Objectives

The review aims to estimate the clinical effectiveness and cost-effectiveness of strontium ranelate for the prevention of osteoporotic fractures in postmenopausal women, at different levels of absolute fracture risk. This considers secondary prevention in women who have sustained a previous fracture and primary prevention in those women without a previous fracture, as women with osteoporosis are asymptomatic until a fracture is sustained.

Epidemiology and background

Osteoporosis is a common disease in the elderly, with an estimated 1.1 million female sufferers in England and Wales. It is defined as possessing a T-score of -2.5 standard deviations or lower. The main consequence of osteoporosis is an increased incidence of fractures, which increase as a woman ages. These result not only in morbidity for the patient (with a risk of mortality following fractures at some sites), but also in the consumption of scarce NHS resources. A recent estimate of the projected cost in the UK by 2010 of osteoporotic fractures in females put this figure at £2.1 billion.

Methods

A systematic review was carried out to determine clinical effectiveness. Major electronic bibliographic databases were searched in September 2004 and updated in March 2005. In addition, the reference lists of relevant articles and sponsor submissions were handsearched. Data from selected studies were assessed and included in the meta-analyses, if appropriate.

The model used to calculate cost-effectiveness ratios was an updated version of Sheffield Health Economic Model for Osteoporosis. The model calculated the number of fractures that occur and provided as output data the costs associated with osteoporotic fractures, and the quality-adjusted life-years (QALYs) accrued by a cohort of 100 osteoporotic women, with each fracture being detrimental to health and incurring a cost. When the costs of the intervention were included, the incremental cost compared with no treatment was calculated and divided by the gain in QALYs to calculate cost-effectiveness measures. Treatment with strontium ranelate was calculated against a no-treatment option to evaluate whether it could be given cost-effectively. An incremental analysis against alendronate was also conducted to estimate the cost-effectiveness of strontium ranelate relative to a current standard treatment. The cost-effectiveness of strategies for identifying and treating women without a prior fracture used the risk of fracture as an input to the cost-effectiveness model.

Results

Conclusions

Strontium ranelate was shown to be clinically effective in the prevention of osteoporotic fractures. Scenarios have been found where strontium ranelate can be used cost-effectively; however, given the probabilistic sensitivity analyses conducted, this intervention appears to be less cost-effective than the bisphosphonate alendronate.

Work has been presented on the cost-effectiveness of identifying asymptomatic women who could be treated cost-effectively. This work is part of an ongoing  project undertaken with the NICEGDG and will be further reviewed and be used as part of the guidelines issued for the management of women at high risk of osteoporotic fracture.

Recommendations for research

The evidence base for the efficacy of fracture prevention for strontium ranelate needs to be strengthened, particularly for hip fractures, where there is currently a non-significant reduction.

If it were believed that the efficacy of strontium ranelate is dependent on either age or absolute risk, this would need to be proven.

The evidence base on the T-score by age of the general female population needs to be strengthened, particularly in women over the age of 80 years. The prevalence of risk factors associated with fracture rates, over and above that provided by BMD, also needs to be significantly strengthened to ensure that the estimated number of women that could be cost-effectively treated is accurate.

Until head-to-head comparisons of strontium ranelate and bisphosphonates are undertaken, decision-makers will have to make choices based on indirect evidence; for example, comparing the results for bisphosphonates plus calcium and vitamin D versus calcium and vitamin D, with those for strontium ranelate plus calcium and vitamin D versus calcium and vitamin D. Given the large number of patients that would be needed to show statistical difference in efficacy between patients these trials are unlikely to be conducted; however, high-quality observational databases may provide further insight into relative efficacies.

Publication

• Stevenson M, Davis S, Lloyd-Jones M, Beverley C. The clinical effectiveness and cost-effectiveness of strontium ranelate for the prevention of osteoporotic fragility fractures in postmenopausal women. Health Technol Assess 2007;11(4). [PubMed: 17280622]

NIHR Health Technology Assessment Programme

The Health Technology Assessment (HTA) Programme, now part of the National Institute for Health Research (NIHR), was set up in 1993. It produces high-quality research information on the costs, effectiveness and broader impact of health technologies for those who use, manage and provide care in the NHS. 'Health technologies' are broadly defined to include all interventions used to promote health, prevent and treat disease, and improve rehabilitation and long-term care, rather than settings of care.

The research findings from the HTA Programme directly influence decision-making bodies such as the National Institute for Health and Clinical Excellence (NICE) and the National Screening Committee (NSC). HTA findings also help to improve the quality of clinical practice in the NHS indirectly in that they form a key component of the 'National Knowledge Service'.

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Reviews in Health Technology Assessment are termed 'systematic' when the account of the search, appraisal and synthesis methods (to minimise biases and random errors) would, in theory, permit the replication of the review by others.

The research reported in this monograph was commissioned and funded by the HTA Programme on behalf of NICE as project number 04/28/01. The protocol was agreed in November 2004. The assessment report began editorial review in November 2005 and was accepted for publication in June 2006. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors' report and would like to thank the referees for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.

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