What is Osteogenesis Imperfecta?
Also known as brittle bone disease, Lobstein syndrome, fragilitas ossium, and Vrolik disease, osteogenesis imperfecta is marked by bones that break easily, often with little or no apparent cause. Precise typing is often difficult and depends heavily on the clinician's experience. Severity ranges from mild forms to forms that are lethal in the perinatal period.
Classification
Forlino and Marini, in 2015, offered an alternate way to understand the genetics by sorting it into five functional categories. Group A is primary defects in collagen structure and function. Group B is collagen modification defects. Group C is collagen folding and crosslinking defects. Group D is ossification or mineralization defects. Group E is osteoblast development defects with collagen insufficiency.
Pathophysiology
Type I collagen, the most abundant protein in the body and roughly 90% of the organic matrix of bone, is defective in osteogenesis imperfecta. Most cases trace to mutations in COL1A1 or COL1A2, the genes that encode type I collagen (StatPearls, Osteogenesis Imperfecta). The genetic subtypes include:
- Calcification of the intraosseous membranes. Generally moderate severity, but patients frequently develop hyperplastic calluses in long bones after a fracture or after orthopedic surgery involving osteotomies.
- SERPINF1 (Type VI). Caused by homozygous mutation in the SERPINF1 gene; autosomal recessive inheritance.
- CRTAP/LEPRE1/PPIB (Type VII-IX). Cartilage-associated protein (CRTAP) is required for prolyl-3-hydroxylation and, with the LEPRE1 and PPIB gene products, forms a heterotrimeric protein crucial for post-translational modification of collagen I.
- SERPINH1 (Type X). Genetic testing found a previously described homozygous mutation in the SERPINH1 gene.
- FKBP10 (Type XI). Caused by a homozygous mutation in the FKBP10 gene; autosomal recessive.
- SP7 (Type XII). Homozygous deletions in the SP7 gene; autosomal recessive.
- BMP1 (Type XIII). Caused by homozygous mutation in the BMP1 gene; autosomal recessive.
- WNT1 (Type XV). Caused by homozygous or compound heterozygous mutations in the WNT1 gene; autosomal recessive.
- CREB3L1 (Type XVI). CREB3L1 encodes the endoplasmic reticulum stress transducer protein OASIS, which regulates expression of type 1 procollagen.
- SPARC (Type XVII). SPARC (secreted protein, acidic, cysteine-rich) is a glycoprotein that binds multiple matrix proteins, including collagen I.
Statistics and Incidences
In the United States, osteogenesis imperfecta is estimated to affect about 1 in 15,000 to 20,000 births, and considering all types the worldwide prevalence is roughly 6 to 7 per 100,000 people (StatPearls, Osteogenesis Imperfecta). Mild forms are underdiagnosed, so the true figure may be higher. COL1A1 and COL1A2 mutations account for the large majority of cases, about 80% to 85% in Western countries, with a higher share of recessive forms in populations with frequent consanguinity (GeneReviews). No differences are reported by sex or race. Age at symptom onset varies widely: some patients have no fractures until adulthood, while others fracture in infancy.
Causes
This is an inherited disorder. In types I to V, the mode of inheritance is autosomal dominant and often involves a new dominant mutation. Germ cell mosaicism may explain cases in families with healthy parents who have more than one affected child. Somatic mosaicism has been noted in parents who have had multiple children with the same dominant form.
Clinical Manifestations
Manifestations vary by classification. The sclera may run bluish to whitish, though this color change also occurs in other diseases such as progeria and Menkes syndrome. Dentinogenesis imperfecta makes the teeth break easily and erode gradually. Lifetime fracture counts may reach a hundred or more. Patients may have a high tolerance for pain, so old fractures are sometimes found in infants only on a radiograph ordered for another reason. Height is extremely variable, from near-normal to significantly short stature.
Complications
Repeated respiratory infections can complicate severe disease. Basilar impression can cause brainstem compression and is a major neurologic complication in children. Hydrocephalus can be communicating or non-communicating and sometimes requires CSF shunting. Cerebral hemorrhage from birth trauma is another possible complication.
Assessment and Diagnostic Findings
Diagnostic tests help rule out other metabolic bone diseases. Collagen synthesis analysis is done by culturing dermal fibroblasts from a skin biopsy. Prenatal DNA mutation analysis can be performed in at-risk pregnancies using uncultured chorionic villus cells. Bone mineral density, measured by dual-energy radiographic absorptiometry, is generally low in children and adults with the disorder. X-ray may show thinning of the long bones with thin cortices, or beaded ribs, broad bones, and numerous fractures with deformities of the long bones. Prenatal ultrasonography can detect limb-length abnormalities at 15 to 18 weeks gestation.
Medical Management
Osteogenesis imperfecta is genetic and has no cure. Nutritional evaluation is paramount to ensure appropriate calcium and vitamin D intake. In utero bone marrow transplantation of adult marrow has been shown to decrease perinatal lethality. In a preclinical study, RANKL inhibition improved density and some geometric and biomechanical properties of oim/oim mouse bone but did not decrease fracture incidence versus placebo.
Pharmacologic Therapy
Cyclic IV pamidronate reduces fracture incidence and increases bone mineral density while reducing pain and increasing energy levels. Oral bisphosphonates such as risedronate may have some effect in reducing fractures.
Surgical Management
Orthopedic surgery is a pillar of treatment. In patients with bowed long bones, intramedullary rod replacement may improve weight bearing and let the child walk earlier than otherwise. Surgery for basilar impression is reserved for cases with neurologic deficits, especially from brainstem compression. Correcting scoliosis is difficult because of bone fragility, but spinal fusion may benefit patients with severe disease.
Nursing Management
Care is multidisciplinary.
Nursing Assessment
Assess the medical history, since this is a genetic disorder. Fracture is common, and many symptoms are detectable on physical exam. Laboratory results may reveal the disorder.
Nursing Diagnosis
- Risk for injury related to fragile bones.
- Impaired dentition related to genetic predisposition.
- Impaired physical mobility related to loss of integrity of bone structures.
Nursing Care Planning and Goals
The patient should modify the environment to enhance safety, stay free of injury, display healthy teeth in good repair, verbalize and demonstrate effective dental hygiene, follow through on referrals for dental care, and increase strength and function of affected or compensatory body parts.
Nursing Interventions
Offer genetic counseling to the parents so germline mosaicism can be discussed, since it is the mechanism behind some apparent new dominant mutations. Encourage adequate calcium, vitamin D, and phosphorus intake with appropriate caloric management. Educate parents on positioning the child in the crib and handling the child to avoid fractures.
Evaluation
Confirm the outcomes: the environment was modified for safety, the patient stayed free of injury, displayed healthy teeth in good repair, verbalized and demonstrated effective dental hygiene, followed through on dental referrals, and increased strength and function of affected or compensatory body parts.
Discharge and Home Care Guidelines
Physical therapy should target joint mobility and muscle strength. Periodic nutritional evaluation and intervention should continue. Patients need scrupulous oral hygiene and frequent followup with a pediatric dentist familiar with the disorder.
Documentation Guidelines
Document individual risk factors and current physical findings; availability and use of resources; factors influencing dentition problems; description of the oral cavity and structures; level of function and ability to participate in desired activities; the plan of care; the teaching plan; individual responses to interventions, teaching, and actions performed; attainment or progress toward desired outcomes; and modifications to the plan of care.
Frequently Asked Questions
What is osteogenesis imperfecta?
It is a genetic disorder of bone fragility, also called brittle bone disease, in which bones break easily, often with little or no apparent force. Severity ranges from mild to forms that are lethal in the perinatal period (StatPearls, Osteogenesis Imperfecta).
What causes osteogenesis imperfecta?
Most cases are caused by mutations in the COL1A1 or COL1A2 genes, which encode type I collagen, the most abundant protein in the body and the main organic component of bone. These mutations leave collagen reduced in amount or abnormal in structure, so bone is weak. Most types are inherited in an autosomal dominant pattern, and some arise as new mutations (GeneReviews).
How common is osteogenesis imperfecta?
It is rare. In the United States it affects roughly 1 in 15,000 to 20,000 births, and the worldwide prevalence across all types is about 6 to 7 per 100,000 people. Mild forms are underdiagnosed, so the true rate may be somewhat higher (StatPearls, Osteogenesis Imperfecta).
Why is positioning and handling so important in OI?
Because bones fracture from minimal force, careful handling, positioning, and fracture prevention drive the entire plan of care. Lift and support the infant or child gently and evenly, avoid pulling or twisting limbs, and teach caregivers safe handling to prevent new fractures.
Is there a cure for osteogenesis imperfecta?
There is no cure. Management is supportive and aims to reduce fractures, control pain, preserve mobility, and maximize function. This includes bisphosphonates to strengthen bone, physical therapy for joint mobility and muscle strength, orthopedic surgery such as rodding when needed, and dental and nutritional care.
Can a person with osteogenesis imperfecta have an unaffected child?
It depends on the inheritance pattern. Autosomal dominant forms carry about a 50% chance of passing the variant to each child, while recessive forms require a variant from both parents. Genetic counseling helps families understand recurrence risk and testing options (GeneReviews).