ArticleThe Journal of clinical investigation2000
A selective inhibitor of the osteoclastic V-H(+)-ATPase prevents bone loss in both thyroparathyroidectomized and ovariectomized rats.
Article in The Journal of clinical investigation, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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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.
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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
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 129 citations in OpenAlex.
- Use of acid-suppressive drugs and risk of fracture: a meta-analysis of observational studies.Annals of family medicinePooled it
- Bone Disease in Primary Hyperparathyroidism-Changes Occurring in Bone Metabolism and New Potential Treatment Strategies.International journal of molecular sciences · 2024Review
- Small-molecule amines: a big role in the regulation of bone homeostasis.Bone research · 2023Review
- Advances in Drug Discovery Targeting Lysosomal Membrane Proteins.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Proton Pump Inhibitors and Bone Health: An Update Narrative Review.International journal of molecular sciences · 2022Review
- Radiodynamic Therapy with Acridine Orange Is an Effective Treatment for Bone Metastases.Biomedicines · 2022Article
- Role of Biomolecules in Osteoclasts and Their Therapeutic Potential for Osteoporosis.Biomolecules · 2021Review
- Membrane Transport Proteins in Osteoclasts: The Ins and Outs.Frontiers in cell and developmental biology · 2021Review
- Pantoprazole impairs fracture healing in aged mice.Scientific reports · 2020Article
- Lysosomes as a therapeutic target.Nature reviews. Drug discovery · 2019Review
- V-ATPases and osteoclasts: ambiguous future of V-ATPases inhibitors in osteoporosis.Theranostics · 2018Review
- PA1b inhibitor binding to subunits c and e of the vacuolar ATPase reveals its insecticidal mechanism.The Journal of biological chemistry · 2014Article
- Risk of fracture and pneumonia from acid suppressive drugs.World journal of methodology · 2011Review
- Versatile roles of V-ATPases accessory subunit Ac45 in osteoclast formation and function.PloS one · 2011Article
- The vacuolar ATPase in bone cells: a potential therapeutic target in osteoporosis.Molecular biology reports · 2010Review
- Article
- Osteoclast-targeting small molecules for the treatment of neoplastic bone metastases.Cancer science · 2009Review
- Advances in osteoclast biology resulting from the study of osteopetrotic mutations.Human genetics · 2009Review
- Structure of the yeast vacuolar ATPase.The Journal of biological chemistry · 2008Article
- Drug-induced osteoporosis: beyond glucocorticoids.Current rheumatology reports · 2008Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A potent and selective inhibitor of the osteoclastic V-H(+)-ATPase, (2Z,4E)-5-(5,6-dichloro-2-indolyl)-2-methoxy-N-(1,2,2,6, 6-pentamethylpiperidin-4-yl)-2,4-pentadienamide (SB 242784), was evaluated in two animal models of bone resorption. SB 242784 completely prevented retinoid-induced hypercalcemia in thyroparathyroidectomized (TPTX) rats when administered orally at 10 mg/kg. SB 242784 was highly efficacious in the prevention of ovariectomy-induced bone loss in the rat when administered orally for 6 months at 10 mg/kg/d and was partially effective at 5 mg/kg/d. Its activity was demonstrated by measurement of bone mineral density (BMD), biochemical markers of bone resorption, and histomorphometry. SB 242784 was at least as effective in preventing bone loss as an optimal dose of estrogen. There were no adverse effects of compound administration and no effects on kidney function or urinary acidity. Selectivity of the inhibitor was further studied using an in situ cytochemical assay for bafilomycin-sensitive V-H(+)-ATPase using sections of osteoclastoma and numerous other tissues. SB 242784 inhibited the osteoclast enzyme at 1,000-fold lower concentrations than enzymes in any of the other tissues evaluated. SB 242784 demonstrates the utility of selective inhibition of the osteoclast V-H(+)-ATPase as a novel approach to the prevention of bone loss in humans.
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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.