Journal ArticleDOI
Bisphosphonates, specific inhibitors of osteoclast function and a class of drugs for osteoporosis therapy.
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TLDR
Understanding of N‐containing bisphosphonates is updated, finding that their unique pharmacokinetic features make N‐BPs a good candidate as a bone‐seeking agent and underlie the drugs' high efficacy, minor side effects, and intermittent dosing regimens.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 Ca2+ 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 J Cell Biochem 112: 1229–1242, 2011 © 2011 Wiley-Liss, Incread more
Citations
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Occurrence and risk indicators of medication-related osteonecrosis of the jaw after dental extraction: a systematic review and meta-analysis.
TL;DR: The risk of MRONJ after dental extraction in patients treated with ARD exists, especially in patients treating for oncologic reasons, and this risk tends to decrease with adjusted extraction protocols.
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Chlorogenic Acid Prevents Osteoporosis by Shp2/PI3K/Akt Pathway in Ovariectomized Rats
Rong Ping Zhou,Si Jian Lin,Wen Bing Wan,Hui Ling Zuo,Fen Fen Yao,Hui Bing Ruan,Jin Xu,Wei Song,Yi Cheng Zhou,Shi Yao Wen,Jiang Hua Dai,Mei Lan Zhu,Jun Luo +12 more
TL;DR: This study found that CGA improved the BMD and trabecular micro-architecture for the OVX-induced osteoporosis and might be an effective alternative treatment for postmenopausal osteopOrosis.
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Mitigating osteonecrosis of the jaw (ONJ) through preventive dental care and understanding of risk factors.
TL;DR: Evidence to date suggests that health care providers can lower the risk of osteonecrosis of the jaw by dental evaluations and care prior to initiating antiresorptive therapies and by monitoring dental health during and after treatment.
Journal ArticleDOI
Clinical role of bisphosphonate therapy.
Greeta Hampson,Ignac Fogelman +1 more
TL;DR: The structure, pharmacology and mode of action of BPs are described, focusing on their role in clinical practice, and controversies and side effects surrounding their use will be discussed.
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Chondroitin sulfate-E mediates estrogen-induced osteoanabolism
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References
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Journal ArticleDOI
Osteoclast differentiation and activation
TL;DR: Discovery of the RANK signalling pathway in the osteoclast has provided insight into the mechanisms of osteoporosis and activation of bone resorption, and how hormonal signals impact bone structure and mass.
Journal ArticleDOI
Regulation of the mevalonate pathway.
TL;DR: The mevalonate pathway produces isoprenoids that are vital for diverse cellular functions, ranging from cholesterol synthesis to growth control, and could be useful in treating certain forms of cancer as well as heart disease.
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The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors.
Anne J. Ridley,Alan Hall +1 more
TL;DR: Rho, a ras-related GTP-binding protein, rapidly stimulated stress fiber and focal adhesion formation when microinjected into serum-starved Swiss 3T3 cells, implying that rho is essential specifically for the coordinated assembly of focal adhesions and stress fibers induced by growth factors.
Journal ArticleDOI
Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis
Dennis M. Black,Pierre D. Delmas,Richard Eastell,Ian R. Reid,Steven Boonen,Jane A. Cauley,Felicia Cosman,Peter L. Lakatos,Ping Chung Leung,Z. Man,Carlos Mautalen,Peter Mesenbrink,Huilin Hu,John Caminis,Karen Tong,Theresa Rosario-Jansen,Joel S. Krasnow,Trisha F. Hue,Deborah E. Sellmeyer,Erik Fink Eriksen,Steven R. Cummings +20 more
TL;DR: Treatment with zoledronic acid reduced the risk of morphometric vertebral fracture by 70% during a 3-year period, as compared with placebo.
Journal ArticleDOI
osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification
N. Bucay,Ildiko Sarosi,Colin R. Dunstan,Sean Morony,John E. Tarpley,C. Capparelli,S. Scully,Hong Lin Tan,Weilong Xu,David L. Lacey,William J. Boyle,William S. Simonet +11 more
TL;DR: It is demonstrated that OPG is a critical regulator of postnatal bone mass and regulation of OPG, its signaling pathway, or its ligand(s) may play a role in the long observed association between osteoporosis and vascular calcification.
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