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Head and Neck Pathology Dec 2023The differential diagnosis for an isolated lytic mastoid lesion is broad, encompassing various conditions requiring careful consideration. These include granulomatous...
The differential diagnosis for an isolated lytic mastoid lesion is broad, encompassing various conditions requiring careful consideration. These include granulomatous disorders such as Langerhans cell histiocytosis and sarcoidosis, neoplastic processes like multiple myeloma, leukemia, lymphoma, and metastases, primary bone diseases such as Paget's disease, fibrous dysplasia, and osteitis fibrosa cystica, as well as infectious causes like osteomyelitis. In this report, we present a patient with otalgia and an isolated lytic mastoid lesion.
Topics: Humans; Mastoid; Earache; Bone Diseases; Osteitis Fibrosa Cystica; Osteitis Deformans; Fibrous Dysplasia of Bone
PubMed: 37735288
DOI: 10.1007/s12105-023-01583-5 -
The American Journal of the Medical... Jun 2024Paget disease of bone (PDB) is a disorder of accelerated bone remodeling resulting in bone overgrowth and impaired integrity that traditionally is described to be more...
BACKGROUND
Paget disease of bone (PDB) is a disorder of accelerated bone remodeling resulting in bone overgrowth and impaired integrity that traditionally is described to be more frequent in individuals of European descent. Based on clinical observation, we hypothesized that among the US Southeastern Veteran population, the disease is more common among African American patients.
MATERIALS AND METHODS
We conducted a cross-sectional study using the Veterans Affairs' Clinical Data Warehouse (CDW) and review of electronic medical records (EMR). Using the CDW, we identified patients from the Birmingham VA Medical Center (BVAMC) with an International Classification of Diseases code for PDB between January 2000 and December 2020. We extracted their self-reported race from the CDW and determined the proportion of African American patients, which we compared to the proportion of White patients. As a secondary goal, we extracted relevant clinical characteristics from the EMR. The statistical analysis was done using Stata/SE 14.2 for Mac.
RESULTS
We identified 285 individuals from the BVAMC with PDB between January 2000 and December 2020. The proportion of African American patients was significantly higher than White patients (0.51 vs. 0.4, p = 0.0036). African American patients presented at a younger age than their peers (mean[standard deviation] age at diagnosis: 64.6[11.6] vs. 70.1[10.7] years, p = 0.0009) but did not have higher alkaline phosphatase levels, higher proportion of polyostotic disease, or of symptoms and complications.
CONCLUSIONS
In the BVAMC population, PDB is more common among African American patients than White patients. Our findings and other publications hint at the existence of a cluster of PDB among the African American population in the US Southeast.
Topics: Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Black or African American; Cross-Sectional Studies; Osteitis Deformans; Southeastern United States; United States; Veterans; White
PubMed: 38364993
DOI: 10.1016/j.amjms.2024.02.005 -
Journal of Bone and Mineral Metabolism Jan 2024We conducted an all-case postmarketing surveillance study between 2008 and 2017 to evaluate the safety and effectiveness of risedronate for Paget's disease of bone (PDB)...
INTRODUCTION
We conducted an all-case postmarketing surveillance study between 2008 and 2017 to evaluate the safety and effectiveness of risedronate for Paget's disease of bone (PDB) in Japan.
MATERIAL AND METHODS
This study registered all patients who received once-daily risedronate 17.5 mg for the treatment of PDB and collected data over a 48-week follow-up period per treatment cycle for each patient.
RESULTS
The safety analysis set included 184 patients (mean age, 63.7 years), 81 (44.0%) of whom previously received a bisphosphonate. Of them, 41 (22.3%) experienced 72 adverse drug reactions (ADRs), and 8 (4.3%) experienced 14 serious ADRs. Common ADRs included gastrointestinal disorders (20 patients, 10.9%) and hypocalcemia (6 patients, 3.3%). The effectiveness analysis set included 182 patients, 124 of whom completed only one treatment cycle and 58 of whom completed multiple treatment cycles. The proportions of patients who normalized serum alkaline phosphatase (ALP) concentration were 71.1% (113/159 patients) and 67.3% (33/49 patients) for the first and second treatment cycles, respectively. The relapse rate according to ALP levels after the end of treatment for the first cycle was 5.0% (95% confidence interval [CI] = 2.1-11.5) at 24 weeks and 12.9% (95% CI = 7.5-21.7) at 40 weeks. Regarding pain relief, the achievement rates were 70.0% (49/70 patients) and 30.8% (4/13 patients) for the first and second treatment cycles, respectively.
CONCLUSION
To conclude, risedronate 17.5 mg/day is safe and effective for treating patients with PDB in daily practice.
Topics: Humans; Middle Aged; Risedronic Acid; Osteitis Deformans; Etidronic Acid; Japan; Diphosphonates
PubMed: 38197974
DOI: 10.1007/s00774-023-01486-z -
Bone Nov 2023Paget's disease of bone (PDB) is a focal bone disorder characterized by an increased bone remodeling and an anarchic bone structure. A decline of prevalence and...
BACKGROUND
Paget's disease of bone (PDB) is a focal bone disorder characterized by an increased bone remodeling and an anarchic bone structure. A decline of prevalence and incidence of PDB has been observed in some countries. No epidemiological data are available on PDB in Canada.
AIMS
We aimed at examining the evolution of the prevalence and incidence of PDB in Quebec (Canada) by analyzing health administrative databases.
METHODS
PDB case definition relied on one or more hospitalizations, or one or more physician-billing claims with a diagnosis code of PDB. To identify incident cases, a 'run-in' period of four years (1996-1999) was used to exclude prevalent cases. For each fiscal year from 2000 to 2001 to 2019-2020 (population size 2,914,480), crude age and sex-specific prevalence and incidence rates of PDB among individuals aged ≥55 years were determined, and sex-specific rates were also standardized to the 2011 age structure of the Quebec population. Generalized linear regressions were used to test for linear changes in standardized prevalence and incidence rates.
RESULTS
Over the study period, standardized prevalence of PDB has remained stable in Quebec, from 0.44 % in 2000/2001 to 0.43 % in 2019/2020 (mean change -0.002, p-value = 0.0935). For the 2019-2020 fiscal year, 13,165 men and women had been diagnosed with PDB and prevalence of PDB increased with age. Standardized incidence of PDB has decreased over time from 0.77/1000 in 2000/2001 to 0.28/1000 in 2019-2020 (mean change -0.228/year, p-value<0.0001), the incidence decreasing from 0.82/1000 to 0.37/1000 in men and from 0.76/1000 to 0.22/1000 in women, respectively. This decrease was observed in all age categories.
CONCLUSION
With the exception of a slight increase in PDB prevalence up to 0.55 % in years 2005 to 2007, the prevalence of PDB has remained stable in Quebec over the past 20 years, 13,160 men and women being currently diagnosed with PDB. The incidence has decreased over time. Our results support the epidemiological changes of PDB reported in other countries.
Topics: Male; Female; Humans; Quebec; Incidence; Osteitis Deformans; Prevalence; Canada
PubMed: 37683713
DOI: 10.1016/j.bone.2023.116895 -
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 -
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 -
Muscle & Nerve Jun 2024VCP multisystem proteinopathy 1 (MSP1), encompassing inclusion body myopathy (IBM), Paget's disease of bone (PDB) and frontotemporal dementia (FTD) (IBMPFD), features...
INTRODUCTION/AIMS
VCP multisystem proteinopathy 1 (MSP1), encompassing inclusion body myopathy (IBM), Paget's disease of bone (PDB) and frontotemporal dementia (FTD) (IBMPFD), features progressive muscle weakness, fatty infiltration, and disorganized bone structure in Pagetic bones. The aim of this study is to utilize dual-energy x-ray absorptiometry (DXA) parameters to examine it as a biomarker of muscle and bone disease in MSP1.
METHODS
DXA scans were obtained in 28 patients to assess body composition parameters (bone mineral density [BMD], T-score, total fat, and lean mass) across different groups: total VCP disease (n = 19), including myopathy without Paget's ("myopathy"; n = 12) and myopathy with Paget's ("Paget"; n = 7), and unaffected first-degree relatives serving as controls (n = 6).
RESULTS
In the VCP disease group, significant declines in left hip BMD and Z-scores were noted versus the control group (p ≤ .03). The VCP disease group showed decreased whole body lean mass % (p = .04), and increased total body fat % (p = .04) compared to controls. Subgroup comparisons indicated osteopenia in 33.3% and osteoporosis in 8.3% of the myopathy group, with 14.3% exhibiting osteopenia in the Paget group. Moreover, the Paget group displayed higher lumbar L1-L4 T-score values than the myopathy group.
DISCUSSION
In MSP1, DXA revealed reduced bone and lean mass, and increased fat mass. These DXA insights could aid in monitoring disease progression of muscle loss and secondary osteopenia/osteoporosis in MSP1, providing value both clinically and in clinical research.
Topics: Humans; Male; Female; Absorptiometry, Photon; Middle Aged; Cross-Sectional Studies; Aged; Bone Density; Myositis, Inclusion Body; Osteitis Deformans; Adult; Frontotemporal Dementia; Body Composition; Valosin Containing Protein; Adenosine Triphosphatases; Muscular Dystrophies, Limb-Girdle
PubMed: 38551101
DOI: 10.1002/mus.28095 -
Journal of Clinical and Translational... Aug 2023Paget's disease of the bone refers to a chronic cumulative disorder characterized by enhanced osteoclastic function followed by a secondary surge in osteoblastic...
BACKGROUND AND AIM
Paget's disease of the bone refers to a chronic cumulative disorder characterized by enhanced osteoclastic function followed by a secondary surge in osteoblastic activity. The condition can manifest as a polyostotic or monostotic bone disease with most patients having an asymptomatic presentation, although some may complain of pain localized to the affected bone while others express symptoms of nerve compression. A pagetic bone is predisposed to develop pathological fractures, bony deformities, and a rare yet detrimental transformation into osteosarcoma. Detection is often accidental when performing radiographic tests for other indications or when elevated blood levels of alkaline phosphatase (ALP) are detected. Treatment with third-generation bisphosphonates is helpful in preventing further bone resorption and, additionally, reduces bony pains that are believed to be caused by excessive metabolic activity. Here, we present a case of a middle-aged asymptomatic female with elevated serum ALP levels up to 1537 IU/L (reference range 40-150 U/L) during her pre-operative evaluation for elective cholecystectomy. Tc-methylene diphosphonate bone scintigraphy revealed diffuse uptake in the skull and, hence, was diagnosed as a case of isolated Paget's disease of the skull.
RELEVANCE FOR PATIENTS
The rarity of this disease in Southeast-Asians, its uncontrived detection, and the isolated skull involvement, imparts high clinical relevance on this case. Early detection and management of this disease can help prevent the development of life-threatening complications in affected patients, hence decreasing the morbidity.
PubMed: 37593243
DOI: No ID Found -
Calcified Tissue International Nov 2023Paget's disease of bone (PDB) is a common, late-onset bone disorder, characterized by focal increases of bone turnover that can result in bone lesions. Heterozygous...
Paget's disease of bone (PDB) is a common, late-onset bone disorder, characterized by focal increases of bone turnover that can result in bone lesions. Heterozygous pathogenic variants in the Sequestosome 1 (SQSTM1) gene are found to be the main genetic cause of PDB. More recently, PFN1 and ZNF687 have been identified as causal genes in patients with a severe, early-onset, polyostotic form of PDB, and an increased likelihood to develop giant cell tumors. In our study, we screened the coding regions of PFN1 and ZNF687 in a Belgian PDB cohort (n = 188). In the PFN1 gene, no variants could be identified, supporting the observation that variants in this gene are extremely rare in PDB. However, we identified 3 non-synonymous coding variants in ZNF687. Interestingly, two of these rare variants (p.Pro937His and p.Arg939Cys) were clustering in the nuclear localization signal of the encoded ZNF687 protein, also harboring the p.Pro937Arg variant, a previously reported disease-causing variant. In conclusion, our findings support the involvement of genetic variation in ZNF687 in the pathogenesis of classical PDB, thereby expanding its mutational spectrum.
Topics: Humans; Osteitis Deformans; Nuclear Localization Signals; Sequestosome-1 Protein; Genetic Testing; Transcription Factors; Mutation; Profilins
PubMed: 37728743
DOI: 10.1007/s00223-023-01137-5 -
Medicine Mar 2024Extramammary Paget disease is a relatively rare and less malignant intraepithelial adenocarcinoma. t is found in areas with abundant distribution of apocrine sweat...
BACKGROUND
Extramammary Paget disease is a relatively rare and less malignant intraepithelial adenocarcinoma. t is found in areas with abundant distribution of apocrine sweat glands such as the external genitalia, external genitalia, and perianal area, with fewer armpits. The disease progresses slowly and is prone to misdiagnosis in clinical practice.
METHODS
We retrospectively analyzed a female patient. She had a left axillary mass for more than 2 years. Recently, the mass increased and the surface skin was ulcerated. Then she went to Jiangxi Provincial Dermatology Hospital for left axillary lesion resection, and the postoperative pathology showed Paget disease outside the breast. For further diagnosis and treatment, she came to our hospital. We diagnosed a tumor with uncertain or unknown dynamics in the left axillary breast. Under general anesthesia, left subaxillary mass resection, freezing and left breast cancer breast conserving surgery was performed.
RESULTS
The postoperative pathology of the left axillary mass combined with morphological and immunohistochemical results was consistent with Paget disease. Postoperative immunohistochemistry showed estrogen receptor (+, 20%), progesterone receptor (-), human epidermal growth factor receptor-2 (3+), Ki-67 (30%), cytokine7 (+), and p63 (-). Following up for 22 months, there has been no local recurrence, no swelling of the right axillary lymph node, no distant metastasis found on follow-up, and no complications such as upper limb lymphedema, upper limb sensory abnormalities, or motor disorders have been observed.
CONCLUSION
Paget disease outside the axillary breast is relatively rare, and surgical resection is the best choice. The prognosis is good, and the recurrence rate is low.
Topics: Humans; Female; Retrospective Studies; Adenocarcinoma; Paget Disease, Extramammary; Lymph Nodes; Breast; Osteitis Deformans; Breast Neoplasms
PubMed: 38552095
DOI: 10.1097/MD.0000000000037541