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J Bone Miner Res ; 28(8): 1738-50, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23427025

RESUMO

Zoledronic acid (Zol) is used to treat bone disease in both multiple myeloma (MM) and breast cancer patients with bone metastasis (BC). However, bones of MM and BC patients show a difference in retention of the bisphosphonate used for bone scintigraphy. Therefore, we hypothesized that disease-specific factors may differently influence Zol retention in MM and BC patients. We tested this hypothesis in an investigator initiated phase II clinical trial in which we compared the whole-body retention (WBrt) of Zol in a cohort of 30 multiple myeloma (MM) and 30 breast cancer (BC) (20 Zol naive and 40 with six or more previous administrations). On average, 62% of the administered Zol was retained in the skeleton of both MM and BC patients and independently of the number of treatments. WBrt of Zol did not correlate with cross-linked C-telopeptide (CTX) levels, but linear regression analyses showed that WBrt of Zol correlated with bone-specific alkaline phosphatase (bALP) levels in BC (p = 0.001), and with CTX/bALP in Zol naive MM patients (p = 0.012). Especially in BC patients, WBrt correlated with age (p = 0.014) independently of kidney function. In MM patients WBrt was found to primarily correlate with the extent of bone disease (p = 0.028). Multivariate linear regression analyses of the entire cohort pointed out that WBrt of Zol was best predicted by age (p < 0.000), osseous lesions (p < 0.001), and the preceding Zol dosing (p < 0.005) (r(2) = 0.97). Comparing bone scintigrams with CT/X-ray images showed a poor correlation between sites of active bone disease and binding of scintigraphy bisphosphonate in 36% of MM patients and in 13% of BC patients. We conclude that WBrt of Zol is primarily determined by two non-disease related factors and only one disease related, but that there may be differences in retention or drug delivery at individual sites of bone disease between MM and BC patients. In order to find the optimal dosing of Zol, these observations should be taken into account.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Osso e Ossos/patologia , Neoplasias da Mama/patologia , Difosfonatos/uso terapêutico , Imidazóis/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Fatores Etários , Idoso , Fosfatase Alcalina/metabolismo , Biomarcadores/metabolismo , Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/diagnóstico por imagem , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Estudos de Coortes , Colágeno Tipo I/metabolismo , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Peptídeos/metabolismo , Cintilografia , Ácido Zoledrônico
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