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American Family Physician May 2002Paget's disease of bone (also known as osteitis deformans) is a nonmalignant disease involving accelerated bone resorption followed by deposition of dense, chaotic, and... (Review)
Review
Paget's disease of bone (also known as osteitis deformans) is a nonmalignant disease involving accelerated bone resorption followed by deposition of dense, chaotic, and ineffectively mineralized bone matrix. The origin of the disease is unknown, and it is frequently asymptomatic; however, the patient may present with symptoms depending on the bones involved. The most common symptom is pain in the affected bone; neurologic, hearing, vision, cardiac, and oncologic complications are possible. Diagnosis is primarily made by radiographs. Bisphosphonates are the most common treatment.
Topics: Calcitonin; Diphosphonates; Humans; Osteitis Deformans
PubMed: 12046775
DOI: No ID Found -
European Spine Journal : Official... Oct 2003Lumbar spinal stenosis is a common condition in elderly patients and also one of the most common reasons to perform spinal surgery at an advanced age. Disc degeneration,... (Review)
Review
Lumbar spinal stenosis is a common condition in elderly patients and also one of the most common reasons to perform spinal surgery at an advanced age. Disc degeneration, facet degeneration and hypertrophy, and ligamentum flavum hypertrophy and calcification usually participate in the genesis of a stenotic condition in the elderly. These changes can lead to symptoms by themselves or decompensate a preexisting narrow canal. Although some lesions are more central or more lateral, this classic dichotomy is less present in the elderly patient, in whom the degenerative process usually encroaches both central and lateral pathways. Some less common causes of lumbar spinal stenosis are found in the aging subject, such as Paget's disease. However, it must be stressed that so-called stenotic images (sometimes severe) are present on imaging studies in a great number of symptom-free individuals, and that the relationship between degenerative lesions, importance of abnormal images, and complaints is still unclear. Lumbar stenosis is a very common reason for decompressive surgery and/or fusion. Various conditions can lead to a narrowing of the neural pathways and differential diagnosis with vascular troubles, also common in the elderly, can be challenging. The investigation of stenotic symptoms should be extremely careful and thorough and include a choice of technical examinations including vascular investigations. This is of utmost importance, especially if a surgical sanction is considered to avoid disappointing results.
Topics: Aged; Aging; Diagnosis, Differential; Humans; Lumbar Vertebrae; Occupational Diseases; Osteitis Deformans; Radiography; Spinal Stenosis; Spondylolisthesis
PubMed: 13680315
DOI: 10.1007/s00586-003-0612-1 -
European Spine Journal : Official... Oct 2001A review of the literature was conducted to study the pathomechanics by which Paget's Disease of bone (PD) alters the spinal structures that result in distinct spinal... (Review)
Review
A review of the literature was conducted to study the pathomechanics by which Paget's Disease of bone (PD) alters the spinal structures that result in distinct spinal pathologic entities such as pagetic spinal arthritis, spinal stenosis, and other pathologies, and to assess the best treatment options and available drugs. The spine is the second most commonly affected site with PD. About one-third of patients with spinal involvement exhibit symptoms of clinical stenosis. In only 12-24% of patients with PD of the spine is back pain attributed solely to PD, while in the majority of patients back pain is either arthritic in nature or a combination of a pagetic process and coexisting arthritis. Neural element dysfunction may be attributed to compressive myelopathy by pagetic bone overgrowth, pagetic intraspinal soft tissue overgrowth, ossification of epidural fat, platybasia, spontaneous bleeding, sarcomatous degeneration and vertebral fracture or subluxation. Neural dysfunction can also result from spinal ischemia, when blood is diverted by the so-called "arterial steal syndrome". Because the effectiveness of pharmacologic treatment for pagetic spinal stenosis has been clearly demonstrated, surgical decompression should only be instituted after failure of antipagetic medical treatment. Surgery is indicated as a primary treatment when neural compression is secondary to pathologic fractures, dislocations, spontaneous epidural hematoma, syringomyelia, platybasia, or sarcomatous transformation. Since, in the majority of cases with pagetic spinal involvement, there are also coexisting osteoarthritic changes, antipagetic medical treatment alone may be disappointing. Therefore, one must be careful before attributing low back pain to PD alone. Five classes of drugs are available for the treatment of PD: bisphosphonates, calcitonins, mithramycin (plicamycin), gallium nitrate, and ipriflavone. Bisphosphonates are the most popular, and several forms have been investigated, but only the following forms have been approved for clinical use: disodium etidronate, clodronate, aledronate, risedronate, neridronate, pamidronate, tiludronate, ibadronate, aminohydroxylbutylidene bisphosphonate, olpadronate, and zoledronate. Several of these forms are still under investigation.
Topics: Humans; Osteitis Deformans; Prevalence; Spinal Diseases
PubMed: 11718191
DOI: 10.1007/s005860100329 -
Journal of Bone and Mineral Research :... Aug 2020
Topics: Bone and Bones; Genetic Predisposition to Disease; Humans; Osteitis Deformans; Profilins
PubMed: 32589291
DOI: 10.1002/jbmr.4090 -
Journal of Bone and Mineral Research :... Oct 1999Paget's disease of bone is associated with involvement of the central and peripheral nervous system. The brain, spinal cord, cauda equina, spinal roots, and cranial... (Review)
Review
Paget's disease of bone is associated with involvement of the central and peripheral nervous system. The brain, spinal cord, cauda equina, spinal roots, and cranial nerves can be affected in Paget's disease due to their anatomic relationship to bone. Neurologic syndromes are uncommon but include headache, dementia, brain stem and cerebellar dysfunction, cranial neuropathies, myelopathy, cauda equina syndrome, and radiculopathies. The central complications result from pagetic involvement of the skull. Expansion of diseased bone can result in compression of cranial nerves as they exit their bony foramina. Softening of the skull leads to basilar invagination with compression of the brain stem, cerebellum, and lower cranial nerves. Brain stem compression can cause hydrocephalus. Rarely, there is direct compression of the brain from acute epidural hematoma or hypertrophy of the calvarium. Myelopathy, cauda equina syndrome, and radiculopathies most commonly result from hypertrophy of the spine with direct compression. Spinal stenosis can also result from ossification of extradural structures or pathologic fractures. Ischemia from vascular compression or a steal syndrome has also been described. Neurologic complications rarely occur due to sarcomatous transformation of pagetic bone. Magnetic resonance imaging (MRI), computerized tomography (CT)-myelography, and bone X-rays are helpful to localize the lesion and direct therapy. Treatment options include surgical decompression, ventricular shunt placement, and medical management with calcitonin and/or the bisphosphonates. The selection of treatment will vary depending upon the rate of progression and the severity of the neurologic deficit.
Topics: Humans; Nervous System Diseases; Osteitis Deformans
PubMed: 10510221
DOI: 10.1002/jbmr.5650140218 -
Journal of Bone and Mineral Research :... Dec 2006Paget's disease of bone (PDB) is a focal disorder of bone metabolism first described by Sir James Paget in 1876. It is presumed benign in nature and mediated by abnormal... (Review)
Review
Paget's disease of bone (PDB) is a focal disorder of bone metabolism first described by Sir James Paget in 1876. It is presumed benign in nature and mediated by abnormal osteoclast function. The incidence of osteosarcomas complicating PDB is estimated at <1%. These cancers occur mostly in persons with long-standing, polyostotic disease and affect patients in their seventh decade or when osteosarcoma is remarkably rare in the general population. Epidemiological studies suggest that this late peak of osteosarcomas is absent in regions where Paget's is infrequently reported. Whereas PDB has a predilection for the axial skeleton, skull, femurs, and tibias, pagetic osteosarcoma tend to spare the spine, and are reported more commonly in the pelvis, femur, humerus, and skull. A molecular basis for the association of osteosarcoma with Paget's disease is unclear. These osteosarcomas are osteogenic in origin, consistently arise in sites of pagetic bone, and may present as metachronous, multifocal lesions. On histopathology, the lesions are usually osteoblastic, and the tumor phenotype is sometimes characterized as an exaggerated, chaotic form of the accelerated bone remodeling that characterizes PDB. New insights from the biology of adolescent osteosarcomas, VCP and SQSTM1 mutations now defined in patients with Paget's disease, and emerging evidence that stromal lesions are present in patients with Paget's disease are changing the way we think about the pathogenesis of PDB and the rare complication of pagetic osteosarcomas.
Topics: Bone Remodeling; Humans; Osteitis Deformans; Osteosarcoma
PubMed: 17229010
DOI: 10.1359/jbmr.06s211 -
Clinical Medicine (London, England) Nov 2020Adult Paget's disease of bone is the second commonest metabolic bone condition after osteoporosis. The condition is characterised by increased bone cell activity, with...
Adult Paget's disease of bone is the second commonest metabolic bone condition after osteoporosis. The condition is characterised by increased bone cell activity, with bone-resorbing osteoclasts often larger and containing more nuclei than normal and osteoblasts producing increased amounts of disorganised bone. This leads to expanded bone of poor quality possessing both sclerotic and lytic areas. Paget's disease of bone has a strong genetic element, with a family history being noted in 10-20% of cases. A number of genetic defects have been found to be associated with the condition. The most common disease-associated variants identified affect the gene, providing insights into disease aetiology, with the clinical value of knowledge of mutation status currently under active investigation. The diagnosis may be suggested by an isolated raised total alkaline phosphatase (ALP) without other identifiable causes. This can be confirmed on plain X-ray and the extent determined by isotope bone scan. The mainstay of treatment are the bisphosphonates, especially intravenous zoledronate which results in long-term suppression of bone turnover. ALP is the usual means of monitoring the condition, although more specific bone turnover markers can be helpful, especially in coincident liver disease. Patients should be followed up to monitor for biochemical relapse or development of complications, which may require medical or surgical intervention.
Topics: Adult; Bone Remodeling; Diphosphonates; Humans; Mutation; Osteitis Deformans; Osteoporosis
PubMed: 33199322
DOI: 10.7861/clinmed.20.6.page -
Journal of Bone and Mineral Research :... Apr 1995We have measured the free and peptide-bound type I collagen cross-link excretions in normal women and in patients with metabolic bone disease using the HPLC technique...
We have measured the free and peptide-bound type I collagen cross-link excretions in normal women and in patients with metabolic bone disease using the HPLC technique and immunoassays recognizing specifically the free or peptide-bound forms of pyridinoline (Pyr). After menopause, free deoxypyridinoline (free D-Pyr) excretion measured by HPLC without urine hydrolysis and expressed as a fraction of the total excretion was lower than in premenopausal women (45 +/- 15% vs. 59 +/- 12%, p < 0.005), whereas the fraction of free Pyr was not changed. In normal pre- and postmenopausal women (n = 43), the fraction of free D-Pyr was negatively correlated with bone turnover rate as assessed by the total urinary excretion of Pyr (r = -0.64, p < 0.001). In patients with a variety of metabolic bone diseases characterized by increased bone turnover (osteoporosis, Paget's disease, and hyperthyroidism), the fractions of free Pyr and free D-Pyr were significantly lower than in premenopausal controls (p < 0.001 for all diseases). After 3 days of intravenous (iv) treatment with the bisphosphonate pamidronate in patients with Paget's disease and osteoporosis, the urinary excretion of cross-linked peptides measured by high performance liquid chromatography (HPLC) or enzyme-linked immunoassay (ELISA) (NTX and CrossLaps) was markedly decreased (-52% and -85% for NTX, -71% and -93% for CrossLaps in Paget's disease and osteoporosis, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Adult; Aged; Aged, 80 and over; Amino Acids; Bone Development; Chemical Fractionation; Chromatography, High Pressure Liquid; Diphosphonates; Enzyme-Linked Immunosorbent Assay; Estrogen Replacement Therapy; Female; Humans; Hydrolysis; Hyperthyroidism; Male; Middle Aged; Osteitis Deformans; Osteoporosis, Postmenopausal; Pamidronate; Postmenopause; Premenopause
PubMed: 7610936
DOI: 10.1002/jbmr.5650100418 -
Drug Design, Development and Therapy 2011Paget's disease of bone (PDB) is a progressive monostotic or polyostotic metabolic bone disease characterized by focal abnormal bone remodeling, with increased bone... (Review)
Review
Paget's disease of bone (PDB) is a progressive monostotic or polyostotic metabolic bone disease characterized by focal abnormal bone remodeling, with increased bone resorption and excessive, disorganized, new bone formation. PDB rarely occurs before middle age, and it is the second most frequent metabolic bone disorder after osteoporosis, affecting up to 3% of adults over 55 years of age. One of the most striking and intriguing clinical features is the focal nature of the disorder, in that once the disease is established within a bone, there is only local spread within that bone and no systemic dissemination. Despite many years of intense research, the etiology of PDB has still to be conclusively determined. Based on a detailed review of genetic and viral factors incriminated in PDB, we propose a unifying hypothesis from which we can suggest emerging strategies and therapies. PDB results in weakened bone strength and abnormal bone architecture, leading to pain, deformity or, depending on the bone involved, fracture in the affected bone. The diagnostic assessment includes serum total alkaline phosphatase, total body bone scintigraphy, skull and enlarged view pelvis x-rays, and if needed, additional x-rays. The ideal therapeutic option would eliminate bone pain, normalize serum total alkaline phosphatase with prolonged remission, heal radiographic osteolytic lesions, restore normal lamellar bone, and prevent recurrence and complications. With the development of increasingly potent bisphosphonates, culminating in the introduction of a single intravenous infusion of zoledronic acid 5 mg, these goals of treatment are close to being achieved, together with long-term remission in almost all patients. Based on the recent pathophysiological findings, emerging strategies and therapies are reviewed: ie, pulse treatment with zoledronic acid; denosumab, a fully human monoclonal antibody directed against RANK ligand; tocilizumab, an interleukin-6 receptor inhibitor; odanacatib, a cathepsin K inhibitor; and proteasome and Dickkopf-1 inhibitors.
Topics: Animals; Bone Resorption; Clinical Trials as Topic; Diphosphonates; Humans; Osteitis Deformans
PubMed: 21607019
DOI: 10.2147/DDDT.S11306 -
Revista Brasileira de Reumatologia 2017To evaluate the parameters associated with quality of life in patients with Paget's disease of bone.
OBJECTIVE
To evaluate the parameters associated with quality of life in patients with Paget's disease of bone.
METHODS
Patients with Paget's disease of bone were evaluated with SF-36 and WHOQOL-bref questionnaires. Patients with other diseases that could cause significant impairment of their quality of life were excluded. We searched for correlations between the results and: age, time from diagnosis, type of involvement, pain related to Paget's disease of bone, limitation to daily activities, deformities, bone specific alkaline phosphatase, the extent of involvement and treatment.
RESULTS
Fifty patients were included. Results of the SF-36 total score and its domains, physical and mental health, were significantly correlated with bone pain and deformities. Marital status was significantly correlated with the SF-36 total score and Mental Health Domain. BAP levels and disease extension were significantly correlated to SF-36 Physical Health Domain. After multivariate analysis, the only parameters that remained significantly associated with the SF-36 total score and to its Mental Health and Physical Health Domains were pain and marital status. The WHOQOL-bref total score was significantly associated with pain, physical impairment and deformities. WHOQOL-bref Domain 1 (physical) score was significantly associated with marital status, pain and deformities, while Domain 2 (psychological) score was associated with marital status, physical impairment and kind of involvement. After multivariate analysis, the presence of pain, deformities, and marital status were significantly associated with results of the WHOQOL-bref total score and its Domain 1. WHOQOL-bref domain 2 results were significantly predicted by pain and marital status.
CONCLUSION
The main disease-related factor associated with SF-36 results in Paget's disease of bone patients was bone pain, while bone pain and deformities were associated with WHOQOL-bref.
Topics: Aged; Female; Health Status; Humans; Male; Middle Aged; Osteitis Deformans; Osteoarthritis; Pain; Quality of Life; Surveys and Questionnaires
PubMed: 28967630
DOI: 10.1016/j.rbre.2017.06.002