Paget’s Disease of Bone: Osteoimmunology and Osteoclast Pathology

Rabjohns, Emily M.; Hurst, Katlyn; Ghosh, Arin; Cuellar, Maria C.; Rampersad, Rishi R.; Tarrant, Teresa K.

doi:10.1007/s11882-021-01001-2

Cited by 16 publications

(16 citation statements)

References 91 publications

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“…The main causes of hyperhomocysteinemia in elderly individuals include folate and vitamin B12 deficiency, as well as deterioration of renal function (37,38). HCY is known to modulate this process via several known mechanisms, such as increase in osteoclast activity, decrease in osteoblast activity and direct action on bone matrix (43)(44)(45). The patient in the present case exhibited no renal impairment and the onset of both anemia and bone-related symptoms was dated to before the initiation of bisphosphonate therapy.…”

Section: Discussionmentioning

confidence: 99%

“…As regards PDB, research should focus on in-depth analysis of the mechanisms underlying this disorder, identifying any possible correlations with other comorbidities, immune-related or other (21,43), and broadening the opportunities of identifying a possible adjuvant therapy beyond bisphosphonates (44)(45)(46). There is a pressing need to fully elucidate the pathogenesis of this illness and to find modalities to prevent long-term complications.…”

Section: Discussionmentioning

confidence: 99%

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Paget's disease of bone and megaloblastic anemia in a 72‑year‑old patient: A case report and systematic literature review

Oprea¹,

Bojincă

Balanescu

et al. 2022

Exp Ther Med

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Paget's disease of bone (PDB) is characterized by abnormal osteoclastic bone resorption with disorganized bone neo-formation, primarily affecting elderly (>55 years) patients. Although the majority of patients are asymptomatic, some patients may experience bone pain due to local periosteal involvement or osteoarthritic lesions in the spine; in addition, limb deformities may lead to secondary gait problems or degenerative joint changes. Anemia has an overall prevalence of 12-17% in elderly adults (>65 years old), with macrocytic anemia being the less common type. Megaloblastic anemia is a macrocytic anemia characterized by the presence of large, immature, nucleated cells (megaloblasts) in the blood, with the most common cause being a deficiency of folate and/or vitamin B12. We herein report the rare case of a 72-year-old male patient exhibiting both these conditions, with the aim of discussing the possible association between the two and, most importantly, the clinical management of the patient in a real-life setting over a period of 10 years. The patient was diagnosed based on clinical symptoms (bone pain), radiological imaging and specific laboratory tests, and received discontinuous courses of bisphosphonates and cyanocobalamin supplementation therapy, based mainly on aggravated symptomatology. A systematic literature review was also performed and revealed not only the scarcity of reports on similar cases, but also the mechanisms that may underlie the possible association of PDB with macrocytic anemia due to vitamin B12 deficiency in elderly patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Paget's disease of bone and megaloblastic anemia in a 72‑year‑old patient: A case report and systematic literature review

Oprea¹,

Bojincă

Balanescu

et al. 2022

Exp Ther Med

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“…Primary Cell Culture. Primary bone marrow cells were extracted from the femurs and tibias of 6-week-old male C57BL/6 mice and cultured in α-modified minimal essential medium (α-MEM, Gibco, USA) containing 10% fetal bovine serum (FBS, Gibco) and 1% PS (100 U/ml penicillin, 100 μg/ ml streptomycin, Thermo Fisher Scientific, USA), and 25 ng/ ml M-CSF was added to induce bone marrow-derived macrophage (BMMs) formation [3,4,28]. The cells were cultured at 37 °C in a cell incubator with 5% CO 2 until they reached 90% confluence.…”

Section: Methodsmentioning

confidence: 99%

“…In normal bone tissue, homeostasis is maintained by the delicate balance between osteoblast-mediated bone formation and osteoclast-(OC-) mediated bone resorption, and dysregulation of this balance can lead to a variety of skeletal disorders [1,2]. Excessive OC activation and OC dysfunction disrupt the balance between bone formation and bone resorption, thus leads to increased bone resorption and results in most skeletal diseases, such as pathological bone loss or reduction, osteoporosis, and Paget's disease [3,4]. However, there are no effective treatments for OC-related skeletal diseases.…”

Section: Introductionmentioning

confidence: 99%

FTY720 Attenuates LPS-Induced Inflammatory Bone Loss by Inhibiting Osteoclastogenesis via the NF-κB and HDAC4/ATF Pathways

Chen

Zong

Wang

et al. 2023

Journal of Immunology Research

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Osteoclast (OC) abnormalities lead to many osteolytic diseases, such as osteoporosis, inflammatory bone erosion, and tumor-induced osteolysis. Exploring effective strategies to remediate OCs dysregulation is essential. FTY720, also known as fingolimod, has been approved for the treatment of multiple sclerosis and has anti-inflammatory and immunosuppressive effects. Here, we found that FTY720 inhibited osteoclastogenesis and OC function by inhibiting nuclear factor kappa-B (NF-κB) signaling. Interestingly, we also found that FTY720 inhibited osteoclastogenesis by upregulating histone deacetylase 4 (HDAC4) expression levels and downregulating activating transcription factor 4 (ATF4) expression levels. In vivo, FTY720 treatment prevented lipopolysaccharide- (LPS-) induced calvarial osteolysis and significantly reduced the number of tartrate-resistant acid phosphatase- (TRAP-) positive OCs. Taken together, these results demonstrate that FTY720 can inhibit osteoclastogenesis and ameliorate inflammation-induced bone loss. Which may provide evidence of a new therapeutic target for skeletal diseases caused by OC abnormalities.

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“…Instead of a healthy lamellar bone mineralization, the collagen fibers are randomly oriented and have a woven appearance. Increased vasculature and numerous abnormal osteoclasts are also visible [ 85 ].…”

Section: Sclerosing Disordersmentioning

confidence: 99%

Hereditary Metabolic Bone Diseases: A Review of Pathogenesis, Diagnosis and Management

Charoenngam

Nasr

Shirvani

et al. 2022

Genes

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Hereditary metabolic bone diseases are characterized by genetic abnormalities in skeletal homeostasis and encompass one of the most diverse groups among rare diseases. In this review, we examine 25 selected hereditary metabolic bone diseases and recognized genetic variations of 78 genes that represent each of the three groups, including sclerosing bone disorders, disorders of defective bone mineralization and disorder of bone matrix and cartilage formation. We also review pathophysiology, manifestation and treatment for each disease. Advances in molecular genetics and basic sciences has led to accurate genetic diagnosis and novel effective therapeutic strategies for some diseases. For other diseases, the genetic basis and pathophysiology remain unclear. Further researches are therefore crucial to innovate ways to overcome diagnostic challenges and develop effective treatment options for these orphan diseases.

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Paget’s Disease of Bone: Osteoimmunology and Osteoclast Pathology

Cited by 16 publications

References 91 publications

Paget's disease of bone and megaloblastic anemia in a 72‑year‑old patient: A case report and systematic literature review

Paget's disease of bone and megaloblastic anemia in a 72‑year‑old patient: A case report and systematic literature review

FTY720 Attenuates LPS-Induced Inflammatory Bone Loss by Inhibiting Osteoclastogenesis via the NF-κB and HDAC4/ATF Pathways

Hereditary Metabolic Bone Diseases: A Review of Pathogenesis, Diagnosis and Management

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