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Erschienen in: Osteoporosis International 4/2012

01.04.2012 | Original Article

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)

verfasst von: P. Vestergaard, P. Hermann, J.-E. B. Jensen, P. Eiken, L. Mosekilde

Erschienen in: Osteoporosis International | Ausgabe 4/2012

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Abstract

Summary

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.

Introduction

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.

Methods

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).

Results

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.

Conclusion

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.
Literatur
1.
Zurück zum Zitat Kinjo M, Setoguchi S, Schneeweiss S, Solomon D (2005) Bone mineral density in subjects using central nervous system-active medications. Am J Med 118:1414.e7–1414.e12CrossRef Kinjo M, Setoguchi S, Schneeweiss S, Solomon D (2005) Bone mineral density in subjects using central nervous system-active medications. Am J Med 118:1414.e7–1414.e12CrossRef
2.
Zurück zum Zitat Daniell H (2002) Hypogonadism in men consuming sustained-action oral opioids. J Pain 3:377–384CrossRefPubMed Daniell H (2002) Hypogonadism in men consuming sustained-action oral opioids. J Pain 3:377–384CrossRefPubMed
3.
Zurück zum Zitat Hallinan R, Byrne A, Agho K, McMahon CG, Tynan P, Attia J (2009) Hypogonadism in men receiving methadone and buprenorphine maintenance treatment. Int J Androl 32:131–139CrossRefPubMed Hallinan R, Byrne A, Agho K, McMahon CG, Tynan P, Attia J (2009) Hypogonadism in men receiving methadone and buprenorphine maintenance treatment. Int J Androl 32:131–139CrossRefPubMed
4.
Zurück zum Zitat Vestergaard P, Rejnmark L, Mosekilde L (2006) Fracture risk associated with use of morphine and opiates. J Intern Med 260:76–87CrossRefPubMed Vestergaard P, Rejnmark L, Mosekilde L (2006) Fracture risk associated with use of morphine and opiates. J Intern Med 260:76–87CrossRefPubMed
5.
Zurück zum Zitat Bauer D, Orwoll E, Fox K, Vogt T, Lane N, Hochberg M, Stone K, Nevitt M (1996) Aspirin and NSAID use in older women: effect on bone mineral density and fracture risk Study of Osteoporotic Fractures Research Group. J Bone Miner Res 11:29–35CrossRefPubMed Bauer D, Orwoll E, Fox K, Vogt T, Lane N, Hochberg M, Stone K, Nevitt M (1996) Aspirin and NSAID use in older women: effect on bone mineral density and fracture risk Study of Osteoporotic Fractures Research Group. J Bone Miner Res 11:29–35CrossRefPubMed
6.
Zurück zum Zitat Carbone L, Tylavsky F, Cauley J, Harris T, Lang T, Bauer D, Barrow K, Kritchevsky S (2003) Association between bone mineral density and the use of nonsteroidal anti-inflammatory drugs and aspirin: impact of cyclooxygenase selectivity. J Bone Miner Res 18:1795–1802CrossRefPubMed Carbone L, Tylavsky F, Cauley J, Harris T, Lang T, Bauer D, Barrow K, Kritchevsky S (2003) Association between bone mineral density and the use of nonsteroidal anti-inflammatory drugs and aspirin: impact of cyclooxygenase selectivity. J Bone Miner Res 18:1795–1802CrossRefPubMed
7.
Zurück zum Zitat Raisz L (1995) Physiologic and pathologic roles of prostaglandins and other eicosanoids in bone metabolism. J Nutr 125:2024S–2027SPubMed Raisz L (1995) Physiologic and pathologic roles of prostaglandins and other eicosanoids in bone metabolism. J Nutr 125:2024S–2027SPubMed
8.
Zurück zum Zitat Raisz L (1999) Prostaglandins and bone: physiology and pathophysiology. Osteoarthritis Cartilage 7:419–421CrossRefPubMed Raisz L (1999) Prostaglandins and bone: physiology and pathophysiology. Osteoarthritis Cartilage 7:419–421CrossRefPubMed
9.
Zurück zum Zitat Raisz L (2001) Potential impact of selective cyclooxygenase-2 inhibitors on bone metabolism in health and disease. Am J Med 110(Suppl 3A):43S–45SCrossRefPubMed Raisz L (2001) Potential impact of selective cyclooxygenase-2 inhibitors on bone metabolism in health and disease. Am J Med 110(Suppl 3A):43S–45SCrossRefPubMed
10.
Zurück zum Zitat van Staa T, Leufkens H, Cooper C (2000) Use of nonsteroidal anti-inflammatory drugs and risk of fractures. Bone 27:563–568CrossRefPubMed van Staa T, Leufkens H, Cooper C (2000) Use of nonsteroidal anti-inflammatory drugs and risk of fractures. Bone 27:563–568CrossRefPubMed
11.
Zurück zum Zitat Vestergaard P, Rejnmark L, Mosekilde L (2006) Fracture risk associated with use of nonsteroidal anti-inflammatory drugs, acetylsalicylic acid, and acetaminophen and the effects of rheumatoid arthritis and osteoarthritis. Calcif Tissue Int 79:84–94CrossRefPubMed Vestergaard P, Rejnmark L, Mosekilde L (2006) Fracture risk associated with use of nonsteroidal anti-inflammatory drugs, acetylsalicylic acid, and acetaminophen and the effects of rheumatoid arthritis and osteoarthritis. Calcif Tissue Int 79:84–94CrossRefPubMed
12.
Zurück zum Zitat Aisen P, Schafer K, Grundman M, Pfeiffer E, Sano M, Davis K, Farlow M, Jin S, Thomas R, Thal L (2003) Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. JAMA 289:2819–2826CrossRefPubMed Aisen P, Schafer K, Grundman M, Pfeiffer E, Sano M, Davis K, Farlow M, Jin S, Thomas R, Thal L (2003) Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. JAMA 289:2819–2826CrossRefPubMed
13.
Zurück zum Zitat Bannwarth B, Treves R, Euller-Ziegler L, Rolland D, Ravaud P, Dougados M (2003) Adverse events associated with rofecoxib therapy: results of a large study in community-derived osteoarthritic patients. Drug Saf 26:49–54CrossRefPubMed Bannwarth B, Treves R, Euller-Ziegler L, Rolland D, Ravaud P, Dougados M (2003) Adverse events associated with rofecoxib therapy: results of a large study in community-derived osteoarthritic patients. Drug Saf 26:49–54CrossRefPubMed
14.
Zurück zum Zitat Silberstein S, Tepper S, Brandes J, Diamond M, Goldstein J, Winner P, Venkatraman S, Vrijens F, Malbecq W, Lines C, Visser W, Reines S, Yuen E (2004) Randomized, placebo-controlled trial of rofecoxib in the acute treatment of migraine. Neurology 62:1552–1557PubMed Silberstein S, Tepper S, Brandes J, Diamond M, Goldstein J, Winner P, Venkatraman S, Vrijens F, Malbecq W, Lines C, Visser W, Reines S, Yuen E (2004) Randomized, placebo-controlled trial of rofecoxib in the acute treatment of migraine. Neurology 62:1552–1557PubMed
15.
Zurück zum Zitat Walker PC, Alrawi A, Mitchell JF, Regal RE, Khanderia U (2005) Medication use as a risk factor for falls among hospitalized elderly patients. Am J Health Syst Pharm 62:2495–2499CrossRefPubMed Walker PC, Alrawi A, Mitchell JF, Regal RE, Khanderia U (2005) Medication use as a risk factor for falls among hospitalized elderly patients. Am J Health Syst Pharm 62:2495–2499CrossRefPubMed
16.
Zurück zum Zitat Barden J, Edwards J, Moore R, McQuay H (2004) Single dose oral diclofenac for postoperative pain. Cochrane Database Syst Rev (2):CD004768. Barden J, Edwards J, Moore R, McQuay H (2004) Single dose oral diclofenac for postoperative pain. Cochrane Database Syst Rev (2):CD004768.
17.
Zurück zum Zitat Hegeman J, van den Bemt BJF, Duysens J, van Limbeek J (2009) NSAIDs and the risk of accidental falls in the elderly: a systematic review. Drug Saf 32:489–498CrossRefPubMed Hegeman J, van den Bemt BJF, Duysens J, van Limbeek J (2009) NSAIDs and the risk of accidental falls in the elderly: a systematic review. Drug Saf 32:489–498CrossRefPubMed
18.
Zurück zum Zitat 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 30:384–395CrossRefPubMed 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 30:384–395CrossRefPubMed
19.
Zurück zum Zitat García-Martínez O, Díaz-Rodríguez L, Rodríguez-Pérez L, De Luna-Bertos E, Botella CR, Ruiz CC (2010) Effect of acetaminophen, ibuprofen and methylprednisolone on different parameters of human osteoblast-like cells. Arch Oral Biol 56:317–323CrossRefPubMed García-Martínez O, Díaz-Rodríguez L, Rodríguez-Pérez L, De Luna-Bertos E, Botella CR, Ruiz CC (2010) Effect of acetaminophen, ibuprofen and methylprednisolone on different parameters of human osteoblast-like cells. Arch Oral Biol 56:317–323CrossRefPubMed
20.
Zurück zum Zitat Díaz-Rodríguez L, García-Martínez O, Arroyo-Morales M, Rubio-Ruiz B, Ruiz C (2010) Effect of acetaminophen (paracetamol) on human osteosarcoma cell line MG63. Acta Pharmacol Sin 31:1495–1499CrossRefPubMed Díaz-Rodríguez L, García-Martínez O, Arroyo-Morales M, Rubio-Ruiz B, Ruiz C (2010) Effect of acetaminophen (paracetamol) on human osteosarcoma cell line MG63. Acta Pharmacol Sin 31:1495–1499CrossRefPubMed
21.
Zurück zum Zitat Mosekilde L, Hermann A, Beck-Nielsen H, Charles P, Nielsen S, Sørensen O (1999) The Danish Osteoporosis Prevention Study (DOPS): project design and inclusion of 2016 normal perimenopausal women. Maturitas 31:207–219CrossRefPubMed Mosekilde L, Hermann A, Beck-Nielsen H, Charles P, Nielsen S, Sørensen O (1999) The Danish Osteoporosis Prevention Study (DOPS): project design and inclusion of 2016 normal perimenopausal women. Maturitas 31:207–219CrossRefPubMed
22.
Zurück zum Zitat 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 36:181–193CrossRefPubMed 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 36:181–193CrossRefPubMed
23.
Zurück zum Zitat 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 44:93–98CrossRefPubMed 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 44:93–98CrossRefPubMed
24.
Zurück zum Zitat Lund B, Sorensen O (1979) Measurement of 25-hydroxyvitamin D in serum and its relation to sunshine, age and vitamin D intake in the Danish population. Scand J Clin Lab Invest 39:23–30CrossRefPubMed Lund B, Sorensen O (1979) Measurement of 25-hydroxyvitamin D in serum and its relation to sunshine, age and vitamin D intake in the Danish population. Scand J Clin Lab Invest 39:23–30CrossRefPubMed
25.
Zurück zum Zitat Abrahamsen B, Gram J, Hansen T, Beck-Nielsen H (1995) Cross-calibration of QDR-2000 and QDR-1000 dual energy X-ray densitometers for bone mineral and soft tissue measurements. Bone 16:385–391CrossRefPubMed Abrahamsen B, Gram J, Hansen T, Beck-Nielsen H (1995) Cross-calibration of QDR-2000 and QDR-1000 dual energy X-ray densitometers for bone mineral and soft tissue measurements. Bone 16:385–391CrossRefPubMed
26.
Zurück zum Zitat 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 16:1330–1338CrossRef 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 16:1330–1338CrossRef
27.
Zurück zum Zitat Lovell S, Taira T, Rodriguez E, Wackett A, Gulla J, Singer A (2004) Comparison of valdecoxib and an oxycodone-acetaminophen combination for acute musculoskeletal pain in the emergency department: a randomized controlled trial. Acad Emerg Med 11:1278–1282PubMed Lovell S, Taira T, Rodriguez E, Wackett A, Gulla J, Singer A (2004) Comparison of valdecoxib and an oxycodone-acetaminophen combination for acute musculoskeletal pain in the emergency department: a randomized controlled trial. Acad Emerg Med 11:1278–1282PubMed
28.
29.
Zurück zum Zitat Marshall D, Johnell O, Wedel H (1996) Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 312:1254–1259CrossRefPubMed Marshall D, Johnell O, Wedel H (1996) Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 312:1254–1259CrossRefPubMed
30.
Zurück zum Zitat Dimmen S, Nordsletten L, Engebretsen L, Steen H, Madsen JE (2008) Negative effect of parecoxib on bone mineral during fracture healing in rats. Acta Orthop 79:438–444CrossRefPubMed Dimmen S, Nordsletten L, Engebretsen L, Steen H, Madsen JE (2008) Negative effect of parecoxib on bone mineral during fracture healing in rats. Acta Orthop 79:438–444CrossRefPubMed
31.
Zurück zum Zitat Dimmen S, Nordsletten L, Madsen JE (2009) Parecoxib and indomethacin delay early fracture healing: a study in rats. Clin Orthop Relat Res 467:1992–1999CrossRefPubMed Dimmen S, Nordsletten L, Madsen JE (2009) Parecoxib and indomethacin delay early fracture healing: a study in rats. Clin Orthop Relat Res 467:1992–1999CrossRefPubMed
32.
Zurück zum Zitat Bischoff H, Stahelin H, Urscheler N, Ehrsam R, Vonthein R, Perrig-Chiello P, Tyndall A, Theiler R (1999) Muscle strength in the elderly: its relation to vitamin D metabolites. Arch Phys Med Rehabil 80:54–58CrossRefPubMed Bischoff H, Stahelin H, Urscheler N, Ehrsam R, Vonthein R, Perrig-Chiello P, Tyndall A, Theiler R (1999) Muscle strength in the elderly: its relation to vitamin D metabolites. Arch Phys Med Rehabil 80:54–58CrossRefPubMed
33.
Zurück zum Zitat Bischoff H, St. helin H, Dick W, Akos R, Knecht M, Salis C, Nebiker M, Theiler R, Pfeifer M, Begerow B, Lew R, Conzelmann M (2003) Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. J Bone Miner Res 18:343–351CrossRefPubMed Bischoff H, St. helin H, Dick W, Akos R, Knecht M, Salis C, Nebiker M, Theiler R, Pfeifer M, Begerow B, Lew R, Conzelmann M (2003) Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. J Bone Miner Res 18:343–351CrossRefPubMed
Metadaten
Titel
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)
verfasst von
P. Vestergaard
P. Hermann
J.-E. B. Jensen
P. Eiken
L. Mosekilde
Publikationsdatum
01.04.2012
Verlag
Springer-Verlag
Erschienen in
Osteoporosis International / Ausgabe 4/2012
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-011-1692-0

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