Determining causation—A case study: Adrenocorticosteroids and osteoporosis
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It is generally accepted that exogenous adrenocorticosteroids cause clinically important osteoporosis. We have reviewed the evidence regarding causation in two stages: an examination of the strength of the methods used, and an application of five "diagnostic tests" for causation. The methods that have been used to investigate the association are weak: there have been no randomized clinical trials or prospective cohort studies. The measures of bone density used to quantify osteoporosis do not bear a close relation to clinically important outcomes. Nine analytic surveys and two before-after studies have examined the relation between steroids and osteoporosis. Although some have shown a strong relation, this finding has not been consistent. Evidence regarding temporality , dose-response gradient, and underlying mechanisms are conflicting. The available evidence does not substantiate a causal role of exogenous adrenocorticosteroids in producing clinically important osteoporosis, and does not support withholding steroid therapy on the basis of fears of osteoporosis induced pain and disability.
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