Drug Insight: choosing a drug treatment strategy for women with osteoporosis-an evidence--based clinical perspective

Abstract

Many randomized controlled trials (RCTs) have investigated drug treatment for women at high risk of fracture, with a reduction in fracture risk as their end point. There has also been progress in identifying women at the highest risk of fractures. The most important clinical determinant contributing to the clinical decision of initiating and choosing drug therapy for fracture prevention is a woman's fracture risk, which, in RCTs, was determined by menopausal state, age, bone mineral density, fracture history, fall risks and glucocorticoid use. Women with secondary osteoporosis were excluded, except in studies of glucocorticoid use. A second determinant of drug therapy is the evidence for fracture prevention in terms of spectrum (vertebral, nonvertebral and/or hip fractures), size and speed of effect. In the absence of head-to-head RCTs with fracture risk as the end point, however, the efficacy of antifracture drugs cannot be directly compared. Other determinants include the potential extraskeletal benefits and safety concerns of the drug, patient preferences and reimbursement issues.

Figure 1

Pyramidal approach to prevention of fractures in patients at high risk of fracture. All women with postmenopausal osteoporosis and glucocorticoid-induced osteoporosis need lifestyle advice (bottom level), which relates to diet, exercise, fall prevention, cessation of smoking and moderation of alcohol intake. The next step is the differential diagnosis of contributors to secondary osteoporosis, such as diseases and drugs (middle level), followed by treatment with antiresorptive or anabolic drugs in those at high risk of fractures (top level). Modified from US Department of Health and Human Services (2004) Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD: US Department of Health and Human Services, made available by the National Library of Medicine.

Figure 2

Reduction in nonvertebral fractures versus placebo as reported in analyses at the end of primary antifracture studies. The reduction in fracture risk is expressed as a relative risk (RR) with 95% confidence intervals. The risk reduction varied between studies, but the size of effect cannot be compared in the absence of head-to-head trials between drugs. Abbreviations: BMD, bone mineral density; FIT, Fracture Intervention Trial with alendronate in patients with an existing vertebral fracture (FIT1) and in patients with low BMD but without vertebral fracture (FIT2); HORIZON, Health Outcomes and Reduced Incidence with Zoledronic acid ONce yearly pivotal fracture trial; HORIZON RFT, HORIZON recurrent fracture trial; MORE, Multiple Outcomes of Raloxifene Evaluation study; SOTI, Spinal Osteoporosis Therapeutic Intervention; teriparatide, study using recombinant human parathyroid hormone 1–34; TOP, Treatment of Osteoporosis with Parathyroid hormone study (with recombinant human parathyroid hormone 1–84); TROPOS, TReatment Of Peripheral OSteoporosis studies with strontium ranelate; VERT MN and VERT NA, Vertebral Efficacy with Risedronate Therapy studies (Multinational and North America). The following studies were not included: BONE (oral iBandronate Osteoporosis vertebral fracture trial in North America and Europe), as no RRs were indicated for nonvertebral fractures (no effect in total group); and PROOF (the Prevent Recurrence Of Osteoporotic Fractures study), as the RR for nonvertebral fractures was only significant at the low dose (100 IU/day; RR = 0.64 (95% CI 0.41–0.99) but not at 200 and 400 IU/day.