Prevalence Of Paget's Disease Of Bone Research Articles

Prevalence and incidence of Paget's disease of bone: Temporal trend over 20years in the province of Quebec, Canada.

Paget's disease of bone (PDB) is a focal bone disorder characterized by an increased bone remodeling and an anarchic bone structure. A decline of prevalence and incidence of PDB has been observed in some countries. No epidemiological data are available on PDB in Canada. We aimed at examining the evolution of the prevalence and incidence of PDB in Quebec (Canada) by analyzing health administrative databases. PDB case definition relied on one or more hospitalizations, or one or more physician-billing claims with a diagnosis code of PDB. To identify incident cases, a 'run-in' period of four years (1996-1999) was used to exclude prevalent cases. For each fiscal year from 2000 to 2001 to 2019-2020 (population size 2,914,480), crude age and sex-specific prevalence and incidence rates of PDB among individuals aged ≥55years were determined, and sex-specific rates were also standardized to the 2011 age structure of the Quebec population. Generalized linear regressions were used to test for linear changes in standardized prevalence and incidence rates. Over the study period, standardized prevalence of PDB has remained stable in Quebec, from 0.44% in 2000/2001 to 0.43% in 2019/2020 (mean change -0.002, p-value=0.0935). For the 2019-2020 fiscal year, 13,165 men and women had been diagnosed with PDB and prevalence of PDB increased with age. Standardized incidence of PDB has decreased over time from 0.77/1000 in 2000/2001 to 0.28/1000 in 2019-2020 (mean change -0.228/year, p-value<0.0001), the incidence decreasing from 0.82/1000 to 0.37/1000 in men and from 0.76/1000 to 0.22/1000 in women, respectively. This decrease was observed in all age categories. With the exception of a slight increase in PDB prevalence up to 0.55% in years 2005 to 2007, the prevalence of PDB has remained stable in Quebec over the past 20years, 13,160 men and women being currently diagnosed with PDB. The incidence has decreased over time. Our results support the epidemiological changes of PDB reported in other countries.

The changing countenance of Paget's Disease of bone

Paget's disease of bone (PDB) manifests fairly late in life and currently affects up to 3% of individuals older than 55 years of age. An about 60% decline in the prevalence of PDB between 1970 and 1990 was documented in England, particularly in Lancashire, where the disease was initially most common. Although wide regional variations exist, the overall prevalence is decreasing, as confirmed by a recent meta-analysis. This secular decline is associated with a decrease in mortality due to the disappearance of sarcomatous transformation of PDB lesions. Another reported change is a decrease in the severity of the clinical PDB phenotype, with a gradual increase in the age at diagnosis of 4 years per decade. In familial forms related to an SQSTM1 mutation, the first manifestations are detected about 10 years later from one generation to the next, and the disease is less severe, with smaller elevations in serum alkaline phosphatase levels and less extensive lesions. Although incompletely understood, the reasons for these changes might involve environmental factors such as the correction of childhood deficiencies in calcium and/or vitamin D, a less rural lifestyle, and decreased contact with domestic animals and consumption of bovine organ meats during childhood. Childhood exposure to industrial waste and products of combustion has also been incriminated. Finally, although classical, the role for paramyxoviruses such as the measles virus in the pathogenesis of PDB remains debated in the literature.

Paget disease of bone: A classic case report

Paget disease of bone (PDB) is a chronic progressive disease of the bone of uncertain etiology, characterized initially by an increase in bone resorption, followed by a disorganized and excessive formation of bone, leading to pain, fractures, and deformities. It can manifest as a monostotic or polyostotic disease. The prevalence of PDB is common in the Anglo-Saxon population, but relatively rare in India. The disease is often asymptomatic and commonly seen in an aging population. The diagnosis of the disease is mostly based on radiological examination and on biochemical markers of bone turnover. Markedly elevated serum alkaline phosphatase (SAP) is a constant feature while calcium and phosphate levels are typically within normal limits. It is being successfully treated by biphosphonates, a group of anti-resorptive drugs, thereby decreasing the morbidity and mortality associated with the disease. We report a classic case of PDB with craniofacial involvement resulting in Leontiasis Ossea (lion like face), cotton wool appearance of the skull and elevated SAP.

Paget’s disease of bone: analysis of 134 cases from an island in Southern Brazil: another cluster of Paget’s disease of bone in South America

Paget's disease of bone (PDB) exhibits a marked geographic variation. In Brazil, the prevalence of PDB is unknown and only a few clinical data are available. The aim is to determine clinical, laboratory, imaging and response to treatment data in a large PDB case series in the city of Florianopolis, Brazil. We have performed a retrospective study based on charts reviews of all patients with PDB followed at the University Hospital of the Federal University of Santa Catarina and at five different private rheumatology outpatient offices in Florianopolis, between 1995 and 2009. One hundred and thirty-four patients with PDB were identified. Mean age at diagnosis was 63.2 ± 10.5 years, 67.2% were women, and 91.1% were Caucasian. Positive family history was reported in only 8.2%. Polyostotic disease was found in 75.0% of the cases, bone pain in 77.9%, and bone deformities in 15.9%. Higher levels of AP were significantly associated with polyostotic disease and skull involvement. Pelvic bones were the most frequently affected (53.7%). Complications included deafness in 8.2%, bone fractures in 3.0%, hydrocephalus in 2.2%, and cauda equina syndrome in 0.7% of the cases. Treatment with zoledronic acid achieved the best response with only 2.9% failing to respond adequately. According to literature data, PDB in South America seems to be characterized by an overall low prevalence, but with localized clusters with higher prevalence. The authors have described a cluster of PDB in Florianopolis, in Southern Brazil. Further properly designed studies are necessary to clarify the PDB epidemiology in South America.

Epidemiological, clinical, and genetic characteristics of Paget’s disease of bone in a rural area of Calabria, Southern Italy

The prevalence of Paget's disease of bone (PDB) is unknown in peninsular Southern Italy, although an elevated clinical severity of the disease was reported in patients from Campania. This study was performed to evaluate the epidemiological and genetic characteristics of PDB in a rural area of Calabria, the southernmost region in the Italian peninsula. We examined 1068 consecutive pelvic radiographs of patients older than 40 yr referred for any reason to the "Spinelli" Hospital, Belvedere Marittimo, from January 1st 2004 to December 31st 2006. In subjects with radiological findings of pelvic PDB, a 99m Technetium methylene diphosphonate bone scan and the sequence analysis of the sequestosome 1 (SQSTM1) gene were subsequently performed. In the examined geographic area, the crude radiographic prevalence of pelvic PDB was 0.74% (8/1068; male:female 5:3, mean age 71.6 ± 13.1 yr) whereas the estimated overall prevalence of PDB between 0.82% and 1.21%. PDB patients from Calabria showed clinical characteristics similar to those reported in patients from Campania. The disease was also frequently complicated by osteoarthritis and the right side of the body was more affected than the left. The SQSTM1 gene analysis revealed the presence of a novel missense mutation (M401V) in exon 8 in one subject with a familial and aggressive form of PDB. The study results confirmed that patients with PDB from rural districts of Southern Italy show an earlier onset and an increased clinical severity of the disease that appears mostly independent from the presence of germinal SQSTM1 mutations.

Characteristics of Paget’s disease of bone in the city of Recife, Brazil

In South America the incidence of Paget's disease of bone (PDB) is low and more than half of the cases published in the last 30 years come from Brazil and Argentina. The aim of this study was to describe the clinical and epidemiological characteristics of PDB in two institutions in Pernambuco. PDB patients in Recife, Brazil were studied retrospectively. A total of 108 cases were diagnosed from 1984 to 2005. Over 90% of the patients were of European descent. The average age was 66.2 years and 49.1% were male. The polyostotic form was the more common. Pain and bone deformity were significantly more frequent in this group and in the total group. Clear eyes were observed in 22.2% of the patients and 23.1% had a family history record of PDB. The most frequently affected bones were the pelvis, lumbar vertebrae, femurs, and skull. Zoledronate was the most effective drug in reducing the alkaline phosphatase. Our data show that PDB in Recife occurs predominantly among those of European descents, usually in the polyostotic presentation, thus providing evidence of genetic and historical factors in the prevalence of PDB in that region.

Paget's Disease of Bone in Italy

Epidemiological studies of Paget's disease of bone (PDB) suggest a pronounced geographical variation in the prevalence of the disease and a decrease in prevalence and clinical severity over time. To analyze epidemiological and clinical features of PDB in Italy, we recently established a registry of Italian PDB cases and performed radiological, biochemical, and bone scan surveys in the towns of Siena and Turin. The overall prevalence of PDB in Italy varied between 0.7% and 2.4%. Prevalence rates increased with age and were higher in men than in women. We observed clinically confirmed familial aggregation in 15-26% of cases. Pedigree analysis indicated an autosomal dominant pattern of inheritance with variable penetrance. SQSTM1 gene analysis in two Italian studies revealed the presence of at least three different mutations accounting for both familial and sporadic cases. Interestingly, no decrease in the prevalence of PDB over time was observed, the opposite of what is described in populations of British descent. However, clinical severity of PDB cases included in the Registry in 2002-2004 seemed reduced with respect to that of PDB patients from the previous epidemiological studies, including a 1950-1956 Italian study. Of interest, a consistent association between PDB and animal-related factors and a significantly higher prevalence of the disease in rural than in urban districts were observed. These findings are in keeping with an important role of the environment in the pathogenesis of PDB, perhaps facilitating the expression of the disease in genetically susceptible subjects. Finally, there was also preliminary evidence indicating regional clustering of PDB in Italy, with a concentration of cases in rural districts of Campania and Tuscany. These districts may represent high prevalence areas of PDB in Italy, similar to what has been observed in other countries. Extrapolation estimates suggest that approximately 150,000-300,000 subjects may be affected with PDB in our country. These results confirm PDB to be the most common bone remodeling disorder in elderly people in Italy, excluding osteoporosis.

Update on the Epidemiology of Paget's Disease of Bone

Paget's disease of bone (PDB) is characterized by rapid bone remodeling and the formation of bone that is structurally abnormal. Recent studies have confirmed that both genetic and environmental factors are important in its etiology. Epidemiological studies in Europe and North America have revealed that PDB shows an increasing frequency of occurrence with age and is more prevalent among men than women. There is marked geographic variation in the prevalence of PDB throughout western nations, with the highest rates reported during the 1970s in Britain. Recent studies of the secular trends in PDB suggest declining rates in both prevalence and severity at diagnosis. Thus, the overall age/sex standardized prevalence rate in Britain during the period 1993-1995 was found to be 2.5% among men and 1.6% among women > or = 55 years of age. Prevalence rates had fallen by approximately 50% in several of the centers studied, suggesting an environmental contribution to the etiology of this disorder. Similar findings have been reported from other European countries and New Zealand. Recent study of the incidence and clinical manifestations of PDB have emerged from large cohort studies in primary care record linkage resources, such as the General Practice Research Database. Over the period 1988-1999, the incidence rate of clinically diagnosed PDB was found to be 5 per 10,000 person-years among men and 3 per 10,000 person-years among women 75 years of age. The disorder was associated with an increased risk of back pain (RR, 2.1; 95% CI, 1.9-2.3); osteoarthritis (RR, 1.7; 95% CI, 1.5-1.9); and fracture (RR, 1.2; 95% CI, 1.0-1.5). Using life table methodology, the estimated proportion of patients dying within 5 years of follow-up was 32.7% among the cohort with PDB compared with 28.0% among control patients (p < 0.05).

Guidelines for diagnosis and management of Paget's disease of bone in Japan

We here propose guidelines for the diagnosis and management of Paget's disease of bone (PDB) in Japan. These guidelines provide basic information on the epidemiology, pathophysiology, clinical signs and symptoms, diagnosis, indications for treatment, and available therapy, including orthopedic surgery. PDB is a chronic disorder characterized by focal abnormalities of bone turnover. The characteristic feature of PDB is excessive osteoclastic bone resorption coupled to increased and disorganized bone formation. The most common symptom of PDB is pain in involved bones. The most serious complication of PDB is malignant bone or soft-tissue tumor. PDB is uncommon in Japan; our survey in 2003 found 169 patients with PDB. The prevalence of PDB in Japan is 0.15/100 000; in patients aged 55 years or more, the proportion reaches 0.41/100 000. A careful medical history and physical examination are essential for the diagnosis. The diagnosis of PDB is based on finding the typical features on radiographs. Bone scintigraphy and measurement of serum alkaline phosphatase are sensitive means of screening for PDB. Since PDB is a rare disease in Japan, bone biopsy is quite often used to exclude bone metastases. The only evidence-based indication for treatment of PDB is pain in involved bones. In Japan, etidronate and calcitonin are approved by the Ministry of Health, Labour and Welfare for treating PDB, but currently risedronate is also under development for treating PDB in Japan. Indications for surgical intervention in PDB include unstable fractures, osteoarthritis, malignant soft-tissue tumor, osteosarcoma, and bone deformity.

Ubiquitin-Associated Domain Mutations of SQSTM1 in Paget's Disease of Bone: Evidence for a Founder Effect in Patients of British Descent

Mutations in the UBA domain of SQSTM1 are a common cause of Paget's disease of bone. Here we show that the most common disease-causing mutation (P392L) is carried on a shared haplotype, consistent with a founder effect and a common ancestral origin. Paget's disease of bone (PDB) is a common condition with a strong genetic component. Mutations affecting the ubiquitin-associated (UBA) domain of sequestosome 1 (SQSTM1) have recently been shown to be an important cause of PDB. The most common mutation results in a proline to leucine amino acid change at codon 392 (P392L), and evidence has been presented to suggest that there may be a recurrent mutation rather than a founder mutation on an ancestral chromosome. Because marked geographical differences exist in the prevalence of PDB, we have investigated the frequency of SQSTM1 mutations in different populations and looked for a founder effect on chromosomes bearing SQSTM1 UBA domain mutations. We conducted mutation screening of SQSTM1 and performed haplotype analysis using the PHASE software program in 83 kindreds with familial PDB, recruited mainly through clinic referrals in the United Kingdom, Australia, and New Zealand. Similar studies were conducted in 311 individuals with PDB who did not have a family history and 375 age- and sex-matched controls from the United Kingdom. The proportion of patients with familial PDB who had SQSTM1 UBA domain mutations varied somewhat between referral centers from 7.1% (Sydney, Australia) to 50% (Perth, Australia), but the difference between centers was not statistically significant. Haplotype analysis in 311 British patients with PDB who did not have a family history and 375 age- and sex-matched British controls showed that two common haplotypes accounted for about 90% of alleles at the SQSTM1 locus, as defined by common single nucleotide polymorphisms (SNPs) in exon 6 (C916T, G976A) and the 3'UTR (C2503T, T2687G). These were H1 (916T-976A-2503C-2687T) and H2 (916C-976G-2503T-2687G). There was no significant difference in haplotype distribution in PDB cases and controls, but the P392L mutation was found on the H2 haplotype in 25/27 cases (93%), which is significantly more often than expected given the allele frequencies in the normal population (odds ratio, 13.2; 95% CI, 3.1-56.4; p < 0.0001). Similar findings were observed in familial PDB, where 12/13 (92%) of P392L mutations were carried on H2 (odds ratio 17.2; 95% CI, 2.2-138; p = 0.001). These results provide strong evidence for a founder effect of the SQSTM1 P392L mutation in PDB patients of British descent, irrespective of family history. Our results imply that these individuals share a common ancestor and that the true rate of de novo mutations may be lower than previously suspected.