Is retention of zoledronic acid onto bone different in multiple myeloma and breast cancer patients with bone metastasis?

Søe, Kent; Plesner, Torben; Jakobsen, Erik; Hansen, Charlotte Toftmann; Jørgensen, Henrik Boel; Delaissé, Jean‐Marie

doi:10.1002/jbmr.1897

Cited by 6 publications

(3 citation statements)

References 45 publications

(124 reference statements)

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“…( 35,36 ) Immediately after infusion of 4‐mg Zol, a plasma concentration of around 2.4μM is reached, ( 37 ) and 24 hours after administration of Zol, around half of the dose is excreted into the urine. ( 37,38 ) Thus, approximately half of the Zol administered will be retained on accessible bone surfaces. However, plasma concentrations are not an exact measure of how much Zol has truly bound to a given bone surface within the human body.…”

Section: Discussionmentioning

confidence: 99%

Zoledronic Acid Is Not Equally Potent on Osteoclasts Generated From Different Individuals

et al. 2020

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Zoledronic acid is a bisphosphonate commonly used to treat bone diseases such as osteoporosis and cancer-induced bone disease. Patients exhibit a variable sensitivity to zoledronic acid; the underlying explanation for this remains unclear. The objective of this study was to obtain more knowledge in this regard. We hypothesized that osteoclasts generated from different individuals would show a variable sensitivity to zoledronic acid in vitro. Osteoclasts were generated using monocytes from 46 healthy female blood donors (40 to 66 years). Matured osteoclasts were reseeded onto bone slices precoated with different concentrations of zoledronic acid. IC50 values were determined based on total eroded bone surface after 3 days of resorption. The IC50 for inhibition of osteoclastic bone resorption varied from 0.06 to 12.57μM zoledronic acid; thus, a more than 200-fold difference in sensitivity to zoledronic acid among osteoclasts from different individuals was observed. Multiple linear regression analyses showed that the determined IC50 correlated with smoking status, and the average number of nuclei per osteoclast in vitro. Further analyses showed that: (i) increasing protein levels of mature cathepsin K in osteoclast cultures rendered the osteoclasts less sensitive to zoledronic acid; (ii) surprisingly, neither the gene nor the protein expression of farnesyl diphosphate synthase was found to correlate with the IC50; and (iii) trench-forming osteoclasts were found to be more sensitive to zoledronic acid than pit-forming osteoclasts within the same cell culture. Thus, we conclude that there indeed is a high degree of variation in the potency of zoledronic acid on osteoclasts when generated from different individuals. We propose that our findings can explain some of the varying clinical efficacy of zoledronic acid therapy observed in patients, and may therefore be of clinical importance, which should be investigated in a clinical trial combining in vitro and in vivo investigations.

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Section: Discussionmentioning

confidence: 99%

Zoledronic Acid Is Not Equally Potent on Osteoclasts Generated From Different Individuals

et al. 2020

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“…Zoledronic acid (ZA) was demonstrated to be superior in decreasing SREs relative to clodronate in the MRC Myeloma IX trial. Pamidronate and ZA have greater potency in inhibiting the transformation of monocytes to OCs and might facilitate the apoptosis of OCs [55][56][57][58]63]. In large-scale, randomized clinical studies, improved progression-free survival and overall survival by novel BPs in the treatment of MBD has been shown in subanalyses of the overall population.…”

Section: Bpsmentioning

confidence: 99%

Management of Myeloma Bone Lesions

Yen

Hsu

et al. 2021

IJMS

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Multiple myeloma (MM) is a B-cell neoplasm characterized by clonal plasma–cell proliferation. The survival and prognosis of this condition have been significantly improved by treatment with active anti-MM drugs such as bortezomib or lenalidomide. Further, the discovery of novel agents has recently paved the way for new areas of investigation. However, MM, including myeloma-related bone diseases, remains fatal. Bone disease or bone destruction in MM is a consequence of skeletal involvement with bone pain, spinal cord compression, and bone fracture resulting from osteolytic lesions. These consequences affect disease outcomes, including patients’ quality of life and survival. Several studies have sought to better understand MM bone disease (MBD) through the classification of its molecular mechanisms, including osteoclast activation and osteoblast inhibition. Bisphosphonates and the receptor activator of the nuclear factor-kappa B (NF-κB) ligand (RANKL) inhibitor, denosumab, prevent skeletal-related events in MM. In addition, several other bone-targeting agents, including bone-anabolic drugs, are currently used in preclinical and early clinical evaluations. This review summarizes the current knowledge of the pathogenesis of MBD and discusses novel agents that appear very promising and will soon enter clinical development.

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“…The bone metastasis of breast cancer is related to the age at the onset. With aging, the incidence rate of bone metastasis keeps rising (3).…”

Section: Introductionmentioning

confidence: 99%

Clinicopathological characteristics and prognostic risk factors of breast cancer patients with bone metastasis

Pan¹,

Lin²,

Mi³

2021

Ann Transl Med

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Background: A retrospective study was performed to summarize the clinicopathological characteristics of breast cancer patients with bone metastasis, to clarify the metastasis sites, and to explore the risk factors affecting prognosis.Methods: Breast cancer patients with bone metastasis diagnosed in our hospital from January 2008 to January 2019 were included. Through follow-up by telephone call or return visit, the metastasis sites and clinicopathological characteristics were summarized. The risk factors influencing prognosis were analyzed by univariate and multivariate regression analyses.Results: Multifocal bone metastases were dominant in the 150 patients, and the metastatic rates in the spine, chest, pelvis, limbs, and skull were 75.3%, 74.0%, 56.0%, 46.7%, and 28.7%, respectively, with significant differences (P<0.01). Kaplan-Meier univariate analysis showed that age, menstrual status, number of metastatic lymph nodes, clinical stage, endocrine therapy, alkaline phosphatase level, visceral metastasis, and number of bone metastasis sites affected the overall survival. Cox multivariate regression analysis revealed that endocrine therapy, number of metastatic lymph nodes, visceral metastasis, number of bone metastasis sites, and c-erbB-2 expression were independent prognostic factors.Conclusions: Middle-aged and elderly patients with breast cancer, mainly aged 40-60 years old, are prone to bone metastasis. The incidence rate of bone metastasis is high within 3 years after surgery, involving the spine, chest, pelvis, limbs, and skull in descending order. The number of metastatic lymph nodes, endocrine therapy, visceral metastasis, number of bone metastasis lesions at the first onset, and c-erbB-2 expression are independent prognostic factors influencing the survival rate of breast cancer patients with bone metastasis.

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Is retention of zoledronic acid onto bone different in multiple myeloma and breast cancer patients with bone metastasis?

Cited by 6 publications

References 45 publications

Zoledronic Acid Is Not Equally Potent on Osteoclasts Generated From Different Individuals

Zoledronic Acid Is Not Equally Potent on Osteoclasts Generated From Different Individuals

Management of Myeloma Bone Lesions

Clinicopathological characteristics and prognostic risk factors of breast cancer patients with bone metastasis

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