Abstract
With the increasing consumption of antithrombotic drugs among old people, expected as well as unexpected side effects on bone health are considerable, e.g. osteoporosis, fragility fractures, etc. This review focuses on antithrombotic drugs and their effects on bone health. The following groups were reviewed: parenteral long-term use of unfractionated heparin (UFH) is associated with osteopenia. The oral intake of vitamin K antagonists (VKA) makes them more convenient than UFH but chronic use also results in osteopenia. Limited reports of bone loss have been associated with low molecular weight heparins (LMWH) and indirect factor Xa inhibitors but in contrast to VKA and UFH they are less associated with osteopenia. There have been limited studies evaluating the effect of new oral anticoagulants (NOACs) on bones. Overall, they are considered safer than other drugs. There have been no reports about acetylsalicylic acid (ASA) and clopidogrel causing osteopenia but their metabolism by the kidneys and liver can cause reduced 25-hydroxy-vitamin D levels and can theoretically contribute to osteoporosis. Some reports suggested that high dosage clopidogrel can also negatively affect bones. After a detailed literature review long-term use of antithrombotic drugs can negatively affect the bones. Their role in bone health needs to be studied in detail and the clinical use in geriatric patients should be prudent.
Zusammenfassung
Mit dem zunehmenden Verbrauch antithrombotischer Arzneimittel bei geriatrischen Patienten sind deren Nebenwirkungen auf die Knochen beträchtlich, z. B. Osteoporose, Fragilitätsfrakturen etc. Diese Übersicht konzentriert sich auf Antithrombotika und deren Auswirkungen auf die Knochengesundheit. Folgende im folgenden beschriebenen Gruppen wurden berücksichtigt. Die parenterale Langzeitanwendung von unfraktioniertem Heparin (UFH) ist mit Osteopenie verbunden. Die orale Einnehme von Vitamin-K-Antagonisten (VKA) macht sie komfortabler als UFH, langfristig ist die Anwendung aber ebenfalls mit einer verstärkten Neigung zur Osteopenie verbunden. Niedermolekulare Heparine (LMWH) und indirekter Faktor-Xa-Inhibitor wurden nur in begrenztem Umfang mit Knochenschwund in Verbindung gebracht, insgesamt sind sie jedoch im Gegensatz zu VKA und UFH wohl geringer mit einer Osteopenie assoziiert. Zu den neuen oralen Antikoagulanzien (NOAK) wurden begrenzte Studien durchgeführt, um deren Wirkung auf die Knochen zu bewerten. Insgesamt gelten sie als sicherer als andere Medikamente. Bezüglich Acetylsalicylsäure (ASS) und Clopedogrel gibt es keine Berichte darüber, dass diese Osteopenie verursachen, jedoch kann ihr Metabolismus durch Nieren und Leber einen verringerten Spiegel an 25-Hydroxy-Vitamin D zur Folge haben und daher theoretisch eine Osteoporose begünstigen. Nach einer ausführlichen Literaturrecherche kann die Langzeitanwendung von Antithrombotika die Knochen negativ beeinflussen. Ihre Rolle für die Knochengesundheit muss eingehend untersucht werden und die klinische Anwendung bei geriatrischen Patienten sollte umsichtig erfolgen.
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References
Abdulameer AH, Sulaiman SABS, Kader MBSA (2017) An assessment of osteoporotic conditions among users and non-users of warfarin: a case-control study. J Clin Diagn Res 11(3):OC21–OC24. https://doi.org/10.7860/JCDR/2017/23829.9483
Mahmoud AN, Gad MM, Elgendy AY, Elgendy IY, Bavry AA (2019) Efficacy and safety of aspirin for primary prevention of cardiovascular events: a meta-analysis and trial sequential analysis of randomized controlled trials. Eur Heart J 40(7):607–617. https://doi.org/10.1093/eurheartj/ehy813
Akkawi I, Osteoporosis ZH (2018) Current concepts. Joints 6(2):122–127. https://doi.org/10.1055/s-0038-1660790
Bauer DC, Orwoll ES, Fox KM, Vogt TM, Lane NE, Hochberg MC, Stone K, Nevitt MC (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(1):29–35
Chin KY (2017) A review on the relationship between aspirin and bone health. J Osteoporos 2017:3710959. https://doi.org/10.1155/2017/3710959
Hulisz D (2006) Drug-induced osteoporosis, effects of medications on bone density. Us Pharm 12:HS3–HS6
Gage BF, Birman-Deych E, Radford MJ, Nilasena DS, Binder EF (2006) Risk of osteoporotic fracture in elderly patients taking warfarin: results from the National Registry of Atrial Fibrillation 2. Arch Intern Med 166(2):241–246
Gajic-Veljanoski O, Phua CW, Shah PS, Cheung AM (2016) Effects of long-term low-molecular-weight heparin on fractures and bone density in non-pregnant adults: a systematic review with meta-analysis. J Gen Intern Med 31(8):947–957. https://doi.org/10.1007/s11606-016-3603-8
Gu ZC, Zhou LY, Shen L et al (2018) Non-vitamin K antagonist oral anticoagulants vs. Warfarin at risk of fractures: a systematic review and meta-analysis of randomized controlled trials. Front Pharmacol 9:348. https://doi.org/10.3389/fphar.2018.00348
Griffith GC, Nichols G Jr., Asher JD et al (1965) Heparin Osteoporosis. JAMA 193(2):91–94
Hak DJ, Stewart RL, Hazelwood SJ (2006) Effect of low molecular weight heparin on fracture healing in a stabilized rat femur fracture model. J Orthop Res 24(4):645–652
Handschin AE, Trentz OA, Hoerstrup SP, Kock HJ, Wanner GA, Trentz O (2005) Effect of low molecular weight heparin and Fondaparinux on human osteonblasts in vitro. Br J Surg 92(2):177–183
Pountos I, Georgouli T, Blokhuis TJ, Chistoph Pape H, Giannoudis PV (2007) Pharmacological agents and impairment of fracture healing: what is the evidence? Injury 39(4):384–394. https://doi.org/10.1016/j.injury.2007.10.035
Jorgensen NR, El Grove, Schwarz P, Vestergaard P (2012) Clopidogrel and the risk of osteoporotic fractures: a nationwide cohort study. J Intern Med 272(4):385–393. https://doi.org/10.1111/j.1365-2796.2012.02535
Kock HJ, Werther S, Uhlenkott H, Taeger G (2002) Influence of unfractionated and low-molecular-weight heparin on bone healing: an animal model. Unfallchirurg 105(9):791–796
Kok-Yong C (2017) A Review on the Relationship between Aspirin and Bone Health. Journal of Osteoporosis. Article ID 3710959. https://doi.org/10.1155/2017/3710959
Lau WC, Chan EW, Cheung CL, Sing CW, Man KK, Lip GY, Siu CW, Lam JK, Lee AC, Wong IC (2017) Association between Dabigatran vs warfarin and risk of Osteoporotic fractures among patients with nonvalvular atrial fibrillation. JAMA 317(11):1151–1158. https://doi.org/10.1001/jama.2017.1363
Laura S. Lehman, PharmD; Does Warfarin Use Affect Bone Health?
Lindner T, Cockbain AJ, El Masry MA, Katonis P, Tsiridis E, Schizas C, Tsiridis E (2008) The effect of anticoagulant pharmacotherapy on fracture healing. Expert Opin Pharmacother 9(7):1169–1187. https://doi.org/10.1517/14656566.9.7.1169
Namba S, Yamaoka Tojo M, Kakizaki R, Nemoto T, Fujiyoshi K, Hashikata T, Kitasato L, Hashimoto T, Kameda R, Meguro K, Shimohama T, Tojo T, Ako J (2017) Effects on bone metabolism markers and arterial stiffness by switching to rivaroxaban from warfarin in patients with atrial fibrillation. Heart Vessels 32(8):977–982. https://doi.org/10.1007/s00380-017-0950-2
Jørgensen NR, Schwarz P, Iversen HK, Vestergaard P (2017) P2Y12 receptor antagonist, Clopidogrel, does not contribute to risk of Osteoporotic fractures in stroke patients. Front Pharmacol 8:821. https://doi.org/10.3389/fphar.2017.00821
Pietschmann P, Woloszczuk WS, Panzer S, Kyrle P, Smolen J (1988) Decreased serum osteocalcin levels in Phenprocoumon-treated patients. J Clin Endocrinol Metab 66(5):1071–1074
Resch H, Pietschmann P, Krexner E, Woloszczuk W, Willvonseder R (1991) Decreased peripheral bone mineral content in patients under anticoagulant therapy with phenprocoumon. Eur Heart J 12(3):439–441
Rezaieyazdi Z, Falsoleiman H, Khajehdaluee M, Saghafi M, Mokhtari-Amirmajdi E (2009) Reduced bone density in patients on long-term warfarin. Int J Rheum Dis 12(2):130–135. https://doi.org/10.1111/j.1756-185X.2009.01395.x
Rosen HN, Drezner MK, Mulder JE Drugs that affect bone metabolism. https://www.uptodate.com. Accessed 3 June 2019
Sambrook P, Cooper C (2006) Osteoporosis. Lancet 367(9527):2010–2018
Street JT, McGrath M, O’Regan K et al (2000) Thromboprophylaxis using a low molecular weight heparin delays fracture repair. Clin Orthop Relat Res 381:278–289
Syberg S, Brandao-Burch A, Patel JJ, Hajjawi M, Arnett TR, Schwarz P et al (2012) Clopidogrel (Plavix), a P2Y12 receptor antagonist, inhibits bone cell function in vitro and decreases trabecular bone in vivo. J Bone Miner Res 27(11):2373–2386. https://doi.org/10.1002/jbmr.1690
https://www.dv-osteologie.org/dvo_leitlinien/dvo-leitlinie-2017; accessed on 2 June 2019.
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G. Dadwal, T. Schulte-Huxel and G. Kolb declare that they have no competing interests.
For this article no studies with human participants or animals were performed by any of the authors. All studies performed were in accordance with the ethical standards indicated in each case.
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Dadwal, G., Schulte-Huxel, T. & Kolb, G. Effect of antithrombotic drugs on bone health. Z Gerontol Geriat 53, 457–462 (2020). https://doi.org/10.1007/s00391-019-01590-8
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DOI: https://doi.org/10.1007/s00391-019-01590-8