Gene-environment interactions in Paget's disease of bone

Numan, Mohamed S; Jean, Sonia; Dessay, Mariam; Gagnon, Édith; Amiable, Nathalie; Brown, Jacques P.; Michou, Laëtitia

doi:10.1016/j.jbspin.2018.12.007

Cited by 10 publications

(6 citation statements)

References 36 publications

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“…A previous study in our French-Canadian cohort suggested that indoor air pollutants such as tobacco smoke may contribute to PDB pathogenesis ( Numan et al, 2019 ). Moreover, Audet et al found an association of PDB in the French-Canadian cohort with wood fire heating in childhood and/or adolescence but no association with measles immunization or childhood sickness ( Audet et al, 2017 ).…”

Section: Discussionmentioning

confidence: 88%

Clinical phenotype of adult offspring carriers of the p.Pro392Leu mutation within the SQSTM1 gene in Paget's disease of bone

et al. 2020

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Paget's disease of bone (PDB) is a common chronic bone disorder. In the French-Canadian population, the p.Pro392Leu mutation within the SQSTM1 gene is involved in 46% of familial forms. In New Zealand, the emergence of PDB in offspring inheriting SQSTM1 mutations was reported to be delayed by a decade compared to their parents. We aimed at assessing the clinical phenotype of offspring carriers of this mutation in our French-Canadian cohort. We reviewed research records from adult offspring carriers of this mutation aged <90 years and their affected parents. In parents, we collected data on sex, age at diagnosis, number of affected bones, total serum alkaline phosphatase levels (tALPs) at diagnosis. In offspring, PDB extended phenotype assessment relying on tALPs, bone specific alkaline phosphatase levels (bALPs), procollagen type 1 amino-terminal propeptide (P1NP), whole body bone scan and skull and pelvis radiographs, was performed at inclusion from 1996 to 2009 and updated in 2016 to 2018, if not done during the past 8 years. The results showed that among the 36 offspring with an updated phenotype, four of them developed a clinical phenotype of PDB characterized by monostotic or polyostotic increased bone uptake associated with typical radiographic lesions in the affected sites, representing an incidence of 1.83 per 1000 person-years. Moreover, the age at PDB diagnosis was delayed by at least 10 years in the adult offspring carriers of the p.Pro392Leu mutation versus their affected parents. Our findings support the utility of a regular monitoring of the adult offspring without PDB but carriers of this mutation.

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Section: Discussionmentioning

confidence: 88%

Clinical phenotype of adult offspring carriers of the p.Pro392Leu mutation within the SQSTM1 gene in Paget's disease of bone

et al. 2020

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“…The etiology of PDB remains unclear, but some studies suggest that several genes involved in the differentiation or function of osteoclasts[ 6 - 9 ] and environmental factors, such as viral infection, particularly measles, animal contact, pesticides, and tobacco smoke, together play important roles in its pathogenesis[ 10 ]. Furthermore, rapidly increased bone resorption accompanied by abnormal new bone formation is a substantial PDB pathological characteristic.…”

Section: Discussionmentioning

confidence: 99%

Paget’s disease of bone: Report of 11 cases

Miao¹,

Wang²,

Lyu³

et al. 2021

WJCC

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BACKGROUND Paget’s disease of bone (PDB) is a rare metabolic bone disease in China and is characterized by increased bone resorption and disorganized bone formation. The main clinical symptoms of PDB are focal or multiple bone pain and deformity with high disability. The disease has high missed diagnosis and misdiagnosis rates. This report summarizes the clinical manifestations, imaging and pathological features, and treatments of 11 patients with PDB at our hospital from 1993 to 2020 in order to improve the recognition and prognosis of PDB. CASE SUMMARY There were eight male and three female patients whose average age was 48.7 ± 11.0 years with a PDB course of 1-16 years. Nine patients had bone pain and bone deformities in different parts of the body, the majority of which involved the long bones. Laboratory examinations revealed elevated serum alkaline phosphatase (ALP) in all patients with an average of 618 ± 460 IU/L (normal range 0-130 IU/L), and serum calcium and phosphorus levels were in the normal range. Imageology showed that osteolysis was usually combined with osteosclerosis and/or bone deformities in single or multiple bones. 99m Tc-methylene diphosphonate bone scintigraphy revealed increased radionuclide uptake in the bone lesions. Six patients underwent bone tissue biopsy, and the typical pathological changes were a mosaic structure of the bone trabeculae with irregularly arranged cement lines and multinuclear osteoclasts. Ten of the 11 patients were effectively treated with bisphosphonates. CONCLUSION Early diagnosis of the rare disease PDB can be made through elevated ALP levels and typical presentations on bone X-ray and from bone tissue biopsy.

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“…A diet that is high in saturated fats and low in calcium and vitamin D can contribute to the development of the disease, as can a sedentary lifestyle. Exercise and a diet that is rich in calcium and vitamin D can help to prevent the development of PDB and slow the progression of the disease ( Numan et al, 2019 ). Furthermore, experiments revealed a relationship between the SQSTM1 gene and exposure to cadmium and tobacco smoke condensates, in certain patients with non-familial PDB ( Numan et al, 2019 ).…”

Section: Epidemiology Of Pdbmentioning

confidence: 99%

Paget’s disease: a review of the epidemiology, etiology, genetics, and treatment

et al. 2023

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Paget’s disease of bone (PDB) is the second most prevalent metabolic bone disorder worldwide, with a prevalence rate of 1.5%–8.3%. It is characterized by localized areas of accelerated, disorganized, and excessive bone production and turnover. Typically, PDB develops in the later stages of life, particularly in the late 50s, and affects men more frequently than women. PDB is a complex disease influenced by both genetic and environmental factors. PDB has a complex genetic basis involving multiple genes, with SQSTM1 being the gene most frequently associated with its development. Mutations affecting the UBA domain of SQSTM1 have been detected in both familial and sporadic PDB cases, and these mutations are often associated with severe clinical expression. Germline mutations in other genes such as TNFRSF11A, ZNF687 and PFN1, have also been associated with the development of the disease. Genetic association studies have also uncovered several PDB predisposing risk genes contributing to the disease pathology and severity. Epigenetic modifications of genes involved in bone remodelling and regulation, including RANKL, OPG, HDAC2, DNMT1, and SQSTM1, have been implicated in the development and progression of Paget’s disease of bone, providing insight into the molecular basis of the disease and potential targets for therapeutic intervention. Although PDB has a tendency to cluster within families, the variable severity of the disease across family members, coupled with decreasing incidence rates, indicates that environmental factors may also play a role in the pathophysiology of PDB. The precise nature of these environmental triggers and how they interact with genetic determinants remain poorly understood. Fortunately, majority of PDB patients can achieve long-term remission with an intravenous infusion of aminobisphosphonates, such as zoledronic acid. In this review, we discuss aspects like clinical characteristics, genetic foundation, and latest updates in PDB research.

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Gene-environment interactions in Paget's disease of bone

Cited by 10 publications

References 36 publications

Clinical phenotype of adult offspring carriers of the p.Pro392Leu mutation within the SQSTM1 gene in Paget's disease of bone

Clinical phenotype of adult offspring carriers of the p.Pro392Leu mutation within the SQSTM1 gene in Paget's disease of bone

Paget’s disease of bone: Report of 11 cases

Paget’s disease: a review of the epidemiology, etiology, genetics, and treatment

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