A 6-year-old boy has a history of 5 bone fractures, 3 of them occurring after only minimal trauma. His birth was unremarkable following a normal pregnancy. The patient has been in the 50th percentile for both height and weight since birth, and he has reached all developmental milestones. On physical examination, he is a pleasant, interactive child with small, malformed teeth. Further evaluation shows the finding in the image below. This patient's condition is most likely associated with impairment of which of the following processes?

Question

A 6-year-old boy has a history of 5 bone fractures, 3 of them occurring after only minimal trauma.  His birth was unremarkable following a normal pregnancy.  The patient has been in the 50th percentile for both height and weight since birth, and he has reached all developmental milestones.  On physical examination, he is a pleasant, interactive child with small, malformed teeth.  Further evaluation shows the finding in the image below.  This patient's condition is most likely associated with impairment of which of the following processes?

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11ec160b_3a5f_a22b_9249_15b5ccc92636_MD0001_00 This child has blue sclerae and a history of several fractures after only minimal trauma. These findings are suggestive of osteogenesis imperfecta (OI), a disease caused by impaired synthesis of type 1 collagen by osteoblasts. Clinical manifestations are variable and can range from mild defects to lethal disease in utero. In most patients, OI is transmitted by autosomal dominant inheritance. Type 1 collagen is the predominant collagen in osteoid (organic portion of bone matrix) and allows bone to be somewhat flexible while still maintaining strength. Type 1 collagen is also present in teeth, ligaments, skin, and sclerae. In OI, deficiency of type 1 collagen causes brittle bones that are prone to fracture. Other manifestations include blue sclerae due to the deficient connective tissue allowing transparency of underlying vessels and small, malformed teeth (dentinogenesis imperfecta). Joints can have excessive laxity, and some patients are also susceptible to bruising and hearing loss. (Choice A) Bones are formed by endochondral ossification (eg, long bones) and intramembranous ossification (eg, flat bones). Endochondral ossification involves the deposition of hyaline cartilage by chondrocytes and is impaired in achondroplasia, which is unlikely in a patient of normal stature. (Choice B) Bone matrix comprises inorganic (eg, hydroxyapatite crystals) and organic (eg, type 1 collagen) components. Osteoblasts release calcium-binding proteins (eg, osteocalcin) and phosphatases that promote bone mineralization. Defective mineralization of bone matrix is a characteristic feature of vitamin D deficiency. (Choice D) Bone remodeling strengthens and repairs bone through the removal of old bone by osteoclasts and replacement with new bone by osteoblasts. Impaired remodeling leads to osteopetrosis (denser but more fragile bones). Pathologic fractures can occur, but blue sclerae are not associated with this disorder. (Choice E) Long bones have multiple arteries that are essential for growth and maintenance. If the blood supply to the epiphysis is disrupted, the bone dies, resulting in avascular necrosis (eg, Legg-Calvé-Perthes disease). Avascular necrosis typically presents with pain and limited mobility but not pathologic fractures. Educational objective: Osteogenesis imperfecta results from defective synthesis of type 1 collagen by osteoblasts. Clinical findings include a history of fractures after only minimal trauma, blue sclerae, and small, malformed teeth. In most patients, osteogenesis imperfecta is transmitted by autosomal dominant inheritance. __________ References: Osteogenesis imperfecta. (http://www.ncbi.nlm.nih.gov/pubmed/19753756)

A 6-Year-Old Boy Has a History of 5 Bone Fractures