Bisphosphonates in the management of postmenopausal osteoporosis--optimizing efficacy in clinical practice

Abstract

Nitrogen-containing bisphosphonates are potent inhibitors of osteoclastic bone resorption. With their individually proven efficacy to significantly reduce the incidence of vertebral and/or non-vertebral fractures and with their overall beneficial safety profile, alendronate, ibandronate, risedronate, and zoledronate are considered today a treatment of first choice in postmenopausal osteoporosis. However, treatment effects in an individual patient and cost-effectiveness in public health perspective are vitally dependent on the long-term patient adherence as well as on compliance and persistence. As compliance and persistence with daily oral bisphosphonates are shown to be suboptimal in many patients, leading to an increased fracture incidence in non-compliant patients, there is a need to improve overall adherence for bisphosphonate treatment in order to achieve maximum treatment effects. One option is to extend dosing intervals to weekly (alendronate, risedronate) or monthly (ibandronate) oral regimens. Less frequent oral regimens are generally preferred by majority of patients. Another alternative is intravenous, instead of oral application (ibandronate, zoledronate). Treatment acceptance could be further improved by IV bisphosphonates with their benefit of only quarterly, or even once-yearly, application. Treatment decisions should be based on anti-fracture efficacy data first. In addition, to ensure best possible patient adherence and maximum treatment benefits, physicians should consider individual patient conditions affecting compliance and persistence as well as patient preferences.

Figure 1

Generic bisphosphonate structure with functional domains.

Figure 2

Mortality as a secondary endpoint in the HORIZON-RFT (Recurrent Fracture Trial) with zoledronate: in the safety analysis, a total of 242 of 2111 patients (11.5%) died during the study, 101 of 1054 (9.6%) were in the zoledronate group and 141 of 1057 (13.3%) were in the placebo group (hazard ratio for the zoledronate group, 0.72; 95% CI, 0.56–0.93; p = 0.01). Adapted with permission from Lyles KW, Colón-Emeric CS, Magaziner JS, et al. 2007. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med, 357:1799–809. Copyright © 2007 Massachusetts Medical Society. All rights reserved.

Figure 3

Adherence and its components. Adapted with permission from Payer J, Killinger Z, Sulková I, Celec P. 2007. Therapeutic adherence to bisphosphonates. Biomed Pharmacother, 61:191–3. Copyright © 2007 Elsevier.

Figure 4

Persistence refers to the duration of time during which a medication is taken. Compliance is the proportion of medication taken at a given time according to instructions while persistent. Adherence represents compliance over time and can be estimated within discrete periods using the medication possession ratio. Reproduced with permission from Badamgarav E, Fitzpatrick LA. 2006. A new look at osteoporosis outcomes: the influence of treatment, compliance, persistence, and adherence. Mayo Clin Proc, 81:1009–12. Copyright © 2006 Mayo Foundation for Medical Education and Research. All rights reserved.

Figure 5

Probability of fracture in 24 months in the bisphosphonate-treated patients. Reproduced with permission from Siris ES, Harris ST, Rosen CJ, et al. 2006. Adherence to bisphosphonate therapy and fracture rates in osteoporotic women: relationship to vertebral and nonvertebral fractures from 2 US claims databases. Mayo Clin Proc, 81:1013–22. Copyright © 2006 Mayo Foundation for Medical Education and Research. All rights reserved. Abbreviation: MPR, medication possession ratio.

Figure 6

IOF Survey 2005: Patient drawbacks associated with oral bisphosphonates. Some patients stated more than one drawback. (Derived from IOF 2005).