Osteosarcoma in Paget's Disease of Bone

Hansen, Marc F.; Seton, Margaret; Merchant, Anand S.

doi:10.1359/jbmr.06s211

Cited by 163 publications

(116 citation statements)

References 65 publications

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“…Moreover, the occurrence of GCT was associated with a consistent increase in ALP levels, as previously described in the case of osteosarcomas complicating PDB. (22) Clinical characteristics of PDB patients from this pedigree were compared with those observed in a cohort of 150 unrelated familial and sporadic PDB cases from the same geographic region (Table 3). Overall, the affected members of the pedigree showed an increased number of affected skeletal sites and an increased prevalence of polyostotic disease than either sporadic or familiar PDB cases from the same region.…”

Section: Resultsmentioning

confidence: 99%

“…(22,26) GCT is also a very rare but well-recognized neoplastic complication of PDB, accounting for only a small proportion of all neoplasms arising from pagetic bone. (16) All GCTs complicating PDB occur exclusively in bone affected by the disease and generally differ in the age of onset and the skeletal localization with respect to GCTs occurring in nonpagetic subjects.…”

Section: Discussionmentioning

confidence: 99%

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Giant cell tumor occurring in familial Paget's disease of bone: Report of clinical characteristics and linkage analysis of a large pedigree

Gianfrancesco¹,

Rendina²,

Merlotti³

et al. 2012

Journal of Bone and Mineral Research

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Neoplastic degeneration represents a rare but serious complication of Paget's disease of bone (PDB). Although osteosarcomas have been described in up to 1% of PDB cases, giant cell tumors are less frequent and mainly occur in patients with polyostotic disease. We recently characterized a large pedigree with 14 affected members of whom four developed giant cell tumors at pagetic sites. The high number of affected subjects across multiple generations allowed us to better characterize the clinical phenotype and look for possible susceptibility loci. Of interest, all the affected members had polyostotic PDB, but subjects developing giant cell tumors showed an increased disease severity with a reduced clinical response to bisphosphonate treatment and an increased prevalence of bone pain, deformities, and fractures. Together with an increased occurrence of common pagetic complications, affected patients of this pedigree also evidenced a fivefold higher prevalence of coronary artery disease with respect to either the unaffected family members or a comparative cohort of 150 unrelated PDB cases from the same geographical area. This association was further enhanced in the four cases with PDB and giant cell tumors, all of them developing coronary artery disease before 60 years of age. Despite the early onset and the severe phenotype, PDB patients from this pedigree were negative for the presence of SQSTM1 or TNFRSF11A mutations, previously associated with enhanced disease severity. Genome-wide linkage analysis identified six possible candidate regions on chromosomes 1, 5, 6, 8, 10, and 20. Because the chromosome 8 and 10 loci were next to the TNFRSF11B and OPTN genes, we extended the genetic screening to these two genes, but we failed to identify any causative mutation at both the genomic and transcription level, suggesting that a different genetic defect is associated with PDB and potentially giant cell tumor of bone in this pedigree. ß

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Giant cell tumor occurring in familial Paget's disease of bone: Report of clinical characteristics and linkage analysis of a large pedigree

Gianfrancesco¹,

Rendina²,

Merlotti³

et al. 2012

Journal of Bone and Mineral Research

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“…As the disease progresses, bone formation predominates, resulting in sclerotic bone overgrowth and deformity. 5 Elevation in ALP, urinary deoxypyridinoline and osteocalcin typically reflects these increases of bone turnover. Sarcoma that arises in PDB is rare and presents with increasing age.…”

Section: Discussionmentioning

confidence: 99%

“…Malignant sarcomatous degeneration is a rare (< 1%) and often fatal complication of PDB. [5][6][7][8] Osteosarcoma is considered to be a rare and devastating complication of PDB. We report on a confirmed case of very rare telangiectatic osteosarcoma in monostotic PDB.…”

Section: Introductionmentioning

confidence: 99%

Telangiectatic osteosarcoma, a rare complication of Paget's disease of bone

Zyl

Conradie

Barnard

et al. 2014

Journal of Endocrinology, Metabolism and Diabetes of South Afri

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“…Approximately 1% of patients with PDB develop osteosarcoma. 1 PDB is inherited as an autosomal dominant trait with genetic heterogeneity and affects 2-3% of the population over the age of 55 years. Both genetic and environmental factors are involved in the pathogenesis of PDB.…”

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confidence: 99%

CXCL5 stimulation of RANK ligand expression in Paget's disease of bone

Sundaram¹,

Rao

Ries

et al. 2013

Laboratory Investigation

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Paget's disease of bone (PDB) is a chronic focal skeletal disorder that affects 2-3% of the population over 55 years of age. PDB is marked by highly localized areas of bone turnover with increased osteoclast activity. Evidence suggests a functional role for measles virus nucleocapsid protein (MVNP) in the pathogenesis of PDB. In the present study, we identified elevated levels (B180-fold) of CXCL5 mRNA expression in bone marrow cells from patients with PDB compared with that in normal subjects. In addition, CXCL5 levels are increased (five-fold) in serum samples from patients with PDB. Furthermore, MVNP transduction in human bone marrow monocytes significantly increased CXCL5 mRNA expression. Realtime PCR analysis showed that CXCL5 stimulation increased (6.8-fold) RANKL mRNA expression in normal human bone marrow-derived stromal (SAKA-T) cells. Moreover, CXCL5 increased (5.2-fold) CXCR1 receptor expression in these cells. We further showed that CXCL5 treatment elevated the expression levels of phospho-ERK1/2 and phospho-p38. CXCL5 also significantly increased phosphorylation of CREB (cAMP response element-binding) in bone marrow stromal/preosteoblast cells. Chromatin immuneprecipitation (ChIP) assay confirmed phospho-CREB binding to RANKL gene promoter region. Further, the suppression of p-CREB expression by the inhibitors of ERK1/2, p38 and PKA significantly decreased CXCL5 stimulation of hRANKL gene promoter activity. Thus, our results suggest that CREB is a downstream effector of CXCL5 signaling and that increased levels of CXCL5 contribute to enhanced levels of RANKL expression in PDB. Paget's disease of bone (PDB) is characterized by highly localized areas of bone turnover with increased osteoclast (OCL) activity followed by poor quality new bone formation due to an exaggerated osteoblast response. Approximately 1% of patients with PDB develop osteosarcoma. 1 PDB is inherited as an autosomal dominant trait with genetic heterogeneity and affects 2-3% of the population over the age of 55 years. Both genetic and environmental factors are involved in the pathogenesis of PDB. Mutations in the ubiquitin-associated domain of sequestosome 1 (SQSTM1/p62) have been identified at 40% in familial and 10% in sporadic cases. 2 Environmental factors such as paramyxoviruses are implicated in PDB. 3 We have previously detected the expression of measles virus nucleocapsid (MVNP) transcripts in OCL from patients with PDB. 4 Moreover, the expression of MVNP in OCL precursors develops pagetic OCL in mice. 5 Receptor activator for nuclear factor-kB ligand (RANKL) is expressed by marrow stromal/osteoblast cells in response to several osteotropic factors such as 1,25 dihydroxy vitamin D 3 , parathyroid hormone (PTH), prostaglandin E 2 and interleukin 1b (IL-1b). 6-8 RANKL-RANK signaling is critical for osteoclast differentiation/bone resorption activity. Enhanced levels of RANKL are associated with PDB. 9,10 In addition, elevated levels of IL-6, macrophage colony-stimulating factor (M-CSF) and endothelin-1 have been reported in PD...

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Osteosarcoma in Paget's Disease of Bone

Cited by 163 publications

References 65 publications

Giant cell tumor occurring in familial Paget's disease of bone: Report of clinical characteristics and linkage analysis of a large pedigree

Giant cell tumor occurring in familial Paget's disease of bone: Report of clinical characteristics and linkage analysis of a large pedigree

Telangiectatic osteosarcoma, a rare complication of Paget's disease of bone

CXCL5 stimulation of RANK ligand expression in Paget's disease of bone

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