FMAR  Vol.2 No.3 , July 2014
Effect of Bisphosphonate on Osteoclast of Bone
ABSTRACT
Bisphosphonates are synthetic analogues of naturally occurring pyrophosphate molecule and are potent inhibitors of osteoclastic bone resorption. Bisphosphonates bind to hydroxyapatite crystals with high affinity and after incorporation by osteoclasts, the primary target cell, it inhibits osteoclastic bone resorption. The anti-resorptive effect has been shown to occur in organ culture as well as in-vivo, but the precise mechanism by which it exerts its bone resorbing effect is not yet fully understood. In vitro and in vivo studies have demonstrated that zoledronate is a more potent inhibitor of osteoclasts than earlier bisphosphonates. Bisphosphonates have now emerged as a leading therapeutic agent for the treatment of hypercalcaemia of malignancy, bone metabolic diseases, Paget’s disease and postmenopausal osteoporosis.

Cite this paper
Ralte, S. and Bhattacharyya, A. (2014) Effect of Bisphosphonate on Osteoclast of Bone. Forensic Medicine and Anatomy Research, 2, 56-62. doi: 10.4236/fmar.2014.23011.
References
[1]   Simmons, D.J. (1963) Cellular Changes in the Bones of Mice as Studied with Tritiated Thymidine and the Effects of Estrogen. Clinical Orthopaedics and Related Research, 26, 176-189.

[2]   Young, M.H. and Crane, W.A. (1964) Effect of Hydrocortisone on the Utilization of Tritiated Thymidine for Skeletal Growth in the Rat. Annals of the Rheumatic Diseases, 23, 163-168.
http://dx.doi.org/10.1136/ard.23.2.163

[3]   Russell, R.G., Kisling, A.M., Casey, P.A., Fleisch, H., Thornton, J., Schenk, R. and Williams, D.A. (1973) Effect of Diphosphonates and Calcitonin on the Chemistry and Quantitative Histology of Rat Bone. Calcified Tissue Research, 11, 179-195. http://dx.doi.org/10.1007/BF02547218

[4]   Stutzer, A., Fleisch, H. and Trechsel, U. (1988) Short- and Long-Term Effects of a Single Dose of Bisphosphonates on Retinoid-Induced Bone Resorption in Thyroparathyroidectomized Rats. Calcified Tissue International, 43, 294-299. http://dx.doi.org/10.1007/BF02556639

[5]   Wronski, T.J., Dann, L.M., Scott, K.S. and Crooke, L.R. (1989) Endocrine and Pharmacological Suppressors of Bone Turnover Protect against Osteopenia in Ovariectomized Rats. Endocrinology, 125, 810-816. http://dx.doi.org/10.1210/endo-125-2-810

[6]   Lin, B.Y., Jee, W.S., Ma, Y.F., Ke, H.Z., Kimmel, D.B. and Li, X.J. (1994) Effects of Prostaglandin E2 and Risedronate Administration on Cancellous Bone in Older Female Rats. Bone, 15, 489-496.
http://dx.doi.org/10.1016/8756-3282(94)90272-0

[7]   Turan, B., Balcik, C. and Akkas, N. (1997) Effect of Dietary Selenium and Vitamin E on Biochemical Properties of Rabbit Bone. Clinical Rheumatology, 16, 441-449. http://dx.doi.org/10.1007/BF02238935

[8]   Fleisch, H. (1998) Bisphosphonates: Mechanisms of Action. Endocrine Reviews, 19, 80-100.
http://dx.doi.org/10.1210/edrv.19.1.0325

[9]   Fleisch, H., Russell, R.G. and Francis, M.D. (1969) Diphosphonates Inhibit Hydroxyapatite Dissolution in Vitro and Bone Resorption in Tissue Culture and in Vivo. Science, 165, 1262-1264.
http://dx.doi.org/10.1126/science.165.3899.1262

[10]   Francis, M.D., Graham, R., Russell, R.G. and Fleisch, H. (1969) Diphosphonates Inhibit Formation of Calcium Phosphate Crystals in Vitro and Pathological Calcification in Vivo. Science, 165, 1264-1266. http://dx.doi.org/10.1126/science.165.3899.1264

[11]   Green, J.R., Muller, K. and Jaeggi, K.A. (1994) Preclinical Pharmacology of CGP 42’446, a New, Potent, Heterocyclic Bisphosphonate Compound. Journal of Bone and Mineral Research, 9, 745-751.
http://dx.doi.org/10.1002/jbmr.5650090521

[12]   Menschutkin, N. (1865) Ueber die Einwirkung des Chloracetyles auf Phosphorige Saure. Justus Liebigs Annalen der Chemie, 133, 317-320. http://dx.doi.org/10.1002/jlac.18651330307

[13]   Fleisch, H., Russell, R.G., Bisaz, S., Casey, P.A. and Muhlbauer, R.C. (1968) The Influence of Pyrophosphate Ana-Logues (Diphosphonates) on the Precipitation and Dissolution of Calcium Phosphate in Vitro and in Vivo. Calcified Tissue Research, 2, 10-10A. http://dx.doi.org/10.1007/BF02065192

[14]   Ernst, D.S., Brasher, P., Hagen, N., Paterson, A.H., MacDonald, R.N. and Bruera, E. (1997) A Randomized, Controlled Trial of Intravenous Clodronate in Patients with Metastatic Bone Disease and Pain. Journal of Pain and Symptom Management, 13, 319-326. http://dx.doi.org/10.1016/S0885-3924(97)00075-4

[15]   Rossini, M., Gatti, D., Girardello, S., Braga, V., James, G. and Adami, S. (2000) Effects of Two Intermittent Alendronate Regimens in the Prevention or Treatment of Postmenopausal Osteoporosis. Bone, 27, 119-122. http://dx.doi.org/10.1016/S8756-3282(00)00291-X

[16]   Reitsma, P.H., Teitelbaum, S.L., Bijvoet, O.L. and Kahn, A.J. (1982) Differential Action of the Bisphosphonates (3-Amino-1-hydroxypropylidene)-1, 1-Bisphosphonate (APD) and Disodium Dichloromethylidene Bisphosphonate (Cl2MDP) on Rat Macrophage-Mediated Bone Resorption in Vitro. Journal of Clinical Investigation, 70, 927-933. http://dx.doi.org/10.1172/JCI110704

[17]   Schenk, R., Merz, W.A., Muhlbauer, R., Russell, R.G. and Fleisch, H. (1973) Effect of Ethane-1-hydroxy-1, 1-diphos- phonate (EHDP) and Dichloromethylene Diphosphonate (Cl2MDP) on the Calcification and Resorption of Cartilage and Bone in the Tibial Epiphysis and Metaphysis of Rats. Calcified Tissue Research, 11, 196-214. http://dx.doi.org/10.1007/BF02547219

[18]   Miller, S.C. and Jee, W.S. (1979) The Effect of Dichloromethylene Diphosphonate, a Pyrophosphate Analog, on Bone and Bone Cell Structure in the Growing Rat. Anatomical Record, 193, 439-462. http://dx.doi.org/10.1002/ar.1091930309

[19]   Ito, M., Amizuka, N., Nakajima, T. and Ozawa, H. (1999) Ultrastructural and Cytochemical Studies on Cell Death of Os-Teoclasts Induced by Bisphosphonate Treatment. Bone, 25, 447-452.
http://dx.doi.org/10.1016/S8756-3282(99)00197-0

[20]   Coxon, F.P., Helfrich, M.H., Van’t Hof, R., Sebti, S., Ralston, S.H., Hamilton, A. and Rogers, M.J. (2000) Protein Geranylgeranylation Is Required for Osteoclast Formation, Function, and Survival: Inhibition by Bisphosphonates and GGTI-298. Journal of Bone and Mineral Research, 15, 1467-1475.
http://dx.doi.org/10.1359/jbmr.2000.15.8.1467

[21]   Alakangas, A., Selander, K., Mulari, M., Halleen, J., Lehenkari, P., Monkkonen, J., Salo, J. and Vaananen, K. (2002) Alendronate Disturbs Vesicular Trafficking in Osteoclasts. Calcified Tissue International, 70, 40-47. http://dx.doi.org/10.1007/s002230010047

[22]   Lehenkari, P.P., Kellinsalmi, M., Napankangas, J.P., Ylitalo, K.V., Monkkonen, J., Rogers, M.J., Azhayey, A., Vaananen, H.K. and Hassinen, I.E. (2002) Further Insight into Mechanism of Action of Clodronate: Inhibition of Mito- Chondrial ADP/ATP Translocase by a Nonhydrolyzable, Adenine-Containing Metabolite. Molecular Pharmacology, 61, 1255-1262. http://dx.doi.org/10.1124/mol.61.5.1255

[23]   Mayahara, M. and Sasaki, T. (2003) Cellular Mechanism of Inhibition of Osteoclastic Resorption of Bone and Calcified Cartilage by Long-Term Pamidronate Administration in Ovariectomized Mature Rats. Anatomical Record Part A, 274, 817-826. http://dx.doi.org/10.1002/ar.a.10092

[24]   Ralte, S., Khatri, K. and Nagar, M. (2011) Short-Term Effects of Zoledronate on the Histomorphology of Osteoclast in Young Albino Rats. Annals of Anatomy, 193, 509-515.
http://dx.doi.org/10.1016/j.aanat.2011.03.009

[25]   Hughes, D.E., MacDonald, B.R., Russell, R.G. and Gowen, M. (1989) Inhibition of Osteoclast-Like Cell Formation by Bisphosphonates in Long-Term Cultures of Human Bone Marrow. Journal of Clinical Investigation, 83, 1930-1935. http://dx.doi.org/10.1172/JCI114100

[26]   Flanagan, A.M. and Chambers, T.J. (1991) Inhibition of Bone Resorption by Bisphosphonates: Interactions between Bisphosphonates, Osteoclasts, and Bone. Calcified Tissue International, 49, 407-415. http://dx.doi.org/10.1007/BF02555852

[27]   Sato, M., Grasser, W., Endo, N., Akins, R., Simmons, H., Thompson, D.D., Golub, E. and Rodan, G.A. (1991) Bisphosphonate Action. Alendronate Localization in Rat Bone and Effects on Osteoclast Ultrastructure. Journal of Clinical Investigation, 88, 2095-2105. http://dx.doi.org/10.1172/JCI115539

[28]   Vitte, C., Fleisch, H. and Guenther, H.L. (1996) Bisphosphonates Induce Osteoblasts to Secrete an Inhibitor of Osteoclast-Mediated Resorption. Endocrinology, 137, 2324-2333.

[29]   Murakami, H., Takahashi, N., Sasaki, T., Udagawa, N., Tanaka, S., Nakamura, I., Zhang, D., Barbier, A. and Suda, T. (1995) A Possible Mechanism of the Specific Action of Bisphosphonates on Osteoclasts: Tiludronate Preferentially Affects Polarized Osteoclasts Having Ruffled Borders. Bone, 17, 137-144. http://dx.doi.org/10.1016/S8756-3282(95)00150-6

[30]   Hughes, D.E., Wright, K.R., Uy, H.L., Sasaki, A., Yoneda, T., Roodman, G.D., Mundy, G.R. and Boyce, B.F. (1995) Bisphosphonates Promote Apoptosis in Murine Osteoclasts in Vitro and in Vivo. Journal of Bone and Mineral Research, 10, 1478-1487. http://dx.doi.org/10.1002/jbmr.5650101008

[31]   Derenne, S., Amiot, M., Barille, S., Collette, M., Robillard, N., Berthaud, P., Harousseau, J.L. and Bataille, R. (1999) Zoledronate Is a Potent Inhibitor of Myeloma Cell Growth and Secretion of IL-6 and MMP-1 by the Tumoral Environment. Journal of Bone and Mineral Research, 14, 2048-2056.
http://dx.doi.org/10.1359/jbmr.1999.14.12.2048

[32]   Jagdev, S.P., Croucher, P.I. and Shipman, C.M. (2000) Taxol and Zoledronate Induce Apoptosis in Breast Cancer Cells in Vitro: Evidence for Action via Inhibition of Mevalonate Pathway. Bone, 26, S30.

[33]   Biossier, S., Ferreras, M., Peyruchaud, O., Magnetto, S., Ebetino, F.H., Colombel, M., Delmas, P., Delaissé, J.M. and Clézardin, P. (2000) Biphosphonates Inhibit Breast and Prostrate Carcinoma Cell Invasion, an Early Event in the Formation of Bone Metastases. Cancer Research, 60, 2949-2954.

 
 
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