OI has a very complicated pathogenesis that has yet to be fully elucidated. The pathogenesis in 90% of patients is secondary to an autosomal dominant structural or quantitative genetic mutation in COL1A1 or COL1A2 genes, which encode type I collagen. A defect in the synthesis of type I collagen can lead to bone deformities and systemic and oral maxillofacial malformations as observed in OI. The remaining 10% of etiologies include qualitative mutations affecting collagen processing, folding, cross-linking, posttranslational modifications, bone mineralization, and osteoblast development. Quantitative genetic mutations with normal collagen structure usually present with a milder form of the disease such as type I OI. In contrast, mutations affecting collagen structure can present with a lethal (type II), severe (type III), or moderate (type IV) forms.
Patients with OI commonly have brittle but hypodense bones. Their bone scan is typically characterized by diminished growth, hypermineralization, increased turnover, and disrupted bone architecture. Patients with OI are also at increased risk for cardiovascular disease, fractures, primary osteoporosis, and restrictive lung disease. Laboratory studies show vitamin D deficiency. Vitamin D supplementation improves symptoms. Patients who receive bisphosphonate therapy before closure of epiphyseal plates commonly present with the “zebra stripe sign,” which is associated with type I OI. Type V OI has a unique radiographic feature caused by calcified interosseous membranes and hypertrophic callus.
Early diagnosis and intervention can substantially improve the clinical outcome for a patient with OI. Management of these patients is multifactorial and involves caregivers of multiple specialties, including cardiology, dentistry, genetics, orthopedics, otolaryngology, and pediatrics.
Treatment includes bisphosphonates and normalizing vitamin D levels. Bisphosphonates have been associated with increased bone mass, improved bone architecture, and decreased rate of fractures. Improved clinical outcomes are most significant among infants.
Mild OI is typically treated with the oral form of bisphosphonates while moderate to severe OI is treated intravenously. Standard guidelines for bisphosphonate dosage, frequency, and time frame of treatment remain to be established. Common side effects include acute phase reaction and hypocalcemia but are not detrimental.
Surgical repairment is indicated for patients who present with recurrent fractures or severe scoliosis.
Several members of our patient’s family, including her mother, grandmother, 9 of 12 siblings, and her daughter, have OI. Her daughter, who is now 22 years old, has had a total of 17 fractures, yet none in the last 4 years.
The etiology of our patient’s urticarial dermatitis could not be determined. She was treated with a 12-day tapering course of oral prednisone, topical triamcinolone 0.1% cream, and hydroxyzine (25 mg each evening). There was complete resolution of her dermatitis without recurrence.
OI is an inborn error of metabolism often associated with defects in type I collagen synthesis. Patients typically present with brittle bones. Blue sclera is most commonly associated with type I OI; however, it has been observed, albeit less frequently, in other types of OI. The differential diagnosis of blue sclera includes not only other genetic disorders and noninherited conditions, but it also can be an adverse effect from systemic medications. The most widely used intervention in OI is intravenous bisphosphonates. Importantly, the care of patients with OI requires the combined contributions of health care workers from various specialties.