Bisphosphonate therapy: how long is long enough?

Excerpt

The unique pharmacological properties of bisphosphonates (tight binding to bone mineral, long retention in the skeleton) provide both opportunities and challenges for clinicians [1]. Unlike all the other drugs used to treat osteoporosis, the effects of bisphosphonates on bone remodeling persist after stopping therapy. Knowledge of these properties prompted studies to evaluate the duration of effects on bone remodeling, bone mineral density, and fracture risk upon stopping treatment, beginning with the early phase 2 and phase 3 studies with alendronate and risedronate and continuing until the extension of the most recent phase 3 bisphosphonate fracture study, the HORIZON trial with annual intravenous dosing of zoledronic acid [2‐11]. The initial studies with alendronate demonstrated gradual decreases in BMD and increases in biochemical markers of bone turnover toward baseline values over several years [2‐8]. In contrast, resolution of the effects of risedronate on bone mineral density and bone turnover within 1 year was reported [9, 10]. At the other end of the spectrum, minimal changes in both BMD and turnover markers were observed in the first 3 years upon stopping annual intravenous zoledronic acid therapy after three doses [11]. The more limited information about the effects of discontinuing therapy on fracture risk suggests that, after 3–5 years of treatment, protection from fracture persists for 1–2 years and then gradually wanes [8, 9, 11, 12]. …