Osteogenesis imperfecta in cats

© Evason, MD et al http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1800945

Osteogenesis imperfecta is a disorder leading to bone fragility. This disorder is most commonly caused by a mutation in 1 of the 2 genes coding for type 1 collagen ( 1– 4); which is the most abundant structural component of skin, bone, cartilage, tendons, and ligaments. This structural collagen defect leads to bone fragility and pathological fractures. Osteogenesis imperfecta is a well-characterized heritable disorder in humans and can vary in severity ( 4). In humans, there are several distinct clinical variants of the disease, with greater than 90% of the cases caused by autosomal dominant mutations in the genes coding for type 1 collagen ( 1– 4). All types are characterized by fragile bones that shatter spontaneously or secondarily to minimal trauma. Osteogenesis imperfecta has been documented in the dog ( 1– 3) and there is a single report of presumed osteogenesis imperfecta in a cat ( 5).

The clinical features of osteogenesis imperfecta in small animals have typically included lameness and multiple fractures occurring with minimal or no associated trauma ( 1– 3, 5). Onset of clinical disease is most common in puppies and kittens between 10 and 18 wk of age ( 1– 3, 5). Most of the fractures have been reported to occur when young animals jump to the floor from a low height, as from a bed or a chair ( 1– 3). Radiographs reveal long bone cortices that are less opaque than normal and with pathological fractures. It is not uncommon to find concurrent evidence of old healing fractures. Hematologic values, serum chemical, and measured hormone concentrations are normal, making metabolic disorders, such as primary and secondary hyperparathyroidism, unlikely.

Because the organic matrix of dentine is composed primarily of type 1 collagen, animals with osteogenesis imperfecta also commonly have abnormal dentine development in the teeth, leading to dentinogenesis imperfecta ( 3). The teeth in these young animals have severe thinning of the dentine layer, leading to a translucent appearance, pink discoloration, and multiple tooth fractures ( 1– 3, 5). This appears quite distinct from the brown, yellow, or gray staining that can occur with tetracycline administration ( 6). Not all dogs with osteogenesis imperfecta have had dentinogenesis imperfecta at the time of initial presentation for pathologic fractures ( 1). This may develop later in the course of disease, as in the kitten reported here.

No clinical dermatologic abnormalities are noted in humans and animals affected with osteogenesis imperfecta, and microscopic examination of skin is normal, despite the abundance of type 1 collagen present in skin ( 1– 5, 7). Analysis of type 1 collagen obtained from cultured skin fibroblasts can, however, be used to achieve a definitive diagnosis ( 1, 2). This test was unavailable at the time this kitten was evaluated.

Once a diagnosis of osteogenesis imperfecta is suspected in cats, therapy normally requires using vitamin C, which is essential in collagen formation and tissue repair ( 6, 7). Initiating therapy with alendronate, was also recommended, since bisphos-phonates are synthetic analogs of inorganic pyrophosphate that inhibit osteoclast activity, thus decreasing bone resorption ( 1, 8, 9). They may also promote architectural changes in cancellous bone, reducing fracture risk ( 8, 9). These drugs have been effective in some post menopausal women with osteoporosis, increasing mineral density and decreasing pathological fractures ( 1, 8, 9). Their use is also being investigated in the treatment of hypercalcemia of malignancy and the treatment of lytic skeletal metastases in dogs ( 9). Bisphosphonates administered to children with osteogenesis imperfecta over a 2-year period were effective in increasing bone mineral density and decreasing the frequency of fractures ( 1). The effectiveness of bisphosphonates in treating osteogenesis imperfecta in dogs and cats has not been evaluated.

Although osteogenesis imperfecta is rare in cats and dogs, it should be considered as a differential diagnosis whenever a puppy or kitten is presented for multiple pathological bone fractures. Historical and biochemical evaluation can be used to rule out other causes of multiple fractures or bone fragility. Clinical evidence of concurrent dentinogenesis imperfecta can raise the index of suspicion of this disorder; however, definitive diagnosis requires analysis of cultured skin fibroblasts, a test that is not readily available.

	Figure 3.77 A lateral radiograph of the lumbar spine, pelvis, and hind legs of a cat in which there is a loss of bone density and a pathologic fracture of the fifth lumbar vertebra. These findings are the result of congenital osteogenesis imperfecta-like disease.
	Figure 3-76 shows the radius and ulna of a dog in which there are pathologic fractures of the distal diaphyses of both bones. The fractures were the result of a generalized loss of bone density caused by osteogenesis imperfecta.