RESUMO
This short note illustrates facial and head features found in a stone sculpture of the ancient, Precolumbian period in a temple of the Mayan city of Copan (Honduras). The authors believe that this observation may support paleoanthropological evidence of Paget's disease of bone, an osteodystrophy described in the Mesoamerican Indian populations before the first millennium A.D.
Assuntos
Doenças Ósseas Metabólicas/patologia , Osteíte Deformante/patologia , Escultura/história , Crânio/patologia , Idoso , Feminino , História Antiga , Humanos , Indígenas Centro-AmericanosRESUMO
A 40-year-old Filipina presented with a 2-year history of progressive bilateral inguinal and hip pain with limited range of motion. She had a bad fall which led to widespread body pains for 6 months partially relieved on multiple analgesic and anti-inflammatory agents. There was progressive weight loss and anemia. Focused musculoskeletal examination revealed moderate degree of generalized muscle atrophy, pain-limited range of motion of bilateral hip and shoulder joints, with equivocal muscle strength of both proximal and distal muscle groups of all extremities. Metastatic bone disease was ruled out when skeletal survey disclosed mixture of osteolytic and osteoblastic lesions, predominantly osteoblastic, on multiple sites. Bone turnover markers were elevated. Bone biopsy revealed histopathologic results compatible with Paget's disease of the bone. Management included oral calcium and vitamin D supplement followed by parenteral zoledronic acid, and a rehabilitation program. Four months after bisphosphonate therapy, the patient reported significant relief of symptoms with complete resolution of the previously noted generalized body pains, although she ambulates with use of an assistive device. Due to the rarity of the condition among Filipinos, this case was a diagnostic dilemma in itself, as it is most likely the first published case in the Philippine literature.
Assuntos
Osteíte Deformante/patologia , Conservadores da Densidade Óssea/uso terapêutico , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Compostos de Cálcio/administração & dosagem , Suplementos Nutricionais , Difosfonatos/uso terapêutico , Terapia por Exercício , Feminino , Humanos , Imidazóis/uso terapêutico , Osteíte Deformante/fisiopatologia , Osteíte Deformante/reabilitação , Filipinas , Radiografia Torácica , Amplitude de Movimento Articular , Resultado do Tratamento , Vitamina D/administração & dosagem , Ácido ZoledrônicoAssuntos
Doenças Ósseas/metabolismo , Doenças Ósseas/terapia , Osteíte Deformante/tratamento farmacológico , Osteíte Deformante/metabolismo , Animais , Artrite/metabolismo , Remodelação Óssea , Inglaterra , Hormônios/metabolismo , Hormônios/uso terapêutico , Humanos , Neoplasias/metabolismo , Osteíte Deformante/imunologia , Osteíte Deformante/patologia , Osteoblastos/imunologia , Osteoblastos/metabolismo , Fatores de TempoRESUMO
UNLABELLED: Paget's disease is a focal condition of bone. To study changes in cells within pagetic lesions, we cultured osteoblasts and stromal cells from 22 patients and compared gene expression in these cells to cells from healthy bone. We identified several differentially regulated genes, and we suggest that these changes could lead to the formation of the lesions. INTRODUCTION: Paget's disease is a focal condition of bone of unknown cause. Although it is regarded as primarily an osteoclast disorder, the tight coupling of the activity of osteoclasts and osteoblasts suggests that the osteoblast could play a key role in its pathogenesis. The aim of the study was to identify possible changes in pagetic osteoblasts and stromal cells that might contribute to the development of pagetic lesions. MATERIALS AND METHODS: Candidate genes were identified based on known bone cell regulators, supplemented with microarray analysis. Gene expression was determined by real-time PCR in primary cultures of osteoblasts and bone marrow stromal cells from pagetic patients and control subjects. Concentrations of secreted proteins were determined by ELISA. RESULTS: Dickkopf1 mRNA and protein levels were increased in both pagetic osteoblast and stromal cell cultures, and interleukin (IL)-1 and IL-6 were overexpressed in pagetic osteoblasts. These changes parallel recent findings in myeloma bone disease, which shares some clinical similarities with Paget's disease. Alkaline phosphatase was overexpressed, and bone sialoprotein and osteocalcin were underexpressed in pagetic osteoblasts, consistent with their circulating levels in pagetic patients. It is hypothesized that overexpression of Dickkopf1, IL-1, and IL-6 would result in stimulation of osteoclast proliferation and inhibition of osteoblast growth, leading to the development of the characteristic lytic bone lesions. By stimulating osteoblast differentiation, Dickkopf1 and IL-6 may also promote mineralization, leading to the conversion of lytic lesions to sclerotic. CONCLUSIONS: These findings suggest that dysregulated gene expression in pagetic osteoblasts could cause the changes in bone cell number and function characteristic of Paget's disease.
Assuntos
Células da Medula Óssea/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Osteíte Deformante/genética , Osteoblastos/metabolismo , Células Estromais/metabolismo , Idoso , Idoso de 80 Anos ou mais , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Osteíte Deformante/metabolismo , Osteíte Deformante/patologia , RNA Mensageiro/genéticaRESUMO
Current recommendations for the total dose of intravenous pamidronate to be used in the treatment of Paget's disease range up to 400 mg per course, although up to 980 mg has been suggested for resistant cases. However, in a proportion of Paget's disease patients remission is difficult to induce and maintain. In five patients with resistant symptomatic Paget's disease, in whom a variety of antipagetic therapies had failed to induce remission, we have examined the effects of high dose pamidronate (1.44-2.52 g intravenously over 12-42 weeks). All five subjects had a marked symptomatic improvement, and disease activity was suppressed to a greater extent than had been achieved previously, but in only one did alkaline phosphatase activity suppress into the normal range. A plateau in the biochemical response was evident, with successive pamidronate doses of 120 mg producing smaller decrements in alkaline phosphatase. The plateau was reproducible on repeated courses. Bone biopsies in two patients showed continued pagetic activity with an increased mineralization rate and no osteomalacia. Worthwhile clinical and biochemical improvements can be obtained in patients with resistant Paget's disease by the use of high-dose pamidronate. Though this approach does not seem to cause defective mineralization, it may be difficult to suppress disease activity completely.
Assuntos
Difosfonatos/uso terapêutico , Osteíte Deformante/tratamento farmacológico , Idoso , Fosfatase Alcalina/metabolismo , Reabsorção Óssea/patologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteíte Deformante/metabolismo , Osteíte Deformante/patologia , Pamidronato , Resultado do TratamentoAssuntos
Osteíte Deformante/história , Paleopatologia , Osso e Ossos/patologia , História Antiga , Humanos , Islândia , Literatura Medieval , Masculino , Medicina na Literatura , Osteíte Deformante/patologia , Osteíte Deformante/fisiopatologia , Poesia como Assunto , Países Escandinavos e Nórdicos , Esqueleto , Crânio/patologiaRESUMO
OBJECTIVES: The objective of this article was to critically review the current knowledge on Paget's disease of bone, focusing primarily on possible etiologies and trends in management. Current courses of treatment are described, including calcitonin, diphosphonate and mithramycin therapy and the efficacy of each drug regime is analyzed. Finally, newer, more experimental pharmaceutical agents, such as gallium nitrate, are described. DATA SOURCES: Information was obtained from English language medical and scientific journals and medical/physiology text books. Index Medicus (1983-1989) and MEDLINE computerized data base were used. Paget's disease of bone, paramyxovirus, osteoclast, calcitonin and diphosphonate were the terms indexed directly. Key authors indexed included Rebel, Baste and Paget. Further information was obtained from the National Association for the Relief of Paget's Disease (England). CONCLUSIONS: Current research focuses primarily on histological and hybridization studies over the past 15 yr in favor of a slow virus as the causative agent in the disease, and the evidence supporting this is analyzed in some detail. In particular, the discovery of nuclear and cytoplasmic inclusion bodies within the osteoclasts of patients with Paget's disease and their similarity to respiratory syncytial virus and measles virus are discussed. Some form of environmental or physiological trigger may be involved, but the exact mechanism remains obscure. The current treatment of Paget's disease is based around the prevention of bone resorption using various diphosphonates and calcitonins, but many of these are associated with severe side effects. Newer pharmaceutical agents to control bone turnover, including gallium nitrate, have given promising results in preliminary medical trials.
Assuntos
Osteíte Deformante/tratamento farmacológico , Calcitonina/uso terapêutico , Quiroprática , Difosfonatos/efeitos adversos , Difosfonatos/uso terapêutico , Humanos , Corpos de Inclusão/ultraestrutura , Corpos de Inclusão Viral/ultraestrutura , Osteíte Deformante/etiologia , Osteíte Deformante/patologia , Osteoclastos/ultraestrutura , Plicamicina/uso terapêuticoRESUMO
Intravenous 3-amino-1-hydroxypropylidene-1, 1-bisphosphonic acid (APD) was used to treat 26 patients with Paget's disease. Three daily dosages were studied; 20-30 mg/day in 20 patients, 45 mg/day in three patients and 60 mg/day in three patients, by daily 4-hour infusions for 2-10 days. The fasting urinary hydroxyproline excretion (HypE) declined exponentially, reaching 50% of pretreatment values at 1.92 +/- 0.16 (mean +/- SEM) days. This initial rapid decline was complete by 4 days following treatment to a mean of 28.0 +/- 3.4% of pretreatment values. Thereafter, there was no significant decline in HypE. The initial rate of decline of HypE was unchanged by increasing the daily dose of APD. Transient non-symptomatic hypocalcaemia with secondary hyperparathyroidism occurred in all patients. No adverse changes in the renal handling of calcium or phosphate, as seen with high-dose 1-hydroxyethylidene-1, 1-bisphosphonate (EHDP), were seen in any patient on any daily dose. Fever occurred in 73% of patients in the first 2 days of treatment. Overall, there was a significant fall in the lymphocyte count (P less than 0.005 febrile group, n = 19; P less than 0.02 non-febrile group, n = 7) and a fever-dependent rise in the neutrophil count (P less than 0.005 febrile group only). The occurrence of fever was associated with a more rapid decline in HypE, compared to the non-febrile group, so that HypE was significantly lower in the febrile group by day 5 (P less than 0.025). Seventy-two per cent of patients with bone and/or joint pain reported a reduction in pain.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Difosfonatos/uso terapêutico , Osteíte Deformante/tratamento farmacológico , Adulto , Idoso , Osso e Ossos/patologia , Difosfonatos/administração & dosagem , Difosfonatos/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Hidroxiprolina/urina , Infusões Intravenosas , Contagem de Leucócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Osteíte Deformante/diagnóstico por imagem , Osteíte Deformante/metabolismo , Osteíte Deformante/patologia , Pamidronato , RadiografiaRESUMO
Histopathology of mandibular swellings in two women aged 68 and 73 years respectively provided a diagnosis of Paget's disease. The complementary biological tests (phosphorus-calcium metabolism, alkaline phosphatase, hydroxyprolinuria) performed showed the increase in bone metabolism, while imaging techniques (conventional radiography, scintigraphy, CT scan) demonstrated numerous subclinical bony foci. Treatment of the facial deformity, if desirable esthetically or functionally necessary (alveolitis, osteitis) can only be surgical. If there is biological bone hypermetabolism, medical (diphosphonate, calcitonin) can be discussed with the rheumatologists. Evolutive risks are represented by rare sarcomatous transformations, osteomyelitis on Paget and monstrous deformities of the face, as in one of the patients reported who had refused all treatment over 37 years.
Assuntos
Ossos Faciais/patologia , Doenças Maxilomandibulares/patologia , Osteíte Deformante/patologia , Idoso , Feminino , Humanos , Doenças Maxilomandibulares/tratamento farmacológico , Doenças Maxilomandibulares/cirurgia , Osteíte Deformante/tratamento farmacológico , Osteíte Deformante/cirurgiaRESUMO
Fifty-one patients with Paget's disease were treated during 6 months with ethane-01 hydroxy-1, 1 diphosphonate (EHDP, etidronate) in doses of 5 mg/kg/day. The drug was most effective in relieving pain, at the same time diminishing the uptake of pagetic lesions on quantitative bone scans and lowering by almost 70% the abnormally high serum alkaline phosphatase levels and 24-hour hydroxyproline urinary levels. Histologically, the resorption surfaces and the number of osteoclasts per mm2 of bone tissue were significantly reduced. On follow-up, the improvement persisted for at least one year after treatment was discontinued. EHDP was well tolerated clinically and biologically, and on histological sections no accumulation of osteoid tissue due to impaired mineralization was seen. EHDP at the 5 mg/kg/day dose appears to be effective in the treatment of Paget's disease.
Assuntos
Ácido Etidrônico/uso terapêutico , Osteíte Deformante/tratamento farmacológico , Adulto , Idoso , Fosfatase Alcalina/sangue , Cálcio/metabolismo , Ácido Etidrônico/administração & dosagem , Feminino , Seguimentos , Humanos , Hidroxiprolina/urina , Masculino , Pessoa de Meia-Idade , Osteíte Deformante/patologia , Hormônio Paratireóideo/sangue , Fósforo/sangueAssuntos
Ácido Etidrônico/uso terapêutico , Osteíte Deformante/tratamento farmacológico , Fosfatase Alcalina/sangue , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Calcitonina/uso terapêutico , Cálcio/metabolismo , Surdez/tratamento farmacológico , Ácido Etidrônico/administração & dosagem , Ácido Etidrônico/farmacologia , Fraturas Ósseas/etiologia , Gastroenteropatias/induzido quimicamente , Hemodinâmica/efeitos dos fármacos , Humanos , Hidroxiprolina/urina , Osteíte Deformante/diagnóstico por imagem , Osteíte Deformante/metabolismo , Osteíte Deformante/patologia , Dor/induzido quimicamente , Hormônio Paratireóideo/sangue , Fósforo/metabolismo , CintilografiaRESUMO
A patient with histologically proven coexistent Paget's disease of the bone and parathyroid adenomatosis is described. She developed coma associated with hypercalcemia and underwent successfully surgical removal of two parathyroid adenomata. The differential diagnosis of hypercalcemia in patients with this rare association is discussed and the importance of early surgical treatment is stressed. A review of similar reported case is presented.