title: Is retention of zoledronic acid onto bone different in multiple myeloma and breast cancer patients with bone metastasis?
abstract: 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.
authors: Department of Clinical Cell Biology, Institute of Regional Health Research, University of Southern Denmark, Vejle Hospital/Lillebaelt Hospital, 7100 Vejle, Denmark. kent.soee@slb.regionsyddanmark.dk
authors: Kent
authors: K
authors: Søe
authors: Torben
authors: T
authors: Plesner
authors: Erik H
authors: EH
authors: Jakobsen
authors: Charlotte T
authors: CT
authors: Hansen
authors: Henrik B
authors: HB
authors: Jørgensen
authors: Jean-Marie
authors: JM
authors: Delaissé
mesh_terms: D000367:Age Factors; D000368:Aged; D000469:Alkaline Phosphatase / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000556:secondary*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D015331:Cohort Studies; D024042:Collagen Type I / Q000378:metabolism; D004164:Diphosphonates / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D010455:Peptides / Q000378:metabolism; D011877:Radionuclide Imaging; D000077211:Zoledronic Acid
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D004164:Diphosphonates; D007093:Imidazoles; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D000077211:Zoledronic Acid; D000469:Alkaline Phosphatase
keywords: BISPHOSPHONATE; BONE SCINTIGRAPHY; BREAST CANCER; CLINICAL TRIAL; MULTIPLE MYELOMA