Effects of paracetamol, non-steroidal anti-inflammatory drugs, acetylsalicylic acid, and opioids on bone mineral density and risk of fracture: results of the Danish Osteoporosis Prevention Study (DOPS)
- 969 Downloads
Pain medication has been associated with fractures. We found higher weight in paracetamol and non-steroidal anti-inflammatory drugs (NSAID) users and lower vitamin D levels in opioid and acetylsalicylic acid users. None of the pain medications influenced bone mineral density or loss. NSAID were associated with an increased fracture risk.
To study the effects of use of paracetamol, non-steroidal anti-inflammatory drugs (NSAID), acetylsalicylic acid (ASA), and opioids on bone mineral density (BMD) and risk of fractures.
Two-thousand sixteen perimenopausal women followed for 10 years as part of a partly randomised comprehensive cohort study on hormone therapy (HT). BMD was measured at baseline and after 10 years by DXA (Hologic).
Paracetamol users were heavier (70.4 ± 13.4 vs. 67.7 ± 11.9 kg, 2p < 0.01) than non-users. NSAID users were heavier (71.6 ± 15.6 vs. 67.8 ± 11.9 kg, 2p = 0.04) than non-users. ASA users had lower 25-hydroxy-vitamin D (25OHD) levels (21.9 ± 9.3 vs. 25.3 ± 12.4 ng/ml, 2p < 0.01) than non-users. Opioid users had lower 25OHD (21.4 ± 8.4 vs. 25.2 ± 12.3 ng/ml) and lower intake of vitamin D (2.2 ± 1.1 vs. 3.1 ± 3.0 μg/day, 2p < 0.01) than non-users. Despite these differences, no baseline differences were present in spine, hip, forearm or whole body BMD. Over 10 years, no differences were present in BMD alterations except a small trend towards a higher BMD gain in the spine in users of paracetamol, NSAID, ASA, and opioids compared to non-exposed. After adjustment, NSAID exposed sustained more fractures (HR = 1.44, 95% CI 1.07–1.93) than non-users. For users of paracetamol and opioids, a non-significant trend towards more fractures was present after adjustment. For ASA users, no excess risk of fractures was present.
Significant differences exist between subjects exposed to pain medications and non-users. Despite an absence of an effect over time on BMD, users of NSAID experienced more fractures than expected. The reasons for this have to be explored in further studies.
KeywordsAcetylsalicylic acid Bone mineral Fracture Non-steroidal anti-inflammatory drugs Opioid Paracetamol
The study was made possible through financial support from the A.P. Møller Foundation (Fonden til Lægevidenskabens Fremme), and by Karen Elise Jensen’s Foundation, the Danish Medical Research Council. Novo Nordisk Denmark, Novartis Denmark, and Leo Denmark provided the study medication free of charge. None of these had any influence on study design and conduct.
Conflicts of interest
- 16.Barden J, Edwards J, Moore R, McQuay H (2004) Single dose oral diclofenac for postoperative pain. Cochrane Database Syst Rev (2):CD004768.Google Scholar
- 18.Hegeman J, Nienhuis B, van den Bemt B, Weerdesteyn V, van Limbeek J, Duysens J (2010) The effect of a non-steroidal anti-inflammatory drug on two important predictors for accidental falls: postural balance and manual reaction time. A randomized, controlled pilot study. Hum Mov Sci 30:384–395CrossRefPubMedGoogle Scholar
- 22.Mosekilde L, Beck-Nielsen H, Sørensen O, Nielsen S, Charles P, Vestergaard P, Hermann A, Gram J, Hansen T, Abrahamsen B, Ebbesen E, Stilgren L, Jensen L, Brot C, Hansen B, Tofteng C, Eiken P, Kolthoff N (2000) Hormonal replacement therapy reduces forearm fracture incidence in recent postmenopausal women—results of the Danish Osteoporosis Prevention Study. Maturitas 36:181–193CrossRefPubMedGoogle Scholar
- 23.Brixen K, Nielsen HK, Eriksen EF, Charles P, Mosekilde L (1989) Efficacy of wheat germ lectin-precipitated alkaline phosphatase in serum as an estimator of bone mineralization rate: comparison to serum total alkaline phosphatase and serum bone Gla-protein. Calcif Tissue Int 44:93–98CrossRefPubMedGoogle Scholar
- 26.De Laet C, Kanis J, Oden A, Johanson H, Johnell O, Delmas P, Eisman J, Kroger H, Fujiwara S, Garnero P, McCloskey E, Mellstrom D, Melton LJ III, Meunier P, Pols H, Reeve J, Silman A, Tenenhouse A (2005) Body mass index as a predictor of fracture risk: a meta-analysis. Osteoporosis Int 16:1330–1338CrossRefGoogle Scholar