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European Spine Journal : Official... Oct 2003Osteoporosis is the most common contributing factor of spinal fractures, which characteristically are not generally known to produce spinal cord compression symptoms.... (Review)
Review
Osteoporosis is the most common contributing factor of spinal fractures, which characteristically are not generally known to produce spinal cord compression symptoms. Recently, an increasing number of medical reports have implicated osteoporotic fractures as a cause of serious neurological deficit and painful disabling spinal deformities. This has been corroborated by the present authors as well. These complications are only amenable to surgical management, requiring instrumentation. Instrumenting an osteoporotic spine, although a challenging task, can be accomplished if certain guidelines for surgical techniques are respected. Neurological deficits respond equally well to an anterior or posterior decompression, provided this is coupled with multisegmental fixation of the construct. With the steady increase in the elderly population, it is anticipated that the spine surgeon will face serious complications of osteoporotic spines more frequently. With regard to surgery, however, excellent correction of deformities can be achieved, by combining anterior and posterior approaches. Paget's disease of bone (PD) is a non-hormonal osteometabolic disorder and the spine is the second most commonly affected site. 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. In this context, one must be certain before attributing low back pain to PD exclusively, and antipagetic medical treatment alone may be ineffective. 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. Five classes of drugs are available for the treatment of PD. Bisphosphonates are the most popular antipagetic drug and several forms have been investigated.
Topics: Aged; Aging; Humans; Orthopedic Procedures; Osteitis Deformans; Osteoporosis; Spinal Diseases; Spinal Stenosis
PubMed: 14505119
DOI: 10.1007/s00586-003-0600-5 -
Annals of the Rheumatic Diseases Jul 1992
Topics: Aged; Diphosphonates; Hallucinations; Humans; Male; Osteitis Deformans; Pamidronate
PubMed: 1632675
DOI: 10.1136/ard.51.7.927-d -
Discovery Medicine Sep 2010Paget's Disease of Bone (PDB) is the second most common metabolic bone disease following osteoporosis. PDB is characterized by an increase in bone resorption and bone... (Review)
Review
Paget's Disease of Bone (PDB) is the second most common metabolic bone disease following osteoporosis. PDB is characterized by an increase in bone resorption and bone deposition. For this reason antiresorptives were indicated as the ideal therapy for PDB. Recently, the availability of newer, more potent nitrogen-containing bisphosphonates has improved treatment outcomes, allowing a more convenient management of this disorder. However, no firm evidence exists to show that bisphosphonates can prevent the complications of PDB, and further work is needed to evaluate the influence of pharmacological therapy on long-term clinical outcomes, so that clinicians can make better-informed choices about the risks and benefits of treatment. This article will focus on the present status and future pharmacological developments in PDB.
Topics: Animals; Bone Density Conservation Agents; Diphosphonates; Humans; Osteitis Deformans
PubMed: 20875342
DOI: No ID Found -
Arthritis and Rheumatism Aug 2003
Review
Topics: Diphosphonates; Drug Resistance; Humans; Osteitis Deformans
PubMed: 12905461
DOI: 10.1002/art.11135 -
International Journal of Medical... 2018Paget´s disease of bone (PDB) is characterized by increased bone resorption followed by an excessive compensatory bone formation, with an abnormal bone structure with...
Paget´s disease of bone (PDB) is characterized by increased bone resorption followed by an excessive compensatory bone formation, with an abnormal bone structure with altered mechanical properties. Pagetic bone also has a higher vascularization and marrow fibrosis. Despite of pagetic bone being a highly vascularized tissue, there are no studies on the plasma levels of angiogenic mediators in the different states of the disease; moreover, the effect of PDB treatment on plasma levels of these angiogenic mediators is not very well known. The aim of this study was to analyse plasma levels of cytokines implicated in the increased bone turnover (OPG, RANKL, sclerostin) and hypervascularization (VEGF, PGF, ENG) observed in PDB and their evolution and response to zoledronic acid treatment in 70 PDB patients, 29 with an active disease measured by plasma alkaline phosphatase (ALP). Plasma ALP concentration was higher in active PDB than in inactive PDB patients, whereas there were no differences in OPG, RANKL, sclerostin, VEGF, PGF and ENG plasma levels between active and inactive PDB patients. ALP decreased at 3 and 12 months after zoledronic acid treatment. RANKL levels were reduced and sclerostin levels were increased after 12 months of treatment. PGF levels were lower 12 months after zoledronic acid treatment, whereas there were no differences in plasma VEGF and ENG after zoledronic acid treatment. Summarizing, zoledronic acid treatment is associated to decreases in plasma levels of ALP, RANKL, sclerostin and P1GF in active PDB patients. This treatment may reduce bone turnover and might reduce the pathological vascularisation typical of pagetic bone.
Topics: Aged; Aged, 80 and over; Bone Density Conservation Agents; Bone Remodeling; Cohort Studies; Cytokines; Female; Humans; Male; Neovascularization, Pathologic; Osteitis Deformans; Osteoprotegerin; RANK Ligand; Spain; Zoledronic Acid
PubMed: 30123059
DOI: 10.7150/ijms.26580 -
Annals of the Rheumatic Diseases Mar 2024Paget's disease of bone (PDB) frequently presents at an advanced stage with irreversible skeletal damage. Clinical outcomes might be improved by earlier diagnosis and... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Paget's disease of bone (PDB) frequently presents at an advanced stage with irreversible skeletal damage. Clinical outcomes might be improved by earlier diagnosis and prophylactic treatment.
METHODS
We randomised 222 individuals at increased risk of PDB because of pathogenic variants to receive 5 mg zoledronic acid (ZA) or placebo. The primary outcome was new bone lesions assessed by radionuclide bone scan. Secondary outcomes included change in existing lesions, biochemical markers of bone turnover and skeletal events related to PDB.
RESULTS
The median duration of follow-up was 84 months (range 0-127) and 180 participants (81%) completed the study. At baseline, 9 (8.1%) of the ZA group had PDB lesions vs 12 (10.8%) of the placebo group. Two of the placebo group developed new lesions versus none in the ZA group (OR 0.41, 95% CI 0.00 to 3.43, p=0.25). Eight of the placebo group had a poor outcome (lesions which were new, unchanged or progressing) compared with none of the ZA group (OR 0.08, 95% CI 0.00 to 0.42, p=0.003). At the study end, 1 participant in the ZA group had lesions compared with 11 in the placebo group. Biochemical markers of bone turnover were significantly reduced in the ZA group. One participant allocated to placebo required rescue therapy with ZA because of symptomatic disease. The number and severity of adverse events did not differ between groups.
CONCLUSIONS
Genetic testing for pathogenic variants coupled with intervention with ZA is well tolerated and has favourable effects on the progression of early PDB.
TRIAL REGISTRATION NUMBER
ISRCTN11616770.
Topics: Humans; Diphosphonates; Osteitis Deformans; Sequestosome-1 Protein; Zoledronic Acid; Genetic Testing; Biomarkers
PubMed: 38123339
DOI: 10.1136/ard-2023-224990 -
Journal of Bone and Mineral Research :... Oct 1999Pagetic sarcoma is a rare anaplastic malignancy with a peak incidence in the seventh and eighth decades of life; it usually occurs in patients with polyostotic Paget's... (Review)
Review
Pagetic sarcoma is a rare anaplastic malignancy with a peak incidence in the seventh and eighth decades of life; it usually occurs in patients with polyostotic Paget's disease. The most common tumor type is osteosarcoma. In one-third of the cases, presentation is a spontaneous pathologic fracture of an affected long bone. Amputation is the most appropriate form of surgical management in most cases because of the aggressive behavior of the sarcoma and its usually late presentation in this elderly population. However, selected patients with extremity lesions may be managed by pre- and postoperative chemotherapy and wide curative resection with limb salvage reconstruction. It is essential to differentiate pagetic sarcoma from metastatic carcinoma in pagetic bone and from a benign giant cell tumor.
Topics: Aged; Bone Neoplasms; Humans; Male; Middle Aged; Osteitis Deformans; Osteosarcoma; Prognosis
PubMed: 10510213
DOI: 10.1002/jbmr.5650140210 -
The Journal of Arthroplasty Jul 2023Patients who have Paget's Disease more frequently require total hip arthroplasty (THA) and total knee arthroplasty (TKA) than matched controls. However, controversy...
BACKGROUND
Patients who have Paget's Disease more frequently require total hip arthroplasty (THA) and total knee arthroplasty (TKA) than matched controls. However, controversy remains regarding their outcome. We aimed to evaluate the literature regarding outcomes following THA and TKA in patients who have Paget's Disease.
METHODS
MEDLINE, EMBASE and Cochrane databases were searched for all articles evaluating outcomes following THA and TKA in patients who have Paget's Disease. Quality of included studies was assessed using the Newcastle-Ottawa Scale.
RESULTS
A total of 19 articles (published between 1976 and 2022) were included, comprising 58,695 patients (48,766 controls and 10,018 patients who have Pagets Disease), from 209 potentially relevant titles. Patients with Paget's Disease have a pooled mortality of 32.5% at a mean of 7.8 years (range, 0.1 to 20) following THA and 31.0% at a mean of 8.5 years (range, 2 to 20) following TKA, with a pooled revision rate of 4.4% at 7.2 years (range, 0 to 20) following THA and 2.2% at 7.4 years (range, 2 to 20) following TKA. Renal and respiratory complications, as well as heterotopic ossification and surgical-site infection were the most common post-operative complications.
CONCLUSION
There is marked heterogeneity in outcome reporting of studies assessing arthroplasty in patients who have Paget's Disease, with studies of low to moderate quality. Patients with Paget's Disease undergoing THA and TKA appear to have similar implant longevity as their unaffected counterparts. However, they appear to have an increased risk of medical and surgical complications and may have a higher mortality risk from their procedure.
Topics: Humans; Arthroplasty, Replacement, Knee; Osteitis Deformans; Arthroplasty, Replacement, Hip; Surgical Wound Infection; Postoperative Complications
PubMed: 36639114
DOI: 10.1016/j.arth.2023.01.004 -
Genetic Testing and Molecular Biomarkers Jun 2016Paget's disease of bone (PDB) is a focal bone disorder affecting the skeleton segmentally. The disease affects osteoclasts which increase in size, number, and activity....
BACKGROUND AND AIMS
Paget's disease of bone (PDB) is a focal bone disorder affecting the skeleton segmentally. The disease affects osteoclasts which increase in size, number, and activity. One of the etiopathogenic hypotheses is that the disease is genetic. It has been reported that Rho GEF Vav3 is an essential factor in the regulation of osteoclast function, and alteration of the VAV3 gene could influence the development of the disease. The aim of our study was to perform an association study between variants of the VAV3 gene and the risk of developing Paget's disease of bone.
PATIENTS AND METHODS
The genotypic and allelic distribution of the VAV3 c.892A>T/p.T298S (rs7528153) polymorphism was compared between a cohort of 238 Spanish subjects with PDB and a cohort of 253 healthy subjects.
RESULTS
Our results indicated that individuals carrying the VAV3 rs7528153 TT genotype were at a significantly increased risk of developing PDB (p < 0.001, odds ratio [OR] = 3.15, 95% confidence interval [95% CI] = 1.77-5.61).
CONCLUSIONS
These results suggest that inheriting the VAV3 rs7528153 polymorphism is a likely susceptibility factor for developing Paget's disease of bone.
Topics: Aged; Case-Control Studies; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Osteitis Deformans; Osteoclasts; Osteoprotegerin; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins c-vav
PubMed: 27172236
DOI: 10.1089/gtmb.2015.0292 -
British Medical Journal Aug 1964
Topics: Humans; Osteitis Deformans; Sodium Fluoride
PubMed: 14160219
DOI: No ID Found