The relationship between osteoporotic fracture risk and a surrogate: apparent discrepancies between analyses based on individual patient data and summary statistics

There is debate within the osteoporosis research community about the relationship between the risk of osteoporotic fracture and the surrogate measures of fracture risk. Meta-regression analyses based on summary data have shown a linear relationship between fracture risk and surrogate measures, whereas analyses based oil individual patient data (IPD) have shown a nonlinear relationship. We investigated the association between changes in a surrogate measure of fracture incidence, in this case a bone turnover marker for resorption assessed in the three risedronate phase III clinical programmes, and incident osteoporosis-related fracture risk using regression models based on patient-level and trial-level information. The relationship between osteoporosis-related fracture risk and changes in bone resorption was different when analysed on the basis of IPD than when analysed on the basis of a meta-analytic approach (i.e., meta-regression) using summary data (e.g., treatment effect based oil treatment group estimates). This inconsistency in our findings was consistent with those in the published literature. Meta-regression based on summary statistics at the trial level is not expected to reflect causal relationships between a clinical outcome and surrogate measures. Analyses based oil IPD make possible a more comprehensive analysis since all relevant data on a patient level are available. Copyright (C) 2004 John Wiley Sons Ltd.