The Experts below are selected from a list of 42 Experts worldwide ranked by ideXlab platform
Steven L. Teitelbaum - One of the best experts on this subject based on the ideXlab platform.
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Juvenile Paget Disease: life-long features of a mildly affected young woman.
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2009Co-Authors: Deborah S. Golob, Steven L. Teitelbaum, William H. Mcalister, Barbara G. Mills, Kenton N. Fedde, William R. Reinus, Suganthi Beeki, Michael P. WhyteAbstract:Unusually mild Juvenile Paget Disease (JPD) was extensively investigated in a mentally retarded 21-year-old white woman. Progressive bowing deformitity of her lower limbs began at age 1 1/2 years. Nontraumatic fractures of both femora and both tibias occurred between ages 9 and 14 years. During adulthood, cortical thickening, osteosclerosis, and bowing affected these Bones. Serum alkaline phosphatase (ALP) activity was persistently elevated. We found her serum osteocalcin and urinary hydroxyproline and pyridinoline/deoxypyridinoline to also be increased. The iliac crest histology, at ages 14 and 21 years, showed wide cortices and enhanced skeletal remodeling yet the Bone was exclusively lamellar. Features of classic Paget Bone Disease (PBD)--such as hypermultinucleated osteoclasts, peritrabecular fibrosis, and mosaic or woven Bone--were absent. Electron microscopy revealed no cytoplasmic or nuclear inclusions. Her dermal fibroblasts in culture synthesized unremarkable levels of ALP with proper membrane topography and lipid anchoring; ALP released into the medium also appeared normal. Six months of synthetic human calcitonin therapy daily appeared to reduce here lower limb pain and warmth, but the radiographs, biochemical parameters of skeletal turnover, and Bone scintigraphy were unaltered. Lamellar Bone has been reported in JPD but accompanied by excessive amounts of woven Bone. Our patient reveals that lamellar Bone without features of PBD can characterize the skeletal histopathology of the especially rare case of mild JPD.
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Extraskeletal Osteoclastomas Responsive to Dexamethasone Treatment in Paget Bone Disease
The Journal of clinical endocrinology and metabolism, 1997Co-Authors: Konstantinos Ziambaras, William A. Totty, Steven L. Teitelbaum, Megan Dierkes, Michael P. WhyteAbstract:Giant cell tumors (GCTs) of Bone, also called osteoclastomas, complicate Paget Bone Disease (PBD), though infrequently. Giant cell reparative granulomas (GCRGs), which are histologically similar to GCTs, also occur rarely in Pagetic patients. A 45-yr-old black woman with neurofibromatosis, type I, and polyostotic PBD developed slowly-growing masses in the right posterior iliac and left upper parasacral regions. She had multiple cutaneous neurofibromas and cafe-au-lait spots. Serum alkaline phosphatase activity and urine hydroxyproline levels were elevated. Skeletal radiographs and Bone scintigraphy showed changes of widespread PBD. Computerized tomography and magnetic resonance imaging (MRI) delineated masses in the right gluteal and the left lower lumbar paraspinal regions. Five additional smaller masses were found in the abdomen and in the pelvis. Biopsy of the right gluteal mass revealed a GCT. However, we found that this lesion had several histologic features distinct from those of giant cell reparative granulomas or GCT. In our patient's tumor, the huge polykaryons, like osteoclasts, expressed abundant tartrate-resistant acid phosphatase activity, whereas those of GCRG lack this enzyme. Although the polykaryons in conventional GCTs and GCTs in PBD express tartrate-resistant acid phosphatase activity, the location of these tumors in Bone differs from the extraskeletal masses encountered in our patient. Furthermore, the larger size of the polykaryons and the greater number of nuclei in our patient's GCT differ from conventional GCTs, but not GCTs in PBD. Her extraskeletal osteoclastoma rapidly shrunk to one third its original size during 2 weeks of oral dexamethasone treatment. Significant clinical improvement lasted about 5 months before additional courses of dexamethasone therapy were necessary. Injections of synthetic salmon calcitonin alone did not affect the tumor's size. Thus, PBD can be complicated by extraskeletal tumors that seem to contain osteoclasts and are responsive to dexamethasone treatment.
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Paget Bone Disease Involving Young Adults in 3 Generations of a Korean Family
Medicine, 1997Co-Authors: Ghi Su Kim, Sun H. Kim, Jae K. Cho, Joong Y. Park, Myung Jin Shin, Young Kee Shong, Kee-up Lee, Hoon Han, Tai-gyn Kim, Steven L. TeitelbaumAbstract: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.
Tanju Yusuf Erdil - One of the best experts on this subject based on the ideXlab platform.
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68Ga-Prostate-Specific Membrane Antigen PET-Positive Paget Bone Disease With Metastatic Prostatic Carcinoma.
Clinical nuclear medicine, 2020Co-Authors: Ceren Ozge Engur, Halil Turgut Turoglu, Salih Ozguven, Yiloren Tanidir, Tanju Yusuf ErdilAbstract:Paget Bone Disease is a chronic benign Bone Disease characterized by excessive and abnormal Bone remodeling. The scintigraphic and Bone SPECT/CT hybrid imaging appearances of the affected Bone(s) depend on the stage of the Disease. We report the case of a patient newly diagnosed with prostate cancer who was found to have multiple osseous metastases, with coexisting Paget Disease in the left hemipelvis diagnosed because of typical scintigraphic and SPECT/CT appearance. Ga-prostate-specific membrane antigen PET/CT was also performed for initial staging. Pagetoid Bones showed increased prostate-specific membrane antigen uptake like skeletal metastases.
Michael P. Whyte - One of the best experts on this subject based on the ideXlab platform.
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Juvenile Paget Disease: life-long features of a mildly affected young woman.
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2009Co-Authors: Deborah S. Golob, Steven L. Teitelbaum, William H. Mcalister, Barbara G. Mills, Kenton N. Fedde, William R. Reinus, Suganthi Beeki, Michael P. WhyteAbstract:Unusually mild Juvenile Paget Disease (JPD) was extensively investigated in a mentally retarded 21-year-old white woman. Progressive bowing deformitity of her lower limbs began at age 1 1/2 years. Nontraumatic fractures of both femora and both tibias occurred between ages 9 and 14 years. During adulthood, cortical thickening, osteosclerosis, and bowing affected these Bones. Serum alkaline phosphatase (ALP) activity was persistently elevated. We found her serum osteocalcin and urinary hydroxyproline and pyridinoline/deoxypyridinoline to also be increased. The iliac crest histology, at ages 14 and 21 years, showed wide cortices and enhanced skeletal remodeling yet the Bone was exclusively lamellar. Features of classic Paget Bone Disease (PBD)--such as hypermultinucleated osteoclasts, peritrabecular fibrosis, and mosaic or woven Bone--were absent. Electron microscopy revealed no cytoplasmic or nuclear inclusions. Her dermal fibroblasts in culture synthesized unremarkable levels of ALP with proper membrane topography and lipid anchoring; ALP released into the medium also appeared normal. Six months of synthetic human calcitonin therapy daily appeared to reduce here lower limb pain and warmth, but the radiographs, biochemical parameters of skeletal turnover, and Bone scintigraphy were unaltered. Lamellar Bone has been reported in JPD but accompanied by excessive amounts of woven Bone. Our patient reveals that lamellar Bone without features of PBD can characterize the skeletal histopathology of the especially rare case of mild JPD.
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Extraskeletal Osteoclastomas Responsive to Dexamethasone Treatment in Paget Bone Disease
The Journal of clinical endocrinology and metabolism, 1997Co-Authors: Konstantinos Ziambaras, William A. Totty, Steven L. Teitelbaum, Megan Dierkes, Michael P. WhyteAbstract:Giant cell tumors (GCTs) of Bone, also called osteoclastomas, complicate Paget Bone Disease (PBD), though infrequently. Giant cell reparative granulomas (GCRGs), which are histologically similar to GCTs, also occur rarely in Pagetic patients. A 45-yr-old black woman with neurofibromatosis, type I, and polyostotic PBD developed slowly-growing masses in the right posterior iliac and left upper parasacral regions. She had multiple cutaneous neurofibromas and cafe-au-lait spots. Serum alkaline phosphatase activity and urine hydroxyproline levels were elevated. Skeletal radiographs and Bone scintigraphy showed changes of widespread PBD. Computerized tomography and magnetic resonance imaging (MRI) delineated masses in the right gluteal and the left lower lumbar paraspinal regions. Five additional smaller masses were found in the abdomen and in the pelvis. Biopsy of the right gluteal mass revealed a GCT. However, we found that this lesion had several histologic features distinct from those of giant cell reparative granulomas or GCT. In our patient's tumor, the huge polykaryons, like osteoclasts, expressed abundant tartrate-resistant acid phosphatase activity, whereas those of GCRG lack this enzyme. Although the polykaryons in conventional GCTs and GCTs in PBD express tartrate-resistant acid phosphatase activity, the location of these tumors in Bone differs from the extraskeletal masses encountered in our patient. Furthermore, the larger size of the polykaryons and the greater number of nuclei in our patient's GCT differ from conventional GCTs, but not GCTs in PBD. Her extraskeletal osteoclastoma rapidly shrunk to one third its original size during 2 weeks of oral dexamethasone treatment. Significant clinical improvement lasted about 5 months before additional courses of dexamethasone therapy were necessary. Injections of synthetic salmon calcitonin alone did not affect the tumor's size. Thus, PBD can be complicated by extraskeletal tumors that seem to contain osteoclasts and are responsive to dexamethasone treatment.
Rocco Tripepi - One of the best experts on this subject based on the ideXlab platform.
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Paget's Disease and Secondary Hyperparathyroidism: Is Healing Possible?
Frontiers in cell and developmental biology, 2020Co-Authors: Vincenzo Panuccio, Rocco TripepiAbstract:Paget Bone Disease (PDB) is often asymptomatic and incidentally diagnosed. It is a cause of osteoporosis and Bone fragility and exposes patients to a high incidence of Bone fractures. In Europe the prevalence varies according to the geographical area of origin, and increases with age. In patients with chronic renal Disease, the prevalence is unknown and only few cases with PDB have been reported. We present a challenging case in an elderly patient with chronic kidney Disease on peritoneal dialysis treatment. Our patients presented extremely high levels of alkaline phosphatase, suggesting a Paget Bone Disease. Secondary hyperparathyroidism was confirmed by the Bone histological examination. The surprising biochemical and clinical response to active vitamin D confirms the well-known role on hyperparathyroidism and may indicate an additional role in the pathogenesis of Paget’s Disease.
Maria T. Diaz-meco - One of the best experts on this subject based on the ideXlab platform.
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To aggregate or not to aggregate? A new role for p62.
EMBO reports, 2009Co-Authors: Jorge Moscat, Maria T. Diaz-mecoAbstract:Cell signalling is carried out by selective and complex metabolic networks that, when impaired, result in Disease. The challenge for the cell is to maintain fidelity during normal processes, while allowing the plasticity that is required to control the complicated machinery of a functional cell. This is achieved through protein hubs that organize the flow of information inside the cell; one such hub is the signalling adapter p62 (Moscat et al , 2006). The identification of p62‐interacting proteins, the analysis of knockout (KO) mice, and the fact that p62 mutations are associated with a human Disease—Paget Bone Disease—have confirmed the importance of p62 in homeostatic cell function and Disease (Moscat et al , 2007). p62 binds to atypical PKCs, the signalling adapter RIP, the E3 ubiquitin ligase TRAF6, the kinase ERK, and caspase 8 through different motifs (Jin et al , 2009; Moscat et al , 2006), thereby eliciting various effects that …
