Influence of Disodium Etidronate on Clinical and Laboratory Manifestations of Paget's Disease of Bone (Osteitis Deformans)

Altman, Roy D.; Johnston, C. Conrad; Khairi, M. R. A.; Wellman, Henry N.; Serafini, Aldo N.; Sankey, R R

doi:10.1056/nejm197312272892601

Cited by 233 publications

(66 citation statements)

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“…They are potent inhibitors of osteoclast-mediated bone resorption (Boonecamp et al, 1986) and are effective in lowering serum calcium concentrations in patients with hypercalcaemia of malignancy (Ryzen et al, 1985;Kanis et al, 1987). Bisphosphonates are also used in the treatment of Paget's disease of bone (Altman et al, 1973;Plasmans et al, 1978) and bone lesions associated with multiple myeloma (Berenson et al, 1996). The mechanisms by which bisphosphonates inhibit osteoclast-mediated bone resorption remain to be determined, but may involve inhibition of formation of osteoclasts from immature precursor cells (Boonecamp et al, 1986;Lowik et al, 1988;Hughes et al, 1989) and/or direct inhibition of resorption via induction of apoptosis in mature osteoclasts (Lowik et al, 1988;Hughes et al, 1995;Selander et al, 1996).…”

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confidence: 99%

Bisphosphonates induce apoptosis in human breast cancer cell lines

et al. 2000

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Over 80% of women with advanced breast cancer ultimately develop bone metastases which account significantly for morbidity and mortality. Breast cancer metastases in bone can cause intractable pain, bone fracture, spinal cord compression and hypercalcaemia. It also signifies that the malignant process is incurable since, once tumour cells become lodged in the skeleton, therapy can only be given with palliative intent. This includes analgesics, radiation therapy and systemic treatments such as hormone or chemotherapy. The events leading to the development of bone lesions in patients with carcinoma of the breast are poorly understood. However, histomorphometric studies have shown that tumour cells are adjacent to actively resorbing osteoclasts (Boyde et al, 1986) and it has been suggested that breast carcinoma cells possess the capacity to recruit and stimulate osteoclasts by producing stimulatory factors (Boyde et al, 1986). Parathyroid hormone related peptide (PTHrP) is thought to be a major candidate factor produced by breast cancer cells which may promote osteoclastic activity at metastatic sites in bone (Powell et al, 1991).Bisphosphonates (BPs) are analogues of endogenous pyrophosphates in which a carbon atom replaces the central atom of oxygen. In vivo, bisphosphonates bind strongly to hydroxyapatite on the bone surface and are preferentially delivered to sites of increased bone formation or resorption. They are potent inhibitors of osteoclast-mediated bone resorption (Boonecamp et al, 1986) and are effective in lowering serum calcium concentrations in patients with hypercalcaemia of malignancy (Ryzen et al, 1985;Kanis et al, 1987). Bisphosphonates are also used in the treatment of Paget's disease of bone (Altman et al, 1973;Plasmans et al, 1978) and bone lesions associated with multiple myeloma (Berenson et al, 1996). The mechanisms by which bisphosphonates inhibit osteoclast-mediated bone resorption remain to be determined, but may involve inhibition of formation of osteoclasts from immature precursor cells (Boonecamp et al, 1986;Lowik et al, 1988;Hughes et al, 1989) and/or direct inhibition of resorption via induction of apoptosis in mature osteoclasts (Lowik et al, 1988;Hughes et al, 1995;Selander et al, 1996). More recently, several reports have indicated that bisphosphonates have direct effects on other cell types which may have important implications in the treatment of patients with cancer-induced bone disease. Treatment with intravenous pamidronate (Hortobagyi et al, 1998) and oral clodronate (Paterson et al, 1993) have been reported to reduce the frequency of skeletal complications in established bone disease. Oral clodronate has also been shown to decrease the frequency of skeletal metastases in women who had recurrent breast cancer but without bony involvement (Kanis et al, 1996). Moreover, oral clodronate has recently been shown to increase survival in women with breast cancer, when given at the time of initial diagnosis to patients who have bone marrow micrometastases at the time of surgery fo...

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Bisphosphonates induce apoptosis in human breast cancer cell lines

et al. 2000

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“…Etidronate was used for the first time in the treatment of PDB in 1971 (37). The recommended dose is 5 mg/kg/day (average dose 400 mg/day) for 6 months (37,38). In general, patients whose disease is very active show a moderate clinical and biochemical improvement and a rapid relapse after the medication is suspended, tending to become more resistant after a repeated course of therapy.…”

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Paget's disease of bone

Griz

Caldas

Bandeira

et al. 2006

Arq Bras Endocrinol Metab

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Paget's disease of bone is a focal disorder of bone remodeling accompanied initially by an increase in bone resorption, followed by a disorganized and excessive formation of bone, leading to pain, fractures and deformities. It exhibits a marked geographical variation in its prevalence. In Brazil it predominantly affects persons of European descent. The majority of the reported cases of the disease in Brazil are from Recife, owing to its peculiar mixed European colonization over approximately four centuries. The etiology is complex and involves both genetic and environmental factors. The disease is often asymptomatic and diagnosis is usually based on biochemical markers of bone turnover, radionuclide bone scan and radiological examination. Bisphosphonates, in particular zoledronic acid, are regarded as the treatment of choice for Paget's disease of bone.

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“…A dose preconizada é de 5 mg/kg ao dia (dose média 400 mg/dia) por 6 meses (17,18). Em geral, pacientes com muita atividade da doença têm moderada melhora clínica e bioquímica e recidiva rápida após a interrupção da medicação, com tendência a tornarem-se resistentes após repetidos cursos da terapia.…”

Section: Tratamentounclassified

Tratamento da doença de Paget óssea: importância do ácido zoledrônico

Griz

Colares

Bandeira

2006

Arq Bras Endocrinol Metab

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RESUMOA doença de Paget é uma doença esquelética, de distribuição monostótica ou poliostótica, podendo ser causada por uma infecção viral e/ou fatores genéticos. É caracterizada por um aumento da remodelação óssea, resultando em anormalidade da arquitetura óssea. A excessiva reabsorção óssea osteoclástica, seguida secundariamente de aumento da atividade osteoblástica, leva à substituição do osso normal por osso desorganizado, aumentado, e com estrutura enfraquecida, propensa a deformidades e fraturas. A doença de Paget pode ser diagnosticada através de exames radiológicos, cintilografia e exames bioquímicos. O objetivo primário do tratamento é reduzir a dor e o risco do aparecimento das complicações a longo prazo. Atualmente dispõe-se de drogas anti-reabsortivas potentes, as quais controlam a reabsorção óssea e proporcionam uma grande melhora no tratamento. O ácido zoledrônico, um bisfosfonato de última geração, tem a vantagem de maior potência e remissão mais prolongada, além de um tempo de infusão curto. Paget's disease is a localised monostotic or polyostotic bone disease of unknown origin. It may be caused by a slow viral infection and/or genetic factors. It is characterised by increased bone remodelling and an initially excessive osteoclastic bone resorption, followed by a secondary increase in osteoblastic activity, leading to replacement of the normal bone by a disorganized, enlarged, and weakened osseous structure prone to deformities and fractures. The disease may be diagnosed by radiography, scintigraphy and biochemical tests. The primary aim of treatment is to reduce pain and risk of developing long-term complications. Potent antiresorptive drugs are now available, which control the increased bone remodelling and have led to a dramatic improvement in treatment. Zoledronic acid, a new generation of bisphosphonates, has the advantage of great potency and long duration of remission and a short infusion time. A DOENÇA DE PAGET FOI DESCRITA pela primeira vez em 1877 pelo médico inglês Sir James Paget (1). É uma doença óssea localizada, monostótica ou poliostótica, caracterizada por um aumento da remodelação óssea, resultando em anormalidade da arquitetura óssea. A excessiva reabsorção óssea osteoclástica, seguida secundariamente de aumento da atividade osteoblástica, leva à substituição do osso normal por revisão Tratamento da Doença de Paget Óssea: Importância do Ácido Zoledrônico

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Influence of Disodium Etidronate on Clinical and Laboratory Manifestations of Paget's Disease of Bone (Osteitis Deformans)

Cited by 233 publications

References 44 publications

Bisphosphonates induce apoptosis in human breast cancer cell lines

Bisphosphonates induce apoptosis in human breast cancer cell lines

Paget's disease of bone

Tratamento da doença de Paget óssea: importância do ácido zoledrônico

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