Introduction - What Do We Know About Antifracture Efficacy?
There are many advances in the treatment of osteoporosis, but many challenges remain. Most drugs studied -- the bisphosphonates (alendronate, risedronate, ibandronate, etidronate), raloxifene, the anabolic agent PTH 1-34 and, more recently, strontium ranelate (a drug that may reduce bone resorption while allowing bone formation to continue) -- reduce vertebral fracture risk. However, risk reduction is only 30%-50%; thus, greater potency in antivertebral fracture efficacy is desirable.
Only 2 drugs, alendronate and risedronate, have been shown in a primary analysis (without posthoc subgroup analysis) to reduce hip fractures, but only the latter was preplanned for this endpoint. Strontium ranelate was found to reduce hip fractures in a posthoc analysis. Only 3 drugs have been shown to reduce nonvertebral fractures in a primary analysis: risedronate, strontium ranelate and parathyroid hormone 1-34 (teriparatide) but only the strontium ranelate trial was preplanned with this as the primary endpoint. For these studies, again, hip fracture risk reduction was about 40%-50% and nonvertebral fracture risk reduction was around 20%. Compelling evidence for antifracture efficacy of etidronate, calcitonin, calcium, vitamin D, and its analogs (eg, calcitriol) is lacking.
Although the benefits of reduction in vertebral fractures appear to persist during follow-up, high patient attrition rates in all trials make this inference less certain.
Furthermore, there have been no trials in human subjects using antifracture efficacy as an endpoint for comparison between antiresorptive agents, treatment with 1 antiresorptive agent vs 2 antiresorptive agents, treatment with antiresorptive agents vs anabolic agents such as parathyroid hormone (PTH), or treatment with PTH vs PTH plus an antiresorptive agent given before, during, or after PTH. Thus, there is no scientific basis for choosing one drug over another or combined therapy over single-agent therapy. The decision to use one drug in favor of another is based solely on the quality of the design and execution of clinical trials comparing single agents with placebo.
Perhaps the hottest data presented at this meeting were the 3-year efficacy and safety results of the ongoing Horizon Pivotal Fracture Trial (Horizon-PFT). (See Table .[2,3]) The Horizon-PFT, a multinational, randomized, double-blind, placebo-controlled trial, evaluated once-yearly ZA for reduction of fracture risk in postmenopausal women. ZA (5 mg intravenous [IV] dose infused over 15 minutes) administered annually was compared with placebo during 3 years in 7736 postmenopausal women with osteoporosis at the femoral neck or osteopenia with a prevalent fracture.
Over the 3-year study, there was a 70% reduction in the incidence of vertebral fracture (P < .0001; relative risk reduction (RRR) vs placebo). The study also showed a 25% reduction in nonvertebral fractures (P = .0002 RRR vs placebo) as well as a 40% reduction in the incidence of hip fracture (P = .0032 RRR vs placebo).
The study subject retention rate at 2-year follow-up was 88%. A flulike illness within the first 3 days of the infusion and an increased incidence of cardiac arrhythmias were the most frequently reported treatment-emergent adverse events, and were more common in the ZA-treated group vs placebo. Whether these events were causally related to treatment, however, is not known.
Overall, the data from the Horizon-PFT study strongly support consideration of ZA as a first-line treatment for fracture prevention.
Medscape Ob/Gyn © 2007 Medscape
Cite this: Highlights of the 28th Annual Meeting of the American Society for Bone and Mineral Research (ASBMR) - Medscape - Jan 10, 2007.