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Changes in bone remodeling and antifracture efficacy of intermittent bisphosphonate therapy: Implications from clinical studies with ibandronate
  1. Socrates E. Papapoulos (m.v.iken{at}
  1. Leiden University Medical Center, Netherlands
    1. Ralph C. Schimmer
    1. F. Hoffmann-La Roche Ltd, Switzerland


      Bisphosphonates reduce the rate of bone resorption and bone remodeling, and when given daily they decrease the risk of fractures in women with postmenopausal osteoporosis. Changes in bone remodeling following bisphosphonate administration at extended drug-free intervals follow a different pattern that can account for the lack, up until recently, of significant antifracture efficacy of such regimens. To explore the relationship between intermittent bisphosphonate therapy, changes in bone resorption and fracture risk, we examined data from randomized clinical studies with ibandronate, a bisphosphonate that has been given orally or intravenously at different doses and variable time intervals to women with osteoporosis. Available data show that the magnitude of the reduction of the rate of bone resorption at the end of the drug- free interval rather than the pattern of its fluctuation following bisphosphonate administration determine antifracture efficacy, provided that these fluctuations occur within the range of values of premenopausal women. In addition, for the design of an efficacious intermittent regimen with bisphosphonate, prolongation of the drug-free interval beyond two weeks should be compensated by a dose higher than the cumulative daily dose during this period. Generalization of these conclusions to the whole class is limited by potential subtle differences in basic pharmacolological properties of bisphosphonates

      • bisphosphonates
      • bone resorption
      • fractures
      • ibandronate
      • osteoporosis

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