Bisphosphonates in osteoporosis

  • H. Fleisch


Bisphosphonates are compounds characterized by a P-C-P structure. They act essentially on bone, inhibiting bone resorption. Through this mechanism they decrease bone loss, increase bone mineral density, and decrease bone turnover. They are therefore administered in diseases with elevated bone destruction, such as Paget’s disease, metastatic bone disease, and osteoporosis. In the latter they diminish both vertebral and nonvertebral fractures. The adverse events are few, mostly gastrointestinal, and can be avoided to a large extent by correct administration. Since there are no other compounds available which have a similar profile, they represent today the drugs of choice in the treatment and the secondary prevention of osteoporosis.


Bisphosphonates Etidronate Alendronate Risedronate Osteoporosis 


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  1. 1.
    Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, Bauer DC, Genant HK, Haskell WL, Marcus R, Ott SM, Torner JC, Quandt SA, Reiss TF, Ensrud KE (1996) Randomized trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 348:1535–1541PubMedGoogle Scholar
  2. 2.
    Boivin GY, Chavassieux PM, Santora AC, Meunier PJ (2000) Alendronate increases bone strength by increasing the mean degree of mineralization of bone tissue in osteoporotic women. Bone 27:697–694CrossRefGoogle Scholar
  3. 3.
    Chapuy MC, Arlot ME, Duboeuf F, Brun J, Crouzet B, Arnaud F, Delmas PD, Meunier PJ (1992) Vitamin D and calcium to prevent hip fractures in the elderly. N Engl J Med 327:1637–1642PubMedGoogle Scholar
  4. 4.
    Cohen S, Levy RM, Keller M, Boling E, Emkey RD, Greenwald M, Zizic TM, Wallach S, Sewell KL, Lukert BP, Axelrod DW, Chines AA (1999) Risedronate therapy prevents corticosteroidinduced bone loss. Arthritis Rheum 42:2309–2318CrossRefPubMedGoogle Scholar
  5. 5.
    De Groen PC, Lubbe DF, Hirsch LJ, Daifotis A, Stephenson W, Freedholm D, Pryor-Tillotson S, Seleznick MJ, Pinkas H, Wang KK (1996) Esophagitis associated with the use of alendronate. N Engl J Med 355:1016–1021CrossRefGoogle Scholar
  6. 6.
    Fleisch H (2000) Bisphosphonates in bone disease — from the laboratory to the patient. Academic, San DiegoGoogle Scholar
  7. 7.
    Fleisch H, Russell RGG, Francis MD (1969) Diphosphonates inhibit hydroxyapatite dissolution in vitro and bone resorption in tissue culture and in vivo. Science 165:1262–1264PubMedGoogle Scholar
  8. 8.
    Francis MD, Russell RGG, Fleisch H (1969) Diphosphonates inhibit formation of calcium phosphate crystals in vitro and pathological calcification in vivo. Science 165:1264–1256PubMedGoogle Scholar
  9. 9.
    Glorieux FH, Bishop NJ, Plotkin H, Chabot G, Lanogu G, Travers R (1998) Cyclic administration of pamidronate in children with severe osteogenesis imperfecta. N Engl J Med 339:947–952CrossRefPubMedGoogle Scholar
  10. 10.
    Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner D, Keller M, Chesnut CH, Brown J, Eriksen EF, Hoseyni MS, Axelrod DW, Miller, PD (1999) Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis. JAMA 14:1344–1352CrossRefGoogle Scholar
  11. 11.
    Liberman UA, Weiss SR, Bröll J, Minne HW, Quan H, Bell NH, Rodriguez-Portales J, Downs RW Jr, Dequeker J, Favus M, Seeman E, Recker RR, Capizzi T, Santora AC II, Lombardi A, Shah RV, Hirsch LJ, Karpf DB (1995) Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. N Engl J Med 333:1437–1443CrossRefGoogle Scholar
  12. 2.
    McClung M, Clemmesen B, Daifotis A, Gilchrist NL, Eisman J, Weinstein RS, El Hajj Fuleihan G, Reda C, Yates AJ, Ravn P (1998) Alendronate prevents postmenopausal bone loss in women without osteoporosis. Ann Intern Med 128:253–261PubMedGoogle Scholar
  13. 13.
    Meunier PJ, Boivin GY (1997) Bone mineral density reflects bone mass but also the degree of mineralization of bone: therapeutic implications. Bone 5:373–377CrossRefGoogle Scholar
  14. 14.
    Mortensen L, Charles P, Bekker PJ, Digennaro J, Johnston CC (1998) Risedronate increases bone mass in an early postmenopausal population: two years of treatment plus one year of followup. J Clin Endocrinol Metab 83:396–402CrossRefPubMedGoogle Scholar
  15. 15.
    Mühlbauer RC, Russell RGG, Williams DA, Fleisch H (1971) The effects of diphosphonates, polyphosphates, and calcitonin on ‘immobilisation’ osteoporosis in rats. Eur J Clin Invest 1:336–344PubMedGoogle Scholar
  16. 16.
    Neer N, Arnaud CD, Zanchetta JR, Prince R, Gaich, GA, Reginster YI, Hodsman AB, Erichsen EF, Ish-Shalom S, Genant HK, Wang O, Mitlak, BH (2001) Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344:1434–1444PubMedGoogle Scholar
  17. 17.
    Pols HAP, Felsenberg D, Hanley DA, Stepan J, Munoz-Torres M, Wilkin TJ, Qin-sheng G, Galich AM, Vandormael K, Yates AJ, Stych B (1999) Multinational, placebo-controlled, randomized trial of the effects of alendronate on bone density and fracture risk in postmenopausal women with low bone mass: results of the FOSIT study. Osteoporos Int 9:461–468PubMedGoogle Scholar
  18. 18.
    Reginster JY, Minne HW, Sorensen OH, Hooper M, Roux C, Brandi ML, Lund B, Ethgen D, Pack S, Roumagnac I, Eastell R (2000) Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Osteoporosis Int 11:83–91CrossRefGoogle Scholar
  19. 19.
    Rogers MJ (2003) New insights into the molecular mechanisms of action of bisphosphonates. Curr Pharmaceut Design (in press)Google Scholar
  20. 20.
    Roussouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J, Writing Group for the Women’s Health Initiative Investigators (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA 288:321–333PubMedGoogle Scholar
  21. 21.
    Saag KG, Emkey R, Schnitzer TJ, Brown JP, Hawkins F, Goemaere F, Thamsborg G, Lieberman UA, Delmas PD, Malice M-P, Czachur M, Daifotis AG (1998) Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis. N Engl J Med 339:292–299PubMedGoogle Scholar
  22. 22.
    Schenk R, Merz WA, Mühlbauer R, Russell RGG, Fleisch H (1973) Effect of ethane-1-hydroxy-1:1-diphosphonate (EHDP) and dichloromethylene diphosphonate (Cl2MDP) on the calcification and resorption of cartilage and bone in the tibial epiphysis and metaphysis of rats. Calcif Tissue Res 11:196–214PubMedGoogle Scholar
  23. 23.
    Schnitzer T, Bone HG, Crepaldi G, Adami S, McClung M, Kiel D, Felsenberg D, Recker RR, Tonino RP, Roux C, Pinchera A, Foldes AJ, Greenspan SL, Levine MA, Emkey R, Santora AC, Kaur A, Thompson DE, Yates J, Orloff JJ (2000) Therapeutic equivalence of alendronate 70mg onceweekly and alendronate 10mg daily in the treatment of osteoporosis. Aging Clin Exp Res 12:1–12Google Scholar
  24. 24.
    Tonino RP, Meunier PJ, Emkey RD, Rodriguez-Portales JA, Menkes CJ, Wasnich RD, Bone HG, Santora AC, Wu M, Desai R, Ross PD (2000) Skeletal benefits of alendronate: 7-year treatment postmenopausal osteoporotic women. Phase III osteoporosis treatment study group. J Clin Endocrinol Metab 85:3109–115CrossRefPubMedGoogle Scholar
  25. 25.
    Toolan BC, Shea M, Myers ER, Borchers RE, Seedor JG, Quartuccio H, Rodan G, Hayes WC (1992) Effects of 4-amino-1-hydroxybutylidene bisphosphonate on bone biomechanics in rats. J Bone Miner Res 7:1399–1406PubMedGoogle Scholar
  26. 26.
    Watts NB, Harris ST, Genant HK, Wasnich RD, Miller PD, Jackson RD, Licata AA, Ross P, Woodson GC, Yanover MJ, Mysiw WJ, Kohse L, Rao MB, Steiger P, Richmond B, Chesnut CH III (1990) Intermittent cyclical etidronate treatment of postmenopausal osteoporosis. N Engl J Med 323:73–329PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2005

Authors and Affiliations

  • H. Fleisch
    • 1
  1. 1.PullySwitzerland

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