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.

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.

Combination treatment of low fluence photodynamic therapy and intravitreal ranibizumab for choroidal neovascular membrane secondary to angioid streaks in Paget's disease – 12 month results.

Angioid streaks also called Knapp striae are small breaks in the Bruch's membrane and have been reported with a host of systemic diseases. Rupture of streaks or development of secondary choroidal neovascular membrane (CNVM) carries a dismal visual prognosis. We report the successful treatment of CNVM secondary to Paget's disease using low fluence photodynamic therapy (PDT) and intravitreal ranibizumab.

A Brazilian family with hereditary inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia

Inclusion body myopathy associated with Paget disease and frontotemporal dementia (IBMPFD) is a progressive and usually misdiagnosed autosomal dominant disorder. It is clinically characterized by a triad of features: proximal and distal myopathy, early onset Paget disease of bone (PDB), and frontotemporal dementia (FTD). It is caused by missense mutations in the valosin-containing protein (VCP) gene. We describe here the clinical and molecular findings of the first Brazilian family identified with IBMPFD. Progressive myopathy affecting the limb girdles was detected by clinical examination followed by muscle biopsy and creatine kinase measurement. PDB was suggested after anatomopathological bone examination and FTD was diagnosed by clinical, neuropsychological and language evaluations. Brain magnetic resonance revealed severe atrophy of the anterior temporal lobes, including the hippocampi. A R93C mutation in VCP was detected by direct sequencing screening in subject W (age 62) and in his mother. Four more individuals diagnosed with "dementia" were reported in this family. We also present a comprehensive genotype-phenotype correlation analysis of mutations in VCP in 182 patients from 29 families described in the literature and show that while IBM is a conspicuously penetrant symptom, PDB has a lower penetrance when associated with mutations in the AAAD1 domain and FTD has a lower penetrance when associated with mutations in the Junction (L1-D1) domain. Furthermore, the R93C mutation is likely to be associated with the penetrance of all the clinical symptoms of the triad.

La importancia del compromiso vertebral en la enfermedad de Paget / Vertebral compromised in Paget's disease

La enfermedad ósea de Paget (EP) se caracteriza por un trastorno focal de esqueleto, inicialmente determinado por una excesiva resorción del hueso y una subsiguiente formación exagerada, adoptando finalmente una configuración histológica típica denominada "en mosaico". Macroscópicamente el hueso se deforma y sus diámetros se agrandan, resultando un hueso de mayor tamaño, muy vascularizado y de estructura desordenada. La anormalidad parece estar en la regulación de los osteoclastos, que están aumentados en número y tamaño. La ubicación más frecuente es el esqueleto axial, especialmente la pelvis, el sacro, la columna lumbar y el cráneo. En nuestra población de pacientes con EP detectamos un compromiso vertebral en el 47% de los pacientes que habíamos calificado previamente con monostóticos y en el 36.8% de los pacientes con EP poliostótica. El compromiso vertebral puede afectar la médula espinal por compromiso de la circulación, generando cuadriparesia o paraparesia, dependiendo del nivel vertebral afectado. La hipótesis sugerida de dicha afectación es el robo o atrapamiento vascular. Esto explica la importancia de medicar tempranamente a los pacientes con compromiso vertebral, ya que estos problemas neurológicos revierten drásticamente con el hoy simple y adecuado tratamiento médico de la EP.

Juvenile paget?s disease.

Juvenile Pagets disease (JPD), a rare genetic disorder characterized by markedly accelerated bone turnover, presents in early childhood. We report a child with typical features of JPD who remained undiagnosed till 15 years of age. Rarity of this disease in Indian literature and need for early diagnosis to prevent progression of disease prompted us to report this case.

Desarrollo de hiperparatiroidismo primario en el seguimiento de un paciente con enfermedad de Paget / Development of primary hyperparathyroidism in the follow-up of a patient with Paget´s disease

La asociación de hiperparatiroidismo primario y enfermedad de Paget varía entre 2.2 y 6%. Hasta el año 2006 se habían descripto 73 casos con simultaneidad de ambos diagnósticos. Se presenta el caso de un paciente varón de 68 años con un Paget poliostótico activo medicado durante 10 años con bisfosfonatos, con buena evolución. A los 10 años de seguimiento se observan elevados niveles de calcemia, calcio iónico, la fosfatasa alcalina (FAL), su isoenzima ósea (FAIO), e intactos los valores de parathormona (PTHi). Se establece el diagnóstico de hiperparatiroidismo primario. Dado el inestable estado general se decide postergar la cirugía y tratarlo con zoledronato IV con buena respuesta.

According to the medical literature, the association of primary hyperparathyroidism and Paget's disease varies from 2.2 to 6%. Up to the year 2006, a total of 73 cases had been described, where both diagnoses occurred simultaneously. However, no manifestation of primary hyperparathyroidism during the follow- up of Paget's disease has been reported in the revised literature. We report the case of a well-controlled patient, who developed primary hyperparathyroidism during the 10-year follow-up of Paget's disease. A 68-yearold male patient with active polyostotic Paget's disease was successfully treated with bisphosphonates for ten years. During follow-up, increased levels of calcemia, ionic calcium, alkaline phosphatase, bone alkaline phosphatase and intact parathyroid hormone values were registered. The patient was diagnosed with primary hyperparathyroidism. As a result of his unstable general health condition, surgery was postponed and intravenous zoledronic acid was prescribed, with a favorable outcome.

Paget's disease scintgraphy and hormonal treatment

Pagetr's Disease is an intense osteoclastic resorption of bone followed by intense osteoblastic activity accompanied by intense vascularity replacement of normal lamellar bone with connective tissue with a significant in mature collagen content and subperiosteal new bone formation resulting in the characteristic cortical thickening. Pagefs disease can cause pain in the bones or joints, headaches and hearing loss, pressure on nerves, increased head size, bowing of limb, or curvature of spine. Tests used to diagnose Paget's disease include X-ray, blood and urine tests and bone scanning. The recommended treatment, in addition to receiving 1000-1500 mg of calcium, adequate sunshine, ca400 units of vitamin D daily, are the bisphosphonates and calcitouin which need to be monitored by hormonal analysis within the treatment period, also serum alkaline phosphatase [SAP] level in the blood is important in monitoring the progress of treatment

Coexistence of carcinoma breast and Paget's disease of bone.

We report a case of a patient with carcinoma breast who was incidentally diagnosed to be also suffering from Paget's disease of bone on a routine radionuclide bone scan. CT-guided biopsy and histopathology later confirmed the diagnosis.

Doença de Paget do osso / Paget’s bone disease

A doença de Paget óssea é uma doença osteometabólica focal comforte componente genético caracterizada por aumento da remodelaçãoóssea que afeta um ou mais sítios do esqueleto. A doença de Pagetóssea pode ser assintomática, porém, freqüentemente, se associa ador óssea, deformidades, fratura patológica, osteoartrite secundária esurdez. A prevalência parece estar diminuindo em algumas regiões domundo. O diagnóstico é realizado habitualmente por meio de achadosradiológicos e laboratoriais. No tratamento medicamentoso, é feitauma terapia padrão utilizando bifosfonatos de última geração, como,por exemplo, o ácido zoledrônico; porém, na avaliação rotineira destespacientes, freqüentemente, não são contemplados itens de qualidadede vida e, além disso, não há reversão de complicações.

Vertex extradural hematoma in association with Paget's disease of the skull.

Paget's disease of skull usually causes neurological complications such as basilar invagination, cranial neuropathies, etc. Occurrence of extradural hematoma in association with Paget's disease of skull is rare. A 48 year old man presented with headache and right upper limb weakness, two days after a fall from scooter. CT Scan of brain showed a large extradural hematoma at the vertex with the cranial vault showing features of Paget's disease. At surgery, no skull fracture or injury to the superior sagittal sinus was evident. There was diffuse oozing from the inner table of the skull, which showed features of Paget's disease. The extradural hematoma was evacuated and the patient made good recovery. He deteriorated a few hours after surgery. Follow up CT Scan showed diffuse brain swelling with minimal recollection of hematoma. Re-exploration showed a small recollection which was evacuated and the part of the oozing diseased skull was excised. The patient recovered completely. This is the first reported case of vertex extradural hematoma in association with the Paget's disease of skull. The unusual features are the absence of skull fracture and injury to the superior sagittal sinus. The increased vascularity of the skull due to Paget's disease has caused the hematoma by diffuse oozing from the inner table.

Enfermedad de Paget en Chile: una serie de 15 pacientes / Paget disease of bone in Chile: report of 15 cases

BACKGROUND: Paget disease of bone (PD) is a localized disorder of bone remodeling, which leads to bone fragility and deformity. In Chile PD is uncommon. AIM: To study clinical and demographic characteristics of patients with PD seen in the Clinical Hospital of the Catholic University. PATIENTS AND METHODS: Patients with typical radiological and clinical features of PD referred to our institution during the last decade were included in this review. RESULTS: We obtained data from 15 patients with PD (ten males, eight Chilean, six European and one Asian), eleven of them were diagnosed during the last 3 years. The mean age at diagnosis was 68.7 +/- 11.1 years old. No one had first degree relatives with PD. Bone pain was the main complaint in 13 patients and elevated total alkaline phosphatases in the other two. The average duration of the symptoms prior to diagnosis was 38.8 months. Eight patients had monostotic lesions; the most commonly involved sites were the pelvis, spine and femur. Radiological evaluation disclosed sclerotic changes in all patients as well as bone deformity and osteoarthritis in eight patients. Total alkaline phosphatases were elevated in 14 cases (mean: 4 times over the upper normal limit). CONCLUSIONS: When compared to series of the Northern hemisphere, PD in Chile is characterized by an older age at diagnosis, a higher frequency of symptomatic presentation, advanced radiological involvement and greater proportion of complications. PD should be suspected in every patient, Chilean or foreigner, with bone pain or elevated alkaline phosphatases.

Asociacion entre enfermedad de Paget e hiperparatiroidismo primario / Association between Paget's disease and primary hyperparathyroidism

El hiperparatiroidismo primario y la enfermedad de Paget son patologías relativamente frecuentes en la población general, pero la asociación entre ambas es excepcional. El mecanismo que vincula ambas entidades es desconocido. En los pacientes pagéticos se producen modificaciones importantes en el funcionamiento paratiroideo; por otro lado, la hipo o hiperfunción paratiroidea modificada significativamente la evolución de la enfermedad de Paget. Durante diez años evaluamos 175 pacientes pagéticos y 60 hiperparatiroideos primarios encontrando sólo 5 casos de associación entre ambas patologías. La distribución por sexos fue similar (mujer/varón: 1,5/1) y la edad media en el momento del diagnóstico fue 63,20 + 2,65 años. La hipercalcemia durante el seguimiento de los pagéticos o la elevación de la fosfatase alcalina en los pacientes operados de adenomas paratiroideos, fueron los datos bioquímicos más orientadores de la existencia de la segunda entidad. En tres pacientes se indicó tratamiento quirúrgico y el resto fue tratado con drogas antirreabsortivas. En ese artículo también revisamos los 27 casos publicados previamente haciendo hincapié en las características clínicas, diagnósticas, tratamiento y evolución en comparación con nuestros casos.

Enfermedad de Paget ósea y carcinoma anexial intermediario / Paget's disease of bone and adnexal intermediary carcinoma

Simultaneidad entre enfermedad de Paget ósea (osteítis deformante) y carcinoma anexial intermediario en cuero cabelludo. Lesión dermatológica que asienta sobre una depresión en la zona central del cráneo producida por deterioro de la tabla ósea. Se plantea la posibilidad de terreno condicionante. No se han encontrado casos similares en la bibliografía referente a la concurrencia de dichas patologías