Tags

Type your tag names separated by a space and hit enter

Bisphosphonates, specific inhibitors of osteoclast function and a class of drugs for osteoporosis therapy.
J Cell Biochem. 2011 May; 112(5):1229-42.JC

Abstract

Osteoporosis is a result of the disruption of bone homeostasis that is carried out by bone-forming osteoblasts and bone-degrading osteoclasts. The most common treatment of osteoporosis is N-containing bisphosphonates, a class of non-hydrolyzable pyrophosphate analogs. They have strong affinity to Ca(2+) of hydroxyapatite with high specificity and can only be liberated from the bone in an acidic environment. These properties bestow them unique pharmacokinetic features including specific and strong retention at bone resorption surface, uptaken specifically by osteoclasts, quick excretion of non-retained free bisphosphonates, long half-life, and recyclability. Such properties underlie the drugs' high efficacy, minor side effects, and intermittent dosing regimens. Further studies show that bisphosphonates inhibit farnesyl pyrophosphate synthase, a critical enzyme required for synthesis of isoprenyl and geranylgeranyl, and inhibit prenylation and geranylgeranylation of small G-proteins such as Rac and Rho. This leads to defective actin ring formation at the sealed zone, a subcellular structure essential for bone resorption, and a decrease in bone resorption. Bisphosphonates are also used to treat Paget's disease of bone, osteolytic bone metastases, and hypercalcemia. Moreover, these properties also make N-BPs a good candidate as a bone-seeking agent. Here we update our understanding of this remarkable class of anti-resorption drugs.

Authors+Show Affiliations

Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China. libj@sjtu.edu.cnNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21465521

Citation

Li, Baojie, et al. "Bisphosphonates, Specific Inhibitors of Osteoclast Function and a Class of Drugs for Osteoporosis Therapy." Journal of Cellular Biochemistry, vol. 112, no. 5, 2011, pp. 1229-42.
Li B, Ling Chau JF, Wang X, et al. Bisphosphonates, specific inhibitors of osteoclast function and a class of drugs for osteoporosis therapy. J Cell Biochem. 2011;112(5):1229-42.
Li, B., Ling Chau, J. F., Wang, X., & Leong, W. F. (2011). Bisphosphonates, specific inhibitors of osteoclast function and a class of drugs for osteoporosis therapy. Journal of Cellular Biochemistry, 112(5), 1229-42. https://doi.org/10.1002/jcb.23049
Li B, et al. Bisphosphonates, Specific Inhibitors of Osteoclast Function and a Class of Drugs for Osteoporosis Therapy. J Cell Biochem. 2011;112(5):1229-42. PubMed PMID: 21465521.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bisphosphonates, specific inhibitors of osteoclast function and a class of drugs for osteoporosis therapy. AU - Li,Baojie, AU - Ling Chau,Jenny Fung, AU - Wang,Xueying, AU - Leong,Wai Fook, PY - 2011/4/6/entrez PY - 2011/4/6/pubmed PY - 2011/7/21/medline SP - 1229 EP - 42 JF - Journal of cellular biochemistry JO - J Cell Biochem VL - 112 IS - 5 N2 - Osteoporosis is a result of the disruption of bone homeostasis that is carried out by bone-forming osteoblasts and bone-degrading osteoclasts. The most common treatment of osteoporosis is N-containing bisphosphonates, a class of non-hydrolyzable pyrophosphate analogs. They have strong affinity to Ca(2+) of hydroxyapatite with high specificity and can only be liberated from the bone in an acidic environment. These properties bestow them unique pharmacokinetic features including specific and strong retention at bone resorption surface, uptaken specifically by osteoclasts, quick excretion of non-retained free bisphosphonates, long half-life, and recyclability. Such properties underlie the drugs' high efficacy, minor side effects, and intermittent dosing regimens. Further studies show that bisphosphonates inhibit farnesyl pyrophosphate synthase, a critical enzyme required for synthesis of isoprenyl and geranylgeranyl, and inhibit prenylation and geranylgeranylation of small G-proteins such as Rac and Rho. This leads to defective actin ring formation at the sealed zone, a subcellular structure essential for bone resorption, and a decrease in bone resorption. Bisphosphonates are also used to treat Paget's disease of bone, osteolytic bone metastases, and hypercalcemia. Moreover, these properties also make N-BPs a good candidate as a bone-seeking agent. Here we update our understanding of this remarkable class of anti-resorption drugs. SN - 1097-4644 UR - https://www.unboundmedicine.com/medline/citation/21465521/Bisphosphonates_specific_inhibitors_of_osteoclast_function_and_a_class_of_drugs_for_osteoporosis_therapy_ L2 - https://doi.org/10.1002/jcb.23049 DB - PRIME DP - Unbound Medicine ER -