Sabooniha Fakhreddin
Sabzevar University of Medical Sciences, Razavi Khorasan Province, Sabzevar, Farmandari St, Amin Building, 3rd Floor, Iran.
Curr Med Imaging. 2023 Mar 27. doi: 10.2174/1573405620666230327111326.
Paget's disease of bone (PDB) is the second most frequent metabolic bone disease affecting about 3 percent of the Caucasian population older than 55 years. Its etiopathogenesis is unknown .while viral agents like measles and respiratory syncytial virus has been proposed, the role of genetic susceptibilities loci such as SQSTM1/p62 gene mutations have been confirmed. A new inhibitory mechanism against osteoprotegerin (OPG) via autoantibodies has been revealed in a patient with occult celiac disease (CD) with a phenotype similar to juvenile Paget's disease, which suggests an immunological mechanism for Paget's disease-like disorders other than genetic causes. But there is no report in the literature searching for shared immunologic mechanisms underlying classic PDB, CD and psoriasis Case Presentation: I report the case of a 50-year-old Caucasian man who presented with progressive bilateral hearing loss. The patient had a history of total blindness which had developed shortly after a cranial osteotomy for optic nerve decompression without any specific diagnosis 15 years ago. He had also been suffering chronic psoriasis vulgaris. Because of his enlarged skull, a diagnosis of bone Paget's disease was suspected and plain radiographs revealed a polyostotic Paget's disease with characteristic radiologic signs. In searching for his refractory constipation causes, an elevated level of tissue transglutaminase IgA (tTG IgA) antibody was demonstrated. Alendronate sodium 40 mg daily was started and a gluten-free diet was recommended to him but he was not adherent to the treatments and lost to follow-up.
This case further supports the idea of considering PDB as an osteoimmunologic disorder, such as psoriasis and CD, because of similar biochemical features, including elevated levels of Cytokines such as interleukin-6 and tumor necrosis factor- α as well as bone resorption markers such as OPG and urinary deoxypyridinoline. So, the treatment of Paget's disease of the bone may benefit from progresses in osteoimmunology-targeted therapies. Also a probable causal relationship between PDB and CD by the production of neutralizing antibodies in CD against OPG or by inducing PDB in genetically susceptible patients through oxidative stress, has been postulated here.
骨佩吉特病（PDB）是第二常见的代谢性骨病，影响约3%的55岁以上白种人。其发病机制尚不清楚。虽然有人提出麻疹和呼吸道合胞病毒等病毒因子，但遗传易感基因座如SQSTM1/p62基因突变的作用已得到证实。在一名患有隐匿性乳糜泻（CD）且表型类似于青少年佩吉特病的患者中，发现了一种通过自身抗体抑制骨保护素（OPG）的新机制，这提示了除遗传原因外，佩吉特病样疾病的免疫机制。但文献中尚无关于经典PDB、CD和银屑病潜在共同免疫机制的报道。病例报告：我报告一例50岁白种男性，表现为进行性双侧听力丧失。该患者有全盲病史，15年前在因视神经减压行颅骨截骨术后不久出现，未明确诊断。他还患有慢性寻常型银屑病。由于颅骨增大，怀疑为骨佩吉特病，X线平片显示为多骨型佩吉特病，具有特征性影像学表现。在寻找其难治性便秘原因时，发现组织转谷氨酰胺酶IgA（tTG IgA）抗体水平升高。开始每日服用40mg阿仑膦酸钠，并建议其采用无麸质饮食，但他未坚持治疗并失访。
该病例进一步支持将PDB视为一种骨免疫性疾病，如银屑病和CD，因为它们具有相似的生化特征，包括细胞因子如白细胞介素-6和肿瘤坏死因子-α水平升高以及骨吸收标志物如OPG和尿脱氧吡啶啉水平升高。因此，骨佩吉特病的治疗可能受益于骨免疫学靶向治疗的进展。此外，本文推测PDB与CD之间可能存在因果关系，即CD中产生针对OPG的中和抗体，或通过氧化应激在遗传易感患者中诱发PDB。
