence among two notable tribes in Zimbabwe, Africa. Age of onset for osteogenesis imperfecta varies greatly but first signs of fracture usually start from adolescence to adulthood. There is slight predilection in males than in females but there are no observable racial predilection noted.

Sex distribution
Age distribution


The basic pathophysiology seen osteogenesis imperfecta is the absence of one of the two genes responsible for the production of collagen type 1. This collagen is needed to produce sturdy and strong bone, dentin, sclera, and ligaments in the body. This genetic defect accounts for almost 80% of all osteogenesis imperfecta cases [3]. Although genetic science has traced its transmission through either autosomal dominant or autosomal recessive traits, there have been cases documented to have originated from spontaneous mutations or due to gonadal mosaicism [4].

Histologically, bone samples from patients with osteogenesis imperfecta will basically appear osteoporotic with marked decrease in the intracellular matrix formation. The bone trabeculae networks will appear thinned and disorganized [5]. Lamellar bone usually persists between the diaphysis and metaphysis of the long bones. There is also a marked delay in the development of the secondary ossification centers in the long bones. Externally, bones in the skull and the spine will appear thinned and wedged in some areas.


It is imperative that couples with strong familial history of osteogenesis imperfecta should submit for genetic counseling before conceiving [10]. High risk patients must submit to an annual medical examination and physical examination to prevent complication.


Osteogenesis imperfecta is a congenital disease characterized by a defective gene that is unable to produce collagen type 1. The collagen type 1 is an important building block for structural integrity of bones in the body. Osteogenesis imperfecta is characterized by soft and fragile bones, hearing defects, curved spine, and brittle dentition. In some literatures, osteogenesis imperfecta is sometimes referred to as “Brittle bone disease”.

Patient Information

Definition: Osteogenesis imperfecta is a congenital disease characterized by a defective gene that is unable to produce collagen type 1 leading to softer bones that are very prone to fractures.
Cause: Osteogenesis imperfecta is caused by a genetic defect transmitted through autosomal dominance. Spontaneous mutations and gonadal mosaicism are also considered an etiologic cause of the disease.
Symptoms: Patients with osteogenesis imperfecta will present with recurrent bouts of fractures at multiple sites of the body. Patients will present with kyphosis and scoliosis in the majority of cases. Patients will have poor dentition and show a bluish tint in the sclerae.
Diagnosis: A thorough medical history and physical examination will easily reach the diagnosis of osteogenesis imperfecta. X-ray and other imaging tools will reveal multiple fractures and bone deformities among the patients.
Treatment and follow-up: Patients are amply given biphosponate therapy to allay the signs of the concurrent osteoporosis in the disease. Supportive casting and bracing can prevent the occurrence of pathologic fractures in patients. Reconstructive surgery can effectively correct the bone deformities associated with the disease. A regular low impact exercise will strengthen the muscles that supports the weakened bones of the body.



  1. Alanay Y, Avaygan H, Camacho N, Utine GE, Boduroglu K, Aktas D, et al. Mutations in the gene encoding the RER protein FKBP65 cause autosomal-recessive osteogenesis imperfecta. Am J Hum Genet. Apr 9 2010; 86(4):551-9.
  2. Plotkin H. Syndromes with congenital brittle bones. BioMed Central Pediatrics. 2004; 4 (16).
  3. Cole WG. The Nicholas Andry Award-1996. The molecular pathology of osteogenesis imperfecta. Clin Orthop. Oct 1997; 235-48.
  4. Eckardt J, Kluth S, Dierks C, Philipp U, Distl O. Population screening for the mutation associated with osteogenesis imperfecta in dachshunds. Vet. Rec. 2013 172 (14): 364.
  5. Rauch F, Travers R, Parfitt AM, Glorieux FH. Static and dynamic bone histomorphometry in children with osteogenesis imperfecta. Bone. Jun 2000; 26(6):581-9.
  6. Sillence D. Osteogenesis imperfecta: an expanding panorama of variants. Clin Orthop. Sep 1981; 11-25.
  7. Francis MJ, Smith R, Bauze RJ. Instability of polymeric skin collagen in osteogenesis imperfecta. Br Med J. Mar 9 1974; 1(905):421-4.
  8. Esposito P, Plotkin H. Surgical treatment of osteogenesis imperfecta: current concepts. Curr Opin Pediatr. Feb 2008; 20(1):52-7.
  9. Jones D, Hosalkar H, Jones S. The orthopaedic management of osteogenesis imperfecta. Clin Orthop. 2002; 16:374-88.
  10. Chen, Harold. Atlas of genetic diagnosis and counseling. Totowa, NJ: Humana Press. 2006 ISBN 1-58829-681-4.

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Last updated: 2019-07-11 20:42