ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2020
Targeting Bortezomib to Bone Increases Its Bone Anabolic Activity and Reduces Systemic Adverse Effects in Mice.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 25 citations in OpenAlex.
- Consequences of Aging on Bone.Aging and disease · 2023Pooled it
- Microgravity-Related Changes in Bone Density and Treatment Options: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- Bone Effects of Anti-Cancer Treatments in 2024.Calcified tissue international · 2025Review
- Bisphosphonates for osteoporosis: from bench to clinic.The Journal of clinical investigation · 2024Article
- Article
- Age-associated callus senescent cells produce TGF-β1 that inhibits fracture healing in aged mice.The Journal of clinical investigation · 2022Article
- Bone-Targeted Bortezomib Inhibits Bortezomib-Resistant Multiple Myeloma in Mice by Providing Higher Levels of Bortezomib in Bone.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- Article
- Efficacy of Bisphosphonate-Conjugated Sitafloxacin in a Murine Model ofFrontiers in cellular and infection microbiology · 2022Article
- Proteasome inhibition-enhanced fracture repair is associated with increased mesenchymal progenitor cells in mice.PloS one · 2022Article
- The role of the bone microenvironment in regulating myeloma residual disease and treatment.Frontiers in oncology · 2022Review
- Anti-RANKL monoclonal antibody and bortezomib prevent mechanical unloading-induced bone loss.Journal of bone and mineral metabolism · 2021Article
- Development of Bisphosphonate-Conjugated Antibiotics to Overcome Pharmacodynamic Limitations of Local Therapy: Initial Results with Carbamate Linked Sitafloxacin and Tedizolid.Antibiotics (Basel, Switzerland) · 2021Article
- Bisphosphonates in dentistry: Historical perspectives, adverse effects, and novel applications.Bone · 2021Article
- Bisphosphonates for delivering drugs to bone.British journal of pharmacology · 2021Review
- Bortezomib Rescues Ovariectomy-Induced Bone Loss via SMURF-Mediated Ubiquitination Pathway.Oxidative medicine and cellular longevity · 2021Article
- Osteocyte Vegf-a contributes to myeloma-associated angiogenesis and is regulated by Fgf23.Scientific reports · 2020Article
- Recent Advances of Osterix Transcription Factor in Osteoblast Differentiation and Bone Formation.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Bortezomib (Btz) is a proteasome inhibitor approved by the FDA to treat multiple myeloma. It also increases bone volume by promoting osteoblast differentiation and inhibiting osteoclastogenesis in mice. However, Btz has severe systemic adverse effects, which would limit its use as a bone anabolic agent. Here, we designed and synthesized a bone-targeted form of Btz by conjugating it to a bisphosphonate (BP) with no antiresorptive activity. We report that BP-Btz inhibited osteoclast formation and bone resorption and stimulated osteoblast differentiation in vitro similar to Btz. In vivo, BP-Btz increased bone volume more effectively than Btz in three mouse models: untreated wild-type mice, mice with ovariectomy, and aged mice with tibial factures. Importantly, BP-Btz had significantly less systemic side effects than Btz, including less thymic cell death, sympathetic nerve damage, and thrombocytopenia, and it improved survival rates in aged mice. Thus, BP-Btz represents a novel anabolic agent to treat conditions, such as postmenopausal and age-related bone loss. Bone targeting is an attractive approach to repurpose approved drugs to treat skeletal diseases. © 2019 American Society for Bone and Mineral Research. © 2019 American Society for Bone and Mineral Research.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.