The Effectiveness of Cyclic and Continuous Oral Clodronate Therapy on Bone Density and Markers in Osteopenic Postmenopausal Women

Abstract

Bisphosphonates have been used effectively to treat established osteoporosis and prevent postmenopausal bone loss. However, the optimal manner of its administration-whether cyclic or continuous-has not been well established. This study investigated the efficacy of cyclic and continuous oral administration of clodronate in 54 newly identified osteopenic postmenopausal women in a randomized, double-blind, crossover fashion. The participants were randomly separated into two groups. The cyclic group (n = 29) received 800 mg twice daily of oral clodronate for 2 weeks every 3 months for the first 12 months followed by placebo for the second 12 months. The continuous group (n = 25) received placebo in the first 12 months and ingested 400 mg of clodronate once daily for the second 12 months. The urinary amino-terminal (NTXtrade mark) and carboxy-terminal (CrossLapstrade mark) cross-linked fragments of type I collagen, both markers of bone resorption, showed a marked decrease (25-50%) with both regimens during the period of active treatment. In the cyclic group, the levels of these two markers increased in the second 12 months with placebo, but did not return to the baseline completely. However, bone mineral density (BMD), determined by dual-energy X-ray absorptiometry (DXA), showed no significant change of BMD at various sites after 1 year of active treatment in both groups. Thoracic and lumbar spine X-ray showed no new vertebral fracture in either group after 2 years of treatment. With the two treatment protocols in this study, oral clodronate was effective in decreasing postmenopausal bone resorption, causing no significant changes in BMD at various sites.

Pharmacokinetic and pharmacodynamic evaluation of intermittent versus continuous alendronate administration in rats

“…11,12 Similar magnitude of drug effects in osteoporosis was found for daily-versus-weekly and cyclic-versus-continuous administration. 10,13 However, clinical investigations pose practical limitations in studying different input regimens. Long-term continuous infusion of bisphosphonates is not applicable in clinical settings, and iǹ`c ontinuous'' (daily) regimens of oral tablets, continuous input of the drug to the body is not provided.…”