Paracetamol (acetaminophen) use, fracture and bone mineral density
Research highlights
► Paracetamol use is associated with a 56% increase in fracture risk. ► The mechanism of action remains to be established. ► Given the widespread use of paracetamol, this is of public health relevance.
Introduction
Paracetamol (acetaminophen), available over the counter in most countries, is among the most widely used medications. Its clinically significant effects are analgaesia and antipyresis but it has negligible antiinflammatory effects [1]. Although paracetamol has been used clinically since 1887, its mechanism of action was unclear until quite recently. It has been reported to exert its effects via cyclooxygenase and endocannabinoid pathways [2], [3], which may affect signalling in bone cells and hence influence bone metabolism. Given the high rates of paracetamol use in the community and the evidence linking its mechanism of action to bone metabolism, we investigated, in a population-based sample of women, the association between paracetamol use, fracture, and bone mineral density (BMD).
Section snippets
Participants
This case–control study set in the Barwon Statistical Division, South East Australia, utilised data from women aged ≥ 50 years enrolled in the Geelong Osteoporosis Study (GOS). Cases (n = 569) were women with incident fracture (excluding pathological fractures and those resulting from motor vehicle accidents), identified prospectively from the two radiological practices servicing the region using a keyword search for the 2-year period, February 1994–1996. The search identified 119 vertebral, 107
Subject characteristics
Characteristics of cases and controls and paracetamol users and non-users are shown in Table 1. There were no differences detected between the cases and controls in age, weight, height, smoking status (current or past), dietary calcium, alcohol intake, number of medical conditions and nitrate and thiazide use, although the cases differed in regards to physical activity, number of falls, previous fracture history and glucocorticoid, HT, ß-blockers, statin, calcium/vitamin D supplement, NSAID,
Discussion
Our case–control data demonstrate that paracetamol use is associated with a 56% increase in fracture risk independent of a number of potential confounders including age, weight, height, smoking, physical activity, alcohol consumption, calcium intake, medications, falls, number of medical conditions and previous fracture. Total body BMD attenuated this association; however, paracetamol use was not associated with BMD among the controls.
These findings are in support of the only other papers to
Conclusions
These data suggest that paracetamol may have an independent impact on fracture risk, although the exact mechanism of action is unknown. Given the widespread use of paracetamol, this is of clear public health relevance, and the result merits replication and validation in other clinical and pre-clinical studies.
Contributions
Lana Williams took part in the conception and design of the study, prepared the data, undertook the statistical analysis, interpreted the findings, wrote the first draft, and contributed to subsequent drafts. Julie Pasco took part in the conception and design of the study, contributed to the analysis, interpreted the findings and critically revised the manuscript. Margaret Henry contributed to the statistical analysis and interpretation of the data and critically revised the manuscript. Kerrie
Funding
The study was funded by the National Health and Medical Research Council of Australia (#251638).
Role of the funding source
The sponsors of the study had no role in study design, data collection, data analysis, data interpretation, writing of the report, and the decision to submit for publication. The corresponding author had full access to all data in the study and had final responsibility for the decision to submit for publication.
Conflicts of interest
Lana Williams and Julie Pasco have received research support from an unrestricted educational grant from Eli Lilly.
Margaret Henry, Kerrie Sanders, Geoffrey Nicholson and Mark Kotowicz have no conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript.
Michael Berk has received Grant/Research Support from the Stanley Medical Research Foundation, MBF, NHMRC, Beyond Blue, Geelong Medical
Acknowledgments
We would like to thank Melissa Borracci for assisting in the preparation of the data.
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