Alcohol intake as a risk factor for fracture

Kanis, John А.; Johansson, Helena; Johnell, Olof; Odén, Anders; Laet, Chris De; Eisman, John A.; Pols, Huibert A. P.; Tenenhouse, Alan

doi:10.1007/s00198-004-1734-y

Cited by 499 publications

(282 citation statements)

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“…This finding further underlines the importance of testosterone as an antiinflammatory molecule, even in a case of relative cortisol deficiency. Ethanol consumption has been shown to increase the risk for bone fractures (36). However, previous studies have failed to find a relationship between low-dose ethanol intake and loss of BMD.…”

Section: Discussionmentioning

confidence: 99%

Ethanol prevents development of destructive arthritis

Jonsson

Verdrengh

Brisslert

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Environmental factors are thought to play a major role in the development of rheumatoid arthritis. Because the use of ethanol is widespread, we assessed the role of ethanol intake on the propensity to develop chronic arthritis. Collagen type II-immunized mice were given water or water containing 10% (vol/vol) ethanol or its metabolite acetaldehyde. Their development of arthritis was assessed, as well as the impact of ethanol on leukocyte migration and activation of intracellular transcription factors. Mice exposed daily to this dose of ethanol did not display any liver toxicity, and the development of erosive arthritis was almost totally abrogated. In contrast, the antibody-mediated effector phase of collageninduced arthritis was not influenced by ethanol exposure. Also, the major ethanol metabolite, acetaldehyde, prevented the development of arthritis. This antiinflammatory and antidestructive property of ethanol was mediated by (i) down-regulation of leukocyte migration and (ii) up-regulation of testosterone secretion, with the latter leading to decreased NF-B activation. We conclude that low but persistent ethanol consumption delays the onset and halts the progression of collagen-induced arthritis by interaction with innate immune responsiveness.inflammation ͉ cytokines ͉ sex hormones ͉ antibodies ͉ immunity E xcessive alcohol consumption depresses the immune system and increases the propensity to severe bacterial infections, including pneumonia (1), tuberculosis (2), and bacterial peritonitis (3), and to viral infections (4-6). However, some epidemiological studies have suggested that light to moderate ethanol consumption has protective effects against several diseases including chronic heart diseases (7, 8) and ischemic stroke (9).Ethanol consumption has also been implicated in the pathogenesis of systemic lupus erythematosus (SLE), a complex autoimmune disease in the development of which environmental and genetic factors interact. Indeed, some investigators have found that exposure to ethanol is associated with a lower risk for developing SLE (10, 11), whereas others did not observe any effect of alcohol consumption on the incidence of SLE (12, 13). The association between ethanol and rheumatoid arthritis (RA) has been discussed in some studies, but definite conclusions could not be drawn (14-16). Studies so far have been of an epidemiological nature and therefore have not provided any hints about the biological mechanisms of environmental stimuli in the development of autoimmune disease. Our aim here was to assess whether low but persistent consumption of ethanol in quantities nontoxic to liver might affect the incidence and disease manifestation of collagen type II (CII)-induced arthritis (CIA), an established model of human RA. Our results suggest that ethanol intake delays the onset and halts the progression of destructive arthritis. Results Effect of Ethanol Consumption on Development of CIA.To assess whether ethanol drinking has any impact on the development of CIA, CII-immunized mice were provided w...

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Section: Discussionmentioning

confidence: 99%

Ethanol prevents development of destructive arthritis

Jonsson

Verdrengh

Brisslert

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…According to the definition of the World Health Organization, DDD is the assumed average maintenance dose per day for a drug used for its main indication in adults. Other exposure variables were the use of drugs known to be associated with fracture risk (corticosteroids), and the occurrence of comorbidities known to affect fracture risk (prior fracture [15] and alcoholism [16]). These factors were chosen as it is known that they may affect fracture risk, and they are regarded as important potential confounders in a setting in which many variables besides the main factor may influence the risk of fractures (confounding by indication).…”

Section: Exposure Variablesmentioning

confidence: 99%

Clopidogrel and the risk of osteoporotic fractures: a nationwide cohort study

Jørgensen

Grove

Schwarz

et al. 2012

Journal of Internal Medicine

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Abstract. Jørgensen NR, Grove EL, Schwarz P, Vestergaard P (Research Center for Aging and Osteoporosis, Copenhagen University Hospital Glostrup; Aarhus University Hospital, Skejby; University of Copenhagen, Copenhagen; The Osteoporosis Clinic, Aarhus University Hospital, Denmark). Clopidogrel and the risk of osteoporotic fractures: a nationwide cohort study. J Intern Med 2012; 272: 385-393.Objectives: The P2Y 12 inhibitor clopidogrel inhibits platelet aggregation and is used in the treatment and prevention of coronary artery disease. It is widely used and, in combination with acetylsalicylic acid, is the standard of care for acute coronary syndrome and percutaneous coronary intervention. The mode of action of clopidogrel involves pathways that are important to the metabolic activity in bone cells, although to our knowledge whether P2Y 12 receptors are involved in the regulation of bone metabolism has not yet been investigated. Therefore, the objective of the present study was to investigate the association between clopidogrel use and risk of fractures. Methods:We investigated the association between clopidogrel use and fracture incidence in a nationwide cohort study within the Danish population of approximately 5.3 million individuals. All patients who were prescribed clopidogrel during the years 1996-2008 were included in the study (n = 77 503), and three nonusers were randomly selected, matched for age and gender (n = 232 510), for each clopidogrel-treated subject.Results: Treatment with clopidogrel was associated with both increased overall fracture risk and increased risk of osteoporotic fractures, especially in subjects with a treatment duration of more than 1 year. However, individuals with low exposure to clopidogrel (<0.01 defined daily dose) had a lower risk of fracture than never users.Conclusions: Use of the P2Y 12 inhibitor clopidogrel is associated with risk of fractures. There seems to be a biphasic relation so that lower doses are associated with decreased fracture risk, whereas higher doses (recommended dose range) are associated with increased risk. More studies are warranted to determine the potential in vivo effect of platelet aggregation inhibitors on bone metabolism.

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“…Due to women's physiological characteristics, they are exposed to further serious consequences of alcohol abuse, such as: increased osteoporosis 19 , breast cancer 20 , reproductive problems 21 , heart disease and stroke 22 , and brain damage 23 . They also show a more rapid progression to dependency as compared to men 24 ; propensity to develop liver cirrhosis in less time and with lower amounts of alcohol 25 ; alcohol use during pregnancy can also lead to toxicity to the embryo and fetal teratogenicity 26 .…”

Section: Discussionmentioning

confidence: 99%