Hypertrophic Osteodystrophy In Great Danes May Have Genetic Link

When pain and lameness in the rear legs struck her 12-week-old mantle Great Dane puppy, "Erik," Mari Lindland was heartbroken. She knew about hypertrophic osteo­dystrophy (HOD), a skeletal disorder affecting rapidly growing large- and giant-breed puppies, but she had never experienced it firsthand.

"The veterinarian examined Erik and took X-rays, which confirmed the diagnosis of hypetrophic osteodystrophy," says Lindland, who breeds Twin Bay Danes in Traverse City, Mich. "Fortunately, the condition was caught early, and we were able to begin treatment with a good prognosis."

A painful disease, hypertrophic osteodystrophy can cause disabilities and deformities. Neither the cause of the condition nor a cure is known.

"The disease can cause so much pain that an animal is debilitated and will not or cannot eat. A dog's health deteriorates unless adequately supported," says Paul Manley D.V.M., DACVS, emeritus professor of orthopedic surgery at the University of Wisconsin-Madison School of Veterinary Medicine.

Signs of the disease include lameness, lethargy, reluctance to stand or walk, fever and loss of appetite. Painful swelling occurs at the ends of long bones, most often in the legs at the carpus (wrist), elbow and hock (ankle). The disorder can appear in puppies as young as 2 months old but generally develops between 5 and 7 months of age.

Normal long bone growth continues until dogs are 8 to 12 months old, so when HOD occurs, the growth of the bones is often affected. Great Danes do not reach their adult height until they are 12 to 15 months of age. Adult males average 34 inches tall, whereas females average 32 inches tall.

"Compared to other developmental orthopedic diseases, HOD has the earliest onset of clinical signs," says Alison N. Starr, Ph.D., research assistant professor of genetics and biochemistry at Clemson University in South Carolina. "The rapid growth experienced by puppies of large and giant breeds makes them more susceptible to skeletal disorders."

"When Great Danes are affected, they often have more severe clinical signs. For them, HOD can be extremely debilitating," Manley says.

The condition usually can be treated with medication and by avoiding overnutrition and preventing dietary imbalances. Surgery can correct extreme deformities, although some dogs will have a resulting limp, and others will completely recover. In a small number of cases, death occurs due to prolonged fever as high as 104 degrees Fahrenheit, loss of appetite or bacteria in the blood. With early diagnosis and proper treatment, many dogs affected by HOD live full, normal lives.

A 2004 survey by the Great Dane Club of America found that around 2 percent of Great Danes suffer from HOD. Other breeds at increased risk include Boxers, Chesapeake Bay Retrievers, Doberman Pinschers, German Shepherd Dogs, Irish Setters, Labrador Retrievers and Weimaraners. The prevalence in certain breeds indicates HOD may have a genetic predisposition.

Searching for a Linked Marker

Promising research at Clemson University supports the theory that HOD may have a possible genetic link. Using a single nucleotide polymorphism (SNP) chip to study DNA extracted from blood samples of affected and healthy Irish Setters, the scientists are seeking genetic similarities and differences. The AKC Canine Health Foundation is funding the two-year study.

Rather than searching for specific genes, the SNP chip will help the scientists pinpoint a genetic region linked to HOD. If a region can be identified, Starr hopes to narrow the study's focus to find a genetic mutation that causes HOD. The discovery might lead to development of a genetic test.

Starr expects to know preliminary results soon, but the research is far from over. "If we map the region for HOD to a highly gene-rich area, it may take a long time to correctly identify the mutation(s) before we can develop a test, if we can do it at all," she says.

Until more is known about the genetic basis of HOD, Starr cautions breeders. "We generally do not recommend that affected dogs be bred," she says. "If owners decide to breed a dog that had HOD as a puppy, extra care should be taken to breed to a dog with no history of the disorder."

Even though dogs can be successfully treated for HOD, the pain and potential long-term effects from the disease should deter breeders from breeding affected dogs. HOD affects a dog's growth plates, which are made of cartilage and located between the tubular part and the ends of long bones.

"Typically the cartilage in growth plates expands, then it eventually mineralizes to become bone," Manley says. "With HOD, there is a delay in mineralization of the cartilage, so the growth plate lengthens but does not differentiate into bone."

That delay in growth plate mineralization may change joint anatomy and cause angular limb deformities. "Sometimes microscopic fractures occur at the cartilage-bone junction, and there is secondary inflammation in response to these fractures, causing swelling and pain," says Manley.

A cycle of deterioration undermines the bone structures and exacerbates the disorder. "When studied microscopically, a series of events can be seen taking place within the affected bones," says Daniel A. Degner, D.V.M., DACVS, of Michigan Veterinary Specialists.

"First, the blood vessels near the growth plate become distended and bleed into the bone. Next, the bone in this region dies, is resorbed and develops microfracturing due to weakening of the bone structure. In response to this, new bone is laid on the surface of the bone."

"The areas of the long leg bones — the radius, ulna and tibia — are especially vulnerable in dogs with HOD," Starr says.

The radius and ulna comprise the foreleg between the elbow and carpus, and the tibia extends between the knee and the hock of the hind leg.

"Severe cases may result in deformities of the front and/or rear legs, and some of these may require surgical intervention," says Starr. "Left untreated, dogs may have difficulty walking and could develop early secondary osteoarthritis."

In some cases, HOD also affects the ribs, pelvis and jaw. Manley is treating a 9-month-old Great Dane that is severely affected in his skull. "In this dog, HOD made it difficult for the dog to open his mouth, but he is responding well to treatment," Manley says. "The owners have been diligent about care, and the dog has been able to re­gain some function as he has matured."

A Treatable Condition

Several theories attempt to explain the cause of HOD. They include excessive levels of dietary calcium or phos­phorus, bacterial or viral infections, a vitamin C deficiency, and an immune reaction to vaccination for distemper or other diseases.

"One study sought to link bacteria to HOD by examining blood cultures," Starr says. "The researchers were unable to identify a cause. Dietary deficiencies of vitamin C have been researched due to the similar effects of HOD and scurvy but have not been substantiated.

"A link between vaccinations and the development of HOD has been suggested since signs of HOD often show up within a few weeks of a puppy's vaccinations. This suggests that HOD may be a result of an overstimulated immune response."

A veterinarian typically prescribes anti-inflammatory medications for a dog suffering from HOD. Antibiotics also might be prescribed if bacterial infection is present. A diet change may be advised if a dog is fed a high-calcium dog food. Acute cases may require hydration via intravenous fluids, and a feeding tube might be inserted if the dog does not eat for up to five days. Monthly evaluations and radiographs are conducted to monitor progress.

"Some dogs do really well with treatment, especially the milder cases, once they reach skeletal maturity," Manley says. "Others have growth defects requiring corrective surgery to straighten bones or realign joints."

The path HOD follows is unpredict­able, as is its resolution. "Hypertrophic osteodystrophy may resolve spontaneously, as quickly as within a week," Degner says. "But, it also can be a recurrent, cyclic disease that goes on for a long time. Between 20 and 25 percent of dogs that experience HOD have a relapse."

Lindland feels fortunate that her Great Dane puppy's HOD was caught early and is being successfully managed. Erik has gone on to complete Canine Good Citizen training and is registered with Therapy Dogs International.

"Though there is a hitch in his gait, there have been no other lasting effects," Lindland says. "We were quite lucky. Erik is doing well. He is active and happy."

Owners of Great Danes Can Participate in HOD Study

Researchers at Clemson University in South Carolina have received funding from the AKC Canine Health Foundation for a two-year study to investigate a possible genetic link to hypertrophic osteodystrophy (HOD). The scientists are seeking DNA samples from healthy and affected Great Danes.

To participate in the study, owners should submit:

  • A small sample of blood collected by a veterinarian;
  • The medical history and pedigree of the dog; and
  • Copies of radiographs or other verification of diagnosis of HOD in affected dogs.

For more information, contact Alison N. Starr, Ph.D., research assistant professor at Clemson University, at astarr@clemson.edu.