Changes in bone remodelling and antifracture efficacy of intermittent bisphosphonate therapy: implications from clinical studies with ibandronate

Abstract

Bisphosphonates reduce the rate of bone resorption and bone remodelling. Given daily, they decrease the risk of fractures in postmenopausal osteoporosis. When bisphosphonates were given at extended drug-free intervals this antifracture efficacy was generally not seen. This may be due to the different pattern of bone remodelling changes. Data from randomised clinical studies of ibandronate, given orally or intravenously, at different doses and for variable time intervals to women with osteoporosis were examined to explore the relationship between intermittent bisphosphonate therapy, changes in bone resorption and fracture risk. The magnitude of the reduction of the rate of bone resorption at the end of the drug-free interval rather than its fluctuation pattern after bisphosphonate administration determines antifracture efficacy, provided that these fluctuations occur within the premenopausal range. Prolongation of the drug-free interval beyond 2 weeks should be compensated by a dose higher than the cumulative daily dose.

Prevention of glucocorticoid induced bone changes with beta-ecdysone

“…The effect of hPTH (1-34) on hip fracture reduction has not been shown in clinical studies in GIOP populations. [55, 57]. In our current study, we found GCs reduced vertebral bone strength, an observation that is consistent with bone loss [35, 41].…”

Clinical role of bisphosphonate therapy

“…3 However, as BPs reside in bone for a long time, daily, weekly, or even monthly administration should have similar efficacy, provided the cumulative doses are similar. This has been described for ibandronate and zoledronate when administration frequency is prolonged 11. During the period of treatment with BPs, bone resorption does not become progressively lower but reaches a new steady-state level, suggesting that, despite accumulation of BPs in the skeleton, bone turnover still continues, albeit at a slower rate.…”

Long-term administration of quarterly IV ibandronate is effective and well tolerated in postmenopausal osteoporosis: 5-year data from the DIVA study long-term extension

“…At the end of 60 months of continuous treatment, median sP1NP values were 57% and 45% lower than at DIVA core baseline, i.e., within the premenopausal range. Although no further reductions in biomarker levels were observed from DIVA core, biomarker levels remained within the premenopausal range [16,17] throughout the study and, therefore, remained clinically relevant in terms of responsiveness to treatment [22].…”