Optimizing the management of postmenopausal osteoporosis with bisphosphonates: the emerging role of intermittent therapy.

BACKGROUND The utility of bisphosphonates in the treatment of postmenopausal osteoporosis is compromised by the requirement of frequent oral administration or complex cyclic regimens. Recognition that simplified dosing regimens and reduced frequency of administration are important factors for improving adherence to therapy has led to the development of bisphosphonates with less frequent dosing regimens that aim to offer greater convenience. OBJECTIVE This paper reviews the available data concerning the efficacy and tolerability of intermittent (less frequent than weekly) bisphosphonate dosing regimens for the treatment of postmenopausal osteoporosis, with particular focus on the potential implications for clinical management. METHODS Papers on intermittent or cyclic bisphosphonate dosing regimens were identified by searching MEDLINE using the following terms: dose, dosing, dosage, or drug therapy; intermittent, cyclic, cyclical, weekly, monthly, month, week, administration, regimen, or schedule; and etidronate, alendronate, risedronate, zoledronate, neridronate, pamidronate, clodronate, ibandronate, or tiludronate. RESULTS Because the currently available bisphosphonates differ in chemical structure, potency, and other physicochemical and biologic characteristics, comparable dose-free intervals may not be appropriate for all drugs. Several bisphosphonates have demonstrated efficacy in terms of an increase in bone mineral density (BMD) and a decrease in markers of bone turnover when administered intermittently. However, evidence of fracture benefit from a less frequent bisphosphonate dosing regimen was demonstrated recently. The nitrogen-containing bisphosphonate ibandronate was associated with a significant decrease in vertebral fracture risk when administered as an intermittent dosing regimen (P < 0.001 vs placebo). This study supports the concept that bisphosphonates such as ibandronate can be effectively administered less frequently than daily or weekly. CONCLUSIONS Bisphosphonate therapy using intermittent schedules with between-dose intervals longer than 1 week is capable of reducing the risk of fracture, improving BMD, and suppressing biochemical markers of bone turnover. Planned and ongoing trials will determine the place of intermittent bisphosphonates in the treatment algorithm for postmenopausal osteoporosis.