ArticleJBMR plus2020
Zoledronic Acid Is Not Equally Potent on Osteoclasts Generated From Different Individuals.
Article in JBMR plus, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Zoledronic Acid for Periprosthetic Bone Mineral Density Changes in Patients With Osteoporosis After Hip Arthroplasty-An Updated Meta-Analysis of Six Randomized Controlled Trials.Frontiers in medicine · 2021Pooled it
- Acute Effects of Kisspeptin Administration on Bone Metabolism in Healthy Men.The Journal of clinical endocrinology and metabolism · 2022Trial
- M-CSF priming enhances the efficiency and reproducibility of hiPSC-derived osteoclast differentiation and pharmacological responsiveness to anti-resorptive agents.Scientific reports · 2026Article
- Engineering osteoclast resorption unitsLab on a chip · 2026Article
- Photobiomodulation Modulates the Response of Zoledronic-Acid-Treated Osteoblast-like SaOs-2 Cells: Implications for Bisphosphonate-Related Osteonecrosis.Bioengineering (Basel, Switzerland) · 2026Article
- Kisspeptin and neurokinin B: roles in reproductive health.Physiological reviews · 2025Review
- Isolation and Generation of Osteoclasts.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Stage-specific modulation of multinucleation, fusion, and resorption by the long non-coding RNA DLEU1 and miR-16 in human primary osteoclasts.Cell death & disease · 2024Article
- Real-time analysis of osteoclast resorption and fusion dynamics in response to bone resorption inhibitors.Scientific reports · 2024Article
- Article
- A variability in response of osteoclasts to zoledronic acid is mediated by smoking-associated modification in the DNA methylome.Clinical epigenetics · 2023Article
- Osteoclastogenesis of human peripheral blood, bone marrow, and cord blood monocytes.Scientific reports · 2023Article
- Dendritic cell-specific transmembrane protein is required for synovitis and bone resorption in inflammatory arthritis.Frontiers in immunology · 2022Article
- Alendronate Use and Risk of Type 2 Diabetes: A Nationwide Danish Nested Case-Control Study.Frontiers in endocrinology · 2021Article
- The Mechanism Switching the Osteoclast From Short to Long Duration Bone Resorption.Frontiers in cell and developmental biology · 2021Article
- Osteoclast Fusion: Physiological Regulation of Multinucleation through Heterogeneity-Potential Implications for Drug Sensitivity.International journal of molecular sciences · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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. © 2020 The Authors.
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