Paget's disease of the bone is a rare and debilihatinng disease. It is a sporadic disease usually involving multiple bones though occasionally isolated sites may occur. The most common sites include the lumbosacral spine, pelvis, and skull. This is an important diagnosis because of the potential for malignant tumors to develop in the diseased bone.
Patients may present with a variety of signs and symptoms depending upon which bones are affected. Arthritis, loss of hearing in one or both ears, heart disease (high output cardiac failure secondary to the heart working harder to pump blood to affected bones, kidney stones, nervous system abnormalities secondary to Pagetic bone causing pressure on the brain, spinal cord, or nerves, and reduced blood flow to the brain and spinal cord. The teeth and vision may also be affected when bones of the skull are involved.
EPIDEMIOLOGY CHARACTERIZATION SYNONYMS Osteitis deformans AGE RANGE-MEDIAN Median 55 years
The epidemiology of Paget's disease.
Metab Bone Dis Relat Res 1981;3(4-5):231-3 Abstract quote
Paget's disease is commoner in men and its prevalence increases with age. It has a remarkable geographical localisation. Britain has the highest recorded prevalence. Somewhat lower rates have been recorded in North America, Australia and Western Europe. The disease is rare in Scandinavia. Within Britain there is a localised area of high prevalence in Lancashire. In North America prevalence is markedly higher in New York than in Atlanta. Rates in American blacks and whites are similar although the disease is rare in Africa. In Australia the prevalence among British born immigrants is intermediate between the British rate and that of native born Australians. There is evidence of a decline in incidence of the disease in Britain and North America.
The epidemiological characteristics of the disease suggest that environmental influences are important in its aetiology. They provide data against which new hypotheses on causation must be tested.
The epidemiology of Paget's disease in Britain: is the prevalence decreasing?
Cooper C, Schafheutle K, Dennison E, Kellingray S, Guyer P, Barker D.
MRC Environmental Epidemiology Unit, Southampton General Hospital, Southampton, United Kingdom
J Bone Miner Res 1999 Feb;14(2):192-7 Abstract quote
To estimate changes in the age- and gender-specific prevalence of Paget's disease in Britain, we performed a radiographic survey of the disorder in 10 British centers, using sampling and radiographic methods identical to a study performed in 1974.
In each center, a sample of abdominal radiographs of people aged 55 years and over was taken from stored films within the radiology department of the principal general hospital. The radiographs were identified by screening radiographic records over the period 1993-1995. Any abdominal radiograph in a subject aged 55 years and over which included the entire pelvis, sacrum, femoral heads, and all lumbar vertebrae was studied. The radiographs were evaluated by a trained observer and the consultant radiologist who participated in the original 1974 survey. Nine thousand eight hundred and twenty-eight radiographs (4625 men, 5203 women) were assessed in the 10 towns. The overall age/gender standardized prevalence rate was 2%, with a male/female ratio of 1.6. Prevalence increased steeply with age among men and women, rising to 6.9% of men and 5.8% of women aged 85 years and over. The prevalence of Paget's disease in the 10 towns in 1994 was only 40% of that observed during the 1974 study. The decline in prevalence was apparent in all 10 centers, but was most marked in those with high rates in the original study.
This survey of Paget's disease in 10 British towns suggests a prevalence of 2.5% among men and 1.6% among women aged 55 years and over. Age-adjusted prevalence rates declined steeply between 1974 and 1994. These declines suggest an environmental contribution to the etiology of this disorder that requires further investigation.
Prevalence of pelvic Paget's disease of bone in the United States.
Altman RD, Bloch DA, Hochberg MC, Murphy WA.
Geriatric Research, Education and Clinical Center, Miami Department of Veterans Affairs Medical Center, University of Miami School of Medicine, Florida, USA.
J Bone Miner Res 2000 Mar;15(3):461-5 Abstract quote
The objective of this article was to estimate the prevalence of Paget's disease of bone in the United States from a statistically derived sample of the general population.
Pelvic radiographs obtained in the First National Health and Nutrition Examination Survey (NHANES-I) were reviewed for the presence of Paget's disease. Age, sex, and geographic distribution of Paget's disease of the pelvic region were determined. The overall prevalence of Paget's disease in the United States was estimated. Pelvic Paget's disease is estimated to be present in 0.71 + 0.18% of the radiographs of the general population. The disease was higher in frequency in people who were in the older decades of life with the highest prevalence of 2.32 + 0.54% in the 65- to 74-year-old people. There is a slight male predominance in the 45- to 74-year age group. The regional distribution suggests the highest prevalence in the Northeast (1.48 + 0.52%) with the lowest prevalence in the South (0.26+0.25%).
The prevalence was equal in white people and black people. An estimate of the overall prevalence of Paget's disease in the United States was at least 1% and perhaps as much as 2 % of the general population with near equal sex distribution and the highest prevalence in the northeastern United States.
DISEASE ASSOCIATIONS CHARACTERIZATION Malignancies Sarcomas are the most frequent association Osteosarcoma 10-30x more frequent in these patients Giant cell tumor of the epiphysis
Malignant fibrous histiocytoma in Paget's disease of bone. A report of seven cases.
Cossetto D, Nade S, Blackwell J.
Department of Surgery (Orthopaedic Surgery), Westmead Hospital Sydney, New South Wales, Australia.
Aust N Z J Surg 1992 Jan;62(1):52-5 Abstract quote
Malignant change in Paget's disease of bone usually has the histological features of osteosarcoma, but follows a different clinical course from cases not associated with paget's disease of bone. Malignant fibrous histiocytoma is an uncommon neoplasm which may be associated with pagetic bone and its clinical course is not well defined.
Seven cases of malignant fibrous histiocytoma in Paget's disease were reviewed from two Australian bone tumour registries. In stage IIB and III disease there was a three year survival rate of 57%, suggesting a better prognosis than for patients with other sarcomas in Paget's disease.
PATHOGENESIS CHARACTERIZATION Virus-like inclusions
J Clin Endocrinol Metab 1995;80:2108-2111
Found in 100% of cases within the osteoclasts of Paget's disease and sarcomas arising with the disease
Measles virus (Paramyxovirus) nucleocapsid transcripts in patient's marrow samples contained point mutations
Failure to detect paramyxovirus sequences in Paget's disease of bone using the polymerase chain reaction.
Ralston SH, Digiovine FS, Gallacher SJ, Boyle IT, Duff GW.
Molecular Immunology Group, Northern General Hospital, Edinburgh, Scotland.
J Bone Miner Res 1991 Nov;6(11):1243-8 Abstract quote
It is widely believed that Paget's disease of bone is due to a "slow virus" infection of osteoclasts with one of the paramyxovirus group. Controversy continues to surround the identity of the virus involved, however, since at different times evidence has been presented implicating measles virus (MV), respiratory syncytial virus (RSV), and canine distemper virus (CDV) as putative infective agents.
In this study we used the technique of reverse transcription and polymerase chain reaction (PCR) to screen for paramyxovirus sequences in ribonucleic acid (RNA) extracted from pagetic bone. We were able to detect viral amplification products of the appropriate size in RNA extracted from as few as 50 cells experimentally infected with a wide range of paramyxoviruses, including measles, canine distemper, parainfluenza 3, and respiratory syncytial virus, but we found no evidence of viral products in RNA extracts of affected bone from 10 consecutive patients with Paget's disease.
This study fails to support the hypothesis that active infection with one of these or a related paramyxovirus is involved in the pathogenesis of Paget's disease.
A negative search for a paramyxoviral etiology of Paget's disease of bone: molecular, immunological, and ultrastructural studies in UK patients.
Helfrich MH, Hobson RP, Grabowski PS, Zurbriggen A, Cosby SL, Dickson GR, Fraser WD, Ooi CG, Selby PL, Crisp AJ, Wallace RG, Kahn S, Ralston SH.
Department of Medicine and Therapeutics, University of Aberdeen, United Kingdom.
J Bone Miner Res 2000 Dec;15(12):2315-29 Abstract quote
Paget's disease of bone is a common bone disease characterized by increased and disorganized bone remodeling at focal sites throughout the skeleton. The etiology of the disease is unresolved. A persistent viral infection has long been suggested to cause the disease. Antigen and/or nucleic acid sequences of paramyxoviruses (in particular measles virus [MV], canine distemper virus [CDV], and respiratory syncytial virus [RSV]) have been reported in pagetic bone by a number of groups; however, others have been unable to confirm this and so far no virus has been isolated from patients.
Here, we reexamined the question of viral involvement in Paget's disease in a study involving 53 patients with established disease recruited from seven centers throughout the United Kingdom. Thirty-seven patients showed clear signs of active disease by bone scan and/or histological assessment of the bone biopsy specimens and 12 of these had not received any therapy before samples were taken. Presence of paramyxovirus nucleic acid sequences was sought in bone biopsy specimens, bone marrow, or peripheral blood mononuclear cells using reverse-transcription polymerase chain reaction (RT-PCR) with a total of 18 primer sets (7 of which were nested), including 10 primer sets (including 3 nested sets) specifically for MV or CDV. For each patient at least one sample was tested with all primer sets by RT-PCR and no evidence for the presence of paramyxovirus RNA was found in any patient. In 6 patients, bone biopsy specimens with clear histological evidence of active disease tested negative for presence of measles and CDV using immunocytochemistry (ICC) and in situ hybridization (ISH). Intranuclear inclusion bodies, similar to those described by others previously, were seen in pagetic osteoclasts. The pagetic inclusions were straight, smooth tubular structures packed tightly in parallel bundles and differed from nuclear inclusions, known to represent MV nucleocapsids, in a patient with subacute sclerosing panencephalitis (SSPE) in which undulating, diffuse structures were found, arranged loosely in a nonparallel fashion.
In the absence of amplification of viral sequences from tissues that contain frequent nuclear inclusions and given that identical inclusions are found in other bone diseases with a proven genetic, rather than environmental, etiology, it is doubtful whether the inclusions in pagetic osteoclasts indeed represent viral nucleocapsids. Our findings in this large group of patients recruited from throughout the United Kingdom do not support a role for paramyxovirus in the etiology of Paget's disease.
Familial Paget's disease of bone: nonlinkage to the PDB1 and PDB2 loci on chromosomes 6p and 18q in a large pedigree.
Good D, Busfield F, Duffy D, Lovelock PK, Kesting JB, Cameron DP, Shaw JT.
Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Brisbane, Australia.
J Bone Miner Res 2001 Jan;16(1):33-8 Abstract quote
Paget's disease of bone is a common condition characterized by bone pain, deformity, pathological fracture, and an increased incidence of osteosarcoma. Genetic factors play a role in the pathogenesis of Paget's disease but the molecular basis remains largely unknown. Susceptibility loci for Paget's disease of bone have been mapped to chromosome 6p21.3 (PDB1) and 18q21.1-q22 (PDB2) in different pedigrees.
We have identified a large pedigree of over 250 individuals with 49 informative individuals affected with Paget's disease of bone; 31 of whom are available for genotypic analysis. The disease is inherited as an autosomal dominant trait in the pedigree with high penetrance by the sixth decade. Linkage analysis has been performed with markers at PDB1; these data show significant exclusion of linkage with log10 of the odds ratio (LOD) scores < -2 in this region. Linkage analysis of microsatellite markers from the PDB2 region has excluded linkage with this region, with a 30 cM exclusion region (LOD score < -2.0) centered on D18S42. These data confirm the genetic heterogeneity of Paget's disease of bone.
Our hypothesis is that a novel susceptibility gene relevant to the pathogenesis of Paget's disease of bone lies elsewhere in the genome in the affected members of this pedigree and will be identified using a microsatellite genomewide scan followed by positional cloning.
Paget disease of bone: mapping of two loci at 5q35-qter and 5q31.
Laurin N, Brown JP, Lemainque A, Duchesne A, Huot D, Lacourciere Y, Drapeau G, Verreault J, Raymond V, Morissette J.
Molecular Endocrinology and Oncology Research Center, CHUL Research Center, Quebec, Qc, Canada G1V 4G2.
Am J Hum Genet 2001 Sep;69(3):528-43 Abstract quote
Paget disease of bone is characterized by focal increases of the bone-remodeling process. It is the second most common metabolic bone disease after osteoporosis. Genetic factors play a major role in the etiology of Paget disease of bone, and two loci have been mapped for the disorder: PDB1 and PDB2. The gene(s) causing the typical form of the disorder remains to be characterized.
To decipher the molecular basis of Paget disease of bone, we performed genetic linkage analysis in 24 large French Canadian families (479 individuals) in which the disorder was segregating as an autosomal dominant trait. After exclusion of PDB2, a genomewide scan was performed on the three most informative family nuclei. LOD scores >1.0 were observed at seven locations. The 24 families were then used to detect strong evidence for linkage to chromosome 5q35-qter. Under heterogeneity, a maximum LOD score of 8.58 was obtained at D5S2073, at straight theta= .1. The same characteristic haplotype was carried by all patients in eight families, suggesting a founder effect. A recombination event in a key family confined the disease region within a 6-cM interval between D5S469 and the telomere. The 16 other families, with very low conditional probability of linkage to 5q35-qter, were further used, to map a second locus at 5q31. Under heterogeneity, a maximum LOD score of 3.70 was detected at D5S500 with straight theta=.00. Recombination events refined the 5q31 region within 12.2 cM, between D5S642 and D5S1972.
These observations demonstrate the mapping of two novel loci for Paget disease of bone and provide further evidence for genetic heterogeneity of this highly prevalent disorder. It is proposed that the 5q35-qter and 5q31 loci be named "PDB3" and "PDB4," respectively.
Computed tomography of Paget disease of the skull versus fibrous dysplasia.
Tehranzadeh J, Fung Y, Donohue M, Anavim A, Pribram HW.
Department of Radiological Sciences, University of California, Irvine Medical Center, Orange 92868-3298, USA.
Skeletal Radiol 1998 Dec;27(12):664-72 Abstract quote
OBJECTIVE: Radiologists are often challenged to review CT examinations of the skull without pertinent clinical information or plain radiographs. Skull lesions of fibrous dysplasia (FD) may often be confused with Paget disease (PD). The purpose of this article is to evaluate radiographic similarities and to find the signs that can differentiate PD from FD of the skull on head CT and to describe the CT imaging features of PD and FD.
DESIGN AND PATIENTS: CT scans of the skull in eight cases of PD, 18 cases of FD (13 cases of skull and facial bones, five cases of only facial bones) and 10 normals were studied retrospectively.
RESULTS: Ten features were found to be similar in PD and FD and 10 other features were found to be dissimilar. The frequency of the 10 differentiating features was evaluated to determine their reliability in distinguishing one disorder from the other. The differentiating features in order of significance include: (1) "groundglass" appearance, (2) symmetry, (3) involvement of the paranasal sinuses, (4) thickness of the cranial cortices, (5) involvement of the sphenoid bone, (6) orbital involvement, (7) nasal cavity involvement, (8) presence of a soft tissue mass, (9) maxillary involvement, and (10) the presence of cyst-like changes.
CONCLUSION: These 10 signs improve the radiologist's skill in differentiating FD and PD.
GROSS APPEARANCE/CLINICAL VARIANTS CHARACTERIZATION General VARIANTS Extraskeletal giant cell tumor (osteoclastoma) Hum Pathol 2000;31:1527-1531
Occurring in the right orbit
Pseudosarcoma in Paget's disease of bone.
Lamovec J, Rener M, Spiler M.
Departments of Pathology, Institute of Oncology, Ljubljana, Slovenia.
Ann Diagn Pathol 1999 Apr;3(2):99-103 Abstract quote
The appearance of a sarcoma of bone is a well-recognized complication of Paget's disease. The most common type of such a sarcoma is osteosarcoma. Much less common are soft tissue lesions adjoining the pagetic bone that clinically and radiologically simulate sarcoma but histologically represent exaggerated periosteal bone formation as a manifestation of the basic pathologic process.
We present a case of a bulky juxtacortical soft tissue mass in the thigh arising from a pagetic femur in a 62-year-old patient with polyostotic Paget's disease that was clinically and radiologically suspected to be a juxtacortical osteosarcoma. Microscopically, the lesion showed features of florid Paget's disease without any evidence of sarcomatous growth.
It is important to be aware of this rare manifestation of Paget's disease to avoid unnecessary overtreatment.
SPECIAL STAINS/IMMUNOPEROXIDASE/OTHER CHARACTERIZATION Electron microscopy (EM) Virus-like inclusions
Found in 100% of cases within the osteoclasts of Paget's disease and sarcomas arising with the disease
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSIS
Post-Paget osteosarcomas of the skull. Remarks on five cases.
Salvati M, Cervoni L, Raguso M, Raco A.
Department of Neurological Sciences-Neurosurgery, University of Rome La Sapienza, Italy.
Tumori 1993 Oct 31;79(5):363-6 Abstract quote
We report our experience with 5 cases of post-Paget osteosarcoma of the skull, a rare lesion of the neurocranium.
Four patients were treated by surgery and radiotherapy and one by surgery alone. Two patients received chemotherapy. Histologically, the tumor was found to be an osteosarcoma, fibroblastic in 2 cases, mixed in 2, and osteoblastic in 1. Combined treatment (surgery, radiotherapy and chemotherapy) positively influenced survival (median survival, 6 months). The prognosis for post-Paget osteosarcomas of the skull seems to be worse than for primary sarcomas, probably due to their intense vascularization. This facilitates the spread of tumor cells to other organs (as observed in our cases) and reduces the reduced effectiveness of chemotherapy.
Although the latter lengthens survival and reduces the incidence of metastases, it is not as efficacious as in primary sarcomas.
Prediction of the outcome of treatment of Paget's disease of bone with bisphosphonates from short-term changes in the rate of bone resorption.
Papapoulos SE, Frolich M.
Department of Endocrinology, University Hospital Leiden, The Netherlands.
J Clin Endocrinol Metab 1996 Nov;81(11):3993-7 Abstract quote\
In Paget's disease of bone, bisphosphonate therapy is usually given for 3-6 months, at which point the success of treatment is assessed by measuring serum alkaline phosphatase activity. The changes, however, in bone resorption and formation after bisphosphonate therapy are predictable, and their correct interpretation may allow a rational therapeutic approach applicable to the individual patient.
We addressed this issue in 21 patients with active Paget's disease treated with 2 different nitrogen-containing bisphosphonates for 10 days. Urine samples were collected daily before and during treatment for the measurement of the following collagen degradation products, as indexes of bone resorption; cross-linked N-telopeptide of collagen type I (NTx), free deoxypyridinoline with 2 different assays, and hydroxyproline. Independently of the structure of the bisphosphonate used, the magnitude of decrease in urinary NTx with treatment was greater than that of both deoxypyridinoline assays and practically identical to the decrease in excess of urinary hydroxyproline. The degree of suppression of NTx on the 9th and 10th days of treatment correlated with the lowest serum alkaline phosphatase activity obtained during 1 yr of follow-up. All patients in whom serum alkaline phosphatase activity normalized during follow-up showed a suppression of NTx greater than 75% of the initial values after 10 days of treatment.
We conclude that urinary NTx is a sensitive and specific index to follow the efficacy of bisphosphonate therapy in patients with Paget's disease and that measurements of its values before and after a short period of treatment can provide a simple and convenient way to predict the final therapeutic outcome and to avoid unnecessary continuation of treatment in many patients with Paget's disease of bone.
Pagetic sarcoma of the calvarium: report of two cases.
Fransen P, Mestdagh C, Dardenne G.
Department of Neurosurgery, Clinique du Parc Leopold, Brussels, Belgium.
Acta Neurol Belg 1998 Dec;98(4):352-5 Abstract quote
Two cases of calvarium sarcoma with intracranial extension, consecutive to Paget disease of the skull are presented. The neurosurgical implications of this rare complication of a common disease are reviewed. In both cases, the symptoms of malignant degeneration were unspecific and blurred by the presence of a well-known Paget disease. Increasing headaches, focal neurological deficits and signs of intracranial hypertension were observed.
Skull X-rays and Computerised Tomography did not allow to make the difference between Pagetic bone and sarcoma. In the second case, Magnetic Resonance Imaging was the most accurate in determining the precise localisation of the tumour, and the subdural invasion. Extensive surgical resection was carried out, by craniectomy of the tumoural bone, followed by cranioplasty. Dural sinus involvement and tumour hypervascularisation caused important peroperative blood loss in both patients. In the second case, the tumour invaded the subdural space through a Pacchioni granulation.
Survival of patients with Pagetic sarcoma seems shorter when compared to post-radiation or primitive osteosarcoma, despite adjuvant therapies, probably because of late diagnosis and incomplete surgical resection. The mean reported survival rate is 6 months. Although the first patient died within 4 months, in the second case, the authors obtained a more than two year survival with aggressive surgery alone.
These cases also illustrate the polymorphism of sarcomatous degeneration of Pagetic calvarium, the interest of MRI, and the need for close surveillance of patients with known Pagets disease of the skull.
Consensus statement on the modern therapy of Paget's disease of bone from a Western Osteoporosis Alliance symposium. Biannual Foothills Meeting on Osteoporosis, Calgary, Alberta, Canada, September 9-10, 2000.
Drake WM, Kendler DL, Brown JP.
Department of Medicine, University of British Columbia, Vancouver, Canada.
Clin Ther 2001 Apr;23(4):620-6 Abstract quote
BACKGROUND: Bisphosphonate therapy remains the most effective way of controlling Paget's disease of bone (PD). Along with salmon calcitonin, etidronate has been the mainstay of therapy for approximately 20 years. However, the advent of newer bisphosphonates with different molecular actions on osteoclasts warrants a reevaluation of optimal treatment.
OBJECTIVE: At a symposium of the Western Osteoporosis Alliance, physicians with experience in the management of PD met to review currently available information and generate this consensus statement as a guideline for clinicians and a source of information for health care payers.
METHODS: All available randomized, double-blind, controlled studies that compared the efficacy of newer bisphosphonates with that of etidronate in the treatment of PD were identified through a search of MEDLINE using the terms Paget's disease, bisphosphonates, pamidronate, etidronate, alendronate, risedronate, tiludronate, clodronate, calcitonin, and salmon calcitonin. Because no such studies have been conducted for pamidronate, clodronate, or calcitonin, these drugs were not included in the analysis.
CONCLUSIONS: The consensus of the symposium was that etidronate has little place in the modern management of PD. Newer bisphosphonates such as alendronate and risedronate provide significant therapeutic advantages over etidronate, both in the extent of reduction in bone-specific alkaline phosphatase (BSAP) and/or total serum alkaline phosphatase (SAP) and in the duration of remission, as measured by normalization of BSAP/SAP. In the absence of a direct comparison between alendronate and risedronate in the treatment of PD, physician choice is likely to be based on personal experience, relative cost, and differences in dosing.
Five bisphosphonates are currently available:
Didronel® (etidronate disodium)
Aredia® (pamidronate disodium)
Fosamax® (alendronate sodium)
Skelid® (tiludronate disodium)
Actonel® (risedronate sodium)
Calcitonin Miacalcin® is administered by injection
A double-blind, multicentre, placebo-controlled study of tiludronate in Paget's disease of bone.
Fraser WD, Stamp TC, Creek RA, Sawyer JP, Picot C.
University Department of Clinical Chemistry, Royal Liverpool Hospital, UK.
Postgrad Med J 1997 Aug;73(862):496-502 Abstract quote
A multicentre, randomised, placebo-controlled, dose-ranging study was conducted to investigate the therapeutic activity and sustained efficacy of tiludronate (200 mg, 400 mg and 600 mg once daily) taken orally for 12 weeks in patients with Paget's disease.
Serum alkaline phosphatase concentrations were compared with baseline at weeks 12 and 24; treatment success was defined as a 50% reduction compared with baseline. Changes in the hydroxyproline: creatinine ratio were also measured. Pain was assessed using the Huskisson Visual Analogue Scale and by questionnaire. Patients completing at least 11 weeks of treatment were followed-up 18 months later by postal questionnaire. Significantly greater numbers of patients in the tiludronate groups successfully responded to treatment compared with the placebo group. A dose-response was observed; the percentage of patients responding to treatment being 31% (200 mg), 52% (400 mg) and 82% (600 mg) at week 12 and 45% (200 mg), 70% (400 mg) and 82% (600 mg) at week 24. Tiludronate treatment also significantly reduced hydroxyproline: creatinine ratios compared with placebo, again showing a dose response. Dose-related gastrointestinal symptoms were the commonest adverse events, occurring in 2.4%, 11.0%, 5.5% and 18.9% of patients receiving placebo and tiludronate 200, 400 and 600 mg daily, respectively. The response to oral tiludronate was sustained for more than 18 months in some patients and there was evidence of a reduction in the longer term complications of the disease.
These results show that oral tiludronate is an effective, well-tolerated treatment for Paget's disease; the 400 mg once daily dose appears to offer the optimum balance of efficacy and tolerance.
Treatment of Paget's disease of bone with alendronate.
Merck Research Laboratories, Rahway, NJ, USA.
Bone 1999 May;24(5 Suppl):59S-61S Abstract quote
In summary, the clinical efficacy studies provide clear evidence that treatment with oral alendronate markedly suppresses bone turnover and produces clinical improvement in pagetic patients.
Serum alkaline phosphatase was greatly decreased by treatment, and the response to alendronate was superior to that observed for currently available therapies such as etidronate and calcitonin, which usually reduce alkaline phosphatase, on average, by 40%-50%. Alendronate also markedly reduced urinary resorption markers and induced radiologic improvement of pagetic osteolysis. A majority of alendronate-treated patients normalized their serum alkaline phosphatase by month 6. This observation is likely to be relevant to the duration of response to treatment, as previous studies have shown that the degree of suppression of alkaline phosphatase after antiresorptive treatment correlates with the duration of remission.
Therefore, patients who responded to treatment with alendronate, especially those who normalized their alkaline phosphatase levels, are likely to maintain the biochemical remission for several years. Indeed, preliminary unpublished data seem to indicate that alendronate is capable of producing long-term biochemical remission in the majority of patients. In addition to its efficacy, the safety and tolerability profile of alendronate 40 mg/day was very favorable and, overall, comparable to that of placebo.
A randomized, double-blind comparison of risedronate and etidronate in the treatment of Paget's disease of bone.
Paget's Risedronate/Etidronate Study Group. Miller PD, Brown JP, Siris ES, Hoseyni MS, Axelrod DW, Bekker PJ.
Colorado Center for Bone Research, Lakewood 80227, USA.
Am J Med 1999 May;106(5):513-20 Abstract quote
PURPOSE: To compare the efficacy and tolerability of oral risedronate and etidronate for treatment of Paget's disease of bone.
PATIENTS AND METHODS: Patients from 12 centers in North America received risedronate 30 mg daily for 2 months (62 patients) or etidronate 400 mg daily for 6 months (61 patients) in a prospective, randomized, double-blind study. Serum alkaline phosphatase (the primary variable), serum bone-specific alkaline phosphatase, and urinary deoxypyridinoline concentrations were monitored for 12 to 18 months.
RESULTS: Serum alkaline phosphatase concentration normalized by month 12 in 73% of risedronate-treated patients, compared with 15% of those receiving etidronate (P <0.001). Median time to normalization was 91 days for risedronate-treated patients and >360 days for etidronate-treated patients (P <0.001); relapse rates were 3% in the risedronate group and 15% in the etidronate group (P <0.05). At month 18, 53% of the risedronate group and 14% of the etidronate group remained in biochemical remission. Urinary deoxypyridinoline normalized in 87% of patients on risedronate and 57% of patients receiving etidronate (P <0.01); serum bone-specific alkaline phosphatase normalized in 73% of patients on risedronate and 18% of patients on etidronate (P <0.001). Patients who had received etidronate previously had a blunted response to etidronate, but not to risedronate. Reductions in pain were statistically significant in the risedronate group, but not in the etidronate group. Both drugs were well tolerated.
CONCLUSION: Although etidronate is effective, risedronate offers a shorter duration of therapy, better and longer-lasting remission, significant reductions in pain, and provides additional remission in subjects who exhibited an incomplete response to previous etidronate treatment.
SURGICAL Surgery for fractures, severe degenerative arthritis, or bone deformity
Surgical management of neoplastic complications of Paget's disease.
Department of Orthopaedic Surgery, California-Pacific Medical Center and the University of California-San Francisco, San Francisco, California 94118, USA.
J Bone Miner Res 1999 Oct;14 Suppl 2:45-8 Abstract quote
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.
Hydroxyapatite-coated total hip replacement in Paget's disease: 20 patients followed for 4-8 years.
Kirsh G, Kligman M, Roffman M.
Department of Orthopaedics, St George Private Hospital, Sydney, Australia.
Acta Orthop Scand 2001 Apr;72(2):127-32 Abstract quote
20 patients, who had had total hip replacements for symptomatic osteoarthrosis secondary to Paget's disease, were followed for a mean of 6 (4-8) years.
Proximal hydroxyapatite-coated stems were implanted in all patients. 12 patients received hydroxyapatite-coated, 2 cemented (Muller type) and 6 cementless cups (Morsher type). The mean Harris hip score was 31 (7-40) points preoperatively and 88 (74-100) postoperatively. The radiographic evaluation revealed good stability and fixation using Engh's criteria. One stem subsided early more than 5 mm and then seemed to stabilize.
Our findings support the use of hydroxyapatite total hip implants for patients with this disease and osteoarthrosis.
Sternberg S. Diagnostic Surgical Pathology. Third Edition. Lipincott Williams and Wilkins 1999.
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