These data are not supportive of a hypothesis that PPIs modify the quality or quantity of bone. The FDA review considered that the biological mechanisms for an increased risk of fractures with PPIs are not known. Despite this, the FDA review concluded that the available data suggested a possible increased risk of fractures with PPI use. In our view, evidence for drug effects should not be used on an assessment
of deviations of summary RRs from unity but rather on an assessment on whether specific hypotheses of biological mechanisms of drug effects are supported by evidence. Given the weak and conflicting evidences, not only from epidemiological studies, but also for a pharmacological effect of PPIs on bone mineral density in humans, we feel that the label change of PPIs is premature. Conflicts of interest The Department of Pharmacoepidemiology and LY3023414 Clinical Histone Acetyltransferase inhibitor Pharmacology, Utrecht Institute for Pharmaceutical Sciences, has received unrestricted research funding from the Netherlands Organisation for Health Research and Development (ZonMW), the private–public funded Top Institute Pharma (www.tipharma.nl, includes co-funding from universities, Thiazovivin cost government and industry), the EU Innovative Medicines Initiative, the Dutch Medicines Evaluation Board, the Dutch Ministry of Health and GlaxoSmithKline. GPRD is owned
by the UK Department of Health and operates within the Medicines and Healthcare products Regulatory Agency (MHRA). GPRD is funded by the MHRA, Medical Research Council, various universities, contract research organisations and pharmaceutical companies. HGML is Chair of the Dutch Medicines Evaluation Board and co-opted member of the Committee for Medicinal
Products for Human Use of the European Medicines Agency in London, United Kingdom. None of the views in this letter represent any of the official positions of any of these regulatory bodies. Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. References 1. de Vries F, de Vries C, Cooper C, Leufkens B, van Adenosine triphosphate Staa T-P (2006) Reanalysis of two studies with contrasting results on the association between statin use and fracture risk: the General Practice Research Database. Int J Epidemiol 35:1301–1308PubMedCrossRef 2. US Food and Drug Administration FDA (2010) Possible fracture risk with high dose, long-term use of proton pump inhibitors. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm213206.htm. Accessed 28 May 2010 3. Yang YX, Lewis JD, Epstein S, Metz DC (2006) Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA 296:2947–2953PubMedCrossRef 4.