Paget’s disease of bone: Report of 11 cases

BACKGROUND Paget’s disease of bone(PDB)is a rare metabolic bone disease in China and is characterized by increased bone resorption and disorganized bone formation.The main clinical symptoms of PDB are focal or multiple bone pain and deformity with high disability.The disease has high missed diagnosis and misdiagnosis rates.This report summarizes the clinical manifestations,imaging and pathological features,and treatments of 11 patients with PDB at our hospital from 1993 to 2020 in order to improve the recognition and prognosis of PDB.CASE SUMMARY There were eight male and three female patients whose average age was 48.7±11.0 years with a PDB course of 1-16 years.Nine patients had bone pain and bone deformities in different parts of the body,the majority of which involved the long bones.Laboratory examinations revealed elevated serum alkaline phosphatase(ALP)in all patients with an average of 618±460 IU/L(normal range 0-130 IU/L),and serum calcium and phosphorus levels were in the normal range.Imageology showed that osteolysis was usually combined with osteosclerosis and/or bone deformities in single or multiple bones.^(99m)Tc-methylene diphosphonate bone scintigraphy revealed increased radionuclide uptake in the bone lesions.Six patients underwent bone tissue biopsy,and the typical pathological changes were a mosaic structure of the bone trabeculae with irregularly arranged cement lines and multinuclear osteoclasts.Ten of the 11 patients were effectively treated with bisphosphonates.CONCLUSION Early diagnosis of the rare disease PDB can be made through elevated ALP levels and typical presentations on bone X-ray and from bone tissue biopsy.

Sequestosome 1/p62： a multi-domain protein with multi-faceted functions

The sequestosome 1/p62 protein has been implicated in the regulation of a multitude of cellular processes such as NF-κB signaling, NRF2-driven oxidative stress response, protein turnover through the ubiquitin-proteasome pathway and the autophagosome/lysosome pathway, apoptosis and cellular metabolism. The domain structure of p62 also reflects this functional complexity since the protein appears to be a mosaic of protein interaction domains and motifs. Deregulation of the level and function of p62 and/or p62 mutations have been linked to a number of human diseases including Paget＇s disease of the bone, obesity, liver diseases, tumorigenesis and neurodegenerative diseases such as amyotrophic lateral sclerosis and Alzheimer＇s disease. In this article, we review the current understanding of the involvement of p62 in cellular processes under physiologic and pathological conditions.