Does Chiropractic Treatment Prevent Spondylosis Deformans in Dogs?

While rigorous scientific research is the best way to evaluate most proposed medical treatments, there are circumstances in which scientific study can actually be quite misleading. Studies of implausible therapies using unreliable methods rife with uncontrolled bias serve only to create the false impression of scientific legitimacy for useless practices. The bulk of the research literature concerning homeopathy illustrates this phenomenon quite well.

One of the clearest characterizations of this problem is Dr. Harriet Hall’s description of the phenomenon of Tooth Fairy Science. Extensive controlled research can be done to evaluate the behavior of the Tooth Fairy. The relative monetary value of different teeth from children of different ages or genders, the geographic distribution of Tooth Fairy activity, and many other related variables can be analyzed, complete with complex statistics. At the end of the day, however, all this data proves nothing because the underling phenomenon being studied is imaginary. The same is often true of research into alternative medical therapies

The latest example of such Tooth fairy science is a study purporting to show that chiropractic manipulation prevents spinal spondylosis deformans in dogs. 

Halle KS, Granhus A. Veterinary Chiropractic Treatment as a Measure to Prevent the Occurrence of Spondylosis in Boxers. Vet Sci. 2021 Sep 17;8(9):199. doi: 10.3390/vetsci8090199. PMID: 34564593; PMCID: PMC8473340.

Spondylosis deformans is a condition in which new bone forms gradually in the spinal column of dogs over years. It is very common in dogs, and does not appear to cause pain or other clinical symptoms, though it can reduce the flexibility of the spine in advanced cases. Spondylosis is believed to occur due to small tears in the cartilage disks between vertebrae that, which cause inflammation and perhaps excess movement, leading to reactive bone formation. There are also genetic influences, and the condition is moderately heritable in some breeds, such as Boxers.

The theory presented in this paper is that spondylosis is caused by decreased flexibility in the spine, and that chiropractic assessment and treatment can detect this excess rigidity and correct it. The study was conducted to prove this by comparing pairs of littermates evaluated and treated by a veterinary chiropractor monthly from 8 weeks to 1 year of age. The authors reported that spondylosis was less common in the treated dogs.

There are many, many issues with this study that make its conclusions unreliable and not useful for evaluating the effects of chiropractic treatment in dogs. The most obvious, which I’ve already mentioned, is that the study is testing an imaginary method of diagnosis and treatment. Chiropractors have never been able to demonstrate that the abnormalities they claim to treat exist or that they are able to reliably detect them by physical examination.1–3 Finding supposed differences in the flexibility of specific spots in the spine is an entirely subjective process, and historically chiropractors haven’t been able to convincingly demonstrate that what they claim to identify is real.

Similarly, the physical manipulation employed by chiropractors, thee low-amplitude, high-velocity thrust,  hasn’t been shown to have meaningful beneficial effects despite decades of trying to prove this. The best we can say about chiropractic in humans is that it might have some small subjective benefits for back pain, no better than many other therapies, and even this rests on weak evidence.4 There is even less reason to believe there are meaningful effects in veterinary species. The idea that a short, hard shove against the bones of the spine once a month based on an unreliable subjective assessment of how flexible they are is going to have meaningful effects on health is pretty far-fetched, and it would take an extraordinary body of evidence to validate such a claim. 

This paper clearly does not constitute such a body of evidence. Despite plenty of opportunities for residual bias in the study design the ultimate findings only barely reached statistical significance for one dubious measure of effect. The authors report that occurrence of spondylosis was lower in treated dogs with a p-value of 0.0478, with 0.05 being the cutoff for statistical significance. None of the other statistical analyses showed any significant results. 

While a thorough explication of the methodological issues with the study is unlikely to be of interest to anyone without an unusual love of epidemiology, I will list the most significant so that the limitations of this piece of evidence can be seen. Ultimately, the fact that an imaginary diagnosis and treatment narrowly showed an effect in a study specifically designed to do so and run by investigators with a deep ideological commitment to the value of chiropractic is a classic example of how Tooth Fairy Science serves primarily to create the illusion of scientific legitimacy for therapies that are instead fundamentally pseudoscientific.

  • Placebo Control, Blinding, Randomization

One way of trying to minimize the impact of variables other than the treatment being tested on the outcome is to have patients randomly assigned to get either the treatment or an indistinguishable placebo, and to make sure that no one knows which patient is getting which so that our beliefs and expectations are less likely to influence how we evaluate or treat patients in each group. This control group in this study were littermates of the treated dogs who received no chiropractic treatment. There was no placebo control, and clearly the investigator knew which puppies were treated and which weren’t. It is likely that the owners also knew, and while the people reading the x-rays to look for spondylosis were apparently blinded to the treatment, it doesn’t appear the individuals doing the statistical analysis were (it isn’t made clear who this was or what potential biases they might have had). And while the study is described as “randomized,” there is no discussion of how this was done. Overall, then, it isn’t clear that most of the core, routine methods for controlling bias and error in a scientific study were used, and one of the most important, blinding to treatment, was not.

  • The subjects were recruited by convenience over an 11-year period. This too opens the door to lots of small decisions which, in aggregate, could influence which dogs are chosen and which group they are placed in, all of which can add up over such a long time to influence the ultimate outcome of the study. This is not at all standard scientific methodology.
  • Spondylosis was not found to be associated with sex or the presence or absence of the condition in parents. This is in conflict with most previous studies of this condition, which find both an influence of sex and a relatively high heritability. This suggests this study either looked at an unusual population or the methods led to atypical findings.
  • The dogs were assessed for spondylosis at 1 year of age. However, this condition is progressive over time and frequently emerges later in life, so whether the findings at one year were representative of the actual emergence of the condition in these dogs over the majority of their lifetime is unclear.
  • The likelihood of spondylosis varies at different sites in the spinal column. Rather than picking a particular site to treat and evaluate, the owners lumped all spondylosis at any site into “Yes” or “No” categories. This can easily misrepresent the extent and severity of the condition. In fact, the authors note that not doing this led to a statistically non-significant result. Given that the statistical analysis was not apparently done blinded, this is a perfect example of how manipulation and statistical testing of data after a study can create a significant result even if the data don’t clearly support a real difference between the groups.
  • The study was described as a “randomized case-control” study. There is actually no such thing, and this is more properly described as a randomized clinical trial with a variation of block randomization by litter. The terminology itself is not relevant to the outcome or conclusions, of course, but it does suggest that the authors may not have extensive familiarity with designing and conducting clinical research studies.

Most importantly, spondylosis is not a cause of significant clinical problems in a majority of dogs, and nearly all dogs will have it to some extent as they age. The very best possible outcome of this study would have been a decrease in the occurrence of something that isn’t a real problem. Chiropractors, of course, would still consider that a success since it would support their claims that what they are doing has real effects on patients. However, this study does not provide reliable evidence that this is true. It certainly does not warrant ignoring the decades of research that have failed to find that chiropractic is a real treatment for any real physical problem. 

 References

1.        Mirtz TA, Morgan L, Wyatt LH, Greene L. An epidemiological examination of the subluxation construct using Hill’s criteria of causation. Chiropr Osteopat. 2009;17(1):13. doi:10.1186/1746-1340-17-13

2.        Hestbaek L, Leboeuf-Yde C. Are chiropractic tests for the lumbo-pelvic spine reliable and valid? A systematic critical literature review. J Manipulative Physiol Ther. 2000;23(4):258-275. http://www.ncbi.nlm.nih.gov/pubmed/10820299. Accessed November 18, 2018.

3.        French SD, Green S, Forbes A. Reliability of chiropractic methods commonly used to detect manipulable lesions in patients with chronic low-back pain. J Manipulative Physiol Ther. 2000;23(4):231-238. http://www.ncbi.nlm.nih.gov/pubmed/10820295. Accessed November 18, 2018.

4.        McKenzie B. Placebos for Pets: The Truth About Alternative Medicine for Animals. Ockham Publishing; 2019.

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From the Washington Post- An Article Discussing Neutering

Neuter or not? The answer is no longer automatic.

Posted in Presentations, Lectures, Publications & Interviews | 2 Comments

Cone of Shame: 30-year-old Dogs? The Science of Pet Aging

I recently had another chance to visit my friends Dr. Andy Roark on his Cone of Shame podcast. We talked about my favorite subject–aging in dogs and what we can do about it. Enjoy!

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Do Fit Dogs Live Longer?

It is well established that exercise has health benefits in humans. Regular physical activity can significantly reduce the occurrence of age-associated diseases and help maintain function. Exercise is also a powerful anti-aging tool which can extend both healthspan and lifespan. But what about dogs? Is it time to start a chain of canine fitness centers?

Just as in humans, one of the biggest risk factors for illness and premature death in dogs is obesity. Surveys of dog owners have found that low levels of exercise are associated with an increased risk of obesity, so it is possible that regular physical activity may be protective against becoming overweight. 

A few studies have investigated exercise as an adjunct to caloric restriction for weight loss in dogs. Some have found benefits, but not all, and it is clear that exercise without caloric restriction is unlikely to be an effective treatment for obesity. However, overweight dogs may still benefit from exercise during dieting in other ways, such as preserving lean body mass.

Exercise also improves comfort and function in dogs with osteoarthritis, and it appears to trigger the activation of metabolic pathways associated with glucose regulation. These same pathways are implicated in the effects of caloric restriction on health and longevity, which suggests that exercise could extend healthspan and lifespan in dogs by mechanisms similar to those demonstrated in other species.

More research is needed, but there it is highly likely that increased physical exercise will be beneficial for dogs in maintaining health and slowing aging. There’s also plenty of evidence that exercising with our dogs is good for our health. So take your for a walk right now!

Posted in Aging Science | 1 Comment

How Long Do Dogs Live?

Dogs’ lives are too short. Their only fault, really.
Agnes Sligh Turnbull

How long should a dog live? The obvious answer for any dog lover, of course, is “Forever!” Unfortunately, since this does not appear possible, we must settle for trying to understand the current patterns of longevity in dogs, including lifespan, causes of death, and the variables that may influence these. There is a substantial body of research investigating longevity and mortality in dogs, and we are beginning to develop sufficient knowledge to enable us to understand, and even influence, how long dogs live.

The optimal way to assess longevity and risk factors for mortality is a prospective cohort study, in which a large number of individuals are followed from early in life until death and extensive data is collected on lifestyle and environmental exposures, clinical laboratory values, disease occurrence, and the circumstances associated with their deaths. Such studies are standard in human epidemiology, but nearly non-existent in veterinary medicine. The first canine study of this kind is the Golden Retriever Lifetime Study (GRLS),1 run by the Morris Animal Foundation, which promises to be an invaluable source of data about longevity, morbidity, and mortality in this breed. Other efforts, such as the Dog Aging Project are also under way.2

Most of the data we currently have about canine longevity is derived from retrospective analyses of a variety of data sets. Data sources have included veterinary medical college patient data,3–7 medical records from private practice,8–10 and pet insurance company records.11–15 Owner surveys have also been used to investigate mortality and longevity in companion dogs.16–18 Some studies have even used records from pet cemeteries to investigate lifespan in dogs.19,20 Each of these sources has their own strengths and limitations. 

Veterinary medical school datasets are often large and contain extensive diagnostic test results. They are also likely to have complete and accurate diagnoses. However, the population of dogs seen at such tertiary care institutions is not representative of the general owned dog population. Patients in such settings may have more severe and more uncommon disease and owners who provide different husbandry and medical care and make different decisions regarding treatment and euthanasia than canine patients in primary care settings. Generalizations based on data derived in this setting can be unreliable.

Primary care records are likely to be much more representative of owned dogs in general, and the types of health issues, husbandry, and owners they have. However, such records can be difficult to access due to the variety of medical record systems in use and the lack of standardization in record keeping practices. Primary care patients also may not receive as extensive a diagnostic evaluation as those seen in academic centers, so the information available may be more limited and potentially inaccurate. The benefits of such “real-world” data sources are somewhat offset by the lack of standardization and quality control.

Surveys of owners are the most convenient and least expensive type of morbidity and mortality to collect. They are also likely the least reliable, with numerous potential sources of uncontrolled bias and error not seen in medical records. Likewise, pet cemetery data rely primarily on information from a small subset of pet owners unlikely to be representative of the general population or consistently accurate.

Considering the variety of data sources used to study canine longevity, the general findings are remarkably consistent. Overall median lifespans for all breeds have been reported between about 8 and 15 years, with most estimates falling between 10 and 12 years, though given the differences in study populations and methods, these figures are not strictly comparable.8–10,12,16–22 (Table 1)

Different data sets also show similar lifespan distributions, typically with a dip in mortality in young adulthood followed by a steady increase in deaths peaking at about 10-14 years of age and then a sharp decline after age 15. (Figure 1) The truncation of the right end of these distributions may reflect some limitations in the data collection as well as a sharp decline in survival past the early to mid-teens.

Little effort has been made to assess changes in global canine life expectancy over time. Many owners and veterinarians believe dogs are living longer than they used to due to improvements in preventative and therapeutic interventions, nutrition, husbandry, and other factors. There is not much evidence to confirm this suspicion. Periodic analyses of the medical record systems at Banfield have been cited to show that dog life expectancy is increasing. Comparisons of life expectancy estimates from different years have also suggested increased longevity in dogs. Analysis of cemetery and insurance records in Japan, for example, have estimated higher life expectancy in recent decades compared with earlier studies.19,20,23 However, these are not results from prospective studies specifically designed to evaluate changes in canine life expectancy over time, and studies done at different times are not truly comparable due to changes in sample populations and methods.

Similar questionable comparisons between surveys at different times have been used to make the opposite argument, that dogs are dying younger than they used to do to purported harm from environmental toxins and contemporary husbandry, nutrition, and healthcare practices. Surveys conducted by the U.K. Kennel Club in 2004 and 2014 show different results for lifespan in specific breeds. Some breeds have a longer lifespan in the earlier study and others have a longer reported life expectancy in the more recent study. There is no clear overall pattern showing a change in lifespan, but even if such a pattern were evident, comparison between the two studies would not be appropriate due to differences between them. As the authors point out: 

“Given the difference in methodologies between the surveys, the data from each is not fully comparable and differences observed do not definitively imply changes in population parameters. Furthermore, there were 5,864 deaths reported in the 2014 survey compared to 15,881 deaths reported in the 2004 survey. This significant drop reduces the likelihood of the sample accurately representing the wider dog population, and so would likely have an impact on median longevity figures if the two sets of data were compared, which would not be reliable.”

Of course, assessments of overall longevity and mortality aren’t particularly useful since there is significant variation in lifespan by breed, size, neuter status, and other factors. The one datum owners are most interested in, of course, is “How long will my dog live?” That is, sadly, not something we are likely to ever be able to predict with great accuracy. However, in terms of setting reasonable expectations and thinking about what we and owners can do to maximize the chances of as long and healthy a life as possible for each dog, it is helpful to understand some of the variables that influence lifespan on a population level. 

One of the most complex factors is neuter status. I have written previously about the health effects and overall risks and benefits of neutering,24 as well as considerations for what age is optimal for neutering dogs. The general conclusions we can draw from the extensive literature is that neutering has both risks and benefits, and these will vary by breed in complex and often unpredictable ways. Neutering increases the risk of some health conditions in some breeds and lowers the risks of others. However, with respect to lifespan, the evidence is pretty consistent that neutered dogs tend to live longer than intact dogs.5,9,10,24–27

Typically, this effect is more pronounced in females, which may be due to the high incidence of diseases such as mammary neoplasia and pyometra, which are much more common in intact females. However, neutering has been associated with increased longevity in both males and females of other species as well.28 The relationship between sex hormones, environmental conditions, and lifespan is complex, and we do not yet have a complete understanding of it. It is reasonable to tell dog owners that neutering appears to increase lifespan in dogs, especially female dogs, but there are risks as well as benefits, and there is still significant uncertainty about the impact on the life of any individual dog.Body size is another factor that clearly impacts longevity. Once aspect of this is largely beyond the control of owners, which is the size of a dog determined by its breed. There is a roughly linear inverse relationship between body size and lifespan, with giant breed dogs often living half as long as small breeds.3,6,9,10,16,17,20,21,25,27 (Figure 2) This relationship holds even when breed is factored in, showing that it is not simply genetic risk factors for specific diseases in specific breeds causing the apparent association but a true causal relationship between body size and overall mortality.

There are a number of possible mechanisms for negative effect of body size on longevity. Several researchers argue that large and giant breed dogs age at a faster rate, and this accelerated aging is responsible for their shorter lifespan.6,7,29Body size is determined by a small number of genes in dogs,30,31 and one hypothesis is that the shortened life expectancy for larger breeds is an example of antagonistic pleiotropy. This is an evolutionary explanation for age-associated disease that argues genes which convey fitness advantages during the early, reproductive period of life will be retained by natural selection even if they cause harm or shorten overall lifespan through effects later in life, when reproductive output is less. Dogs, of course, have been the subject of very intensive artificial selection, and it is possible that the selection for large body size has preserved genes which contribute to accelerated aging and shorter overall lifespan.

All studies evaluating lifespan in dogs show significant breed variation in longevity. Some of this variation may be attributed to body size, but when that is controlled for in analysis, some breeds do still live longer on average than others. These differences sometimes have straightforward explanations in terms of the incidence of specific diseases, but some breeds may have consistently shorter lives that cannot be explained by obvious genetic predisposition to particular maladies. It is likely that there are differences in the underlying mechanisms of aging between breeds, but this is not a subject that has been extensively investigated in enough breeds to allow confident explanations for many breeds.

One interesting finding concerns telomeres. Telomeres are repetitive non-coding base sequences at the ends of chromosomes that allow for complete replication of the coding portion of the DNA. These shorten with each replication event in the absence of the reparative enzyme telomerase, which is not usually present in somatic cells. When telomeres become too short to protect the coding section of a chromosome, replication is impeded, and cells become dysfunctional. Telomere shortening accompanies aging, and accelerated aging is associated with telomerase deficiency or induced telomere attrition. 

Research has shown that telomeres shorten with age in dogs much more rapidly than in humans at a ratio roughly corresponding to the difference in average lifespan between the species. The length of telomeres also differs between breeds, and those breeds with longer telomeres tend to have longer lifespan than breeds with shorter telomeres. These findings support the importance of telomere attrition in canine aging and suggest that one of the fundamental underlying mechanisms of aging may explain some of the difference in longevity between breeds.32,33

Another breed-related variable that does seem consistently related to longevity is purebred versus mixed-breed status. Mixed breeds appear to have greater lifespans in most7,10,16,19,25,34,35, though not all9 studies. Genetic analyses suggest that there is some relationship between the degree of inbreeding and lifespan, both between and within breeds, but this relationship is not simple or straightforward, and it is complicated by confounding variables such as body size.7

When considering longevity in dogs, it is of course necessary to look at what causes of death limit lifespan. Patterns in cause of death can be informative for understanding variability in lifespan and for formulating strategies to extend canine lifespan (the number of years lived) and healthspan (the number of years without significant disease or disability). Once again, differences in study populations and methods limit direct comparisons, but research has identified some apparent patterns in the causes of death seen in dogs. Table 2 lists the most common causes of death reported in various epidemiologic studies.

Overall, neoplasia is almost always a leading cause of death. Diseases of the nervous, musculoskeletal, urinary, and respiratory systems are also very commonly listed. The order in which these appear, and the specific diagnoses identified as leading to death, vary between studies, again due to differences in the populations studied, the methods used to acquire data, and the definitions employed of various causes of death. 

The specific diseases leading to death and the organ systems involved also vary in association with several key patient variables. Old dogs tend to die of neoplasia and degenerative diseases more often than young dogs, who experience more mortality related to trauma and infectious disease. Differences are also seen associated with sex, neuter status, and breed. The details are complex and not always consistent between studies, but again the patterns are useful in targeting interventions. Reduction in infectious disease through vaccination, for example, has much. More impact on mortality early in life than interventions targeting neoplasia. Treatments for degenerative musculoskeletal diseases may prolong healthspan and lifespan significantly for dogs in the latter phases of the life cycle, while they are less likely to be useful or to justify potential adverse effects in younger dogs.

Many studies include a generic category of “old age” in asking owners about cause of death. While this is not a very specific nor clearly defined diagnosis, it represents the deleterious functional impact aging can have on dogs even in the absence of specific diagnoses. In humans, frailty is a recognized phenomenon of aging that has significant effects on quality of life and mortality rates, and while such a syndrome is not yet well-characterized in dogs, it is likely also present and relevant to end-of-life decisions for dog owners.42,43

The proximate cause of death for the majority of owned dogs is almost always euthanasia.25,35,44 Though there is usually some underlying ultimate disease or dysfunction precipitating the decision to euthanize, it is important to recognize that death in dogs is most often the result of a human decision-making process. This has significant implications for any efforts to prolong lifespan and healthspan and mitigate the impact of specific causes of mortality, and understanding the reasons owners choose to euthanize their dogs, and the clinical presentations that drive such decisions, is vital to such efforts. 

While specific clinical diagnoses are often part of owners’ decisions to euthanize their canine companions, more commonly people cite symptoms or perceived deficits in comfort and quality of life.45–49 Dogs without a clearly fatal disease will often be euthanized when they exhibit symptoms that suggest to owners they are in pain or in some other way uncomfortable, or when they exhibit behaviors that are unacceptable for companion dogs. Loss of mobility, change sin social behavior, housesoiling, and many other symptoms that are not inherently life-threatening or associated with fatal disease can still be life-limiting in dogs due to their impact on owners.

Finally, we cannot hope to understand longevity patterns in dogs without understanding canine aging. For a phenomenon we all experience, aging is challenging to define precisely. It involves changes that occur over time, but time is not necessarily the primary driver of those changes. 

A useful general definition in this frame is that aging is “the progressive accumulation of changes with time associated with or responsible for the ever-increasing susceptibility to disease and death.”36 Individual dogs experience progressive loss of function, greater risk of certain types of disease, and a greater likelihood of death as they get older. 

Aging involves many different processes at multiple levels, from changes in molecules and genes at the microscopic scale to changes in appearance and function identifiable to dog owners and veterinarians. There are recognizable patterns to these changes that are seen in most dogs, and even in humans and other animals. However, aging is also a variable and individual process. Biologically, some individuals age faster than others. Biological age is related to, but not synonymous with, chronological age. This is especially clear in the dog, in which larger dogs typically experience deleterious consequences of aging earlier and die younger than smaller breeds.6,37,38

Decades of research into the mechanisms of aging, in laboratory models, humans, and dogs, have revealed both variation and complexity as well as recognizable patterns and evolutionarily conserved processes involved in aging. Research efforts are ongoing, and rapidly expanding, to use our understanding of how aging happens to develop preventative and therapeutic interventions to delay age-associated disease, disability, and death. In addition to prevention and treatment of specific diseases, overall improvement in health, comfort, and function in older dogs and compression of frailty and illness into a shorter period preceding death (i.e., an extension of healthspan) may be possible, which would be a fundamental shift in the perspective and practice of veterinary preventative medicine.

The patterns so far identified in longevity and mortality give us some very limited ability to offer general prognoses for lifespan and causes of death to individual dog owners. They also offer a baseline against which to measure our efforts to improve canine health and give our clients and their dogs more quality time together.

References

1.        Guy MK, Page RL, Jensen WA, et al. The golden retriever lifetime study: Establishing an observational cohort study with translational relevance for human health. Philos Trans R Soc B Biol Sci. 2015;370(1673). doi:10.1098/rstb.2014.0230

2.        Kaeberlein M, Creevy KE, Promislow DEL. The dog aging project: translational geroscience in companion animals. Mamm Genome. 2016;27(7-8):279-288. doi:10.1007/s00335-016-9638-7

3.        Galis F, Van der Sluijs I, Van Dooren TJM, Metz JAJ, Nussbaumer M. Do large dogs die young? J Exp Zool B Mol Dev Evol. 2007;308(2):119-126. doi:10.1002/jez.b.21116

4.        Fleming JM, Creevy KE, Promislow DEL. Mortality in North American Dogs from 1984 to 2004: An Investigation into Age-, Size-, and Breed-Related Causes of Death. J Vet Intern Med. 2011;25(2):187-198. doi:10.1111/j.1939-1676.2011.0695.x

5.        Hoffman JM, Creevy KE, Promislow DEL. Reproductive capability is associated with lifespan and cause of death in companion dogs. PLoS One. 2013;8(4):e61082. doi:10.1371/journal.pone.0061082

6.        Kraus C, Pavard S, Promislow DEL. The size-life span trade-off decomposed: Why large dogs die young. Am Nat. 2013;181(4):492-505. doi:10.1086/669665

7.        Yordy J, Kraus C, Hayward JJ, et al. Body size, inbreeding, and lifespan in domestic dogs. Conserv Genet. 2020;21(1):137-148. doi:10.1007/s10592-019-01240-x

8.        O’Neill DG, Church DB, McGreevy PD, Thomson PC, Brodbelt DC. Longevity and mortality of owned dogs in England. Vet J. 2013;198(3):638-643. doi:10.1016/J.TVJL.2013.09.020

9.        Urfer SR, Kaeberlein M, Promislow DEL, Creevy KE. Lifespan of companion dogs seen in three independent primary care veterinary clinics in the United States. Canine Med Genet. 2020;7(1):7. doi:10.1186/s40575-020-00086-8

10.      Urfer SR, Wang M, Yang M, Lund EM, Lefebvre SL. Risk Factors Associated with Lifespan in Pet Dogs Evaluated in Primary Care Veterinary Hospitals. J Am Anim Hosp Assoc. 2019;55(3):130-137. doi:10.5326/JAAHA-MS-6763

11.      Bonnett BN, Egenvall A, Olson P, Hedhammar Å. Mortality in insured Swedish dogs: rates and causes of death in various breeds. Vet Rec. 1997;141(2):40-44. doi:10.1136/vr.141.2.40

12.      Michell AR. Longevity of British breeds of dog and its relationships with-sex, size, cardiovascular variables and disease. Vet Rec. 1999;145(22):625-629. doi:10.1136/vr.145.22.625

13.      Bonnett BN, Egenvall A. Age patterns of disease and death in insured Swedish dogs, cats and horses. J Comp Pathol. 2010;142 Suppl 1:S33-8. doi:10.1016/j.jcpa.2009.10.008

14.      Bonnett BN, Egenvall A, Hedhammar A, Olson P. Mortality in over 350,000 insured Swedish dogs from 1995-2000: I. Breed-, gender-, age- and cause-specific rates. Acta Vet Scand. 2005;46(3):105-120. doi:10.1186/1751-0147-46-105

15.      Inoue M, Hasegawa A, Hosoi Y, Sugiura K. A current life table and causes of death for insured dogs in Japan. Prev Vet Med. 2015;120(2):210-218. doi:10.1016/j.prevetmed.2015.03.018

16.      Proschowsky HF, Rugbjerg H, Ersbøll AK. Mortality of purebred and mixed-breed dogs in Denmark. Prev Vet Med. 2003;58(1-2):63-74. doi:10.1016/S0167-5877(03)00010-2

17.      Adams VJ, Evans KM, Sampson J, Wood JLN. Methods and mortality results of a health survey of purebred dogs in the UK. J Small Anim Pract. 2010;51(10):512-524. doi:10.1111/j.1748-5827.2010.00974.x

18.      Lewis TW, Wiles BM, Llewellyn-Zaidi AM, Evans KM, O’Neill DG. Longevity and mortality in Kennel Club registered dog breeds in the UK in 2014. Canine Genet Epidemiol. 2018;5(1). doi:10.1186/s40575-018-0066-8

19.      Hayashidani H, Omi Y, Ogawa M, Fukutomi K. Epidemiological studies on the expectation of life for dogs computed from animal cemetery records. Nihon Juigaku Zasshi. 1988;50(5):1003-1008. doi:10.1292/jvms1939.50.1003

20.      Inoue M, Kwan NCL, Sugiura K. Estimating the life expectancy of companion dogs in Japan using pet cemetery data. J Vet Med Sci. 2018;80(7):1153-1158. doi:10.1292/jvms.17-0384

21.      Inoue M, Hasegawa A, Hosoi Y, Sugiura K. A current life table and causes of death for insured dogs in Japan. Prev Vet Med. 2015;120(2):210-218. doi:10.1016/J.PREVETMED.2015.03.018

22.      Hoffman JM, Creevy KE, Promislow DEL. Reproductive Capability Is Associated with Lifespan and Cause of Death in Companion Dogs. Helle S, ed. PLoS One. 2013;8(4):e61082. doi:10.1371/journal.pone.0061082

23.      Inoue M, Hasegawa A, Hosoi Y, Sugiura K. A current life table and causes of death for insured dogs in Japan. Prev Vet Med. 2015;120(2):210-218. doi:10.1016/J.PREVETMED.2015.03.018

24.      Mckenzie B. Evaluating the benefits and risks of neutering dogs and cats. doi:10.1079/PAVSNNR20105045

25.      Michell AR. Longevity of British breeds of dog and its relationships with sex, size, cardiovascular variables and disease. Vet Rec. 1999;145(22):625-629. doi:10.1136/vr.145.22.625

26.      Moore GE, Burkman KD, Carter MN, Peterson MR. Causes of death or reasons for euthanasia in military working dogs: 927 cases (1993-1996). J Am Vet Med Assoc. 2001;219(2):209-214. doi:10.2460/javma.2001.219.209

27.      DG O, DB C, PD M, PC T, DC B. Longevity and mortality of owned dogs in England. Vet J. 2013;198(3). doi:10.1016/J.TVJL.2013.09.020

28.      Austad SN. Sex differences in health and aging: a dialog between the brain and gonad? GeroScience. 2019;41(3):267-273. doi:10.1007/s11357-019-00081-3

29.      Selman C, Nussey DH, Monaghan P. Ageing: It’s a Dog’s Life. Curr Biol. 2013;23(10):R451-R453. doi:10.1016/J.CUB.2013.04.005

30.      Plassais J, Rimbault M, Williams FJ, Davis BW, Schoenebeck JJ, Ostrander EA. Analysis of large versus small dogs reveals three genes on the canine X chromosome associated with body weight, muscling and back fat thickness. Clark LA, ed. PLOS Genet. 2017;13(3):e1006661. doi:10.1371/journal.pgen.1006661

31.      Rimbault M, Beale HC, Schoenebeck JJ, et al. Derived variants at six genes explain nearly half of size reduction in dog breeds. Genome Res. 2013;23(12):1985-1995. doi:10.1101/gr.157339.113

32.      Sándor S, Kubinyi E. Genetic Pathways of Aging and Their Relevance in the Dog as a Natural Model of Human Aging. Front Genet. 2019;10. doi:10.3389/fgene.2019.00948

33.      Fick LJ, Fick GH, Li Z, et al. Telomere Length Correlates with Life Span of Dog Breeds. Cell Rep. 2012;2(6):1530-1536. doi:10.1016/j.celrep.2012.11.021

34.      Patronek GJ, Waters DJ, Glickman LT. Comparative longevity of pet dogs and humans: implications for gerontology research. J Gerontol A Biol Sci Med Sci. 1997;52(3):B171-8. doi:10.1093/gerona/52a.3.b171

35.      O’Neill DG, Church DB, McGreevy PD, Thomson PC, Brodbelt DC. Longevity and mortality of owned dogs in England. Vet J. 2013;198(3):638-643. doi:10.1016/j.tvjl.2013.09.020

36.      Harman D. The aging process. Proc Natl Acad Sci U S A. 1981;78(11):7124-7128. doi:10.1073/pnas.78.11.7124

37.      Egenvall A, Bonnett BN, Hedhammar Å, Olson P. Mortality in over 350,000 insured Swedish dogs from 1995-2000: II. Breed-specific age and survival patterns and relative risk for causes of death. Acta Vet Scand. 2005;46(3):121-136. doi:10.1186/1751-0147-46-121

38.      Miller RA, Austad SN. Growth and Aging. Why Do Big Dogs Die Young? In: Handbook of the Biology of Aging. Elsevier Inc.; 2005:512-533. doi:10.1016/B978-012088387-5/50022-4

39.      BN B, A E, A H, P O. Mortality in over 350,000 insured Swedish dogs from 1995-2000: I. Breed-, gender-, age- and cause-specific rates. Acta Vet Scand. 2005;46(3). doi:10.1186/1751-0147-46-105

40.      O’Neill DG, Elliott J, Church DB, McGreevy PD, Thomson PC, Brodbelt DC. Chronic kidney disease in dogs in UK veterinary practices: prevalence, risk factors, and survival. J Vet Intern Med. 2013;27(4):814-821. doi:10.1111/jvim.12090

41.      Lewis TW, Wiles BM, Llewellyn-Zaidi AM, Evans KM, O’Neill DG. Longevity and mortality in Kennel Club registered dog breeds in the UK in 2014. Canine Genet Epidemiol. 2018;5(1):10. doi:10.1186/s40575-018-0066-8

42.      Hua J, Hoummady S, Muller C, et al. Assessment of frailty in aged dogs. Am J Vet Res. 2016;77(12). doi:10.2460/AJVR.77.12.1357

43.      Banzato T, Franzo G, Di Maggio R, et al. A Frailty Index based on clinical data to quantify mortality risk in dogs. Sci Rep. 2019;9(1):16749. doi:10.1038/s41598-019-52585-9

44.      Pegram C, Gray C, Packer RMA, et al. Proportion and risk factors for death by euthanasia in dogs in the UK. Sci Rep. 2021;11(1):9145. doi:10.1038/s41598-021-88342-0

45.      Mallery KF, Freeman LM, Harpster NK, Rush JE. Factors contributing to the decision for euthanasia of dogs with congestive heart failure. J Am Vet Med Assoc. 1999;214(8):1201-1204. http://europepmc.org/article/med/10212683. Accessed April 6, 2021.

46.      Edney ATB. Reasons for the euthanasia of dogs and cats. Vet Rec. 1998;143(4):114. doi:10.1136/vr.143.4.114

47.      McMullen, S.L., Clark, W.T. , Robertson I. Reasons for the euthanasia of dogs and cats in veterinary practices. Aust Vet Pract. 2001;31(2):80-84.

48.      Bussolari CJ, Habarth J, Katz R, Phillips S, Carmack B, Packman W. The euthanasia decision-making process: A qualitative exploration of bereaved companion animal owners. Bereave Care. 2018;37(3):101-108. doi:10.1080/02682621.2018.1542571

49.      Marchitelli B, Shearer T, Cook N. Factors Contributing to the Decision to Euthanize: Diagnosis, Clinical Signs, and Triggers. Vet Clin North Am – Small Anim Pract. 2020;50(3):573-589. doi:10.1016/j.cvsm.2019.12.007

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The Young Science of Dog Aging

Here is a brief talk and Q&A I participated in recently at Petminded. Hope you find it interesting!

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Rational Use of Diagnostic & Screening Tests

I have written many times about the misuse of diagnostic tests and the risks of misdiagnosis and overdiagnosis associated with improper use of screening tests. Recently, I condensed my rants on these topics into an article I hope will be useful to veterinarians.

McKenzie, B.A. Rational use of diagnostic and screening tests. Journal of Small Animal Practice (2021), 1–6. DOI: 10.1111/jsap.13393

 Veterinarians have a vast and ever-expanding array of diagnostic tests available to them. However, this abundance can be an embarrassment of riches that confounds diagnosis and undermines patient care if we do not make critical and informed decisions about the selection and interpretation of the tests we employ. Effective use of diagnostic tests requires a deliberate and informed approach. We must consider the strengths and weaknesses of the tests themselves and the clinical context, and we must be wary of the many biases that skew our use and interpretation of diagnostic tests. Understanding sensitivity and specificity, likelihood, prevalence and predictive value, the basic principles of Bayesian reasoning, and the cognitive biases that drive inappropriate testing are all critical to ensuring our use of imaging and laboratory testing improves patient outcomes.

Posted in Science-Based Veterinary Medicine | 4 Comments

Can Your Dog’s Face Tell You How Old They Are?

Is this an old dog or a young dog? How do you know? Can you guess his age, and how close do you think you’ll get? 

Age-associated changes in appearance are readily recognized by clinicians and dog owners. We can often identify an old dog of any breed through a gestalt assessment of appearance, movement, and demeanor without being able to detail all the specific features that signal age. One interesting challenge for canine aging science is to be able to break this assessment down into components and quantify phenotypic markers of biological aging.

Age estimation from facial photographs of humans is an active field of research. Artificial intelligence and deep learning techniques are applied to identify and interpret specific facial features to enable estimation of age despite differences in sex, ethnicity, photo quality, and other complicating factors. So far, these systems have gotten pretty good, but they can still only get within 2-5 years of a person’s actual age.

In veterinary medicine, it would be helpful to have a practical and accurate age-estimation tool since the true chronological age of many of our patients is unknown. Such a tool would also be useful in distinguishing chronological age from biological age, informing effective planning of disease surveillance and healthcare for individual dogs based on their unique needs. It might also be helpful in evaluating the effectiveness of antiaging therapies if facial age estimation could be used as a biomarker for the impact of such treatments on health. 

The technical challenges are considerable, especially given the tremendous variability in appearance among breeds. While there are a number of artificial intelligence tools available for identifying breed and recognizing individuals by their faces, there is not yet one to estimate age. There have been a few projects attempting to develop such a tool, and hopefully this will be added to our aging biology toolbox soon!

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Lifespan and Healthspan

The goal of longevity therapies is to prolong both lifespan (the number of years an individual lives) and healthspan (the number of years free of significant disease or disability). Current preventative medical interventions, such as vaccines, have greatly increased lifespan, mostly by preventing death early in life. Medical treatment of age-related diseases also prolongs lifespan by delaying death, and it can increase healthspan somewhat by reducing the negative impact of disease on quality of life.

Unfortuntely, increases in lifespan driven by reduction of early-life mortality have exceeded increases in healthspan, and the period of disability and diminished quality of life preceding death has grown. This is clear for humans and appears true for dogs as well.

Lifecycle trajectories with varying healthspan. Anti-aging therapies can increase lifespan (years lived) and healthspan (years lived in good health) by delaying the onset of age-associated disease and disability. (lifespan ranges based on references below)

The length of life for dogs varies with breed, size, neuter status, and other variables. Lifespan ranges from an average of 6-10 years for the shortest-lived breeds up to 14-18 years for longer-lived dogs.

Regardless of the number of years lived, all dogs progress through a lifecycle that involves changes in physiologic resilience and functional capacity over time (see figure above). There is a rapid increase in function and ability to cope with external stressors from birth to physical maturity. The inevitable decline in health and function from this point can occur along variable trajectories.

The purpose of interventions to promote healthy aging is not only to increase the number of years lived but to maximize the period of good health and confine the loss of resilience and functional capacity to the shortest possible period. Therapies which delay death but do not prolong healthspan can reduce overall quality of life by prolonging the period of disability preceding death. Learning to quantify the impact of aging on health will enable us to better assess the impact of interventions on both lifespan and healthspan and achieve the greatest benefits for our dogs.

References

Lewis TW, Wiles BM, Llewellyn-Zaidi AM, Evans KM, O’Neill DG. Longevity and mortality in Kennel Club registered dog breeds in the UK in 2014. Canine Genet Epidemiol. 2018;5(1). doi:10.1186/s40575-018-0066-8

Michell AR. Longevity of British breeds of dog and its relationships with-sex, size, cardiovascular variables and disease. Vet Rec. 1999;145(22):625-629. doi:10.1136/vr.145.22.625

O’Neill DG, Church DB, McGreevy PD, Thomson PC, Brodbelt DC. Longevity and mortality of owned dogs in England. Vet J. 2013;198(3):638-643. doi:10.1016/J.TVJL.2013.09.020

Adams VJ, Evans KM, Sampson J, Wood JLN. Methods and mortality results of a health survey of purebred dogs in the UK. J Small Anim Pract. 2010;51(10):512-524. doi:10.1111/j.1748-5827.2010.00974.x

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OncoK9 Liquid Biopsy: Should Your Dog have this Test?

It is really never a good sign when a miraculous new breakthrough in veterinary medicine is announced on the internet. That isn’t where true scientific breakthroughs show up. Legitimate science is a slow, detailed process where even brilliant, revolutionary ideas have to go through a long, rigorous process of critique and exploration before they are accepted. Public relations press announcements are about making money and generating hype, not about exploring good science.

It is even less inspiring of confidence when the supposed breakthrough is offered by a person or institution with a track record of promoting pseudoscience. 

In the case of OncoK9 Liquid Biopsy, such red flags abound. Press announcements with hyperbolic language like “pioneering,” “revolution,” and “breakthrough innovation” are not only meaningless but outright misleading when the only evidence offered to support them is a company study that supposedly “will be submitted for publication in a leading peer-reviewed journal” someday. Legitimate science does not start with press releases and then move to possiblepublication in the scientific literature.

It is also not inspiring of confidence that the product is being initially offered for sale by Petco, a company which has a sketchy history when it comes to pet health topics. Selling raw diets, grain-free foods and bogus nutritional supplements while running a vapid and unscientific public relations campaign lauding its ban on “artificial” ingredients in the foods sold at PetCo stores does not establish the chain as a reliable source of information on pet health. 

So what is OncoK9? According to the company that developed the product, it is “a multi-cancer early detection (MCED) test for the detection and characterization of cancer-associated genomic alterations in DNA isolated from canine whole blood samples, using next-generation sequencing (NGS) technology.” Sounds fancy, eh? The idea is plausible. Cancer cells may, depending on the type of cancer and many other factors, circulate in the blood. If such cells are present, it is potentially possible to detect them by identifying genetic markers associated with such abnormal cells. If there are then other tests available to identify and locate the cancer, and if there are therapies that might be more effective in treating the disease when caught at an earlier stage, such a test could improve health and lifespan in dogs.

Notice all the “ifs” and caveats here? The idea is sound, but the devil is in the details, and this company has not even come close to proving that all the steps in this process will work in a way that actually benefits dogs. The test was developed by mixing DNA from cancer cells and healthy canine cells and showing that the test could detect the abnormal DNA. Apparently, the test was then applied to samples from dogs know to have and thought not to have cancer (this is the study that has not yet been submitted for publication but from which the company is reporting results in its marketing materials). That’s a good start, but a long way from proving that regular clinical use of this test will benefit canine patients.

The company recommends using the test as a screening tool, “as an annual screening test for dogs that are 8 years and older and/or belong to breeds that are highly predisposed to cancer.” Screening is a particularly tricky kind of testing because you are looking at dogs without any signs or symptoms of disease. Most apparently healthy dogs are actually healthy, so the risk of false positive results, finding disease that isn’t actually there, is higher than when testing sick patients. 

The risk of overdiagnosis is also high. This is where a test finds a disease that is truly there but isn’t likely to ever cause any symptoms. Many kinds of screening tests in humans, based on the same idea that early detection of asymptomatic disease is better, have been scaled back because it turns out they do more harm than good. Finding a type of cancer that isn’t ever going to progress or make someone sick isn’t in their best interests if subsequent testing and treatment cause harm without any benefit in terms of health or increased lifespan. 

Assuming the methods and controls for error and bias were appropriate and the data is accurate (all of which we have to blindly assume in the absence of any scientific publication), the company study suggests an overall sensitivity of 48% for the test. This means that 48%, less than half, of dogs with cancer will correctly test positive. This is not, on the face of it, a very sensitive test. However, if we are looking for cancer in dogs without any clinical symptoms, that might actually be a good thing. We would rather miss a case in a dog with cancer that is not causing any problems than mistakenly identify a dog as having cancer who doesn’t. 

The specificity, that is the proportion of dogs without cancer who correctly test negative, is reported to be 97%. This is the more important value in this case since we don’t want to falsely diagnose cancer and send a lot of dogs into unnecessary, costly, and potentially dangerous further testing or treatment they don’t need.

However, given that the company actively recommends the test as a screening tool, it is likely most of the dogs tested will be healthy. A rule for screening tests is that the less likely the patients you test are to actually have the disease you are looking for, the more wrong answers your test will give you. One way of looking at this is with the Positive Predictive Value (PPV) of a test.

The company advertising materials calculate the PPV for OncoK9 based on guessing that 10%-20% of dogs tested will have cancer. This seems high (which would make the test look better than guessing a lower rate of hidden cancers), and there aren’t good research data to tell us what the actually prevalence of asymptomatic cancer is in dogs of a specific age or breed. The best data we have are variable and not consistent between studies, so I will give the company the benefit of the doubt on these guesses for the time being. 

Using these numbers, then, the PPV for OncoK9 would be between 64% and 80%. At the low end, that means that 64% of the dogs with a positive test actually have cancer and 36% do not. It seems a bit concerning that we are going to tell over a third of the dogs we test that they might have cancer when they don’t. Presumably, this would be followed by x-rays, ultrasound, other tests, and potentially months to years of anxiety about this supposed hidden cancer, none of which would improve the health or longevity of these dogs. Even at the more optimistic figure of 80% PPV, 20% or 1/5 dogs testing positive would actually be healthy. This raises the potential for significant costs and harms from unnecessary testing and treatment for a lot of dogs.

And remember all of the other caveats about screening tests for cancer? What if the OncoK9 test is correct but we can’t find the cancer anywhere until it progresses? What if it is a type of cancer for which there is no effective treatment? What if it is a type of cancer that is non-progressive and is never going to make the dog sick or lead to death? What if treating the cancer earlier, and for a longer time, doesn’t actually work better than treating it when it causes symptoms that we can detect without this test? All of these are likely scenarios, and in none of these cases would the cost of the test or the cost, anxiety, and risks of further testing and treatment offer any benefits for the dogs. This test has significant potential to cause harm not only when it gets the wrong answer but even when it is correct!

Of course, having a test that reliably detects cancer at a stage where the dog is still healthy and can be effectively treated in a way that preserves health and prolongs life would be a great thing. I would welcome such a test once it was proven to work as intended. Unfortunately, there is no way to know if OncoK9 will lead to net benefit or harm to dogs based on the evidence currently available. Despite the undoubtedly good intentions of the people developing and promoting this test, it is disappointing, even irresponsible to market it without having first done the necessary work to show it will actually make life better for our canine companions. 

I will keep an eye out for the promised publications. I will even hold out a little bit of hope that eventually studies will be done to determine if the test as actually sued in practice reduces disease and saves lives or not. Unfortunately, my fear is that once the test is on the market, the research will stop and continued use will be supported by heartwarming anecdotes about dogs “saved” by an early cancer diagnosis. We will likely never know how much misdiagnosis and overdiagnosis comes from this test since there will be no financial incentive to do the necessary research to figure this out. For now, I would urge dog owners to think very carefully about spending $400 for a test that involves big promises, little evidence, and a lot of uncertainty.

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