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Chemical Compound Review

Fosamax     (4-amino-1-hydroxy-1- phosphono...

Synonyms: Alendros, Arendal, Onclast, alendronate, CHEMBL870, ...
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Disease relevance of MK 217


Psychiatry related information on MK 217


High impact information on MK 217

  • The increase in bone mineral density in the alendronate group was greater than that in the placebo group at all measurement sites (P<0.001) [10].
  • At three years, the mean (+/- SE) differences in bone mineral density between the women receiving 10 mg of alendronate daily and those receiving placebo were 8.8 +/- 0.4 percent in the spine, 5.9 +/- 0.5 percent in the femoral neck, 7.8 +/- 0.6 percent in the trochanter, and 2.5 +/- 0.3 percent in the total body (P < 0.001 for all comparisons) [11].
  • Alendronate decreased the risk of radiographic vertebral fractures by 44% overall (relative risk, 0.56; 95% CI, 0.39-0.80; treatment-control difference, 1.7%; NNT, 60) [12].
  • Inhibition of bone resorption by administration of the bisphosphonate alendronate led to a decrease of the absolute number of osteoblast progenitors; however, it did not influence the stimulating effect of ovariectomy on osteoblastogenesis or osteoclastogenesis [13].
  • The bone-induced H+ extrusion was inhibited by salmon calcitonin (10(-8) M, for 2 h), and was not present after pretreating the bone slices with the aminobisphosphonate alendronate (ALN) [14].

Chemical compound and disease context of MK 217


Biological context of MK 217


Anatomical context of MK 217

  • The bone density of the trochanter and total body also increased significantly in the patients treated with alendronate [19].
  • Bisphosphonate action. Alendronate localization in rat bone and effects on osteoclast ultrastructure [21].
  • 6 d later the label was 600-1,000 microns away from the epiphyseal plate and buried inside the bone, indicating normal growth and matrix deposition on top of alendronate-containing bone [21].
  • All tested aminobisphosphonates (alendronate, ibandronate, and pamidronate) induced significant expansion of gamma delta T cells (V gamma 9V delta 2++ subset) in peripheral blood mononuclear cell cultures of healthy donors at clinically relevant concentrations (half-maximal activity, 0.9-4 mcmol/L) [22].
  • In the treatment model, in which alendronate was given from 10 days after tumor inoculation when macroscopic tumors are already implanted in the peritoneum, the antitumor effect was weaker but still significant [17].

Associations of MK 217 with other chemical compounds


Gene context of MK 217

  • The inhibitory effect of 10(-6) M alendronate on PBMC proliferation was reversed by 10 U/ml recombinant rIL-1 beta, whereas other cytokines such as IL-6, TNF-alpha, and granulocyte-macrophage colony-stimulating factor (GM-CSF) had no effect [27].
  • Alendronate exhibited dose-dependent inhibition of the production of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) by activated monocytes [27].
  • Thus, alendronate acts on monocytes to inhibit their antigen-presenting/accessory cell functions through a mechanism that can be overcome by exogenous IL-1 [27].
  • Evaluation of bone turnover and osteoclastic cytokines in early rheumatoid arthritis treated with alendronate [28].
  • A potent bisphosphonate compound, alendronate, inhibited MMP-2 secretion to block solubilization of collagen 1 [29].

Analytical, diagnostic and therapeutic context of MK 217


  1. Esophagitis associated with the use of alendronate. de Groen, P.C., Lubbe, D.F., Hirsch, L.J., Daifotis, A., Stephenson, W., Freedholm, D., Pryor-Tillotson, S., Seleznick, M.J., Pinkas, H., Wang, K.K. N. Engl. J. Med. (1996) [Pubmed]
  2. Alendronate in postmenopausal osteoporosis. McGrath, H. N. Engl. J. Med. (1996) [Pubmed]
  3. Endoscopic comparison of esophageal and gastroduodenal effects of risedronate and alendronate in postmenopausal women. Lanza, F.L., Hunt, R.H., Thomson, A.B., Provenza, J.M., Blank, M.A. Gastroenterology (2000) [Pubmed]
  4. Alendronate increases lumbar spine bone mineral density in patients with Crohn's disease. Haderslev, K.V., Tjellesen, L., Sorensen, H.A., Staun, M. Gastroenterology (2000) [Pubmed]
  5. Effect of alendronate on the age-specific incidence of symptomatic osteoporotic fractures. Hochberg, M.C., Thompson, D.E., Black, D.M., Quandt, S.A., Cauley, J., Geusens, P., Ross, P.D., Baran, D. J. Bone Miner. Res. (2005) [Pubmed]
  6. Alendronate administration and skeletal response during chronic alcohol intake in the adolescent male rat. Wezeman, F.H., Emanuele, M.A., Moskal, S.F., Steiner, J., Lapaglia, N. J. Bone Miner. Res. (2000) [Pubmed]
  7. Letter re: alendronate in anorexia nervosa. Ott, S.M. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  8. Parathyroid hormone-related protein (PTHrP) as a causative factor of cancer-associated wasting: possible involvement of PTHrP in the repression of locomotor activity in rats bearing human tumor xenografts. Onuma, E., Tsunenari, T., Saito, H., Sato, K., Yamada-Okabe, H., Ogata, E. Int. J. Cancer (2005) [Pubmed]
  9. Alendronate-induced auditory hallucinations and visual disturbances. Coleman, C.I., Perkerson, K.A., Lewis, A. Pharmacotherapy (2004) [Pubmed]
  10. Alendronate for the treatment of osteoporosis in men. Orwoll, E., Ettinger, M., Weiss, S., Miller, P., Kendler, D., Graham, J., Adami, S., Weber, K., Lorenc, R., Pietschmann, P., Vandormael, K., Lombardi, A. N. Engl. J. Med. (2000) [Pubmed]
  11. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study Group. Liberman, U.A., Weiss, S.R., Bröll, J., Minne, H.W., Quan, H., Bell, N.H., Rodriguez-Portales, J., Downs, R.W., Dequeker, J., Favus, M. N. Engl. J. Med. (1995) [Pubmed]
  12. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. Cummings, S.R., Black, D.M., Thompson, D.E., Applegate, W.B., Barrett-Connor, E., Musliner, T.A., Palermo, L., Prineas, R., Rubin, S.M., Scott, J.C., Vogt, T., Wallace, R., Yates, A.J., LaCroix, A.Z. JAMA (1998) [Pubmed]
  13. Loss of estrogen upregulates osteoblastogenesis in the murine bone marrow. Evidence for autonomy from factors released during bone resorption. Jilka, R.L., Takahashi, K., Munshi, M., Williams, D.C., Roberson, P.K., Manolagas, S.C. J. Clin. Invest. (1998) [Pubmed]
  14. Acid extrusion is induced by osteoclast attachment to bone. Inhibition by alendronate and calcitonin. Zimolo, Z., Wesolowski, G., Rodan, G.A. J. Clin. Invest. (1995) [Pubmed]
  15. Gaucher disease: alendronate disodium improves bone mineral density in adults receiving enzyme therapy. Wenstrup, R.J., Bailey, L., Grabowski, G.A., Moskovitz, J., Oestreich, A.E., Wu, W., Sun, S. Blood (2004) [Pubmed]
  16. Alendronate inhibits invasion of PC-3 prostate cancer cells by affecting the mevalonate pathway. Virtanen, S.S., Väänänen, H.K., Härkönen, P.L., Lakkakorpi, P.T. Cancer Res. (2002) [Pubmed]
  17. Alendronate inhibits intraperitoneal dissemination in in vivo ovarian cancer model. Hashimoto, K., Morishige, K., Sawada, K., Tahara, M., Kawagishi, R., Ikebuchi, Y., Sakata, M., Tasaka, K., Murata, Y. Cancer Res. (2005) [Pubmed]
  18. Alendronate inhibits lysophosphatidic acid-induced migration of human ovarian cancer cells by attenuating the activation of rho. Sawada, K., Morishige, K., Tahara, M., Kawagishi, R., Ikebuchi, Y., Tasaka, K., Murata, Y. Cancer Res. (2002) [Pubmed]
  19. Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis. Glucocorticoid-Induced Osteoporosis Intervention Study Group. Saag, K.G., Emkey, R., Schnitzer, T.J., Brown, J.P., Hawkins, F., Goemaere, S., Thamsborg, G., Liberman, U.A., Delmas, P.D., Malice, M.P., Czachur, M., Daifotis, A.G. N. Engl. J. Med. (1998) [Pubmed]
  20. Alendronate prevents postmenopausal bone loss in women without osteoporosis. A double-blind, randomized, controlled trial. Alendronate Osteoporosis Prevention Study Group. McClung, M., Clemmesen, B., Daifotis, A., Gilchrist, N.L., Eisman, J., Weinstein, R.S., Fuleihan G el-H, n.u.l.l., Reda, C., Yates, A.J., Ravn, P. Ann. Intern. Med. (1998) [Pubmed]
  21. Bisphosphonate action. Alendronate localization in rat bone and effects on osteoclast ultrastructure. Sato, M., Grasser, W., Endo, N., Akins, R., Simmons, H., Thompson, D.D., Golub, E., Rodan, G.A. J. Clin. Invest. (1991) [Pubmed]
  22. Stimulation of gammadelta T cells by aminobisphosphonates and induction of antiplasma cell activity in multiple myeloma. Kunzmann, V., Bauer, E., Feurle, J., Weissinger, F., Tony, H.P., Wilhelm, M. Blood (2000) [Pubmed]
  23. Clinical effects of raloxifene hydrochloride in women. Khovidhunkit, W., Shoback, D.M. Ann. Intern. Med. (1999) [Pubmed]
  24. Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro. Fisher, J.E., Rogers, M.J., Halasy, J.M., Luckman, S.P., Hughes, D.E., Masarachia, P.J., Wesolowski, G., Russell, R.G., Rodan, G.A., Reszka, A.A. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  25. Vgamma2Vdelta2 T-cell receptor-mediated recognition of aminobisphosphonates. Das, H., Wang, L., Kamath, A., Bukowski, J.F. Blood (2001) [Pubmed]
  26. The molecular mechanism of action of the antiresorptive and antiinflammatory drug clodronate: evidence for the formation in vivo of a metabolite that inhibits bone resorption and causes osteoclast and macrophage apoptosis. Frith, J.C., Mönkkönen, J., Auriola, S., Mönkkönen, H., Rogers, M.J. Arthritis Rheum. (2001) [Pubmed]
  27. Inhibition of antigen-presenting cell function by alendronate in vitro. Sansoni, P., Passeri, G., Fagnoni, F., Mohagheghpour, N., Snelli, G., Brianti, V., Engleman, E.G. J. Bone Miner. Res. (1995) [Pubmed]
  28. Evaluation of bone turnover and osteoclastic cytokines in early rheumatoid arthritis treated with alendronate. Cantatore, F.P., Acquista, C.A., Pipitone, V. J. Rheumatol. (1999) [Pubmed]
  29. Alendronate blocks TGF-beta1 stimulated collagen 1 degradation by human prostate PC-3 ML cells. Stearns, M.E. Clin. Exp. Metastasis (1998) [Pubmed]
  30. Prevention of bone loss with alendronate in postmenopausal women under 60 years of age. Early Postmenopausal Intervention Cohort Study Group. Hosking, D., Chilvers, C.E., Christiansen, C., Ravn, P., Wasnich, R., Ross, P., McClung, M., Balske, A., Thompson, D., Daley, M., Yates, A.J. N. Engl. J. Med. (1998) [Pubmed]
  31. Meta-analyses of therapies for postmenopausal osteoporosis. II. Meta-analysis of alendronate for the treatment of postmenopausal women. Cranney, A., Wells, G., Willan, A., Griffith, L., Zytaruk, N., Robinson, V., Black, D., Adachi, J., Shea, B., Tugwell, P., Guyatt, G. Endocr. Rev. (2002) [Pubmed]
  32. Combination therapy with hormone replacement and alendronate for prevention of bone loss in elderly women: a randomized controlled trial. Greenspan, S.L., Resnick, N.M., Parker, R.A. JAMA (2003) [Pubmed]
  33. Alendronate and estrogen-progestin in the long-term prevention of bone loss: four-year results from the early postmenopausal intervention cohort study. A randomized, controlled trial. Ravn, P., Bidstrup, M., Wasnich, R.D., Davis, J.W., McClung, M.R., Balske, A., Coupland, C., Sahota, O., Kaur, A., Daley, M., Cizza, G. Ann. Intern. Med. (1999) [Pubmed]
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