Genetic Welfare Problems of Companion Animals

Scottish Deerhound

Osteosarcoma

Related terms: bone tumour, bone cancer, bone neoplasia

Outline: Scottish deerhounds are predisposed to developing osteosarcoma (bone tumours). It has been estimated that more than 15% of animals of this breed become affected during their lifetime. The disease can occur at any age but the average age at diagnosis is 7.7 years. It is an aggressively malignant form of cancer which causes almost 100% mortality unless successfully treated, and treatment is successful in only about 10% of cases. It causes severe and progressive pain which can be difficult or impossible to alleviate. The disease in Scottish deerhounds is associated with a single dominant gene. It seems likely that the prevalence may be reduced by breeding only from lines that do not have a history of the disease.

Summary of Information

(for more information click on the links below)

1. Brief description

Osteosarcoma is the most common bone tumour in dogs, accounting for 80% to 85% of primary bone tumours in the species (Shell & Rosenthal 2007, Modiano 2010), and 90% of bone tumours in large and giant dog breeds (Blackwood 1999). It accounts for 5% of all tumours in dogs (Blackwood 1999).

It is a cancer mainly of middle-aged to older dogs. Those breeds that weigh over 40kg account for 29% of cases whilst breeds weighing less than 15kg account for fewer than 5% (Milner 2004).

Osteosarcoma is a primary bone tumour that develops from bone-forming cells called osteoblasts (Milner 2004). Osteosarcomas can occur anywhere in the dog’s skeleton, and sometimes elsewhere in the body (Shell & Rosenthal 2007). They usually arise in the medullary cavity (the cavity which contains the bone marrow) of long bones in the areas at which the shaft meets the end of the bone - the metaphyses (Ehrhart & Fan 2009). The most common sites for these tumours are the humerus (upper arm) bone just below the shoulder, the forelimb above the carpal (wrist) area and close to, and above or below, the stifle (knee) (Shell & Rosenthal 2007, Ehrhart & Fan 2009). Osteosarcoma is highly invasive tumour that spreads rapidly. The most common site to which it spreads (or metastasises) is the lungs, although it may spread elsewhere (Blackwood 1999 Ehrhart & Fan 2009).

Pain from tumour invasion of the bone is the most significant clinical sign, and as the limb bones are usually affected, the dogs become lame. The pain is major and often rapidly becomes resistant to control using the usual pain-killers (so called refractory pain, Ehrhart & Fan [2009]). Following the development of chronic pain and lameness, affected dogs may show significant pain on gentle touching or manipulation of the limb as the conditions of hyperalgesia (extreme sensitivity to pain) and allodynia (skin pain due to something which would not normally cause pain e.g. being touched) may develop (Ehrhart & Fan 2009). There will often be swelling of the limb at the site of the tumour and it may feel hot to the touch (Milner 2004, Ehrhart & Fan 2009). As metastases occur (sites where the tumour has spread to, also called secondaries), other signs of disease are seen eg weight loss, inappetance and breathing problems, due to damage to other organs.

The outlook for dogs with osteosarcoma is poor despite the availability of various treatment options, as in 90% of cases the tumour has spread to other sites by the time of diagnosis (Blackwood 1999, Shell & Rosenthal 2007). Without treatment the mortality rate is 100% (Milner 2004).

2. Intensity of welfare impact

Osteosarcoma has a huge impact on the welfare of affected dogs as it rapidly causes major bone pain which is constant unless it can be successfully alleviated. The pain is often resistant to control through the use of the usual pain-killing drugs so its relief is not simple (Ehrhart & Fan 2009). Euthanasia is frequently necessary due to disease progression or refractory pain.

3. Duration of welfare impact

Usually this is a condition of middle-aged to older dogs, though it can occur at any age. All affected animals will die without treatment, usually within a few months (Modiano 2010). Only 10% of affected dogs are cured but treatment can prolong survival times (Ehrhart & Fan 2009).

4. Number of animals affected

It has been suggested that over 15% of Scottish deerhounds develop osteosarcoma (Dillberger 1996, Ru et al 1998).

5. Diagnosis

The diagnosis of osteosarcoma is confirmed by radiographs (X-rays) and biopsy. Further diagnostic tests may be necessary to help determine the stage of the disease, the most appropriate treatment protocol and for monitoring response to treatment.

6. Genetics

Osteosarcoma in the Scottish deerhound was found to have a heritability of 0.69 ie 69% of the risk of developing the disease is due to genetic factors (Phillips et al 2007). The condition appears to be inherited as a single dominant gene (Phillips et al 2007). Dogs which have at least one copy of the mutant gene have a greater than 75% chance of developing the disease. Scottish deerhounds without the mutant gene have a less than 5% chance of developing the condition (Phillips et al 2007).

7. How do you know if an animal is a carrier or likely to become affected?

There are no tests to determine which animals are likely to develop osteosarcoma. As indicated above, those with the mutant gene have a 75% chance of developing the disease. However, it may not occur until the dog has been bred from, so dogs that show no signs of the disease can pass the genetic predisposition for the disease on to offspring.

To reduce the prevalence of the disease, only dogs from lineages with little or no history of osteosarcoma should be used for breeding.

8. Methods and prospects for elimination of the problem

Development of a screening test for the causal gene is likely to be helpful in trying to eradicate this condition from the Scottish deerhound breed. As far as we are aware there are no breeding schemes, at present, aimed at trying to reduce its prevalence.

For further details about this condition, please click on the following:
(these link to items down this page)

• Clinical and pathological effects
• Intensity of welfare impact
• Duration of welfare impact
• Number of animals affected
• Diagnosis
• Genetics
• How do you know if an animal is a carrier or likely to become affected?
• Methods and prospects for elimination of the problem
• Acknowledgements
• References

1. Clinical and pathological effects

Osteosarcoma is the most common bone tumour of dogs, accounting for 80% to 85% of primary bone tumour cases in the species (Shell & Rosenthal 2007, Modiano 2010), and 90% of bone tumours in large breeds (Blackwood 1999). It accounts for 5% of all tumours in dogs (Blackwood 1999).

It is a cancer mainly of middle-aged to older dogs. Those breeds that weigh over 40kg account for 29% of cases whilst breeds weighing less than 15kg account for fewer than 5% (Milner 2004).

Bone cancers can either be primary - starting from cells within the bone tissue - or secondary (or metastatic), having started elsewhere in the body and spread to bone. Osteosarcoma is a primary bone tumour which develops from bone-forming cells called osteoblasts (Milner 2004). Normal bones contain various cells and the osteoblasts are responsible for forming the new bone matrix called osteoid - the non-cellular substance in which surrounds the cells.

In tumour cells, their genetic material - the DNA (deoxyribonucleic acid) - has become damaged and the cells become abnormal in both structure and function. The causes of the genetic damage are varied. It may follow damage to the DNA by trauma, viruses or radiation for example and inherited traits may make the cells more vulnerable to becoming neoplastic (cancerous).

In osteosarcoma, neoplastic osteoblasts produce abnormal osteoid and may also sometimes produce cartilage and collagen (Modiano 2010). These cellsbecome invasive – prone to spreading into neighbouring tissue - and canine osteosarcomas are usually described as aggressively malignant tumours (Blackwood 1999, Milner 2004, Modiano 2010). They grow into, invade, and damage surrounding tissues and spread, through the blood stream, to distant parts of the body where they continue to grow as metastases causing further damage to these tissues.

The aetiology (cause) of osteosarcoma in dogs is not fully understood (Blackwood 1999) but the various risk factors listed below are thought to play a role.

1. The size and weight of the dog.  Dogs of large or giant breeds are at significantly increased risk of developing the disease (Kirkwood 1985, Milner 2004, Shell & Rosenthal 2007). Shell and Rosenthal (2007) suggest that this is related to bone length, however Milner (2004) suggested that prevalence correlates most closely with body mass. The reason for the association with size or weight is not clear but it is hypothesised that it may be linked with rapid, early bone growth and/or increased stress in weight-bearing bones leading to micro-fractures within the bone tissue (Blackwood 1999, Dickerson et al 2001, Chun & de Lorimier 2003, Liptak et al 2004). Both lead to increased cell turnover rate and possibly the increased chance of cell gene mutations.
2. Breed. Dogs of some large and giant breeds including Scottish deerhounds, Great Danes, Rottweilers, St Bernard’s, Irish wolfhounds, Borzoi and greyhounds are considered to be particularly predisposed to osteosarcoma. In Scottish deerhounds a specific genetic influence has been identified (Phillips et al 2007, Modiano 2010).
3. Gender. Some studies have shown males to be at slightly increased risk of the condition (Shell & Rosenthal 2007). Modiano (2010) suggested that, in general, male dogs have a 20 to 50% greater risk than females, but Phillips et al (2007) found, in contrast, a higher incidence in female Scottish deerhounds. They suspect that this finding was a reflection of disproportionate high rate of mortality in males due to other causes before osteosarcoma developed.
4. Previous fractures or orthopaedic interventions. These seem to increase the risk, particularly in cases in which there were complications with bone repair and healing (Blackwood 1999), or which involved surgical implants or bone infections (Milner 2004).
5. Neuter status. Some studies have suggested that neutered animals are more at risk than entire ones (Cooley et al 2002, Ru et al 1998).

Canine osteosarcomas usually arise in the medullary (marrow) cavities of the long bones in the areas where the shafts meet the ends of the bones – the metaphyses (Ehrhart & Fan 2009). The metaphyses are the zones in which growth in bone length occurs.

Figure 1. The metaphyses regions of the medullary cavity (located roughly between the epiphyses and diaphysis areas in the diagram), are the areas of bone most commonly affected by osteosarcomas in the dog.

(Image available from Wikipedia: http://en.wikipedia.org/wiki/Bone) 

The most common sites for these tumours are the lower (distal) end of the radius (the main bone of the forelimb below the elbow), the upper (proximal) end of the humerus (the upper forelimb bone) , the lower distal end of the femur (the upper hind leg bone) and the upper end of the tibia (the bone below the stifle/knee) (Shell & Rosenthal 2007, Ehrhart & Fan 2009). Although the bones of the limbs are most often affected, osteosarcomas can occur anywhere in the skeleton and sometimes elsewhere in the body (Shell & Rosenthal 2007).

Figure 2. The areas of the dog most commonly affected by osteosarcomas.

(Image property of http://www.marvistavet.com, to whom we are grateful for permission to reproduce it here).

The signs caused by the tumour depend both on its size and primary location and the size and location of any secondary metastases. The most common site for metastases is the lungs, but the tumour may spread elsewhere (Blackwood 1999, Ehrhart & Fan 2009). Although the tumours tend to start in the medullary cavities of bones, they rapidly invade the hard cortical bone surrounding them and cause significant destruction of it. This can lead to fractures, but even in the absence of fractures the tumour causes pain.

Figure 3. An x-ray of canine osteosarcoma in the distal radius. The difference in bone consistency around the joint (red arrow) compared to higher up the radius is due to the presence of the tumour within the outer cortical bone as well as the inner medullary cavity, resulting in pain.

(Image property of www.marvistavet.com, to whom we are grateful for permission to reproduce it here).

Figure 4. An x-ray of the distal femur of a dog with osteosarcoma. The dark area of the femur (red arrow) indicates the damage caused by the tumour within the bone.  These tumours cause pain. (Image available from Wikipedia: www.wikipedia.org/ osteosarcoma)

When limb bones are affected, there is lameness. Sometimes the pain seems to coincide with minor trauma such as can occur in jumping or rough play and it often responds temporarily to painkillers and rest. However, in these cases, the bone pain returns rapidly and is often then refractory: that is, it does not respond to the frequently used painkillers (Ehrhart & Fan 2009). Often, following the development of this chronic (long-term) pain and lameness, dogs may show significant pain on gentle touching or manipulation of the affected limb as the conditions of hyperalgesia (extreme sensitivity to pain) and allodynia (skin pain due to a gentle stimulus which would not normally cause pain) develop (Ehrhart & Fan 2009).

As well as the significant pain they cause, there will often be swelling of the limb at the site of the tumour and it may feel hot to the touch (Milner 2004, Ehrhart & Fan 2009). As metastatic spread occurs to other parts of the body, signs of disease due to damage to other organs develop. The dogs will generally deteriorate in their demeanour and attitude to life and suffer weight loss and inappetance. Breathing problems may occur if the lungs are affected.

The outlook for dogs with osteosarcoma is poor. Due to the highly malignant nature of the tumour, the mortality rate is 100% without treatment (Milner 2004). A complete cure is achieved in less than 10% of cases (Ehrhart & Fan 2009) as in 90%, the tumour has spread to other parts of the body (secondaries) by the time of diagnosis (Blackwood 1999, Shell & Rosenthal 2007).

A variety of treatments have been tried, including limb amputation, limb-sparing surgeries, various chemotherapy protocols, and radiotherapy. Some of these treatments are aimed at a cure or extension of symptom-free survival. Others are aimed at relieving symptoms, particularly the pain. Despite all the various treatment options, the prognosis (outlook) for individuals with osteosarcoma is poor. A recent study suggested median survival times ranged from three months to one year and that fewer than 20% of dogs survived for more than two years after initial diagnosis, whatever their treatment protocol (Selvarajah & Kirpensteijn 2010). Most of these treatment modalities and other newer research treatments, which may show promise, such as immunotherapy and therapeutic radiopharmaceutical agents are available only from specialist veterinary oncologists (cancer specialists) at referral centres (Ehrhart & Fan 2009). The standard treatment protocol, certainly within the USA, tends to be surgery with chemotherapy (Modiano 2010).  Apparent spontaneous regression (disappearance) of the osteosarcoma has been reported in four cases (Mehl et al 2001).

Deciding the appropriate treatment course for an individual dog is complex and owners are recommended to seek specialist veterinary guidance – the ability to control the animal’s pain and suffering must be central to any decision making process.

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2. Intensity of welfare impact

Osteosarcoma has a huge impact on the welfare of affected dogs. It rapidly causes major bone pain which is constant unless it can be alleviated. The pain is often difficult or impossible to relieve using the usual painkilling drugs, so control is not simple but it often responds, at least for a time, to radiation therapy (Ehrhart & Fan 2009). Unfortunately, dogs also often develop excessive sensitivity (hyperalgesia and allodynia) to touch or manipulation of the affected limb or area (Ehrhart & Fan 2009). Euthanasia, on humane grounds, will be necessary for most affected dogs at some stage.

Treatments can have adverse welfare impacts. Some dogs may be stressed by repeated visits to the vet and treatments may involve major surgery, regular radiation treatment or injections of chemotherapeutic agents. Some of these procedures may cause pain as the affected area is manipulated and treated. Some chemotherapeutic drugs cause significant side effects which affect welfare: eg cisplatin can cause kidney damage and doxorubicin can worsen some heart conditions (Ramsey 2011a, 2011b).

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3. Duration of welfare impact

Osteosarcoma is usually a disease of middle-aged to older dogs, with the average age of onset at seven years, but it can occur at any age and there may be a small peak of cases around the age of eighteen months (Shell & Rosenthal 2007). The average age at which Scottish deerhounds develop the disease was found to be 7 years for males and 8.1 years for females with an overall mean age of 7.7 years, but with a range from 2 to 13.9 years (Phillips et al 2007). Osteosarcoma causes 100% mortality, usually within a few months, if not treated, and only 10% of dogs treated aggressively are cured (Ehrhart & Fan 2009). The disease causes constant and progressive pain until death unless treatment is successful.

In 90% of dogs the cancer has spread by the time of diagnosis. Survival times for these animals range from a few days to a few years with the median survival time being 76 days from diagnosis, but dogs having both chemotherapy and radiation therapy may live longer (Boston et al 2006). Selcarajah & Kirpensteijn (2010) suggested longer median survival times ranging from 3 months to 1 year and but that less than 20% of dogs survive for more than 2 years after the diagnosis, whatever the treatment protocol.

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4. Number of animals affected

Scottish deerhounds are considered to be at very high risk of osteosarcoma; it has been suggested that there is a prevalence of 150 cases per 1000 dogs in this breed (ie 15%). This is much greater than the background prevalence across all dog breeds, which is7 cases per 100,000 dogs (Dillberger 1996, Ru et al 1998).

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5. Diagnosis

Osteosarcoma may be suspected in a Scottish deerhound showing chronic pain with a painful swelling in one of the characteristic locations, in a long bone, and is usually confirmed by radiography (x-rays) of the area and a biopsy of the lesion for microscopic examination (Shell & Rosenthal 2007, Ehrhart & Fan 2009).

As rapid metastatic spread usually occurs, other diagnostic tests will be done to evaluate the stage of the disease and help decide the most appropriate treatment options. These tests may include radiographs of the chest, ultrasound examinations of abdominal organs and nuclear scintigraphy (X-rays taken after injection of a radioactive dye which concentrates in tumour cells) to check for lung or bone metastases (Ehrhart & Fan 2009). Blood tests to measure total and bone alkaline phosphatase may help determine the prognosis. Alkaline phosphatise is an enzyme released from bone cells when they are being damaged – high levels indicate severe bone damage and suggest  survival time may be limited (Shell & Rosenthal 2007).

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6. Genetics

Osteosarcoma in the Scottish deerhound was found to have a heritability of 0.69 ie 69% of the risk of is due to genetic factors (Phillips et al 2007). The condition appears to be associated with a single dominant gene (Phillips et al 2007). Dogs which have at least one copy of this mutant gene have a greater than 75% chance of developing osteosarcoma, whereas those that do not have this gene have a less than 5% chance of developing it (Phillips et al 2007).

Recently this gene for the disease (OSA1) has been tracked down to a locus in the dog’s DNA called CFA34. The precise location of the gene has not yet been identified but research is ongoing to identify the gene and develop a genetic screening test for the cancer in Scottish deerhounds (Phillips et al 2010).

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7. How do you know if an animal is a carrier or likely to become affected?

Presently, there are no tests to determine which animals are likely to develop osteosarcoma. As indicated above, those with the mutant gene have a 75% chance of developing the disease. However, it may not occur until the dog has been bred from, so dogs that show no signs of the disease can pass the genetic predisposition for the disease on to offspring.

To reduce the prevalence of the disease, only dogs from lineages with little or no history of osteosarcoma should be used for breeding. However, this may be difficult because of the high prevalence of the disease in this breed.

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8. Methods and prospects for elimination of the problem

We are unaware of any formal schemes aimed at tackling the high prevalence of osteosarcoma in Scottish deerhounds, although the Scottish Deerhound Club of America encourages breeders and owners to complete a breed health survey questionnaire to gather data to inform research efforts (see http://www.deerhound.org/health_2011survey.htm).

Affected dogs should not be used for breeding. The problem is that most dogs have passed breeding age before developing the condition, and in some cases the parents may develop disease after their offspring’s breeding age has also passed. Ideally dogs with affected relatives should not be bred from. The identification of the gene and development of a screening test would be likely to be helpful in tackling the problem and it is hoped that efforts to develop a test will be successful. 

It is likely that significant numbers of Scottish deerhounds have the causal gene – over 15% of dogs develop the condition and it is likely that others have the gene but die of other causes before developing the cancer. Tackling the problem may therefore mean excluding many from the breeding population. Narrowing the gene pool may result in increased risk of other genetic conditions such as dilated cardiomyopathy and gastric dilatation-volvulus syndrome, to which the breed has known predispositions. These risks must also be considered in breeding strategy and it may be that out-crossing Scottish deerhounds to other breeds free of the condition may be necessary.

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9. Acknowledgements

UFAW is grateful to Rosie Godfrey BVetMed MRCVS and David Godfrey BVetMed FRCVS for their work in compiling this section and to Stephanie Kaufman for assistance in illustrating it.

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10. References

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Kennel Club (2010) The BVA /KC Elbow Dysplasia Scheme http://www.thekennelclub.org.uk/item/309 accessed 17th December 2010

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Meyer-Lindenberg A, Fehr M and Nolte I (2006) Co-existence of ununited anconeal process and fragmented coronoid process of the ulna in the dog. Journal of Small Animal Medicine 47: 61-5

Sampson J (2006) What is required for breeding programmes or Molecular technologies to make impact on the prevalence and incidence of elbow dysplasia in dogs? Proceedings of the British Veterinary Orthopaedics Association Autumn Meeting 2006. 4-5

Schwarz PD (2000) Canine elbow dysplasia. In; Kirks Current Veterinary Therapy XIII editor J.D. Bonagura. WB Saunders, Philadelphia. pp 1004

Shell L and Harasen G (2007) Ununited anconeal process. VIN Associate. (on-line) http://www.vin.com/Members/Associate/Associate.plx?DiseaseId=447. accessed 17.12.2010

Swenson L, Audell L and Hedhammar A (1997) Prevalence and heritance of and selection for elbow dysplasia in Bernese mountain dogs in Sweden and benefit: cost analysis of a screening and control programme. Journal of the American Veterinary Medical Association 210: 215-221

van Ryssen B and van Bree H (1997) Arthroscopic findings in 100 dogs with elbow lameness. Veterinary Record 140: 360-362

Worth AJ, Bridges JP and Jones G (2010) Reduction in the incidence of elbow dysplasia in four breeds of dog as measured by the New Zealand Veterinary Association scoring scheme. New Zealand Veterinary Journal 190: 5

© UFAW 2012

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