Bisphosphonates in the treatment of metabolic bone diseases

Arantes, Henrique Pierotti; Silva, André Gonçalves da; Lazaretti‐Castro, Marise

doi:10.1590/s0004-27302010000200017

Cited by 18 publications

(15 citation statements)

References 45 publications

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“…Bisphosphonates are poorly absorbed in the gut due to their negative charge hindering their transport across the lipophilic cell membrane; they are therefore given mainly intravenously [45,54]. BPs are not metabolised and have very short plasma half lives, being distributed quickly to bone or excreted unchanged by the kidneys [45].…”

Section: Introductionmentioning

confidence: 99%

Tumour macrophages as potential targets of bisphosphonates

2011

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Tumour cells communicate with the cells of their microenvironment via a series of molecular and cellular interactions to aid their progression to a malignant state and ultimately their metastatic spread. Of the cells in the microenvironment with a key role in cancer development, tumour associated macrophages (TAMs) are among the most notable. Tumour cells release a range of chemokines, cytokines and growth factors to attract macrophages, and these in turn release numerous factors (e.g. VEGF, MMP-9 and EGF) that are implicated in invasion-promoting processes such as tumour cell growth, flicking of the angiogenic switch and immunosuppression. TAM density has been shown to correlate with poor prognosis in breast cancer, suggesting that these cells may represent a potential therapeutic target. However, there are currently no agents that specifically target TAM's available for clinical use.Bisphosphonates (BPs), such as zoledronic acid, are anti-resorptive agents approved for treatment of skeletal complication associated with metastatic breast cancer and prostate cancer. These agents act on osteoclasts, key cells in the bone microenvironment, to inhibit bone resorption. Over the past 30 years this has led to a great reduction in skeletal-related events (SRE's) in patients with advanced cancer and improved the morbidity associated with cancer-induced bone disease. However, there is now a growing body of evidence, both from in vitro and in vivo models, showing that zoledronic acid can also target tumour cells to increase apoptotic cell death and decrease proliferation, migration and invasion, and that this effect is significantly enhanced in combination with chemotherapy agents. Whether macrophages in the peripheral tumour microenvironment are exposed to sufficient levels of bisphosphonate to be affected is currently unknown. Macrophages belong to the same cell lineage as osteoclasts, the major target of BPs, and are highly phagocytic cells shown to be sensitive to bisphosphonates in model studies; In vitro, zoledronic acid causes increased apoptotic cell death; in vivo the drug has been shown to inhibit the production of pro-angiogenic factor MMP-9, as well as most recent evidence showing it can trigger the reversal of the TAMs phenotype from pro-tumoral M2 to tumoricidal M1. There is thus accumulating evidence supporting the hypothesis that effects on TAMs may contribute to the anti-tumour effect of bisphosphonates. This review will focus in detail on the role of tumour associated macrophages in breast cancer progression, the actions of bisphosphonates on macrophages in vitro and in tumour models in vivo and summarise the evidence supporting the potential for the targeting of tumour macrophages with bisphosphonates.

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Section: Introductionmentioning

confidence: 99%

Tumour macrophages as potential targets of bisphosphonates

2011

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“…1,2 They are commonly prescribed for bone diseases such as osteoporosis, Paget's disease of bone, hypercalcaemia of malignancy, osteolytic bone metastases, and osteolytic lesions of multiple myeloma. 1,3,4 Their use has resulted in a statistically significant reduction in skeletal complications, including pathological fractures, spinal cord compression, and hypercalcaemia of malignant disease, and has reduced the need for subsequent radiotherapy or surgery to bone. [5][6][7] BPs are synthetic analogues of the naturally occurring pyrophosphate molecule.…”

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confidence: 99%

Treatment strategies and outcomes of bisphosphonate-related osteonecrosis of the jaw (BRONJ) with characterization of patients: a systematic review

Fliefel

Tröltzsch

Kühnisch

et al. 2015

International Journal of Oral and Maxillofacial Surgery

294

213

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“…No Brasil, em um estudo realizado com idosos, foi constatado que as lesões provocadas pela osteoporose são responsáveis pela prevalência dos óbitos nos indivíduos com idade superior a 60 anos. Os números relacionados a estas evidências mos- LAZARETTI-CASTRO, 2010;PINHEIRO et al, 2010). De acordo com a Organização Mundial de Saúde, 1,7 milhões de fraturas de quadril ocorrem no mundo todo.…”

Section: Introductionunclassified

“…Assim, o desacoplamento da remodelação óssea está relacionado à fisiopatologia da osteoporose, com aumento da reabsorção, e redução da formação óssea. A remodelação óssea é definida como um processo relacionado entre a reabsorção óssea e formação óssea (AMADEI et al, 2006;(ARANTES;SIL-VA;LAZARETTI-CASTRO, 2010). Os osteoblastos após a diferenciação em osteoclastos promovem a reabsorção óssea e a remodelação no mesmo local onde se encontra a ondulação óssea.…”

Section: Introductionunclassified

Caracterização Das Plantas Medicinais E Medicamentos Fitoterápicos Para Tratamento Da Osteoporose Utilizados No Brasil

Marques

Lima

Andreotti

et al. 2016

Arq. Ciênc. Saúde Unipar

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Caracterização das plantas medicinais e medicamentos fitoterápicos para tratamento da osteoporose utilizados no Brasil. Arq. Cienc. Saúde UNIPAR, Umuarama, v. 20, n. 3, p, 183-188, set./dez. 2016. RESUMO:A osteoporose é caracterizada por desordem do sistema esquelético caracterizada por baixa massa óssea e deteriorização da microarquitetura do tecido ósseo levando a fragilidade óssea com aumento da suscetibilidade a fraturas. Considerada a doença osteometabólica mais comum, de distribuição global, pode comprometer ambos os sexos, diferentes idades ou raças. As consequências relacionadas a essas doenças são as fraturas vertebrais verificadas em aproximadamente 20% das mulheres acima de 65 anos em pós-menopausa. Além disso, a consequência dessa fragilidade óssea pode levar a consequências graves como dor, deformidades, sequelas, restrições motoras e morte precoce, portanto, associada com alta morbi/mortalidade. Desta forma, sabendo que as medicações utilizadas para o tratamento da osteoporose não são isentas de risco (por exemplo, aumento do risco de tromboses, câncer de mama/ ovário/ endométrio, lesões musculares, entre outras), foi realizado uma revisão bibliográfica com o intuito de avaliar se existem plantas medicinais que possam ter efeitos ósseo protetores com menor número de efeitos adversos em relação aos fármacos sintéticos. Em síntese, verificou-se que os fármacos sintéticos podem acarretar prejuízos à saúde do paciente a longo prazo e que as plantas medicinais ou fitoterápicos utilizadas no Brasil apresentam estudos científicos com menores efeitos colaterais e, portanto, são uma alternativa viável para o tratamento e prevenção da osteoporose, visto que a Politica Nacional de Práticas Integrativas e Complementares na Atenção Básica sustenta esta tendência mediante subsídios como a Farmacopeia Brasileira e o Memento Fitoterápico. PALAVRAS-CHAVE: Brasil. Fitoterapia. Medicamentos Fitoterápicos. Osteoporose. CHARACTERIZATION OF MEDICINAL PLANTS AND HERBAL MEDICINES FOR THE TREATMENT OF OSTEOPOROSIS USED IN BRAZILABSTRACT: Osteoporosis is characterized by skeletal system disorder, consisting of low bone mass and deterioration of the microarchitecture of the bone tissue, leading to bone fragility with increased susceptibility to fractures. Considered the most common osteometabolic disease worldwide, it affects both sexes, different ages and races. The consequences of these diseases are vertebral fractures in approximately 20% of postmenopausal women over 65 years of age. In addition, the consequence of this bone fragility may lead to serious consequences, such as pain, deformities, sequelae, motor restrictions and early death, being therefore associated with high morbidity/mortality. Therefore, knowing the medication used in the treatment of osteoporosis are not free of risk (for example, increased risk of thrombosis, breast/ovarian/endometrial cancer, muscle injuries, among others), a bibliographical review was made with the intent of evaluating whether there are medicinal plants that may have protective ef...

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Bisphosphonates in the treatment of metabolic bone diseases

Cited by 18 publications

References 45 publications

Tumour macrophages as potential targets of bisphosphonates

Tumour macrophages as potential targets of bisphosphonates

Treatment strategies and outcomes of bisphosphonate-related osteonecrosis of the jaw (BRONJ) with characterization of patients: a systematic review

Caracterização Das Plantas Medicinais E Medicamentos Fitoterápicos Para Tratamento Da Osteoporose Utilizados No Brasil

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