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Paget's Disease; evidence for a viral cause
Bone VoI. 17, No. 1 July 1995:97-103
ELSEVIER
ABSTRACTS FROM THE SYMPOSIUM OF THE SPANISH SOCIETY FOR BONE AND MINERAL RESEARCH (SEIOMM) DEVOTED TO PAGET'S DISEASE, Salamanca, Spain, November 3-4, 1994 their potential in diseases such as osteoporosis and bone metastases) may hamper trmeir effective application in Paget's disease. C o n c l u s i o n ; the time is fast approaching when all patients with symptoms, or even in the absence o f symptoms with a reasonable life expectancy, will be offered a single course o f bisphosphonate, and a significant percentage will be cured.
Paget's Disease; evidence for a viral cause D a v i d C A n d e r s o n . D e p a r t m e n t of M e d i c i n e , T h e C h i n e s e U n i v e r s i t y of Hong Kong, Shatln, New Territories, Hong Kong Major problems in establishing the cause o f Paget's disease are that it is clinically silent for so long, and there is great clinical variability, (anatomical as well as possibly environmental and genetic), It is focal and spreads progressively through an affected bone as a lyric front, at about I cm per year, from what appears to be a single focus. Thc disease behaves as if at a single point in time a disseminated blood-borne infection which stimulates osteoclast function has seeded out in osteoclasts and taken hold in bones at random. The p a r a m y x o v i r u s e s are simple negative single-stranded R N A viruses with s propensity to mutate and to establish persistent infections. The first evidence o f a viral cause was the finding of inclusion bodies in Pagetic osteoclasts suggestive of paramyxovirus nucleocapsids; subsequent work has cast doubt on the significance o f these bodies; are they simply a reflection o f excessive osteoelast function? The second evidence, which is also of dubious significance is that of immunocytochemistry, which sugges.*.ed the possible involvement of a number of paramyxoviruses including measles. Our own pursuit in M a n c h e s t e r o f canine distemper virus (CDV) arose from case control studies o f previous dog ownership. Our evidence, not so far oonfirmed by others, is based on in situ hybridisation and PCR, and implicates CDV in about two thirds o f cases. The virus infects the osteoclast in the natural host, although in contrast to Paget's, here the genomic strand is also evident, whereas hybridisation in Paget's disease is only seen to the mKNA strand; the same holds for the canine disease metaphyseal osteopathy. The case for CDV, at least in s o m e cases, as the infectious cause, is suggestive, but not p r o v e n
THE DIAGNOSISOF PAGET$ DISEASE: IMPORTANCEOF CLINICAL. RADIOLOGICALAND IMAGINGFINDINGS. Iain T Boyle. UniversityDepartmentof Medicine.GlasgowRoyal Int-wmary.Scotland. Paget'sdiseaseof bone may affectone, severalor all the bones of the skeletonand may present withpain or deformity- "0steitisdeformans"- at the affectedsites. The typical bone discomfortis an ache whichis not refievedby bed rest and the area is warm. As a result of associatedbony deformity,neighbouringjoints are frequentlythe site of degenerativearthritisleadingto discomforton w¢ightbearingand mobility. Commonsites to be affectedare the lumbarspine,pelvis,long bones and skull with resultingclinical picturesof spinalrigidity,arthritisof hip. coxa vatS.bowed tibiae,calvorialenlargements. deafneSSetc. Nervecompressionsyndromesare ta~. The earliestradlologicalfeaturesinvolveam~ of lucencywhich in the long bones are t'wst seen at the ends and advancealong the boneat the rate of one centimetreper year. Such prominentate.anof increasedn'.sorption,particularly in the skull are called "osteoporosis circumscripta"and me eventuallyreplacedby either scleroticcortical bone or trabocular bone of thickenedand chaoticpattern. PaOtologicalfracturesor pseedofracturesmay be seen. The volumeof an affectedbone is increased. The differentialdiagnosisincludespolyostodcfibronsdysplasin,skeletal metastases (particularlyprostatic)or congenitalformsofcorticulhypemstosis(suchas Engeimann's disease), In rarecaseswhere o~teo~urcemasupervenes,~ acceleratedwansluceneymay be seen.
Indications for treatment of Paget's disease D a v i d C A n d e r s o n . D e p a r t m e n t of M e d i c i n e , T h e C h i n e s e U n i v e r s i t y of Hong K e n g , S h a t l n , New T e r r i t o r i e s , H o n g K o n g Current practice in managillg Paget's disease is dictated by a number of factors. These include the fact that the disease is clinically silent for sn long in s very high percentage o f cases and generally presents in old age; furthermore, little is known o f the true impact o f the disease on the patient's future health, relaxed to age at prezentation and location o f diseased bones. Current atttitudes are also coloured by experience with calcitonin, which has offered no prospect of cure and is intrinsically expensive, and with etidronate, which has such a narrow safety margin. Our experience in Manchester o f the use o f IV pamidronate in nearly 500 cases over the past nine years demonstrates that with this agent there is a quantum leap in efficacy, the drug is very safe, and remission can be achieved with one or more single short c o u r s e s of moderate dosage (210-390 mg as 4 to 7 spaced infusions over 2-10 weeks) in 90%. Cure is evidenced by long-term remission o f biochemistry, bone scans and return o f bone surfaces to normal, and is seen in about 10%: evidently some patients are particularly responsive to this second generation bisphosphonate. There is every reason to believe that one or more of the third generation bisphosphonates, such as alendronate, will be even more effective,, although the fashion to go for oral formulations ( p r i n c i p a l l y f o r © 1995 by Elsevier Science Inc.
of eitherpunctatosclerosisor
Radionuclideimagingof the skeletonis the most sensitivemethodfor the detectionof Paget's disease- often revealingthe presenceof the problemin unsuspectedpromof the skeleton. Affectedbones may be extremely"hot" yieldingimagesthat are larger than the normalbone. Distinctionfrom bonemetastas~ is not atonallya problem. P R E L I M I N A R Y R E S U L T S O F AN E P I D E M I O L O G I C A L STUDY ON P A G E T ' S DISEASE O F BONE IN AN AREA OF CASTILLA-LEON del Pino J*, Mir6n CA**, Vicente AM, Botella PE, Garcla IJ, Terrero PD, Asensio AD, Blaneo A, Gongalves T, by the Grupo de Estudio de Enfermedad Osea de Paget de Salamanca. *Unidad de Metabolismo Oseo. **Departamento de Medieina Preventiva. Centro de Salud de Vitigudino. Universidad de Salamanca. Paget's disease has a heterogeneous geographical distribution, several foc'i of high incidence having been detected in our country. The aim of the present work was to gain insight into the prevalence of this disease in a zone located in the Northwest of the province of Salamanca in cross-sectional study of a representative sample of the population. Sample choice was made through a stratified sampling based on the size of the munieipalities and the ages of the heads of families. A sampling error of 5% and a confidence level of 95% were considered, obtaining a sample of 378 individuals. The final selection of the individuals was made by a system of random paths. Data were collected in personal interviews, implementing a 3 l-item questionnaire and an analytic screening. The field work was carried out over a one-year period (February 1993 to February 1994). 97
8756-3282/95/$9.50 SSDI 8756-3282(95)00142-2
ELSEVIER
ABSTRACTS FROM THE SYMPOSIUM OF THE SPANISH SOCIETY FOR BONE AND MINERAL RESEARCH (SEIOMM) DEVOTED TO PAGET'S DISEASE, Salamanca, Spain, November 3-4, 1994 their potential in diseases such as osteoporosis and bone metastases) may hamper trmeir effective application in Paget's disease. C o n c l u s i o n ; the time is fast approaching when all patients with symptoms, or even in the absence o f symptoms with a reasonable life expectancy, will be offered a single course o f bisphosphonate, and a significant percentage will be cured.
Paget's Disease; evidence for a viral cause D a v i d C A n d e r s o n . D e p a r t m e n t of M e d i c i n e , T h e C h i n e s e U n i v e r s i t y of Hong Kong, Shatln, New Territories, Hong Kong Major problems in establishing the cause o f Paget's disease are that it is clinically silent for so long, and there is great clinical variability, (anatomical as well as possibly environmental and genetic), It is focal and spreads progressively through an affected bone as a lyric front, at about I cm per year, from what appears to be a single focus. Thc disease behaves as if at a single point in time a disseminated blood-borne infection which stimulates osteoclast function has seeded out in osteoclasts and taken hold in bones at random. The p a r a m y x o v i r u s e s are simple negative single-stranded R N A viruses with s propensity to mutate and to establish persistent infections. The first evidence o f a viral cause was the finding of inclusion bodies in Pagetic osteoclasts suggestive of paramyxovirus nucleocapsids; subsequent work has cast doubt on the significance o f these bodies; are they simply a reflection o f excessive osteoelast function? The second evidence, which is also of dubious significance is that of immunocytochemistry, which sugges.*.ed the possible involvement of a number of paramyxoviruses including measles. Our own pursuit in M a n c h e s t e r o f canine distemper virus (CDV) arose from case control studies o f previous dog ownership. Our evidence, not so far oonfirmed by others, is based on in situ hybridisation and PCR, and implicates CDV in about two thirds o f cases. The virus infects the osteoclast in the natural host, although in contrast to Paget's, here the genomic strand is also evident, whereas hybridisation in Paget's disease is only seen to the mKNA strand; the same holds for the canine disease metaphyseal osteopathy. The case for CDV, at least in s o m e cases, as the infectious cause, is suggestive, but not p r o v e n
THE DIAGNOSISOF PAGET$ DISEASE: IMPORTANCEOF CLINICAL. RADIOLOGICALAND IMAGINGFINDINGS. Iain T Boyle. UniversityDepartmentof Medicine.GlasgowRoyal Int-wmary.Scotland. Paget'sdiseaseof bone may affectone, severalor all the bones of the skeletonand may present withpain or deformity- "0steitisdeformans"- at the affectedsites. The typical bone discomfortis an ache whichis not refievedby bed rest and the area is warm. As a result of associatedbony deformity,neighbouringjoints are frequentlythe site of degenerativearthritisleadingto discomforton w¢ightbearingand mobility. Commonsites to be affectedare the lumbarspine,pelvis,long bones and skull with resultingclinical picturesof spinalrigidity,arthritisof hip. coxa vatS.bowed tibiae,calvorialenlargements. deafneSSetc. Nervecompressionsyndromesare ta~. The earliestradlologicalfeaturesinvolveam~ of lucencywhich in the long bones are t'wst seen at the ends and advancealong the boneat the rate of one centimetreper year. Such prominentate.anof increasedn'.sorption,particularly in the skull are called "osteoporosis circumscripta"and me eventuallyreplacedby either scleroticcortical bone or trabocular bone of thickenedand chaoticpattern. PaOtologicalfracturesor pseedofracturesmay be seen. The volumeof an affectedbone is increased. The differentialdiagnosisincludespolyostodcfibronsdysplasin,skeletal metastases (particularlyprostatic)or congenitalformsofcorticulhypemstosis(suchas Engeimann's disease), In rarecaseswhere o~teo~urcemasupervenes,~ acceleratedwansluceneymay be seen.
Indications for treatment of Paget's disease D a v i d C A n d e r s o n . D e p a r t m e n t of M e d i c i n e , T h e C h i n e s e U n i v e r s i t y of Hong K e n g , S h a t l n , New T e r r i t o r i e s , H o n g K o n g Current practice in managillg Paget's disease is dictated by a number of factors. These include the fact that the disease is clinically silent for sn long in s very high percentage o f cases and generally presents in old age; furthermore, little is known o f the true impact o f the disease on the patient's future health, relaxed to age at prezentation and location o f diseased bones. Current atttitudes are also coloured by experience with calcitonin, which has offered no prospect of cure and is intrinsically expensive, and with etidronate, which has such a narrow safety margin. Our experience in Manchester o f the use o f IV pamidronate in nearly 500 cases over the past nine years demonstrates that with this agent there is a quantum leap in efficacy, the drug is very safe, and remission can be achieved with one or more single short c o u r s e s of moderate dosage (210-390 mg as 4 to 7 spaced infusions over 2-10 weeks) in 90%. Cure is evidenced by long-term remission o f biochemistry, bone scans and return o f bone surfaces to normal, and is seen in about 10%: evidently some patients are particularly responsive to this second generation bisphosphonate. There is every reason to believe that one or more of the third generation bisphosphonates, such as alendronate, will be even more effective,, although the fashion to go for oral formulations ( p r i n c i p a l l y f o r © 1995 by Elsevier Science Inc.
of eitherpunctatosclerosisor
Radionuclideimagingof the skeletonis the most sensitivemethodfor the detectionof Paget's disease- often revealingthe presenceof the problemin unsuspectedpromof the skeleton. Affectedbones may be extremely"hot" yieldingimagesthat are larger than the normalbone. Distinctionfrom bonemetastas~ is not atonallya problem. P R E L I M I N A R Y R E S U L T S O F AN E P I D E M I O L O G I C A L STUDY ON P A G E T ' S DISEASE O F BONE IN AN AREA OF CASTILLA-LEON del Pino J*, Mir6n CA**, Vicente AM, Botella PE, Garcla IJ, Terrero PD, Asensio AD, Blaneo A, Gongalves T, by the Grupo de Estudio de Enfermedad Osea de Paget de Salamanca. *Unidad de Metabolismo Oseo. **Departamento de Medieina Preventiva. Centro de Salud de Vitigudino. Universidad de Salamanca. Paget's disease has a heterogeneous geographical distribution, several foc'i of high incidence having been detected in our country. The aim of the present work was to gain insight into the prevalence of this disease in a zone located in the Northwest of the province of Salamanca in cross-sectional study of a representative sample of the population. Sample choice was made through a stratified sampling based on the size of the munieipalities and the ages of the heads of families. A sampling error of 5% and a confidence level of 95% were considered, obtaining a sample of 378 individuals. The final selection of the individuals was made by a system of random paths. Data were collected in personal interviews, implementing a 3 l-item questionnaire and an analytic screening. The field work was carried out over a one-year period (February 1993 to February 1994). 97
8756-3282/95/$9.50 SSDI 8756-3282(95)00142-2