Antifracture Efficacy of Currently Available Therapies for Postmenopausal Osteoporosis

Osteoporosis is a systemic bone disease characterized by low bone mass and bone mineral density, and deterioration of the underlying structure of bone tissue. These changes lead to an increase in bone fragility and an increased risk for fracture, which are the clinical consequences of osteoporosis. The classical triad for consideration in osteoporosis is morbidity, mortality and cost. Vertebral fracture is an important source of morbidity in terms of pain and spinal deformity. On the other hand, hip fracture is associated with the worst outcomes and is widely regarded as a life-threatening event in the elderly; it is the source of the bulk of the cost of the disease in contemporary healthcare. The prevention of osteoporosis-associated fracture should include fall prevention, calcium supplementation and lifestyle advice, as well as pharmacological therapy using agents with proven antifracture efficacy. The most commonly used osteoporosis treatments in Europe are the bisphosphonates alendronate, risedronate, ibandronate and zoledronic acid; the selective estrogen receptor modulator (SERM) raloxifene; teriparatide; and strontium ranelate. Recent additions include the biological therapy denosumab and the SEAM bazedoxifene. In this review, we explore the antifracture efficacy of these agents with the aim of simplifying treatment decisions. These treatments can be broadly divided according to their mode of action. The antiresorptive agents include the bisphosphonates, the SERMs and denosumab, while the bone-forming agents include parathyroid hormone and teriparatide. Strontium ranelate appears to combine both antiresorptive and anabolic activities. We collated data on vertebral and hip fracture efficacy from the pivotal 3-year phase III trials, all of which had a randomized, double-blind, placebo-controlled design. The relative reductions in risk in the osteoporosis trials range from 30% to 70% for vertebral fracture and 30% to 51% for hip fracture. This translates into 3-year number needed to treat values of between 9 and 21 for vertebral fracture and from 48 upwards for hip fracture. International guidelines agree that agents that have been shown to decrease vertebral, nonvertebral and hip fractures should be used preferentially over agents that only demonstrate vertebral antifracture efficacy. This is the case for alendronate, risedronate, zoledronic acid, denosumab and strontium ranelate. Finally, therapeutic decisions should be based on a balance between benefits and risks of treatment, which must be carefully considered in each particular case both by the physician and the patient. Indeed, no single agent is appropriate for all patients and, therefore, treatment decisions should be made on an individual basis, taking into account all measures of treatment effect and risk before making informed judgments about the best individual treatment option.