Topic #4: Legg Calve Perthes Disease (LCP) (Aseptic femoral head necrosis)
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1 Topic #4: Legg Calve Perthes Disease (LCP) (Aseptic femoral head necrosis) Young Westies, and other breeds of purebred dogs, can develop a debilitating condition in which the bones that form the top of the hind leg (the femurs) deteriorate. This condition also occurs in children and was first diagnosed in 1910 by the physician/scientists who the disease is named after. Bone growth and skeletal maturation All dogs are born with an immature skeletal system. Healthy developing long bones, like those in the legs, grow by way of a process known as endochondral ossification. When animals are first developing their skeleton (this occurs during gestation [pregnancy]), all of the bone is made entirely of cartilage. As growth and maturation occur, the cartilage that forms the modeling structures becomes calcified from the center of the bone outward. As this occurs, a thin layer of bone is laid around the outside of the shaft of the bone (also known as the diaphysis). Bone marrow, containing stem cells and maturing blood cells) develops inside the forming bone, as are blood vessels. Eventually, immature bone is formed in as a lacey, woven matrix for further development. The bone ends, or epiphyses, are still made of cartilage and continue to grow. The area where the cartilage epiphysis meets the boney diaphysis meet is known as the growth plate. The bone grows by way of replacing cartilage with bone at the growth plate and within the epiphysis, which has its own center of bone development, or ossification. Eventually, immature woven bone is remodeled into mature regular bone. When the dog is mature, the growth plates slow down or cease activity, and bones stop growing. Depending on the breed, this maturation of the skeleton and bones generally occurs between 1 2 years of age. It is important to realize that all bone, in animals of any age, is alive made up of cells, using nutrients and oxygen from the circulation, responding to demands for support and strength, constantly renewing itself, and capable of repairing injuries, like fractures. Bone growth is a very complex and well regulated activity. The genome of each dog contains instructions for bone and cartilage cells, for the organization of these cells into bones, and for the orderly growth of the skeleton to support the dog s activities. The proper formation of bone is heavily dependent on an adequate supply of nutrients such as protein, calcium and several other minerals, as well as the activity of one or more vitamins and hormones. Bone formation is also controlled by the growth of blood vessels in and around bone and in the covering of bone, the periosteum.
2 The pathogenesis of LCP disease As noted above, bone is a living tissue and, like other body tissues, is vulnerable to all kinds of diseases, ranging from developmental and congenital problems to cancer, infection, metabolic, or biochemical problems. Legg Calvé Perthes is classified as a developmental orthopedic (bone related) disease. Each stage of bone development requires healthy blood vessels to bring nutrients, including oxygen, to the working cells and carry waste from those cells. In LCP disease, blood flow to developing bone is disrupted. Young cartilage and bone cells don t get the nutrients they need, and consequently they die. As a result of this cell death (also known as necrosis ), the head(s) of the femurs do not properly develop and are weak. As a result of this boney weakness, the heads of the femurs in dogs with LCP may fracture, even with normal activity. The blood flow problem that seem to be the inciting cause of LCP appears to be temporary, because the bone will eventually heal itself and remodel. However, this remodeling leaves the femoral head deformed and leads to degenerative joint disease and pain for the patient. It is not known exactly what causes the disruption in blood flow to the femoral head region, despite the fact this disease has been observed in people and in animals for nearly a century. Theories include destruction of the growth plate, repeated blockage of blood flow, compression of the veins, effects of sex hormones (in people, boys are more affected than girls), infection of the hip joint or increased pressure in the joint. A genetic component is suspected because several breeds are overrepresented in presentation, including Westies. Clinical signs Legg Calvé Perthes disease typically affects small breed dogs. Onset is usually between four and eleven months and males and females are at equal risk. Only 12 16% of dogs have both legs affected. Patients experiencing these bone changes will be irritable, may limp and may be in pain. As the disease progresses, the gluteal and quadriceps muscles may atrophy, making them appear smaller. In 6 8 weeks, the patient may not put weight on the affected limb at all. Diagnosis The principal diagnostic tool for Legg Calvé Perthes disease is an x ray or radiograph. Veterinarians look for increased joint space in the hip of the problem leg, decreased density of the bone (giving a grey appearance instead of a strong white), subtle or overt fracture of the head of the femur, and possible dislocation of the hip joint (subluxation). In early stages, patients will experience pain when
3 a veterinarian manipulates the limb outward away from the body (abducts the limb), restricted limb motion, and there may be a crinkly or grating feeling or sound in the hip joint (crepitus). In the radiographic image of a dog, shown to the left, there is a very good example of aseptic necrosis of the femoral head. This radiograph is from a 10 month old dog (not a Westie) with the typical radiographic signs. At the arrow, there is degeneration of the top of the femur and detachment (subluxation) from the hip socket. (This radiograph is courtesy of Dr. Chris Ober). Treatment/Prognosis/Prevention The accepted treatment for Legg Calvé Perthes is surgical removal of the femoral head and neck, the section of bone right under the head. Once the surgery is completed, aftercare involves exercising the dog s legs with a gentle program of exercise that may include walking, and then running and swimming. The exercise encourages the growth of a fibrous false joint, also known as a pseudoarthrosis. Scar tissue actually takes the place of the head of the femur and fits into the hip bone. While this procedure may seem pretty dramatic, patients can have full use of the leg in as little as four weeks. This is dependent, however, on the degree of bony changes in the femur and hip before surgery, and may vary by individuals. Surgery relieves the pain and lameness in dogs suffering from Legg Calvé Perthes in % of cases, regardless of the progression of the condition or age of the patient. Proper surgical technique is critical; many veterinarians are very experienced with the procedure of femoral head resection. Without surgery, dogs with LCP disease patients can be kept comfortable with rest, the judicious use of anti inflammatory drugs and medication to control pain, and attention proper nutrition (to promote natural healing). Lameness resolves with this course of treatment in less than 25% of patients. Recent Research on Legg Calvé Perthes Disease Unfortunately, there has not been much research on canine Legg Calvé Perthes disease in recent years. It was discovered to exist in dogs in the 1960s, but only a handful of studies have been done to explore the causes and treatments for the condition in the last decade.
4 As recently as 2002, researchers looked at the prevalence of developmental orthopedic disorders in dogs for the first time. By exhaustively reviewing veterinary teaching hospital medical records from 1986 to 1995, veterinary researchers were able to rank susceptibility of breeds for being diagnosed with twelve developmental orthopedic disorders. West Highland White Terriers are 33.2 times more likely to have Legg Calvé Perthes than mixed breed dogs. Of the breeds that had been diagnosed with the condition, Westies were the seventh most represented breed. While breed susceptibility suggests a genetic component to any disease, the researchers pointed out that the ultimate method to characterize genetic etiology for a disease is the determination of its heritability and mode of inheritance (Lefond, et al, 2002). This means that mapping the genome of Westies would give us the best opportunity to see what mutations are associated with the development of the disease and how it is inherited. Legg Calvé Perthes has been linked to overactive blood clotting in humans. Clotted blood can create thrombosis, a traveling clot that blocks blood vessels and causes the tissues around the block area to go without nutrients and die. A 1999 study examined the clotting factors in 18 dogs with Legg Calvé Perthes but found clotting to be entirely normal (Bertram, et al, 1999). Based on this work, it appears that factors other than clotting are contributing to the condition in dogs. A promising new diagnostic tool for early detection of LCP disease has come out of human medicine (Isola, et al, 2005). Dual energy x ray absorptiometry is a technique for imaging precise bone mineral density. It can be used for humans and dogs. Quantifying bone mineral density allows veterinarians to track the progress of bone weakening diseases and potentially diagnose such problems earlier. A 2005 study found no significant difference in mineral density between dogs good and bad legs, but attributed this to bone remodeling in the bad leg. Bone remodeling may not be easily seen with conventional radiographic methods used in routine veterinary practice. A better understanding of why patients with Legg Calvé Perthes have blood flow disruptions could potentially greatly contribute to our ability to treat the disorder in a less invasive way than surgery. More research in the area of genetics and genomics would potentially help us wipe out the disorder and keep Westies from experiencing the pain associated with it. Reference articles on LCP disease, with selected short summaries, For further reading
5 Bertram, B, Leeb, T, Jansen, S, Kopp, T, Analysis of blood clotting factor activities in canine Legg Calve Perthes Disease Journal of Veterinary Internal Medicine 13: , 1999 Based on the theory that ischemia results from vascular compression or occlusion and the link to hypercoagulability in humans, researchers looked at mediators of thrombosis. All dogs (18) studied had normal plasma clotting factors and clotting activity. The results of this study appear to indicate that hypercoagulability/thrombosis is not a primary factor in the development of LCP disease in dogs. Demko, J, McLaughlin, R, Developmental orthopedic disease The Veterinary Clinics of North America Small Animal Practice 35: , 2005 Overview of several diseases, well laid out for differential diagnoses. This work defines LCP (avascular necrosis of the femoral head) as a disease of young dogs, 4 11 months old at the time of onset, and as a bilateral (both hips) disease in 12 16% of dogs studied. This work also summarizes current theories and possible causes of LCP disease: Compromise of vessels entering epiphysis, Synovitis Sustained abnormal limb position leading to increase in intra articular press collapsing veins Transient vascular problem because of cyclical reparative fibrosis and osteoblastic activity after initial phase. These authors also outlined current effects and outcomes of treatment. Conservative treatment: rest, pain killers, good food. Lameness associated with disease resolves in less than 25% of dogs managed conservatively. Surgery relieves pain and lameness in % regardless of progression and age. Proper surgery technique is critical. A good reference radiograph of an affected animal is shown on pg of this reference. Isola, M, Zotti, A, Carnier, E, Baroni, E, Busetto, R, Dual energy x ray absorptiometry in canine Legg Calve Perthes Disease Journal of Veterinary Medicine 52:407 10, 2005 Used dual energy x ray absorptiometry (recent advancement in imaging for precise bone mineral density measurement for humans and dogs) to quantify bone changes produced by osteonecrosis in the proximal femur on the affected and unaffected side. Describes radiographic signs/stages used for diagnosis. Found no differences between good and bad legs and concluded that even when
6 radiographic changes are seen, the overall mineral density is not affected. This could be due to bone remodeling that can t be detected in an x ray. LeFond, E, Breur, G, Austin, C, Breed susceptibility of developmental orthopedic diseases in dogs Journal of the American Animal Hospital Association 38: , 2002 Epidemiological study on breed risk for 12 developmental orthopedic diseases in dogs. Examined medical records from veterinary teaching hospitals for the period of Differential analysis of breed susceptibility suggests genetic predisposition. Westies have odds ratio of 1,313/1 for craniomandibular osteopathy, the only breed to have a higher incidence of that disease. They have an odds ratio of 33.2/1 for Legg Calve Perthes, the 7 th highest ratio for that disease. They have a 1.7/1 ratio for panosteitis (acquired self limiting inflammatory condition of undetermined cause that affects the diaphyseal and metaphyseal regions of long bones in young dogs) and 1.8/1 for patella luxation. The ultimate method to characterize genetic etiology for a disease is the determination of its heritability and mode of inheritance. Liu, S, H, T, The role of venous hypertension in the pathogenesis of Legg Perthes Disease The Journal of Bone and Joint Surgery 73 A (2): , 1991 This study examined 32 human patients with Legg Perthes and looked at the venography, intra osseous and intra articular pressures, arthrography and bone imaging. They determined that the difference in arterial blood flow between good and bad femoral heads was not statistically significant, but that there was a marked disturbance of the venous drainage, and, higher intra osseous pressure and intra articular pressure in the bad (affected) hip compared to non affected hips. Other general reference articles: Fujikawa K, Comparative vascular anatomy of the hip of the miniature dog and of the normal size mongrel 38(3):159 65, 1991 Naito M, Schoenecker PL, Owen JH, Sugioka Y, Acute effect of traction, compression, and hip joint tamponade on blood flow of the femoral head: an experimental model Journal of Orthopedic Research 10(6):800 6, 1992
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