Paget’s disease of bone, is a focal disorder involving one or more bones which is usually diagnosed in individuals over 50 years of age and also affects one or more family members in about 20% of cases. The earliest phase begins with increased numbers of osteoclasts in an area of the skeleton followed by a slow progression of bone resorption throughout the bone. This is followed by increased osteoblastic activity which results in a disorganized structure and an overgrowth of bone. This can lead to deformity and fractures. The familial aspects of the disease led to genetic analyses of patients. In 2002, mutations in the sequestosome1 gene were first reported in 11/24 families and in 18/112 apparently sporadic patients. At least 28 different mutations have been reported. Other gene mutations have been described but sequestosome1 mutations are the most common mutation reported in families. Since several investigators have found that not all family members develop Paget’s disease by 50-60 years even if they have a mutation this is not sufficient to account for the disease. Also the prevalence of the disease has dropped significantly in the past several decades, a finding that is unlikely related to genetic factors. Environmental factors have been evaluated and the most likely one of importance is measles virus. Initially electron microscopy detected nuclear and cytoplasmic structures resembling nucleocapsids of the paramyxoviridae family in osteoclasts but not other bone cells. Further studies utilizing immunohistochemical analyses and reverse transcription PCR provided evidence that measles virus nucleocapsids were in the osteoclasts. Several other studies have not confirmed these results. However the fact the prevalence of the disease has decreased since the availability of measles vaccine in 1963 suggests that measles virus is a likely factor in the development of the disease and genetic factors increase susceptibility.
Dr. Singer is a graduate of the University of California in San Francisco School of Medicine and trained in internal medicine at the Wadsworth Veterans Administration Center in Los Angeles. Endocrinology fellowships were done at the Massachusetts General Hospital in Boston and at the Royal Postgraduate Medical School in London. He was also a Clinical Investigator at the Wadsworth Veterans Administration Medical Center. He then moved to the faculty of the University of Southern California for 15 years, spent 4 years at Cedars Sinai Medical Center in Los Angeles and for the past 29 years has been in the Endocrine/Bone disease Program at the John Wayne Cancer Institute at Providence Saint Johns Health Center in Santa Monica. He is a clinical professor of medicine at the David Geffen School of Medicine at UCLA. His research interests have been Paget’s disease of bone, osteoporosis, and primary hyperparathyroidism. He is a past president of the American Society for Bone and Mineral Research and a board member of the National Osteoporosis Foundation.