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Journal of Bone and Mineral Research :... Dec 2006
Review
Topics: Diphosphonates; Drug Resistance; Humans; Osteitis Deformans; Pamidronate
PubMed: 17229015
DOI: 10.1359/jbmr.06s216 -
The Journal of Clinical Investigation Mar 2016Paget's disease (PD) is characterized by focal and dramatic bone resorption and formation. Treatments that target osteoclasts (OCLs) block both pagetic bone resorption...
Paget's disease (PD) is characterized by focal and dramatic bone resorption and formation. Treatments that target osteoclasts (OCLs) block both pagetic bone resorption and formation; therefore, PD offers key insights into mechanisms that couple bone resorption and formation. Here, we evaluated OCLs from 3 patients with PD and determined that measles virus nucleocapsid protein (MVNP) was expressed in 70% of these OCLs. Moreover, transgenic mice with OCL-specific expression of MVNP (MVNP mice) developed PD-like bone lesions that required MVNP-dependent induction of high IL-6 expression levels in OCLs. In contrast, mice harboring a knockin of p62P394L (p62-KI mice), which is the most frequent PD-associated mutation, exhibited increased bone resorption, but not formation. Evaluation of OCLs from MVNP, p62-KI, and WT mice revealed increased IGF1 expression in MVNP-expressing OCLs that resulted from the high IL-6 expression levels in these cells. IL-6, in turn, increased the expression of coupling factors, specifically ephrinB2 on OCLs and EphB4 on osteoblasts (OBs). IGF1 enhanced ephrinB2 expression on OCLs and OB differentiation. Importantly, ephrinB2 and IGF1 levels were increased in MVNP-expressing OCLs from patients with PD and MVNP-transduced human OCLs compared with levels detected in controls. Further, anti-IGF1 or anti-IGF1R blocked Runx2 and osteocalcin upregulation in OBs cocultured with MVNP-expressing OCLs. These results suggest that in PD, MVNP upregulates IL-6 and IGF1 in OCLs to increase ephrinB2-EphB4 coupling and bone formation.
Topics: Animals; Case-Control Studies; Cell Differentiation; Cells, Cultured; Coculture Techniques; Ephrin-B2; Humans; Insulin-Like Growth Factor I; Interleukin-6; Measles virus; Mice, Knockout; Nucleocapsid Proteins; Osteitis Deformans; Osteoblasts; Osteoclasts; Receptor, EphB4
PubMed: 26878170
DOI: 10.1172/JCI82012 -
Journal of Postgraduate Medicine 2016
Topics: Biopsy; Diabetes Complications; Diabetes Mellitus, Type 2; Humans; Male; Middle Aged; Osteitis Deformans; Pubic Bone; Sodium Pertechnetate Tc 99m; Tomography, Emission-Computed; Tomography, Spiral Computed
PubMed: 27424556
DOI: 10.4103/0022-3859.186396 -
Medicine May 1997Although the etiology of Paget bone disease (PBD) is unknown, increasing evidence implicates a "slow virus" infection of the skeleton, perhaps in genetically predisposed... (Review)
Review
Although the etiology of Paget bone disease (PBD) is unknown, increasing evidence implicates a "slow virus" infection of the skeleton, perhaps in genetically predisposed individuals. PBD is rare in Asia. We describe a Korean family with PBD. The propositus noticed bowed limbs at approximately 25 years of age. Radiologic studies made when he was 55 years old revealed essentially panostotic PBD. Serum alkaline phosphatase (ALP) activity and osteocalcin (OC) levels were markedly elevated. An iliac crest specimen showed classic histopathologic changes of PBD. Additionally, palpable swellings were first observed at age 45 years at his occiput, pubic ramus, ileum, and facial bones. They contained numerous multinucleated cells and were originally diagnosed as giant cell tumors. However, we found that, like osteoclasts, these cells expressed considerable tartrate-resistant acid phosphatase activity. These "extraskeletal osteoclastomas" resolved rapidly with dexamethasone treatment. Two daughters, 20- and 24-years-of-age, were discovered by study of his 5 children to have elevated serum ALP activity and OC levels and widespread PBD. Both women, however, are without palpable masses and are asymptomatic. The propositus' father, who died at age 55 years, had similar skeletal deformities beginning at age 20 years, but was not examined. Leukocytopenia was found in the 3 living family members with PBD. There was no evidence for linkage of the PBD to HLA loci. The condition appears to be transmitted as an autosomal dominant trait and is manifest in young adult life. Multicentric extraskeletal osteoclastomas with remarkable sensitivity to dexamethasone treatment appear to be another unusual feature of this family's disorder. In this family, the stimulus for PBD is so great that the PBD is apparent at an early age, affects essentially the entire skeleton, and leads to the formation or extension of osteoclast-like cells into nonosseous tissues (extraskeletal osteoclastomas). This 3-generation kindred in Korea, where PBD is rare, shows a strong clustering of PBD compatible with autosomal dominant inheritance. Leukocytopenia appears to distinguish affected family members, but any role for this abnormality in the pathogenesis of PBD is unclear. Our findings support a heritable diathesis for PBD, perhaps mediated by an immune deficiency.
Topics: Adult; Antineoplastic Agents, Hormonal; Dexamethasone; Female; HLA Antigens; Humans; Korea; Male; Middle Aged; Osteitis Deformans; Paranasal Sinus Neoplasms; Pedigree; Radionuclide Imaging; Soft Tissue Neoplasms; Tomography, X-Ray Computed
PubMed: 9193451
DOI: 10.1097/00005792-199705000-00002 -
Bone Mar 2016Depending on populations, 15 to 40% of patients have a familial form of Paget's disease of bone (PDB), which is transmitted in an autosomal-dominant mode of inheritance...
Depending on populations, 15 to 40% of patients have a familial form of Paget's disease of bone (PDB), which is transmitted in an autosomal-dominant mode of inheritance with incomplete penetrance. To date, only SQSTM1 gene mutations have been linked to the disease. Several single nucleotide polymorphisms (SNPs) have been associated with PDB in patient non-carriers of SQSTM1 mutations, but they have minor size effects. The current clinical practice guidelines still recommend to measure total serum alkaline phosphatase (sALP) for PDB screening. However, genetic or bone biomarkers alone may lack sensitivity to detect PDB. Thus, the objective of this study was to develop a molecular test of PDB, combining genetic and bone biomarkers, in order to detect PDB, which is frequently asymptomatic. We genotyped 35 SNPs previously associated with PDB in 305 patients, and 292 healthy controls. In addition, serum levels of 14 bone biomarkers were assayed in 51 patients and 151 healthy controls. Bivariate and multivariate logistic regression models with adjustment for age and sex were fitted to search for a combination of SNPs and/or bone biomarkers that could best detect PDB in patient non-carriers of SQSTM1 mutations. First, a combination of five genetic markers gave rise to the highest area under the ROC curve (AUC) with 95% confidence interval [95% CI] of 0.731 [0.688; 0.773], which allowed us to detect 81.5% of patients with PDB. Second, a combination of two bone biomarkers had an AUC of 0.822 [0.726; 0.918], and was present in 81.5% of patients with PDB. Then, the combination of the five genetic markers and the two bone biomarkers increased the AUC up to 0.892 [0.833; 0.951], and detected 88.5% of patients with PDB. These results suggested that an algorithm integrating first a screen for SQSTM1 gene mutations, followed by either a genetic markers combination or a combined genetic and biochemical markers test in patients non-carrier of any SQSTM1 mutation, may detect the PDB phenotype better than biomarkers already available in the clinical practice.
Topics: Adaptor Proteins, Signal Transducing; Aged; Biomarkers; Cohort Studies; DNA Mutational Analysis; Female; Genetic Association Studies; Genetic Markers; Genetic Predisposition to Disease; Genetic Techniques; Humans; Male; Mutation; Osteitis Deformans; Polymorphism, Single Nucleotide; ROC Curve; Sequestosome-1 Protein
PubMed: 26772620
DOI: 10.1016/j.bone.2016.01.007 -
Journal of Bone and Mineral Research :... Jun 2002The aim of this investigation was to study the prevalence and distribution of Paget's disease in an archeological population. Paget's disease, first described over 100...
The aim of this investigation was to study the prevalence and distribution of Paget's disease in an archeological population. Paget's disease, first described over 100 years ago, is a well-recognized chronic disorder involving abnormal bone turnover with established radiological features. Prevalence within modern populations varies both within individual countries and between them. Paleopathological examples are uncommon and sporadically reported both from Europe and the Americas and from many periods of history. A large skeletal assemblage (2,770 individuals) from Barton on Humber, UK, provided an opportunity to examine the prevalence of Paget's disease in one area of the northern England over the period 900-1,850 AD. All bones were examined visually for evidence of Paget's disease of the bone (PDB) and all abnormal bones were examined further by plain radiography. Fifteen cases of probable Paget's disease were found. The overall prevalence was 2.1% in those aged >40 years. The prevalence before 1500 AD was 1.7% and post-1500 AD was 3.1%. The distribution of disease mirrored modern disease, with the lumbar spine, pelvis, and proximal femur being the commonest sites. The prevalence of Paget's disease in the United Kingdom over the last 1,000 years has been assessed. Although there is a trend of increasing prevalence, this did not reach statistical significance. This is likely caused by the small sample size, but this is by far the greatest number of cases of PDB described in a single skeletal assemblage to date. The distribution of lesions within the skeleton is unchanged.
Topics: Adult; Female; Fossils; Humans; Male; Middle Aged; Osteitis Deformans; Prevalence; Radiography; United Kingdom
PubMed: 12054169
DOI: 10.1359/jbmr.2002.17.6.1127 -
Lancet (London, England) Feb 1993
Topics: Diphosphonates; Female; Humans; Iritis; Middle Aged; Osteitis Deformans
PubMed: 8094197
DOI: 10.1016/0140-6736(93)93029-z -
Reumatologia Clinica 2012Paget's disease of bone is the paradigm of bone focal distortion with accelerated bone turnover. Over the years, a number of different drugs have been used to control... (Review)
Review
Paget's disease of bone is the paradigm of bone focal distortion with accelerated bone turnover. Over the years, a number of different drugs have been used to control its activity but, since biphosphonates were introduced for the treatment of the disease, they have become the preferred treatment. This review will update the therapeutic indications, available drugs and therapeutic response monitoring.
Topics: Alkaline Phosphatase; Biomarkers; Calcium; Collagen Type I; Diphosphonates; Disease Management; Elective Surgical Procedures; Fractures, Spontaneous; Humans; Hypercalcemia; Nerve Compression Syndromes; Osteitis Deformans; Recurrence; Vitamin D
PubMed: 22230789
DOI: 10.1016/j.reuma.2011.06.003 -
Journal of Bone and Mineral Research :... Oct 2005We examined the prevalence of PDB in Italy from radiological, scintigraphic, and biochemical surveys in two Italian towns. Prevalence rates varied from 0.7% to 2.4%,...
UNLABELLED
We examined the prevalence of PDB in Italy from radiological, scintigraphic, and biochemical surveys in two Italian towns. Prevalence rates varied from 0.7% to 2.4%, were higher in males than in females, and slightly differed between the two towns. Unlike previous studies in populations of British descent, no secular trend for a decreasing prevalence emerged.
INTRODUCTION
Clinical, radiological, and necropsy data from different countries suggested pronounced geographical variations in the prevalence of Paget's disease of bone (PDB). Despite the impact of the disease on the population, there are limited data on the prevalence of PDB in Italy.
MATERIALS AND METHODS
The objective of this study was to estimate the prevalence of PDB in the district of Siena (Central Italy) and Turin (Northern Italy) from radiological, biochemical, and scintigraphic surveys. We examined a sample of 1778 consecutive pelvic radiographs performed between 1999 and 2000 at the Hospital Radiology Unit in Siena and 6609 pelvic radiographs performed in 1986-1987, 1992-1993, and 1999-2002 from the Radiology Department of Molinette Hospital in Turin. In Siena, 7906 consecutive (99m)TC-MDP bone scans performed over a 4-year period (January 2000 to May 2004) were also screened for the presence of PDB, and the prevalence of elevated alkaline phosphatase (ALP) levels (>300 UI/liter) was estimated from 7449 computerized medical records over a 3-year period (January 2000 to February 2003). The finding of PDB on the pelvic radiograph and bone scan was based on standardized radiological criteria.
RESULTS
At the end of the radiological surveys, 16/1778 pelvic PDB cases (8 males and 8 females) were observed in Siena and 41/6609 (27 males and 14 females) in Turin. The crude prevalence of the disease was 0.89% in Siena and 0.62% in Turin. Given that pelvic involvement is commonly described in 60-90% of PDB patients, the estimated overall prevalence of PDB ranged from 1.0% to 1.5% in Siena and from 0.7% to 1.0% in Turin. No decrease in the prevalence of PDB was evident after comparison of prevalence rates from different periods. Biochemical analyses showed 296/7449 subjects with elevated ALP levels and normal liver enzymes, 87 of whom had confirmed diagnosis of PDB. The estimated prevalence of biochemical PDB was 1.5%. The scintigraphic survey showed a PDB prevalence of 194/7906 (2.4%), which was significantly higher than the radiological and biochemical estimates.
CONCLUSIONS
Our surveys suggest that PDB in Italy has an estimated prevalence of at least 1%, comparable with that observed in United States and other European countries, but lower than that described in Britain and New Zealand. No secular trend for a decreasing prevalence of PDB was observed.
Topics: Aged; Aged, 80 and over; Alkaline Phosphatase; Female; Humans; Italy; Male; Middle Aged; Osteitis Deformans; Pelvic Bones; Prevalence; Radiography; Retrospective Studies
PubMed: 16160742
DOI: 10.1359/JBMR.050518 -
The American Journal of Case Reports May 2019BACKGROUND Paget disease is a primary bone disease with adjacent joint involvement that commonly presents with degenerative arthritis. Rheumatoid arthritis (RA) is...
BACKGROUND Paget disease is a primary bone disease with adjacent joint involvement that commonly presents with degenerative arthritis. Rheumatoid arthritis (RA) is mainly an articular disease with symmetric synovitis of the peripheral joints and usually does not involve the lumbar spine. The coexistence of Rheumatoid Arthritis and Paget disease of bone is infrequently reported in the literature. CASE REPORT A 74-year-old African-American man was referred for the investigation of symmetrical polyarthritis, left upper arm joint deformity, and low back pain. X-ray imaging of the hands demonstrated bilateral erosions and deformities of the carpal bones, and the left arm showed mixed lytic and sclerotic bone lesions. Laboratory tests showed high levels of rheumatoid factor and alkaline phosphatase. Analysis of the synovial fluid from the left knee was consistent with inflammatory joint disease. CONCLUSIONS The purpose of this article is to present the diagnostic challenges associated with the rare coexistence of Rheumatoid Arthritis and Paget disease of bone in the same patient. The correct diagnosis of both diseases has important consequences in preventing treatment delay.
Topics: Aged; Arthritis, Rheumatoid; Humans; Male; Osteitis Deformans
PubMed: 31142731
DOI: 10.12659/AJCR.914668