Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Québec, Canada.
Pharmacoepidemiol Drug Saf. 2022 Dec;31(12):1272-1279. doi: 10.1002/pds.5535. Epub 2022 Sep 9.
Glucosamine is a widely used supplement to treat joint pain and osteoarthritis despite inconclusive randomized trial results on its effectiveness. In contrast, observational studies associate glucosamine with significant reductions in mortality and cancer incidence. We evaluated the extent of bias, particularly selection bias, to explain these surprising beneficial effects.
We searched the literature to identify all observational studies reporting on the effect of glucosamine use on major outcomes.
We identified 11 observational studies, reporting a mean 16% reduction in all-cause mortality (hazard ratio [HR] 0.84, 95% CI: 0.81-0.87) with glucosamine use, as well as significant reductions in cancer incidence and other major diseases including cardiovascular, respiratory and diabetes. We show that these significant effects can result from selection bias due to collider stratification, as all studies used "prevalent" cohorts, where glucosamine use started before cohort entry, and where subjects agreed to join the cohorts. Our illustration of the bias using the UK Biobank publication involving a half-million subjects shows how a true rate ratio of mortality of 1.0 in the population can result in a biased rate ratio of 0.82 in the prevalent cohort.
The observational studies reporting significant reductions in mortality, cancer incidence and other outcomes with glucosamine were affected by selection bias from collider stratification. In the absence of properly conducted observational studies that circumvent this bias by considering "new users", the studies to date cannot support the prescription of this supplement as a preventive measure for mortality, cancer, and other chronic diseases.
尽管随机临床试验结果对其疗效尚无定论，但氨基葡萄糖仍是一种广泛应用于治疗关节疼痛和骨关节炎的补充剂。相比之下，观察性研究表明氨基葡萄糖与死亡率和癌症发病率的显著降低有关。我们评估了这些令人惊讶的有益效果背后的偏倚程度，特别是选择偏倚。
我们搜索了文献，以确定所有报告氨基葡萄糖使用对主要结局影响的观察性研究。
我们确定了 11 项观察性研究，报告氨基葡萄糖使用使全因死亡率降低 16%（风险比 [HR]0.84，95%CI：0.81-0.87），癌症发病率以及其他主要疾病（包括心血管疾病、呼吸系统疾病和糖尿病）也显著降低。我们表明，这些显著效果可能是由于基于共同原因分层的选择偏倚导致的，因为所有研究都使用了“现患”队列，其中氨基葡萄糖的使用在队列入组之前开始，且参与者同意加入队列。我们使用涉及 50 万受试者的英国生物库研究结果来说明这种偏倚，表明在人群中死亡率的真实比率为 1.0 时，可能会导致现患队列中存在有偏的死亡率比率为 0.82。
报告氨基葡萄糖可显著降低死亡率、癌症发病率和其他结局的观察性研究受到基于共同原因分层的选择偏倚的影响。在没有通过考虑“新使用者”来规避这种偏倚的适当的观察性研究的情况下，迄今为止的研究不能支持将这种补充剂作为预防死亡率、癌症和其他慢性疾病的措施。
