Paget's disease in patients of Asian descent in New Zealand



Paget's disease is considered to be uncommon in Asian people, but we have noted a recent increase in the number of Asian patients referred to our clinic, on a background of an apparently decreasing prevalence in the population of European descent. In this article, we report clinical and epidemiological features of patients of Asian descent with Paget's disease, referred between 1973 and 2010 to the Auckland Paget's disease clinic. No Asian patients were referred before 1993, but 14 have presented between 1993 and 2010, with a median of 8 years between arrival into New Zealand and time of diagnosis. The patients were predominantly of south Asian origin. None of the 8 patients tested carried a mutation in exon 8 of the sequestosome 1 (SQSTM1) gene. The number of new Paget's disease referrals expressed as a proportion of the potentially at-risk Asian population in the Auckland region (derived from census data) was 1/104 in 2006 to 2011. Amongst Europeans, the corresponding value decreased from 10/104 in 1986 to 1991 to 2/104 in 2006 to 2010. The increased number of people of Asian descent diagnosed with Paget's disease in the Auckland region has paralleled the increasing size of the local Asian population. The continuing decline of Paget's disease in the European population, in conjunction with the emergence of the disease in the Asian population, supports the view that an environmental determinant to the disease exists and that Asians are not genetically protected. It also implies that the apparent reduction in Paget's disease prevalence in western cities is unlikely to be explicable by the rising Asian population of these cities. © 2012 American Society for Bone and Mineral Research


Paget's disease of bone (PDB) is a common disorder, characterized by focal rapid remodeling of affected bones. This can lead to complications such as fracture, deformity, bone pain, and secondary osteoarthritis. The prevalence of PDB varies significantly between countries, but it is common in Britain and Western Europe, where the archeological investigation of skeletal remains suggests that it emerged in the Roman era.1 New Zealand has a high prevalence of PDB, and it is assumed that the disorder was brought to the country by migrants who came in large numbers from Britain in the late 19th and early 20th centuries.2 There is strong evidence for a genetic predisposition to Paget's disease (through mutations in sequestosome 1 [SQSTM1]) that may underlie the apparent transmission of Paget's disease with migrant populations.3

The Paget's disease clinic at Auckland City Hospital (established in 1973) has kept a comprehensive database of all patients referred to the clinic. As published previously,4 we noted that in the period 1973 to 2003 there was a rise in the mean age at presentation and a decline in disease severity, suggesting an important secular trend. Over a similar period, radiographic surveys showed a significant decline in disease prevalence.5 However, despite a continuing decline in the total number of patients referred, we have noticed an increasing number of patients of Asian descent referred with Paget's disease.

Limited literature exists on the prevalence of PDB in Asian countries. In Japan, the prevalence of Paget's disease is said to be very low (<3 per million).6 Reports from large centers in India studying patients in the period 1995 to 2005 indicate that relatively few patients are diagnosed with the disease.7–9 The data from Southeast Asia and China are even more limited with only a small number of case reports.10–15 In light of this limited literature, we report clinical and epidemiological features of the patients of Asian descent referred to our clinic over the period 1973 to 2010.

Materials and Methods


From 1973 to the end of 2010 (37 years), a total of 1668 patients were referred for the first time to our clinic. Data recorded in the database were the year of birth, sex, the year and age at diagnosis, pretreatment total alkaline-phosphatase (ALP) activity, and skeletal involvement on scintigraphy. We defined Asian as being of East, South, or Southeast Asian descent. We identified 14 patients of Asian descent presenting to our clinic and extracted further information on their place of birth and date of arrival into New Zealand.

Census data

In the Auckland region, the population of Asian descent has increased in recent decades. To determine if the apparent increase in the number of patients with Paget's disease paralleled this change, we obtained census data on the Auckland region from Statistics New Zealand. In New Zealand, censuses are conducted every 5 years and include data on self-declared ethnicity. The populations of Europeans and all Asian ethnic groups for the ages >40 years were obtained from the censuses of 1986, 1991, 1996, 2001, and 2006.

SQSTM1 mutation screening

We obtained samples from 8 of the 14 Asian patients for SQSTM1 mutation testing. DNA was extracted from blood samples using the Progene DNA purification kit (Gentra Systems, Minneapolis, MN, USA). Exon 8 of the SQSTM1 gene was amplified by Platinum Taq polymerase (Invitrogen, Carlsbad, CA, USA) in 35 cycles of PCR at an annealing temperature of 62°C and MgCl2 concentration of 1.5 mM. The forward primer 5′-GGCAGAGTTGAGCAGTGTG-3′ and the reverse primer 5′-CCCGTACAGAGACCTGCAAT-3′ produced 445-bp products that were subsequently purified using the High Pure PCR product purification kit (Roche, Mannheim, Germany) and sequenced on ABI PRISM 3130XL Genetic Analyzer capillary sequencer (Applied Biosystems, Inc., Foster City, CA, USA).


No Asian patients were referred between 1973 and 1992. Between 1993 and 2010, 14 Asian patients presented with PDB, 12 of whom were diagnosed in the period 2002 to 2010. There were 13 men, 8 of whom were symptomatic at diagnosis. None of the patients were born in New Zealand, and the diagnosis was made at a median of 8 years after migration (Table 1). None had a family history of the disorder. The severity of the disease in the 14 Asian patients was comparable to that seen in patients of European descent in the same time period, although the Asian patients were somewhat younger (64.5 versus 72 years). None of the 8 patients tested carried mutations in exon 8 of the SQSTM1 gene.

Table 1. Demographic and Clinical Features of Asian Patients With Paget's Disease
DemographyClinical features at diagnosis
Patient no.SexCountry of birthMigration to New ZealandYear of diagnosisAge (years)Alkaline phosphatase (U/L)a SymptomsBones involvedb (n)Skeletal involvementb (%)
  • N/A = not available.

  • a

    Alkaline phosphatase normal range: 30 to 120 U/L.

  • b

    Determined from bone scintiscan.

  • c

    Patients tested for SQSTM1 mutations.

  • d

    All the subjects from Fiji were of Indian descent.

3c FSri Lanka1997200255245No36
4b MFijid 1999200462399Yes15
6MFijid 2000200583244Yes15
7c MFijid 1989200561205No210
8MFijid 2000200757177NoN/AN/A
9c MFijid 200420084895No11
10c MFijid 2007200867299Yes717
12c MChina2008201065129Yes27.5
13c MIndia2003201070140No26
14c MFijid 1994201073203Yes15

Data obtained from Statistics New Zealand showed that in the Auckland region in the period 1986 to 2006, the European population >40 years increased from 271,000 to 317,000, whereas the Asian population >40 years increased from 4000 to 75,000 (Fig. 1). The number of new PDB referrals expressed as a proportion of the total Auckland population >40 years of age increased from being undetected in 1986 to 1991 to 1/104 in 2006 to 2010 in those of Asian descent, whereas in those of European descent the corresponding value decreased from 10/104 in 1986 to 1991 to 2/104 in 2006 to 2010 (Fig. 1).

Figure 1.

Cases of Paget's disease in subjects referred to our clinic, expressed as a proportion of the potentially at-risk population. The vertical columns indicate the total population age 40 to 100 years (both sexes) in the Auckland area of either European descent (light gray) or Asian descent (dark gray) recorded in successive censuses. Note the logarithmic scale. The population of Asian descent has increased steadily from 1986. For the same time periods, the number of patients presenting with Paget's disease is expressed as a percentage of the at-risk population (European descent, gray circles; Asian descent, dark squares). In the most recent time period (2006 to 2010), this proportion was similar in the two groups.


Our study has shown that the increased number of people of Asian descent diagnosed with PDB and referred to our clinic has paralleled the increasing size of the Asian population in the Auckland region. There has been a concurrent decline in the apparent prevalence of PDB in the European population, so that the proportion of the potentially at-risk population referred in the period 2006 to 2010 is now similar in Asians and Europeans. Our data do not necessarily suggest that Paget's disease is becoming more prevalent in people of Asian descent; it could simply be more visible as the size of this population grows. An unusually high proportion of our patients were men, but given the small number of patients in total, the significance of this is uncertain.

Paget's disease is most prevalent in people of Northwestern European origin, but it has also been observed in populations of non-European descent. Prevalence surveys in a number of US cities and South Africa have found no difference in disease prevalence between people of African and European descent.16–18 PDB has also been identified in patients of Caribbean or Asian descent in London.19 Our patients had lived in New Zealand for a median of 8 years before diagnosis, although, of course, we cannot determine when their disease first developed. The most frequently seen group were Fijian Indian migrants to New Zealand, whose ancestors came from widely dispersed rural areas of India to Fiji, predominantly between 1879 and 1916.

There are limitations to our data. First, some patients may have been managed by their general practitioners or other providers and not referred to us. Second, the geographical area defined as Auckland was increased between the censuses of 1986 and 1991. Despite these limitations, our study suggests the emergence of PDB in Asians—a population who were hitherto thought not to be susceptible.

The etiology of Paget's disease is unknown, but both environmental and genetic factors are thought to be important. Mutations in the SQSTM1 gene are associated with familial PDB,3 and genome-wide association studies have demonstrated that polymorphisms in several genes are present in higher frequency in patients with Paget's disease.20 The absence of SQSTM1 mutations in our patients is not surprising, given that 5% or fewer of patients with with nonfamilial Paget's disease carry such mutations.3 However, the recent decline in disease prevalence and severity in populations of European descent argues strongly that there are also significant environmental determinants of the disease. The fact that we have demonstrated both a continuing decline in the European population in conjunction with the appearance of the disease in Asian subjects in our region as the local population has increased suggests not only that there is an environmental determinant but also that Asians are not genetically protected from PDB. It further implies that the recent reduction of Paget's disease prevalence in cities in formerly high prevalence areas cannot be explained, as has been suggested,3 by the rising Asian population in these areas. The nature of the environmental agent (or agents) is not known. Viruses (possibly acquired from animals), environmental pollutants, trauma, and nutritional deficiencies have all been suggested, but no definitive proof of any of these possibilities has been established.3


All the authors state that they have no conflicts of interest.


We thank Greg Gamble for his help with the statistical analyses, and the Health Research Council of New Zealand for financial support.

Authors' roles: Study design: AG and TC. Study conduct: SS and TC. Data collection: SS and DN. Data analysis: SS and TC. Data interpretation: SS, DN, AG, and TC. Drafting manuscript: SS and TC. Revising manuscript content: DN and AG. Approving final version of manuscript: SS, DN, AG, and TC. TC takes responsibility for the integrity of the data analysis.