Previous pet ownership and Paget's disease

53 BAM 60241

Previous pet ownership and Paget’s disease I.M. Holdaway’, H.K. Ibbertson’ , D. Wattie’, R. Scrag& and P. Graham’ Section ofEndocrinology, Deporrments oJ ‘Medicine and ‘Communiry Hralth, School oJMedicine,

Park Road, Auckland,

New Zealand

(Received 3 July 1989) (Accepted

28 Avgurl1989)

Summary The relationship between pet ownership and Paget’s disease (PD) of bane war investigated in 112 patients with FD who were matched with a similar number of community-based controls. There wes a sig ttificantly increased frequency of dog uwnetship by patients with PD aged C6O years. Multivariate lo&istic renression analysis revealed that there wes e sirnificant am-related increase in risk of PD associated with &I or present ownership of either dogs or-cats, withyounger patients hwing the greatest risk. These results suggest that slow virus infection al osteoclasts by paramyxovimses acquired fmm pets may cantribute to the development of Rget’s disease in the younger patient.

Key words: Paget’s diseese; Slow virus; Pets; Paramyxovirus

Intruductioo

There is increasing evidence that Paget’s disease of bone (osteitis deformarts) may

be due to a slow virus infection of osteoclastic cells [l]. On the basis of immunocytological and DNA hybridisation studies, paramyxoviruses such as measles virus or respiratory synctial virus have been implicated in the disorder [2]. In a recent epidemiological study from North East England it was suggested that the paramyxovirus which causes canine distemper (CDV) could also be involved, since previous dog ownership was more frequent in patients with Paget’s disease than controls [3]. Reports from other centres have, however, failed to confirm these findings [4,S] and there appears to be no increase in CDV antibodies in patients with Paget’s disease [6]. However, other paramyxoviruses are found in domestic animals, inchtding parainfluenza virus type 2 in dogs (71and cats [8], and there is antibody evidence for Conespondence to: Dr I.M. Holdaway, M.D. FRACP, pital. Auckland 1. New Zealand.

Department of Endocrinology, Auckland Has-

0169~Mw)9~901$03..50~ 1990 Elsevier Science Publishers B.V. (Biomedical Division)

infection with paminfluenza virus type 3 in cats [9]. New Zealand has a high prevalence of Paget’s disease [lo] and a high rate of pet ownership. so patients attending the Auckland Hospital Paget’s disease clinic were surveyed for the frequency of pet ownership to determine if there was a relationship between these variables.

Methods Subjects

Two hundred and fifty patients with Paget’s disease were selected at random from the records of the only Paget’s disease clinic in the Auckland region, sited at Auckland Hospital. The family practitioner was approached and asked for permission to contact the patient and was also asked to provide an age- (within 5 years) and sexmatched control patient with the same first initial from the practice records. Both subjects were then mailed a questionnaire requesting information “to help obtain data on pet ownership and various metabolic disorders”. Hence subjects were unaware of either the specific study hypotheses or whether they were classified as cases or controls. Type of pet and duration of ownership was recorded, together with any history of bone disorder. One hundred and sixty cases and 124controls returned questionnaires and of these 112 appropriately matched case-control pairs were available for data analyses.

Relative risk estimates were derived from calculation of the matched pairs odds ratio (i.e., ratio of discordant pairs) and 95% confidence limits were derived from the binomial distribution [ll]. Multivariate conditional logistic regression analyses were carried out using the proportional hazards model [12] and any linear associations with age were confirmed by analyses with subjects categorised into age strata. Standardised coefficients were calculated by dividing regression coefficients by their standard errors.

Results The likelihood of pet ownership by patients with Paget’s disease at any time corn. pared with matched controls is shown in Table 1. Dog ownership was more frequent in patients with Pagrt’s disease than in controls but this difference was not statistically significant (odds ratio, 1.7; 95% confidence limits, 0.9-3.2). There was no significant increase in the risk of Paget’s disease associated with dog ownership when the study group was broken down by decades prior to diagnosis (data not shown). However, when the group was divided according to age less than/greater than 60 years there was a significant increase in the risk of having Paget’s disease associated with dog ownership in the patient group age 60 years (Table 1). An increase in the risk of Paget’s disease in the ~60 years age group was also seen for cat ownership al-

55 Table 1 Pet ownership in cas+control pairs, expressed as ratio of discordant pairs

Males

lY14

17110

13118

6/6

2i3

1.7(0.7,4.2)

1.1(0.5,2.4) 0.7(0.3.1.6)

l.O(O.3.3.7) 0.7(O.l,S.S)

Females

11n

8110

7113

514

1.6(0.6*4.8)

0.8(0.2,1.1)

0.5(0.2.1.5)

Allsubjects

X17

23i24

20/31

1.3(0.3,6.3) 11/10 415

1.7(0.9-3.2)

1.0(0.6-1.8)

0.7(0.3-1.2)

1.1(0.4-2.8) 0.8(0.4-2.9)

11111

a2

i.o(n.i,r3.8)

Allsubjects

190

7/.5

113

-SOwan

3.8f1.4.13.01 2.110.9.5.3)

l.OfO.4.2.5)

1.4(0.4,5.6)

0.3(0.4.2)

All&bjects

9/12

4/11

9&

415

312‘

0.310.1.0.8)

0.5f0.2.1.0)

O.SfO.2.3.71

1.5(0.2.18.0)

:9/9

’

XQvcars

0.8fO.4.2.81

' Oddsratio(95%mnfidcncclimits).

though this was not statistically significant (odds ratio, 2.1; confidence limits, 0.9-5.3). There was no apparent increase in risk of Paget’s disease seen with ownership of other animals. Since the age division chosen for the data in Table 1 was arbitrary, the age-related variations in relative risk of Paget’s disease were analysed further using multivariate logistic regression (Table 2). Dog and cat ownership were entered as binary variables (yes = 1, no = 0) and were multiplied by the individual subject’s age to yie!d age-interaction variab!es. When considering the effect of dogowne:ship alone (Model 1) the regression coefficient was not significant (standardised coefficient = 1.63, P > 0.05, Table 2). However, when a dog x age interaction term was added (Model 2) the regression coefficient for both dog ownership and age-interaction

Table 2 of Paget’s disease and exposure to dogs or cats, and their respective age-interaction terms Model

Regresdon(srandsrdised)'caef~cients Dog

Cat

Do8 Xa8eb

Cat x age

0 1

0.5oC(1.63)

2

4.24(2.36)

-152.6 -0.07(-2.17)

3

-0.04(-0.15)

4

3.37(2.17)

5

Log-likelihood -155.3

3.35(1.76)

3.84(2.04)

'P1.96.

bAgeinyears.

’ Antiloeofregression~ei~cient

= relative risk.

-146.7 -155.2

-O.lX(1.41)

-O.W(-2.30)

-147.2

-0.07(-2.12)

-139.5

56 were significant (standardised coefficient, 91.96, P < 0.05, Table 2). As well, the change in the log-likelihood statistic between models 1 and 2 (2 = 5.82, P c 0.05) indicates t!!.?t Model 2 explains the variation in the data significantly better than Model I. A similar pattern was obtained for cat ownership (Models 3 and 4), with both regression coefficients in the latter model being significant (Table 2). Dog ownership and cat ownership variables and their respective age-interaction terms were then entered into the same model to scz if there was co-linearity (i.e., confounding) between cat and dog ownership (Model 5, Table 2). The regression coefficients for dog ownership and the age-interaction term in Model 5 decreased in comparison with Model 2, while the coefficient for cat ownership and its age-interaction term increased in comparison with Model 4. This indicates partial confounding between the age-related variations in the risk of Paget’s disease associated with ownership of both these pets. However since this is only partial it appears that dog ownership and catownership are largely independent of each other in their associations with Paget’s disease.

DIscussion The present study provides support for the previous observation of an increase risk of Paget’s disease associated with dog ownership [3]. Thus, there was a trend to an increased incidence of dog ownership compared to possession of other pets, excluding cats, in patients with Paget’s disease (Table l), and in patients less than 60 years of age there was a significantly increased history of previous dog ownership compared with matched controls (Table 1). This increase was apparent in patients of both sexes but was not observed in those patients more than 60 years of age. A similar pattern was observed for cat uwnership. When the age-pet ownership interaction was explored in more detail the influence of age on the risk of Pagct’s disease in dog owners became more apparent (Table 2). The multivariate logistic regression analysis also indicated a significant age-related increase in risk of Paget’s disease for cat owners, which confirmed the increased risk, albeit not significant, observed for patients aged less than 60 years in Table 1. The age-related variations in risk of Paget’s disease for dog and cat ownership were independent of each other. When considering possible biases in this study. it should be noted that it is unlikely that the results are due to recall bias since subjects were blind to both the study hypotheses and also their case-control status. However, only 64% of patients responded to the questionnaire, and only 45% of the initial group were able to be adequately matched to a control subject. This leaves open the possibility of selection bias in the subject sample, although the use of general practitioner-based controls is considered preferable to hospital-based controls as used in previous studies [3-51, since patients attending general practices are more representative of the general population than hospital patients. It is unclear why the study should indicate that an increased risk of Paget’s disease is associated with cat or dog ownership only in younger patients. It is possible

51 that Paget’s diseasemay have multiple aetiologies. If canine and feline viruses are one of several aetiological agents then exposure may be detected in case control studies only in younger individuals, since the frequency of diseasedue to such viruses may become diluted by the contribution of other causesof the disorder in older patients. Such a phenomenon would also tend to explain the generally increased incidence of Paget’sdiseasewith age [lo]. Others have failed to find a relationship between Paget’s disease and past dog ownership. However, one of these studies (51was carried out in an area where the incidence of Paget’s diseaseis probably lower than either the present study or that of O’Driscoll and Anderson [3]. A second study [4], performed in part in a high incidence area, gave no breakdown of case-control data by age and may have misseda significant trend in younger patients. Previous studies have involved only a relatively small number of patients. Is is also unclear why cat ownership also appears significantly related to the risk of Paget’s diseasein this study, whereas no significant relationship was found by O’Driscoll and Anderson (31. The results of this study thus suggestthat pet ownership may predispose to the development of Paget’s disease.Osteoclast activation by slow infection with a paramyxovirus of animal origin is a potential explanation for this finding, and may be a particularly prominent cause for the disorder in the younger patient. The canine distemper virus seemsa possible candidate relating dog ownership to risk of Paget’s disease. In cats the only paramyxoviruses potentially implicated from current virological knowledge would be parainfluenxa virus types 2 and 3 [7-g], and it is possible that parainfluenxa virus infection of cats or dogs could be implicated in Paget’s disease.

Acknowledgements This study was supported by a grant from the New Zealand Medical Research Council. The authors gratefully acknowledge the help of Dr CR. Wilks, Department of Veterinary Virology, Massey University, Palmerston North, New Zealand in the identification of paramyxovhus diseasesin domestic animals.

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