Tiludronic acid

Names

[ Name ]:
Tiludronic acid

[Synonym ]:
Acide tiludronique
Acido tiludronico
Acidum tiludronicum [INN-Latin]
Tiludronate
Tiludronic Acid
Acido tiludronico [INN-Spanish]
Acide tiludronique [INN-French]
Acidum tiludronicum
UNII-6PNS59HP4Y

Biological Activity

[Description]:

Tiludronate (Tiludronic Acid), an orally active bisphosphonate, can act an osteoregulator. Tiludronate is used for the research of the metabolic bone disorders. Tiludronate is a potent inhibitor of the osteoclast vacuolar H(+)-ATPase. Antiresorptive and anti-inflammatory properties[1][2][3][4].

[Related Catalog]:

Research Areas >> Inflammation/Immunology

Signaling Pathways >> Membrane Transporter/Ion Channel >> Proton Pump

[In Vitro]

The ability of Tiludronate to inhibit proton transport is 5-fold higher in kidney-derived vesicles (IC50=1.1 mM) and 10,000-fold higher in vesicles derived from osteoclasts (IC50=466 nM). Tiludronate also potently inhibited proton transport in yeast microsomal preparations (IC50=3.5 microM) and inhibited the activity of purified yeast V-ATPase. The inhibition of the osteoclast V-ATPase-mediated proton transport by Tiludronate is rapid, pH-dependent, and reversible[3].

[In Vivo]

Tiludronate exerts a dose-dependent inhibitory activity on bone resorption. Tiludronate could act on mature osteoclasts by reducing their capacity to secrete proton into the resorption space and also by favoring their detachment from the bone matrix. Tiludronate is also tested in other models of osteoporosis. In the castrated male rat model, Tiludronate (5-200 mg/kg; p.o.) prevents the decrease in the skeletal mass, assessed physically by measuring the bone weight and density or chemically by determining the calcium and phosphate content[3].

[References]

[1]. Reginster JY, et al. Prevention of postmenopausal bone loss by tiludronate. Lancet. 1989;2(8678-8679):1469-1471.

[2]. Nunes NLT, et al. Effects of local administration of tiludronic acid on experimental periodontitis in diabetic rats. J Periodontol. 2018;89(1):105-116.

[3]. Bonjour JP, et al. Tiludronate: bone pharmacology and safety. Bone. 1995;17(5 Suppl):473S-477S.

[4]. David P, et al. The bisphosphonate tiludronate is a potent inhibitor of the osteoclast vacuolar H(+)-ATPase. J Bone Miner Res. 1996;11(10):1498-1507.