A systematic review and economic evaluation of alendronate, etidronate, risedronate, raloxifene and teriparatide for the prevention and treatment of postmenopausal osteoporosis

Objectives: To establish the clinical effectiveness and cost-effectiveness of selective oestrogen receptor modulators, bisphosphonates and parathyroid hormone (subject to licensing) for the prevention and treatment of osteoporosis and the prevention of osteoporotic fractures in postmenopausal women. Data sources: Electronic databases. Review methods: Studies that met the review’s entry criteria were eligible for inclusion in the meta-analyses provided that they reported fracture incidence in terms of the number of patients suffering fractures. Meta-analysis was carried out using the random-effects model. A model was constructed to estimate the cost-effectiveness of osteoporosis interventions. The model calculated the number of fractures that occurred and provided the costs associated with osteoporotic fractures, and the quality-adjusted life-years (QALYs). In addition, the conditions of breast cancer and coronary heart disease (CHD) were modelled, as some interventions have been shown to affect the risk of these conditions. Results: Ninety randomised controlled trials (RCTs) met the inclusion criteria. They related to the five interventions (alendronate, etidronate, risedronate, raloxifene and teriparatide) and to five comparators (calcium, calcium plus vitamin D, calcitriol, hormone replacement therapy and exercise), as well as placebo or no treatment. All five interventions have been shown to reduce the risk of vertebral fracture in women with severe osteoporosis with adequate calcium intakes. However, none of these drugs has been demonstrated, by direct comparison, to be significantly more effective than either each other or the other active interventions reviewed in this report. The intervention costs of treating all osteoporotic women, for a period of 5 years, were in the region of £900–1500 million for alendronate, etidronate, risedronate and raloxifene. The cost per QALY ratios fell dramatically with age. Assuming the risks of a woman with severe osteoporosis at the threshold of osteoporosis, no treatment had a cost per QALY below £35,000 at 50 years of age. At 60 years of age, the cost per QALY of raloxifene was £26,000 assuming no impact on hip fractures, and £31,000 assuming an adverse effect. However, these results are driven by the effect on breast cancer and the assumptions made regarding this disease state. No other intervention had a cost per QALY below £35,000. When analyses were conducted assuming that the fracture risk is doubled at each site, alendronate and risedronate had cost per QALY ratios below £30,000 at all ages. For women at the threshold of osteoporosis, without a prior fracture and aged 70 years, the cost per QALY of the three bisphosphonates ranged from £34,000 to £41,000. Raloxifene had a cost per QALY of £23,000, assuming no effect on hip fracture, given assumptions regarding breast cancer. At 80 years of age, the cost per QALY of alendronate and risedronate was below £20,000. This was true for etidronate when incorporating observational data, but the value rose to £69,000 when only RCT data were used. No other intervention had a cost per QALY below £35,000. It was assumed that doubling the risk of fracture for women without a prior fracture would give results similar to patients at the threshold of osteoporosis with a prior fracture. Conclusions: Of the five interventions, only raloxifene appeared to reduce the risk of vertebral fracture in postmenopausal women unselected for low bone mineral density (BMD). However, as the full data have not been made public, there is some uncertainty regarding this result. None of the five interventions has been shown to reduce the risk of non-vertebral fracture in women unselected for low BMD. All of the proposed interventions provided gains in QALYs compared with no treatment in women with sufficient calcium and vitamin D intakes. The size of the QALY gain for each intervention was strongly related to the age of the patient. The estimated costs varied widely for the interventions. These net costs were markedly different by age, with some interventions becoming cost-saving at higher age ranges in patients with a prior fracture. Areas for future research include: the evidence base for the efficacy of fracture prevention in the very elderly, reanalysis of raloxifene using a dedicated breast cancer and CHD model, and more trials considering the cost-effectiveness of teriparatide