Artroplastía total de cadera en paciente con enfermedad de Paget: presentación de un caso / Total hip arthroplasty in a patient with Paget's disease. A case report

Introducción: La enfermedad de Paget es un trastorno metabólico de etiología desconocida, secundario a un incremento en la función de los osteoclastos y la consecuente respuesta de los osteoblastos a la formación exagerada de hueso. Compromete con mayor frecuencia el fémur proximal y, a menudo, se diagnostica incidentalmente. Se presenta el caso de una mujer con antecedente de enfermedad de Paget y pseudoartrosis de cadera izquierda, con indicaciones de prótesis total de cadera izquierda y un episodio único de luxación, sin complicaciones posteriores y una adecuada evolución. Conclusión: El manejo quirúrgico en casos de fractura de cadera permite restablecer la marcha y mejorar la calidad de vida de los pacientes con enfermedad de Paget. A pesar de ser una patología que dificulta el manejo de los pacientes, la enfermedad de Paget no es una contraindicación para la artroplastia total de cadera y permite mejorar el dolor y recuperar la funcionalidad. Nivel de Evidencia: IV

Introduction: Paget's disease is a metabolic disorder of unknown etiology, secondary to an increase in the function of osteoclasts and the consequent response of osteoblasts to excessive bone formation. It most commonly involves the proximal femur and is often diagnosed incidentally. We present the case of a woman with a history of Paget's disease and nonunion of the left hip, with indications for a total left hip prosthesis and a single episode of dislocation, without subsequent complications and an adequate evolution. Conclusion: Surgical management in cases of hip fracture allows to restore walking and improves the quality of life of patients with Paget's disease. Despite being a pathology that makes patient management difficult, Paget's disease is not a contraindication for total hip arthroplasty and allows the improvement of pain and restoration of functionality. Level of Evidence: IV

Enfermedad de Paget de hueso esporádica. Serie de casos y revisión de la literatura / Sporadic Paget's disease of the bone. Case series and literature review

RESUMEN La enfermedad de Paget ósea es una enfermedad metabólica del hueso de etiología no esclarecida, que se caracteriza por una fase de resorción aumentada seguida por una fase de osteoformación aberrante. Es frecuente en Europa, Norteamérica, Nueva Zelanda y Australia, pero infrecuente en Asia, Medio Oriente y África. En población colombiana hay reportes de casos. Generalmente cursa asintomática y se diagnostica incidentalmente por hallazgos radiográficos o fosfatasa alcalina elevada. El uso de bifosfonatos favorece el control del recambio óseo y permite prevenir complicaciones como las fracturas. Se presenta una serie de casos en Colombia y una revisión de la literatura.

A B S T R A C T Paget's disease of the bone is a metabolic bone disease of unknown origin, and is characterised by an increased phase of resorption, followed by an aberrant osteoformation phase. It is common in Europe, North America, New Zealand, and Australia, but infrequent in Asia, the Middle East, Africa, and in the Colombian population there are case reports. It is usually asymptomatic and is diagnosed incidentally by radiographic findings or an elevated alkaline phosphatase. The use of bisphosphonates favours the control of bone turnover and prevents complications such as fractures. A series of cases in Colombia is presented, along with a review of the literature.

Paget's Disease of Bone Affecting Peripheral Limb: Difficulties in Diagnosis: A Case Report

In terms of management of Paget's disease of bone (PDB), early diagnosis and proper management achieving remission is essential with lifelong specialist follow-up. We present the case of a 40-year-old woman with PDB affecting mainly the distal extremities (ankle and wrist). The patient visited our hospital in 2012 with heel pain. Plain radiography revealed osteoporosis, and a bone scan revealed hot uptake. Initial laboratory investigations showed normal serum calcium, 25-hydroxy-vitamin D, and parathyroid hormone levels; however, osteocalcin, C-terminal telopeptide of type I collagen, and bone alkaline phosphatase levels were elevated. A bone mineral density scan showed T- and Z-scores of −2.5 and −2.7, respectively, and bisphosphonate treatment was initiated. Biopsy performed on the calcaneal lateral wall revealed inconclusive findings. Follow-up biopsy on the left distal radius was performed 7 years later to investigate wrist pain, and this examination led to a final diagnosis as PDB. We suggest inconclusive biopsy result during the early phase of PDB and highly recommend follow-up evaluation in osteoporosis with atypical behavior.

Enterococcus faecalis causes osteitis deformans in aGolden Lancehead snake (Bothrops insularis): a case report / Enterococcus faecalis causa osteíte deformante em uma serpente Jararaca-ilhoa (Bothrops insularis): relato de caso

Osteitis deformans (Paget's disease) is a chronic bone disorder characterized by excessive osteoclast-mediated bone resorption followed by new bone formation. The present paper reports this condition in an 18-year-old captive golden lancehead (Bothrops insularis) from Brazil. This patient initially exhibited anorexia and swelling in the middle third of the spine associated with locomotor disability. For diagnosis, radiography, ultrasound, computed tomography, cytology, and microbiological culture were performed. Diagnostic imaging showed bone changes, vertebral fusion, and bone proliferation. Cytology revealed blood cells how toxic heterophiles, reactive monocytes, young red blood cells, and polychromasia compatible with an infectious process. A bacterial culture identified an ampicillin-susceptible strain of Enterococcus faecalis. Antibiotic treatment was promptly started, but the snake died 25 days later. Histopathologically, the bone tissue showed a generalized thickening of the vertebral trabeculae. For the first time, the presence of E. faecalisassociated with the development of osteitis deformans in snakes was presented.(AU)

Osteíte deformante (Doença de Paget) é um distúrbio ósseo crônico caracterizado por reabsorção óssea excessiva mediada por osteoclastos, seguida por nova formação óssea. O presente trabalho relata essa condição em uma serpente jararaca-ilhoa (Bothrops insularis) do Brasil de 18 anos. O paciente apresentou inicialmente anorexia e um inchaço no primeiro terço médio da coluna associado com a incapacidade locomotora. O diagnóstico foi estabelecido com o apoio de radiografia, ultrassonografia, tomografia computadorizada, citologia e cultura microbiológica. O diagnóstico por imagem mostrou alterações ósseas, fusão de vértebras e proliferação óssea. A citologia mostrou células sanguíneas como heterófílos tóxicos, monócitos reativos, células sanguíneas jovens e policromasia compatíveis com um processo infeccioso. A cultura bacteriana identificou uma cepa de Enterococcus faecalis suscetível à ampicilina. O tratamento com antibióticos foi iniciado imediatamente, mas a serpente morreu 25 dias depois. Histopatologicamente, o tecido ósseo mostrou um espessamento generalizado das trabéculas vertebrais. Portanto, foi demonstrado pela primeira vez a presença de E. faecalis associada ao desenvolvimento de osteíte deformante em uma serpente.(AU)

Hipercementosis, una alteración de la estructura dentaria: recopilación bibliográfica / Hypercementosis, an alteration of the dental structure: bibliographic compilation

La hipercementosis se presenta como depósitos de cemento en la raíz de uno o más dientes. Siendo más frecuente en dientes que están sometidos a fuerzas de oclusión, particularmente en pacientes con enfermedad de Paget. El aumento de cemento se depositará en una banda que se encuentra situada alrededor del tercio apical de la raíz, es de ayuda útil realizar una evaluación radiográfi ca antes de una extracción dental (AU)

Hypercementosis occurs as cement deposits in the root of one or more teeth. Being more frequent in teeth that are subjected to occlusion forces or in patients with Paget's disease. The cement increase can be deposited in a band that can be found near the apical third of the root, it is a dental aid that a radiographic evaluation is made before a dental extraction (AU)

Distrofia ósea esclerosante mixta / Mixed-sclerosing-bone-dystrophy

El término "distrofia ósea esclerosante mixta" describe la combinación de las características radiológicas correspondientes a melorreostosis, osteopoiquilosis y osteopatía estriada, como entidades individuales, que ocurren en un mismo paciente. El objetivo de esta comunicación es presentar el caso clínico de una paciente con diagnóstico de distrofia ósea esclerosante mixta y, a partir de este caso, realizar una revisión sobre el tema. (AU)

The term "mixed-sclerosing-bone-dystrophy" describes the combination of the radiological characteristics corresponding to melorheostosis, osteopoikilosis and osteopathia striata, as individual conditions, ocurring in the same patient. The aim of this communication is to present the clinical case of a patient diagnosed with mixed-sclerosing-bone-dystrophy and, based on this case, to undertake a review of this condition. (AU)

Determinants of quality of life in Paget's disease of bone / Determinantes da qualidade de vida na doença de Paget óssea

Abstract Objective: To evaluate the parameters associated with quality of life in patients with Paget's disease of bone. Methods: Patients with Paget's disease of bone were evaluated with SF-36 and WHOQOL-bref questionnaires. Patients with other diseases that could cause significant impairment of their quality of life were excluded. We searched for correlations between the results and: age, time from diagnosis, type of involvement, pain related to Paget's disease of bone, limitation to daily activities, deformities, bone specific alkaline phosphatase, the extent of involvement and treatment. Results: Fifty patients were included. Results of the SF-36 total score and its domains, physical and mental health, were significantly correlated with bone pain and deformities. Marital status was significantly correlated with the SF-36 total score and Mental Health Domain. BAP levels and disease extension were significantly correlated to SF-36 Physical Health Domain. After multivariate analysis, the only parameters that remained significantly associated with the SF-36 total score and to its Mental Health and Physical Health Domains were pain and marital status.The WHOQOL-bref total score was significantly associated with pain, physical impairment and deformities. WHOQOL-bref Domain 1 (physical) score was significantly associated with marital status, pain and deformities, while Domain 2 (psychological) score was associated with marital status, physical impairment and kind of involvement. After multivariate analysis, the presence of pain, deformities, and marital status were significantly associated with results of the WHOQOL-bref total score and its Domain 1. WHOQOL-bref domain 2 results were significantly predicted by pain and marital status. Conclusion: The main disease-related factor associated with SF-36 results in Paget's disease of bone patients was bone pain, while bone pain and deformities were associated with WHOQOL-bref.

Resumo Objetivo: Avaliar os parâmetros associados à qualidade de vida em pacientes com doença de Paget óssea (DPO). Métodos: Avaliaram-se pacientes com DPO com os questionários SF-36 e WHOQOL-bref. Excluíram-se pacientes com outras doenças que pudessem causar comprometimento significativo da qualidade de vida. Buscou-se por correlações entre os resultados e idade, tempo de diagnóstico, tipo de envolvimento, dor relacionada com a DPO, limitação às atividades diárias, deformidades, fosfatase alcalina específica do osso, extensão do envolvimento e tratamento. Resultados: Incluíram-se 50 pacientes. Os resultados da pontuação total do SF-36 e seus domínios, saúde física e saúde mental, se correlacionaram significativamente com a dor óssea e deformidades. O estado civil se correlacionou significativamente com a pontuação total do SF-36 e com seu domínio saúde mental. Os níveis de BAP e a extensão da doença se correlacionaram significativamente com o domínio saúde física do SF-36. Depois da análise multivariada, os únicos parâmetros que permaneceram significativamente associados à pontuação total do SF-36 e aos seus domínios saúde mental e saúde física foram a dor e o estado civil. A pontuação total do WHOQOL-bref esteve significativamente associada à dor, ao comprometimento físico e a deformidades. O escore do Domínio 1 (físico) do WHOQOL-bref esteve significativamente associado ao estado civil, dor e deformidades, enquanto o Domínio 2 (psicológico) esteve associado ao estado civil, comprometimento físico e tipo de envolvimento. Depois da análise multivariada, a presença de dor, deformidades e estado civil esteve significativamente associada à pontuação total do WHOQOL-bref e à pontuação do seu Domínio 1. Os resultados do WHOQOL-bref 2 foram significativamente preditos pela dor e pelo estado civil. Conclusão: O principal fator associado aos escores do SF-36 foi a dor óssea, enquanto a dor óssea e as deformidades estiveram associadas ao WHOQOL-bref.

Fosfatasa alcalina ósea sérica elevada no mediada por metástasis en un paciente con cáncer renal / Elevated bone alkaline phosphatase not mediated by metastasis in a patient with renal cancer

Presentamos un paciente de 63 años con cáncer renal y aumento de fosfatasa alcalina sérica de tipo óseo de acuerdo con su reactividad con anticuerpos monoclonales específicos. Se descartaron las causas conocidas de aumento de la isoenzima, incluyendo metástasis óseas. Los niveles enzimáticos cayeron abruptamente con la remoción del tumor, por lo que consideramos a este último como su origen. Diversas isoenzimas de fosfatasa alcalina pueden ser producidas y secretadas por tumores como manifestación paraneoplásica. El conocimiento de esto puede, en ocasiones, orientarnos hacia la presencia de una neoplasia oculta. Además, los cambios en los niveles séricos de esas isoenzimas pueden ser indicadores de respuesta al tratamiento o de recidiva tumoral. (AU)

A 63-year old man was seen in the outpatient clinic because of renal cancer and elevation in bone alkaline phosphatase measured by monoclonal antibodies assay. Known causes of bone isoenzyme augmentation, including bone metastases, were ruled out. The tumoral origin of the isoenzyme was diagnosed because after removal of the tumor the enzymatic levels fell sharply. Several alkaline phosphatase isoenzymes can be produced and secreted by tumors as a paraneoplasic manifestation and their elevation could be a manifestation of an occult neoplasia. Furthermore the monitoring of their blood levels can be useful means of treatment response and a tool to monitoring recurrence if a sharp decrease after removal of the tumor is observed. (AU)

Enfermedad de paget ósea: breve revisión de la literatura a propósito de un caso / Paget ́s bone disease: case report and brief literature review

La osteítis deformante o enfermedad de Paget es un trastorno óseo, crónico, poco frecuente en Chile, que puede afectar típicamente a pacientes después de los 55 años. Su etiología es probablemente multifactorial: actualmente se considera como posiblemente implicados factores ambientales y genéticos.La mayor parte de los pacientes son asintomáticos. Los diagnósticos habitualmente se realizan en base a hallazgos radiológicos. Cuando existen síntomas, suelen ser dolor y/o deformidad ósea. Pueden comprometerse uno o varios huesos.Ante su sospecha clínica, la exploración diagnóstica requiere de al menos el estudio con radiografías simples de las lesiones sospechosas, cintigrama óseo y parámetros de actividad metabólica ósea; recomendándose los niveles séricos de fosfatasas alca-linas, por su bajo costo y elevada disponibilidad.Las metástasis óseas condensantes son un importante diagnóstico diferencial a con-siderar.Sobre el tratamiento, se recomienda el uso de fármacos antirresortivos como terapia específica, y el uso de ortesis y terapia física.El seguimiento es clínico y con biomarcadores de recambio óseo.

Osteitis-deformans or Paget's disease is a chronic bone disorder uncommon in Chile, with a typical presentation after age 55. Its etiology is probably multifactorial: It is actualy considered that environmental and genetic factors are mainly involved.Most patients are asymptomatic. Diagnoses are usualy performed based on radio-logical findings. When symptoms exist, they are pain and/or bone deformity. One or several bones can be affects.If it ́s suspect, the diagnostic exploration requires at least the study with x-rays of the suspicious lesions, bone scintigraphy and parameters of bone metabolic activity, being recommended the serum levels of alkaline phosphatases, for its low cost and high availability.Condensing bone metatases have to be considered like an important differential di-agnosis.For the treatment, the use of antiresorptive drugs as specific therapy is recommend-ed, and the use of orthotics and physical therapy.Follow-up is made with clinical findings and with biomarkers of bone turnover.

Paget's Disease: Skeletal Manifestations and Effect of Bisphosphonates

BACKGROUND: Paget's disease of bone leads to change in the shape and size of the bone and results in reduced bone strength, leading to the complications of deformity, arthritis, and fracture. Due to unknown reasons, Paget's disease is rare in Asian descendants. We report the cases of Paget's disease who visited our institute for 15 years and reviewed the literatures. METHODS: We retrospectively reviewed the medical records and radiograms of 8 patients (6 female and 2 male) who were diagnosed as Paget's disease of bone. Diagnosis was confirmed by typical radiological feature in the involved skeletons and/or pathologic findings. RESULTS: Pelvis, skull and spine were three most frequently involved bones. All involved bones in our cases showed changes in shape and trabecular pattern which resulted in bowing of lower extremity, secondary osteoarthritis, compression fracture of spine and enlargement of skull. Mean follow time was 4.71 years and all patient were treated bisphosphonate (BP). Use of BP controlled the level of serum alkaline phosphatase level effectively. CONCLUSIONS: We have reviewed eight patients who were previously diagnosed as Paget's disease of bone in our institute. We could identify typical radiologic and clinical findings such as bowing deformity of long bone, secondary osteoarthritis, compression fracture and osteomyelitis of mandible that deteriorated the quality of their living.

A FKBP5 mutation is associated with Paget's disease of bone and enhances osteoclastogenesis

Paget's disease of bone (PDB) is a common metabolic bone disease that is characterized by aberrant focal bone remodeling, which is caused by excessive osteoclastic bone resorption followed by disorganized osteoblastic bone formation. Genetic factors are a critical determinant of PDB pathogenesis, and several susceptibility genes and loci have been reported, including SQSTM1, TNFSF11A, TNFRSF11B, VCP, OPTN, CSF1 and DCSTAMP. Herein, we report a case of Chinese familial PDB without mutations in known genes and identify a novel c.163G>C (p.Val55Leu) mutation in FKBP5 (encodes FK506-binding protein 51, FKBP51) associated with PDB using whole-exome sequencing. Mutant FKBP51 enhanced the Akt phosphorylation and kinase activity in cells. A study of osteoclast function using FKBP51V55L KI transgenic mice proved that osteoclast precursors from FKBP51V55L mice were hyperresponsive to RANKL, and osteoclasts derived from FKBP51V55L mice displayed more intensive bone resorbing activity than did FKBP51WT controls. The osteoclast-specific molecules tartrate-resistant acid phosphatase, osteoclast-associated receptor and transcription factor NFATC1 were increased in bone marrow-derived monocyte/macrophage cells (BMMs) from FKBP51V55L mice during osteoclast differentiation. However, c-fos expression showed no significant difference in the wild-type and mutant groups. Akt phosphorylation in FKBP51V55L BMMs was elevated in response to RANKL. In contrast, IκB degradation, ERK phosphorylation and LC3II expression showed no difference in wild-type and mutant BMMs. Micro-CT analysis revealed an intensive trabecular bone resorption pattern in FKBP51V55L mice, and suspicious osteolytic bone lesions were noted in three-dimensional reconstruction of distal femurs from mutant mice. These results demonstrate that the mutant FKBP51V55L promotes osteoclastogenesis and function, which could subsequently participate in PDB development.

Estudio paleorradiológico y tridimensional en momias y cuerpos momificados / Paleo-radiology and three-dimensional study in mummies and mummified bodies

Estudios realizados en momias o en cuerpos momificados con técnicas convencionales y estudios de tomografía computada, revelaron patologíasmaxilofaciales tales como: atrición, pulpitis abscesos y enfermedad periodontal; además de otras enfermedades con mayor compromiso general, a saber: osteomielitis, enfermedad de Paget, defectos cráneomandibulares y traumas. Sin embargo, se observa un bajo porcentaje de caries. Para la continuidad de la vida en el más allá, revestía una importancia fundamental la conservación de loscuerpos en este mundo...

Diagnosis and management of Paget?s disease of bone / Diagnóstico e tratamento da doença de Paget óssea

Objective: To conduct a literature review on the diagnosis and management of Paget’s disease of bone. Materials and methods: This scientific statement was generated by a request from the Brazilian Medical Association (AMB) to the Brazilian Society of Endocrinology and Metabolism (SBEM) as part of its Clinical Practice Guidelines program. Articles were identified by searching in PubMed and Cochrane databases as well as abstracts presented at the Endocrine Society, Brazilian Society for Endocrinology Annual Meetings and the American Society for Bone and Mineral Research Annual Meeting during the last 5 years. Grading quality of evidence and strength of recommendation were adapted from the first report of the Oxford Centre for Evidence-based Medicine. All grades of recommendation, including “D”, are based on scientific evidence. The differences between A, B, C and D, are due exclusively to the methods employed in generating evidence. Conclusion: We present a scientific statement on Paget’s disease of bone providing the level of evidence and the degree of recommendation regarding causes, clinical presentation as well as surgical and medical treatment. Arq Bras Endocrinol Metab. 2014;58(6):587-99 .

Objetivo: Conduzir uma atualização das últimas evidências científicas a respeito da apresentação, diagnóstico e manejo clínico da doença de Paget óssea. Materiais e métodos: Este documento foi concebido pelo Departamento de Metabolismo Ósseo da Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) a partir daquele oriundo do Programa de Diretrizes da Associação Médica Brasileira (AMB). Realizamos uma revisão dos artigos mais relevantes obtidos nos bancos de dados PubMed e Cochrane, além de abstracts apresentados nos encontros anuais da Endocrine Society, Sociedade Brasileira de Endocrinologia e da American Society for Bone and Mineral Research dos últimos cinco anos e classificamos as evidências em níveis de recomendações de acordo com a força científica por tipo de estudo, adaptando o primeiro relato do “Oxford Centre for Evidence-based Medicine”. Todos os graus de recomendação, incluindo-se o “D”, foram baseados em evidência científica, sendo as diferenças entre o A, B, C e D devidas exclusivamente ao desenho empregado na geração da evidência. Conclusão: Apresentamos uma atualização científica a respeito da doença de Paget óssea, classificando e graduando em níveis de recomendações as principais evidências científicas sobre as suas causas, as variadas formas de apresentação, seu diagnóstico e tratamento. .

Estrías angioides y tumor hipofisario: ¿asociación o hallazgo incidental? / Angioid streaks and pituitary tumor: ¿association or incidental finding?

Las estrias angioides de la retina se aprecian como líneas dentelladas rosadas u oscuras radiando irregularmente en todas direcciones desde el área peripapilar hacia la periferia de la retina. Corresponden a roturas del componente elástico de la membrana de Bruch. Su presencia indica una enfermedad sistémica siendo las más importantes el pseudoxantoma elástico, la enfermedad de Paget ósea y la drepanocitosis, Los tumores hipofisiarios raramente se han asociado a está condición existiendo apenas tres descriptores en la literatura. A estas adicionamos tres pacientes más, no obstante, aun no puede asegurarse si se trata de una asociación o de un simple hallazgo incidental.

Retinal angioid streaks can be seen as rough lines pink or dark, irregularly radiating in all directions from the peripapilar area to the periphery of the retina. They correspond of breaks in the elastic component of the Bruch membrane. Its presence indicates a systemic disease being the most important pseudoxanthoma elasticum, bone Paget's disease and sickle cell disease. Pituitary tumors have rarely been associated with this condition and exist just three descriptions in the literature. To these we add three more patients, however, still not be tightened if it's an association or a simple incidental finding.

Intravenous Zoledronate for a Patient with Paget's Disease

Paget's disease (PD) of bone is characterized by increase of bone resorption by atypical osteoclasts, followed by rapid new bone formation resulting in a disorganized mosaic bone. Although the pathophysiology is not fully understood, bisphosphonate, which is a potent anti-resorptive agent for treatment of osteoporosis, have been the most effective agents available for the treatment of PD. We report a case of PD of bone in a 49-year-old woman patient, who was treated with intravenous zoledronate.

Pathobiology of Paget's Disease of Bone

Paget's disease of bone is characterized by highly localized areas of increased bone resorption accompanied by exuberant, but aberrant new bone formation with the primary cellular abnormality in osteoclasts. Paget's disease provides an important paradigm for understanding the molecular mechanisms regulating both osteoclast formation and osteoclast-induced osteoblast activity. Both genetic and environmental etiologies have been implicated in Paget's disease, but their relative contributions are just beginning to be defined. To date, the only gene with mutations in the coding region linked to Paget's disease is sequestosome-1 (SQSTM1), which encodes the p62 protein, and these mutations lead to elevated cytokine activation of NF-B in osteoclasts but do not induce a "pagetic osteoclast" phenotype. Further, genetic mutations linked to Paget's appear insufficient to cause Paget's disease and additional susceptibility loci or environmental factors may be required. Among the environmental factors suggested to induce Paget's disease, chronic measles (MV) infection has been the most studied. Expression of the measles virus nucleocapsid gene (MVNP) in osteoclasts induces pagetic-like osteoclasts and bone lesions in mice. Further, mice expressing both MVNP in osteoclasts and germline mutant p62 develop dramatic pagetic bone lesions that were strikingly similar to those seen in patients with Paget's disease. Thus, interactions between environmental and genetic factors appear important to the development of Paget's disease. In this article we review the mechanisms responsible for the effects of mutant p62 gene expression and MVNP on osteoclast and osteoblast activity, and how they may contribute to the development of Paget's disease of bone.

Diagnosis and treatment of Paget's disease of bone: a mini-review / Diagnóstico e tratamento da doença de Paget dos ossos: uma minirrevisão

Paget's disease of bone (PDB) is a chronic progressive disorder of bone metabolism that may go undetected for many years, and endocrinologists should be alert to its clinical signs and promptly diagnose and treat PDB before it results in irreversible complications, such as deformity, fracture or neurological sequelae. Most commonly, PDB is suspected upon the incidental finding of elevated serum alkaline phosphatase levels or a radiographic abnormality in an otherwise healthy individual above 55 years of age. Some of these individuals may have symptoms such as bone pain or enlargement with increased warmth. In general, a basic laboratory evaluation of bone metabolism, plain radiographies of affected bones and bone scintigraphy are sufficient to corroborate the diagnosis. Antiresorptive therapy with bisphosphonates is the mainstay of treatment of symptomatic PDB, and intravenous zoledronic acid has emerged as an effective and safe treatment option, leading to sustained remission and improved quality of life. It is extremely important, though, to ensure calcium and vitamin D sufficiency before and during treatment in order to prevent hypocalcemia. The benefit of treating all asymptomatic patients is not clear, but treatment is warranted if the pagetic lesion is located in a site where progression to fracture, deformity, or compression would significantly impair the patient quality of life. This mini-review focuses on important aspects of the diagnosis and treatment of PDB.

A doença de Paget dos ossos (PDB) é uma doença progressiva e crônica do metabolismo ósseo que pode passar despercebida por muitos anos. Os endocrinologistas devem ficar alertas aos seus sinais clínicos e diagnosticar e tratar a PDB imediatamente, antes que ela gere complicações irreversíveis, como deformidade, fratura ou sequelas neurológicas. Mais comumente, suspeita-se da PBD após o achado incidental de níveis elevados de fosfatase alcalina no soro, ou anormalidades radiográficas em indivíduos aparentemente saudáveis com mais de 55 anos de idade. Alguns desses indivíduos podem apresentar sintomas, como a dor ou aumento ósseo com temperatura aumentada. Em geral, a avaliação laboratorial básica de metabolismo ósseo, radiografias simples dos ossos afetados e cintilografia óssea são suficientes para corroborar o diagnóstico. O tratamento antirreabsortivo com bifosfonatos é o principal tratamento da PDB sintomática, e o ácido zoledrônico intravenoso passou a ser uma opção de tratamento segura e eficiente, levando à manutenção da remissão e à melhora da qualidade de vida. É extremamente importante, entretanto, garantir níveis adequados de cálcio e vitamina D antes e durante o tratamento para se evitar a hipocalcemia. O benefício de se tratar todos os pacientes assintomáticos não está claro, mas o tratamento é recomendado se a localização da lesão pagética sugerir progressão para fratura, deformidade ou compressão que comprometam a qualidade de vida. Esta minirrevisão concentra-se em importantes aspectos do diagnóstico e tratamento da PDB.

Prevalence of vitamin D deficiency is higher in patients with Paget's disease of bone compared with age-matched controls / Deficiência de vitamina D é maior em pacientes com doença de Paget óssea comparada a controles pareados por idade

OBJECTIVE: To investigate if vitamin D deficiency is more prevalent in patients with Paget's disease of bone (PDB) than in age-matched controls. SUBJECTS AND METHODS: We measured serum 25-OHD in 28 untreated patients with PDB and two control groups: 284 elderly men from an ongoing cohort from our department, and 151 postmenopausal women seen in our outpatient clinic for routine medical evaluation. RESULTS: The mean ± SD serum 25-OHD was significantly lower in subjects with PDB (23.76 ± 6.29 ng/mL) than in the control groups of elderly men (27.86 ± 13.52 ng/mL) and postmenopausal women (30.30 ± 9.59 ng/mL), p = 0.015. The prevalence of vitamin D deficiency considering a cut-off point of serum 25-OHD < 30 ng/mL was 85.7% in patients with PDB, and in elderly men and postmenopausal women it was 66.7 % and 54.3%, respectively (p < 0.001). CONCLUSION: These results suggest a high prevalence of hypovitaminosis D in patients with Paget's disease living in the tropics.

OBJETIVO: Investigar se a deficiência de vitamina D é mais prevalente nos pacientes com doença de Paget óssea (DPO) do que em controles equiparados pela idade. SUJEITOS E MÉTODOS: Neste estudo retrospectivo avaliamos a 25-OHD em 28 pacientes não tratados com DPO e dois grupos controle: 284 homens idosos de uma coorte de nosso departamento e 151 mulheres na pós-menopausa atendidas em nosso ambulatório para avaliação médica de rotina. RESULTADOS: A média ± DP da 25-OHD foi significativamente menor em indivíduos com DPO (23,76 ± 6,29 ng/mL) do que nos grupos controle de homens idosos (27,86 ± 13,52 ng/mL) e de mulheres na pós-menopausa (30,30 ± 9,59 ng/mL), p = 0,015. A prevalência de deficiência de vitamina D, considerando um ponto de corte < 30 ng/mL, foi de 85,7% em pacientes com DPO e, em homens idosos e mulheres na pós-menopausa, foi de 66,7% e 54,3%, respectivamente (p < 0,001). CONCLUSÃO: Esses resultados sugerem uma alta prevalência de hipovitaminose D em pacientes com DPO nos trópicos.