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Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy
SummaryBisphosphonates (BPs) are well established as the leading drugs for the treatment of osteoporosis. There is new knowledge about how they work. The differences that exist among individual BPs… Expand
Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates.
- J. Dunford, K. Thompson, +5 authors M. Rogers
- Medicine, Chemistry
- The Journal of pharmacology and experimental…
- 1 February 2001
It has long been known that small changes to the structure of the R(2) side chain of nitrogen-containing bisphosphonates can dramatically affect their potency for inhibiting bone resorption in vitro… Expand
The molecular mechanism of nitrogen-containing bisphosphonates as antiosteoporosis drugs
- K. Kavanagh, K. Guo, +6 authors U. Oppermann
- Medicine, Chemistry
- Proceedings of the National Academy of Sciences…
- 16 May 2006
Osteoporosis and low bone mass are currently estimated to be a major public health risk affecting >50% of the female population over the age of 50. Because of their bone-selective pharmacokinetics,… Expand
Novel insights into actions of bisphosphonates on bone: differences in interactions with hydroxyapatite.
Bisphosphonates are now the most widely used drugs for diseases associated with increased bone resorption, such as osteoporosis. Although bisphosphonates act directly on osteoclasts, and interfere… Expand
Bisphosphonates inhibit breast and prostate carcinoma cell invasion, an early event in the formation of bone metastases.
The molecular mechanisms by which tumor cells metastasize to bone are likely to involve invasion, cell adhesion to bone, and the release of soluble mediators from tumor cells that stimulate… Expand
Bisphosphonates: an update on mechanisms of action and how these relate to clinical efficacy.
- R. Russell, Zhidao Xia, +12 authors F. Ebetino
- Annals of the New York Academy of Sciences
- 1 November 2007
The bisphosphonates (BPs) are well established as the treatments of choice for disorders of excessive bone resorption, including Paget's disease of bone, myeloma and bone metastases, and… Expand
The relationship between the chemistry and biological activity of the bisphosphonates.
The ability of bisphosphonates ((HO)(2)P(O)CR(1)R(2)P(O)(OH)(2)) to inhibit bone resorption has been known since the 1960s, but it is only recently that a detailed molecular understanding of the… Expand
Structure-activity relationships among the nitrogen containing bisphosphonates in clinical use and other analogues: time-dependent inhibition of human farnesyl pyrophosphate synthase.
- J. Dunford, A. Kwaasi, +5 authors K. Kavanagh
- Chemistry, Medicine
- Journal of medicinal chemistry
- 10 April 2008
The nitrogen-containing bisphosphonates (N-BPs) are the main drugs currently used to treat diseases characterized by excessive bone resorption. The major molecular target of N-BPs is… Expand
Bisphosphonates inhibit prostate and breast carcinoma cell adhesion to unmineralized and mineralized bone extracellular matrices.
The molecular mechanisms by which tumor cells induce osteolytic metastases are likely to involve tumor cell adhesion to bone as well as the release of soluble mediators from tumor cells that… Expand
Heterocycle‐Containing Bisphosphonates Cause Apoptosis and Inhibit Bone Resorption by Preventing Protein Prenylation: Evidence from Structure‐Activity Relationships in J774 Macrophages
- S. P. Luckman, F. Coxon, F. Ebetino, R. Russell, M. Rogers
- Biology, Medicine
- Journal of bone and mineral research : the…
- 1 November 1998
Recent evidence suggests that bisphosphonates (BPs) may inhibit bone resorption by mechanisms that lead to osteoclast apoptosis. We have previously shown that BPs also reduce cell viability and… Expand