-
Journal of Bone and Mineral Research :... Dec 2006Paget's disease of bone is a focal or multifocal disorder characterized by intense disorderly remodeling activity at sites of involvement, producing dramatic alterations... (Review)
Review
Paget's disease of bone is a focal or multifocal disorder characterized by intense disorderly remodeling activity at sites of involvement, producing dramatic alterations of local bone architecture. These functional and structural alterations, interacting with the specific characteristics of the site of involvement, account for most of the complications of the disease. This presentation will focus on selected nonneoplastic complications of particular current interest.
Topics: Fractures, Bone; Hearing Loss; Heart Diseases; Humans; Nervous System Diseases; Osteitis Deformans
PubMed: 17229011
DOI: 10.1359/jbmr.06s212 -
Cleveland Clinic Journal of Medicine Jul 2013Paget disease of bone is a focal disorder of aging bone that may be asymptomatic or may present with pain, bowing deformity, fracture, or a nonspecific rheumatic... (Review)
Review
Paget disease of bone is a focal disorder of aging bone that may be asymptomatic or may present with pain, bowing deformity, fracture, or a nonspecific rheumatic complaint. It is the second most common disease of bone in the elderly after osteoporosis, and the loss of structural integrity in affected bone conveys a risk of fracture. It may occur sporadically or in geographic or familial clusters. This article discusses the prevalence, pathology, workup, and treatment of Paget disease of bone.
Topics: Bone Density Conservation Agents; Diphosphonates; Genetic Predisposition to Disease; Global Health; Humans; Osteitis Deformans; Risk Factors
PubMed: 23821690
DOI: 10.3949/ccjm.80a.12142 -
Indian Pediatrics Apr 2009Juvenile Pagets disease (JPD), a rare genetic disorder characterized by markedly accelerated bone turnover, presents in early childhood. We report a child with typical...
Juvenile Pagets disease (JPD), a rare genetic disorder characterized by markedly accelerated bone turnover, presents in early childhood. We report a child with typical features of JPD who remained undiagnosed till 15 years of age. Rarity of this disease in Indian literature and need for early diagnosis to prevent progression of disease prompted us to report this case.
Topics: Adolescent; Humans; Male; Osteitis Deformans
PubMed: 19383995
DOI: No ID Found -
Australian Journal of General Practice 2021Paget's disease of bone (PDB) is a common destructive condition of bone that affects 1-2% of the population, most typically those over the age of 55 years. It is...
BACKGROUND
Paget's disease of bone (PDB) is a common destructive condition of bone that affects 1-2% of the population, most typically those over the age of 55 years. It is usually asymptomatic.
OBJECTIVE
The aim of this article is to describe the clinical presentation, diagnosis and management of patients with PDB.
DISCUSSION
Most cases of PDB are diagnosed incidentally on radiographs or as an isolated elevation of serum alkaline phosphatase. Symptomatic patients present with bone pain, fractures, arthritis and features of compression neuropathy. Diagnosis is made on the basis of typical radiological features on plain films, while a radionuclide bone scan may be used to assess the extent of disease. The mainstay of treatment for PDB is bisphosphonate therapy, with zoledronic acid being the most effective agent. A single infusion of zoledronic acid leads to a sustained reduction in bone pain and markers of bone turnover. However, bisphosphonates should be reserved for symptomatic patients, as treatment with these agents has been associated with an increase in rates of fracture in patients with asymptomatic PDB.
Topics: Diphosphonates; Fractures, Bone; Humans; Middle Aged; Osteitis Deformans; Radiography; Zoledronic Acid
PubMed: 33543158
DOI: 10.31128/AJGP-10-20-5690 -
Reumatologia Clinica 2011
Topics: Female; Finger Phalanges; Hand; Humans; Middle Aged; Osteitis Deformans; Radiography
PubMed: 21925453
DOI: 10.1016/j.reuma.2010.12.004 -
BMC Musculoskeletal Disorders Apr 2017Radiographic sacroiliitis is the hallmark of ankylosing spondylitis (AS), and detection of acute sacroiliitis is pivotal for early diagnosis of AS. Although radiographic... (Review)
Review
BACKGROUND
Radiographic sacroiliitis is the hallmark of ankylosing spondylitis (AS), and detection of acute sacroiliitis is pivotal for early diagnosis of AS. Although radiographic sacroiliitis is a distinguishing feature of AS, sacroiliitis can be seen in a variety of other disease entities.
CASE PRESENTATION
We present an interesting case of sacroiliitis in a patient with Paget disease; the patient presented with inflammatory back pain which was treated with bisphosphonate. This case demonstrates comorbidity with Paget disease and possible ankylosing spondylitis. We also present a review of the literature for other cases of Paget involvement of the sacroiliac joint.
CONCLUSIONS
In addition, we review radiographic changes to the sacroiliac joint in classical ankylosing spondylitis as well as other common diseases. We compare and contrast features of other diseases that mimic sacroiliitis on a pelvic radiograph including Paget disease, osteitis condensans ilii, diffuse idiopathic skeletal hyperostosis, infections and sarcoid sacroiliitis. There are some features in the pelvic radiographic findings which help distinguish among mimics, however, one must also rely heavily on extra-pelvic radiographic lesions. In addition to the clinical presentation, various nuances may incline a clinician to the correct diagnosis; rheumatologists should be familiar with the imaging differences among these diseases and classic spondylitis findings.
Topics: Diagnosis, Differential; Humans; Male; Middle Aged; Osteitis Deformans; Sacroiliitis; Spondylitis, Ankylosing
PubMed: 28431581
DOI: 10.1186/s12891-017-1525-1 -
Journal of Bone and Mineral Research :... May 2004In a family with IH, a rare high turnover bone disease, two older siblings were wheelchair-bound with severe skeletal deformity by age 15. Their youngest affected... (Review)
Review
UNLABELLED
In a family with IH, a rare high turnover bone disease, two older siblings were wheelchair-bound with severe skeletal deformity by age 15. Their youngest affected sibling was treated intensively with intravenous bisphosphonates for 3 years. The treatment was well tolerated and prevented the development of deformity and disability.
INTRODUCTION
Idiopathic hyperphosphatasia (IH, also known as juvenile Paget's disease) is a rare genetic bone disease characterized by very high bone turnover and progressive bony deformity. Inhibitors of bone resorption have been used to suppress bone turnover in the short term, but there is no published data on long-term efficacy.
MATERIALS AND METHODS
An 11-year-old girl with IH, who had two severely affected older siblings, presented with progressive deformity and deafness and long bone fractures. Conventional pediatric doses of pamidronate had failed to prevent clinical deterioration or suppress bone turnover completely. Intensive bisphosphonate therapy (frequent 5-mg ibandronate infusions) was given to try and arrest progression of the skeletal disease. Growth and development, pure tone audiometry, biochemistry, radiology, densitometry (DXA), and bone histology were monitored.
RESULTS
A total of 45 mg ibandronate was given over 3 years until skeletal maturity was reached (20, 15, and 10 mg for years 1-3, respectively). Ibandronate treatment was well tolerated, and biochemical markers of bone turnover suppressed to within the age-appropriate normal range There was some progression of her thoracic kyphosis, but she had no further fractures and remained mobile and active at an age when her siblings had become wheelchair-bound. A significant recovery of hearing (p < 0.01) was documented, particularly at low frequencies. Radiographs showed improvement in spinal osteoporosis and cortical bone dimensions and arrest of progressive acetabular protrusion. Areal bone density increased substantially (lumbar spine z-score from -2.2 to + 1.8). Tetracycline-labeled bone biopsy specimens were taken before and after 18 months of intensive treatment. The second biopsy showed suppression of bone turnover and a doubling of trabecular thickness, with no mineralization defect, and no osteopetrosis.
CONCLUSIONS
Intensive bisphosphonate treatment prevented the development of deformity and disability and improved hearing in this child with IH. The dose of bisphosphonate, which is substantially greater than is usually used in pediatric bone disease, had no adverse effects, in particular on bone mineralization.
Topics: Alkaline Phosphatase; Audiometry, Pure-Tone; Biomarkers; Biopsy; Bone Conduction; Bone Density; Bone Resorption; Child; Collagen; Collagen Type I; Diphosphonates; Female; Humans; Ibandronic Acid; Infusions, Intravenous; Osteitis Deformans; Pamidronate; Pelvic Bones; Peptides; Radiography; Spine; Treatment Outcome
PubMed: 15068492
DOI: 10.1359/JBMR.040127 -
BMC Biochemistry Nov 2007Multiple steps in the RANK-NF-kappaB signalling pathway are regulated by ubiquitylation. Mutations affecting different components of this pathway, including the... (Review)
Review
Multiple steps in the RANK-NF-kappaB signalling pathway are regulated by ubiquitylation. Mutations affecting different components of this pathway, including the ubiquitin binding p62 signalling adapter protein, are found in patients with Paget's disease of bone or related syndromes. Here, we review the molecular defects and potential disease mechanisms in these conditions and conclude that the mutations may confer a common increased sensitivity of osteoclasts to cytokines, resulting in disordered NF-kappaB-dependent osteoclast function. Modulation of the osteoclast RANK-NF-kappaB signalling axis may represent a viable therapeutic strategy for Paget's disease and other conditions where excessive bone resorption or remodelling is a feature. Publication history: Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com).
Topics: Animals; Humans; Osteitis Deformans; Signal Transduction; Ubiquitin
PubMed: 18047742
DOI: 10.1186/1471-2091-8-S1-S5 -
JCI Insight Mar 2020We report that transgenic mice expressing measles virus nucleocapsid protein (MVNP) in osteoclasts (OCLs) (MVNP mice) are Paget's disease (PD) models and that OCLs from...
We report that transgenic mice expressing measles virus nucleocapsid protein (MVNP) in osteoclasts (OCLs) (MVNP mice) are Paget's disease (PD) models and that OCLs from patients with PD and MVNP mice express high levels of OCL-derived IGF1 (OCL-IGF1). To determine OCL-IGF1's role in PD and normal bone remodeling, we generated WT and MVNP mice with targeted deletion of Igf1 in OCLs (Igf1-cKO) and MVNP/Igf1-cKO mice, and we assessed OCL-IGF1's effects on bone mass, bone formation rate, EphB2/EphB4 expression on OCLs and osteoblasts (OBs), and pagetic bone lesions (PDLs). A total of 40% of MVNP mice, but no MVNP/Igf1-cKO mice, had PDLs. Bone volume/tissue volume (BV/TV) was decreased by 60% in lumbar vertebrae and femurs of MVNP/Igf1-cKO versus MVNP mice with PDLs and by 45% versus all MVNP mice tested. Bone formation rates were decreased 50% in Igf1-cKO and MVNP/Igf1-cKO mice versus WT and MVNP mice. MVNP mice had increased EphB2 and EphB4 levels in OCLs/OBs versus WT and MVNP/Igf1-cKO, with none detectable in OCLs/OBs of Igf1-cKO mice. Mechanistically, IL-6 induced the increased OCL-IGF1 in MVNP mice. These results suggest that high OCL-IGF1 levels increase bone formation and PDLs in PD by enhancing EphB2/EphB4 expression in vivo and suggest OCL-IGF1 may contribute to normal bone remodeling.
Topics: Animals; Bone Remodeling; Disease Models, Animal; Humans; Insulin-Like Growth Factor I; Mice; Mice, Transgenic; Nucleocapsid Proteins; Osteitis Deformans; Osteoclasts
PubMed: 32078587
DOI: 10.1172/jci.insight.133113 -
Journal of Bone and Mineral Research :... Jul 1998Paget's disease of bone is a localized disorder of bone remodeling. Increased numbers of larger than normal osteoclasts initiate the process at affected skeletal sites,... (Review)
Review
Paget's disease of bone is a localized disorder of bone remodeling. Increased numbers of larger than normal osteoclasts initiate the process at affected skeletal sites, and the increase in bone resorption is followed by an increase in new bone formation, altering bone architecture. The signs and symptoms of Paget's disease are varied, depending in part on the location of the involved sites and the degree of increased bone turnover. Recent progress in Paget's disease research includes new data regarding the etiology of this disorder and the ongoing development of more effective therapies. Although the cause of Paget's disease remains unproven, the creation of pagetic osteoclasts seems ever more likely to result from both genetic and environmental factors. Many studies indicate that in patients with Paget's disease, both osteoclasts and their precursors harbor evidence of a paramyxovirus infection, although not all studies confirm this finding. Very recent genetic investigations have identified one candidate gene on chromosome 18q, although genetic heterogeneity is almost certainly present. Advances in treatment have resulted from the availability of several potent bisphosphonate compounds (e.g., pamidronate, alendronate, and risedronate) that, unlike earlier treatments, produce normal or near normal bone turnover indices in a majority of patients. New bone formation after such treatment has a more normal, lamellar pattern, and mineralization abnormalities are rare to absent with the newer compounds. The availability of such agents has prompted a more aggressive management philosophy in which both symptomatic disease and also asymptomatic disease at sites with a risk of progression and future complications are viewed as clear indications for pharmacologic intervention.
Topics: Bone Density; Chromosomes, Human, Pair 18; Diphosphonates; Genetic Predisposition to Disease; Humans; Osteitis Deformans; Respirovirus Infections
PubMed: 9661069
DOI: 10.1359/jbmr.1998.13.7.1061