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Bisphosphonates

Bisphosphonates inhibit bone resorption. They are currently the first choice of treatment in a variety of bone metabolism disorders characterised by high bone resorption. They bring about an increase in bone mass and a decrease in fracture incidence in osteoporosis. There are different types of bisphosphonates which differ widely in their efficacy, side effects and possible routes of administration, thus offering a flexible range of therapeutic options.

Alendronate has been extensively studied for the treatment of osteoporosis under randomized controlled clinical trial conditions. Alendronate increases BMD at all skeletal sites and reduces the incidence of fracture by around 50% in both hip and spine (1,2). Risedronate, has also been shown to increase BMD in postmenopausal women, reduce the rate of vertebral and nonvertebral fractures (3,4) and reduce the risk of hip fractures in elderly women with a low BMD (5). Alendronate and risedronate are given orally, daily or weekly (6,7). Oral ibandronate has also been shown to increase BMD and reduce the risk of vertebral fractures (8). Noninferiority compared to the oral daily dosing has been shown for ibandronate when given every month (9) as an oral formulation or every two or three months, by intravenous injections (10,11). For ibandronate, effects on nonvertebral fractures have been derived from post hoc analysis performed in high risk subjects. A double-blind, placebo-controlled trial, involving over 7,700 postmenopausal women, has demonstrated that intravenous zoledronic acid infusions given once a year, significantly reduced the incidence of all fractures over a treatment period of three years. The results of the study showed a 70% decrease.of morphometric vertebral fractures, as well as a decrease by 41% of hip fractures. Zoledronic acid is also associated with a significant improvement of bone mineral density and bone metabolism markers (12).

References

  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. Randomised trial of effect of alendronate on risk fracture in women with existing vertebral fractures. Lancet. 1996;348:1535-41.
  2. Cummings SR, Black DM, Thomson DE, Applegate WB, Barrett-Connor E, Musliner TA, Palermo L, Prineas R, Rubin SM, Scott JC, Vogt T, Wallace R, Yates AJ, LaCroix AZ for the Fracture Intervention Trial Research Group. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures – Results from the Fracture Intervention Trial. JAMA. 1998;280:2077-82.
  3. Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, Chesnut CH 3rd, Brown J, Eriksen EF, Hoseyni MS, Axelrod D, Miller PD. Effects of risedroante treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis. A randomized controlled trial. JAMA. 1999;282:1344-52.
  4. Reginster JY, Minne HW, Sorensen OH, Hooper M, Roux C, Brandi ML, Lund B, Ethgen D, Pack S, Roumagnac I, Eastell R. Randomized trial of the effects of risedronate on vertebral fractures in women with established posmenopausal osteoporosis. Vertebral Efficacy with Risedroante Therapy (VERT) Study Group. Osteoporos Int. 2000;11:83-91.
  5. McClung MR, Geusens P, Miller PD, Zippel H, Bensen WG, Roux C, Adami S, Fogelman I, Diamond T, Eastell R, Meunier PJ, Reginster JY. Hip Intervention Program Study Group: Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. N Engl J Med. 2001;344:333-40.
  6. 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 2nd, Kaur A, Thompson DE, Yates J, Orloff JJ. Therapeutic equivalence of alendronate 70 mg once weekly and alendronate 10 mg daily in the treatment of osteoporosis. Alendronate Once-Weekly Study Group. Aging (Milano). 2000;12:1-12.
  7. Brown JP, Kendler DL, McClung MR, Emkey RD, Adachi JD, Bolognese MA, Li Z, Blaske A, Lindsay R. The efficacy and tolerability of risedronate once a week for the treatment of postmenopausal osteoporosis. Calcif Tissue Int. 2002;71:103-11.
  8. Delmas PD, Recker RR, Chesnut CH 3rd, Skag A, Stakkestad JA, Emkey R, Gilbride J, Schimmer RC, Christiansen C. Daily and intermittent oral ibandronate normalize bone turnover and provide significant reduction in vertebral fracture risk : results from the BONE study. Osteoporos Int. 2004;15:792-8.
  9. Reginster JY, Adami S, Lakatos P, Greenwald M, Stepan JJ, Silverman SL, Christiansen C, Rowell L, Mairon N, Bonvoisin B, Drezner MK, Emkey R, Felsenberg D, Cooper C, Delmas PD, Miller PD. Efficacy and tolerability of once-monthly oral ibandronate in postmenopausal osteoporosis: 2 year results from the MOBILE study. Ann Rheum Dis 2006;65:654-61
  10. Delmas PD, Adami S, Strugala C, Stakkestad JA, Reginster JY, Felsenberg D, Christiansen C, Civitelli R, Drezner MK, Recker RR, Bolognese M, Hughes C, Masanauskaite D, Ward P, Sambrook P, Reid DM. Intravenous ibandronate injections in postmenopausal women with osteoporosis: one-year results from the dosing intravenous administration study. Arthritis Rheum. 2006;54:1838-46.
  11. Eisman JA, Civitelli R, Adami S, Czerwinski E, Recknor C, Prince R, Reginster JY, Zaidi M, Felsenberg D, Hughes C, Mairon N, Masanauskaite D, Reid DM, Delmas PD, Recker RR. Efficacy and Tolerability of Intravenous Ibandronate Injections in Postmenopausal Osteoporosis: 2-Year Results from the DIVA Study. J Rheumatol. 2008 Feb 1 [Epub ahead of print]
  12. Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR; HORIZON Pivotal Fracture Trial. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007:356:1809-22
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