Glucocorticoid-induced osteoporosis: a systematic review and cost-utility analysis

To determine whether strategies can be devised for the assessment and treatment of glucocorticoid-induced osteoporosis (GIO).

Electronic databases were searched up to October 2002.

A systematic review of interventions was undertaken of all randomised controlled trials in which fracture was measured as an outcome. Effectiveness was compared with effectiveness in postmenopausal osteoporosis. The risk of osteoporotic fractures at any given T-score for bone mineral density (BMD) was determined from published meta-analyses of the relationship between BMD and fracture risk. The risk of an osteoporotic fracture in the presence of a prior osteoporotic fracture was computed from a published meta-analysis of the relationship between the prior occurrence of fracture of each type and the risk of a future fracture of each type. The additional risk due to exposure to glucocorticoids was determined by meta-analysis of prospectively studied population-based cohorts. The consequences of fracture on mortality were assessed for each fracture type. Costs and utilities were determined for osteoporosis in the UK by updating systematic reviews of the literature. A model was prepared that comprised an individual patient-based approach that simulated whether or not events occurred in each subsequent year for each patient. Effectiveness was populated from a systematic review of interventions in GIO and postmenopausal osteoporosis. Treatments were given for 5 years using a 5-year offset time (in this context, offset time is the duration for which an effect on fracture persists after the treatment stops). The analytic framework was set at 10 years. Because of the many uncertainties, extensive sensitivity analysis was undertaken.

Evidence of anti-fracture efficacy was confined to a minority of agents used in the management of GIO. Only risedronate (a bisphosphonate) and calcidiol (vitamin D) were shown to have significant effects on vertebral fracture risk, but neither had significant effects on non-vertebral fracture risk. In further meta-analyses, the effects of bisphosphonates in GIO were compared with effects combining all available data for bisphosphonates in GIO and in postmenopausal osteoporosis. Since calcidiol is not licensed for use in the UK, cost-effectiveness analysis was confined to risedronate and to a pooled bisphosphonate effect. Analysis of cost-effectiveness of risedronate using the empirical data in GIO showed better cost-effectiveness with increasing age, but at no age did cost-effectiveness ratios fall below the threshold value of 30,000 pounds per quality-adjusted life-year gained. When account was taken of BMD, cost-effectiveness was confined to less than 10% of patients with very low T-scores for BMD. Assuming that bisphosphonate efficacy on fracture risk was comparable to that observed with bisphosphonates in postmenopausal osteoporosis, cost-effectiveness was shown in patients with a prior fracture. In patients with no prior fracture, cost-effectiveness was observed in individuals aged 75 years or more. In younger patients without a prior fracture, cost-effective scenarios were found contingent upon a T-score for BMD that was 2.0 SD or less.

Cost-effective scenarios for risedronate in the management of GIO were identified, but only at the extremes of age and T-score, such that less than 10% of patients aged 50 years or more would be eligible for treatment. Greater cost-effectiveness was observed assuming that the effects of bisphosphonate in GIO were similar to those observed in postmenopausal osteoporosis, an assumption tested by meta-analysis. An assessment algorithm is proposed based on age, the presence of a prior fragility fracture and BMD tests in individuals aged 50 years or more with no fracture. The conclusions derived are conservative, mainly because of the assumptions that were made in the absence of sufficient data. Thus, conclusions that treatment scenarios are cost-effective are reasonably secure. By contrast, scenarios shown not to be cost-effective are less secure. As information in these areas becomes available, the implications for cost-effectiveness of interventions should be reappraised. Health economic assessment based on probability of fracture is an important area for further research. Other areas for further research arise from gaps in empirical knowledge on utilities and side-effects that are amenable to primary research. Further secondary research is recommended to evaluate more closely the impact of all vertebral fractures (rather than clinically overt vertebral fractures) on cost-effectiveness and methods of monitoring treatment.