Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ASCO Annual Meeting 2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

2024 ASCO Annual Meeting

Keep up to date with all the top stories and latest evidence with our hub page, including official congress videos and expert takeaways.
ADVANCED SEARCH
Log in
Top
Current Osteoporosis Reports
Published in: Current Osteoporosis Reports 4/2011

01-12-2011 | Epidemiology and Pathophysiology (Mone Zaidi and Jeffrey I. Mechanick, Section Editors)

The Effects of Smoke Carcinogens on Bone

Authors: Carol Yan, Narayan G. Avadhani, Jameel Iqbal

Published in: Current Osteoporosis Reports | Issue 4/2011

Login to get access

Abstract

The greatest cause of preventable morbidity and mortality is smoking, and one of the often-underappreciated effects of smoking is profound bone loss. The existing clinical paradigm for smoking is that there is a low turnover osteoporosis. This review highlights findings from recent clinical trials and animal research demonstrating either support or conflict with the existing paradigm. Clinically, it is noted that markers of bone formation are often normal in smokers; these clinical findings conflict with well-conducted animal research demonstrating that carcinogens acting on the aryl hydrogen receptor can significantly reduce osteoblast formation and function. Regarding bone resorption, highlights from recent clinical studies suggest that bone remodeling is increased in smokers. Directly contradicting this enhanced osteoclastogenesis are several animal studies all demonstrating significant inhibition of osteoclast formation and function upon exposure to smoke carcinogens. Future research is needed to clarify whether smoking is truly a low bone remodeling osteoporosis, or an osteoclast-driven bone destruction, with inappropriately normal bone formation.
Literature
1.
Wipfli H, Samet JM. Global economic and health benefits of tobacco control: part 1. Clin Pharmacol Ther. 2009;86(3):263–71.PubMedCrossRef
2.
Ward KD, Klesges RC. A meta-analysis of the effects of cigarette smoking on bone mineral density. Calcif Tissue Int. 2001;68(5):259–70.PubMedCrossRef
3.
Kanis JA, Johnell O, Oden A, Johansson H, De Laet C, Eisman JA, et al. Smoking and fracture risk: a meta-analysis. Osteoporos Int. 2005;16(2):155–62.PubMedCrossRef
4.
Cornuz J, Feskanich D, Willett WC, Colditz GA. Smoking, smoking cessation, and risk of hip fracture in women. Am J Med. 1999;106(3):311–4.PubMedCrossRef
5.
Hopper JL, Seeman E. The bone density of female twins discordant for tobacco use. N Engl J Med. 1994;330(6):387–92.PubMedCrossRef
6.
MacInnis RJ, Cassar C, Nowson CA, Paton LM, Flicker L, Hopper JL, et al. Determinants of bone density in 30- to 65-year-old women: a co-twin study. J Bone Miner Res. 2003;18(9):1650–6.PubMedCrossRef
7.
Krall EA, Dawson-Hughes B. Smoking and bone loss among postmenopausal women. J Bone Miner Res. 1991;6(4):331–8.PubMedCrossRef
8.
Law MR, Hackshaw AK. A meta-analysis of cigarette smoking, bone mineral density and risk of hip fracture: recognition of a major effect. BMJ. 1997;315(7112):841–6.PubMedCrossRef
9.
Szulc P, Garnero P, Claustrat B, Marchand F, Duboeuf F, Delmas PD. Increased bone resorption in moderate smokers with low body weight: the Minos study. J Clin Endocrinol Metab. 2002;87(2):666–74.PubMedCrossRef
10.
Nguyen TV, Kelly PJ, Sambrook PN, Gilbert C, Pocock NA, Eisman JA. Lifestyle factors and bone density in the elderly: implications for osteoporosis prevention. J Bone Miner Res. 1994;9(9):1339–46.PubMedCrossRef
11.
Walker LM, Preston MR, Magnay JL, Thomas PB, El Haj AJ. Nicotinic regulation of c-fos and osteopontin expression in human-derived osteoblast-like cells and human trabecular bone organ culture. Bone. 2001;28(6):603–8.PubMedCrossRef
12.
Haverstock BD, Mandracchia VJ. Cigarette smoking and bone healing: implications in foot and ankle surgery. J Foot Ankle Surg. 1998;37(1):69–74. discussion 78.PubMedCrossRef
13.
Olofsson H, Byberg L, Mohsen R, Melhus H, Lithell H, Michaelsson K. Smoking and the risk of fracture in older men. J Bone Miner Res. 2005;20(7):1208–15.PubMedCrossRef
14.
Jamsa T, Viluksela M, Tuomisto JT, Tuomisto J, Tuukkanen J. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on bone in two rat strains with different aryl hydrocarbon receptor structures. J Bone Miner Res. 2001;16(10):1812–20.PubMedCrossRef
15.
Miettinen HM, Pulkkinen P, Jamsa T, Koistinen J, Simanainen U, Tuomisto J, et al. Effects of in utero and lactational TCDD exposure on bone development in differentially sensitive rat lines. Toxicol Sci. 2005;85(2):1003–12.PubMedCrossRef
16.
Blanco GA, Cooper EL. Immune systems, geographic information systems (GIS), environment and health impacts. J Toxicol Environ Health B Crit Rev. 2004;7(6):465–80.PubMedCrossRef
17.
Ilvesaro J, Pohjanvirta R, Tuomisto J, Viluksela M, Tuukkanen J. Bone resorption by aryl hydrocarbon receptor-expressing osteoclasts is not disturbed by TCDD in short-term cultures. Life Sci. 2005;77(12):1351–66.PubMedCrossRef
18.
Ramp WK, Lenz LG, Galvin RJ. Nicotine inhibits collagen synthesis and alkaline phosphatase activity, but stimulates DNA synthesis in osteoblast-like cells. Proc Soc Exp Biol Med. 1991;197(1):36–43.PubMed
19.
Ortego-Centeno N, Munoz-Torres M, Jodar E, Hernandez-Quero J, Jurado-Duce A, de la Higuera Torres-Puchol J. Effect of tobacco consumption on bone mineral density in healthy young males. Calcif Tissue Int. 1997;60(6):496–500.PubMedCrossRef
20.
21.
Rothem DE, Rothem L, Soudry M, Dahan A, Eliakim R. Nicotine modulates bone metabolism-associated gene expression in osteoblast cells. J Bone Miner Metab. 2009;27(5):555–61.PubMedCrossRef
22.
Naruse M, Ishihara Y, Miyagawa-Tomita S, Koyama A, Hagiwara H. 3-Methylcholanthrene, which binds to the arylhydrocarbon receptor, inhibits proliferation and differentiation of osteoblasts in vitro and ossification in vivo. Endocrinology. 2002;143(9):3575–81.PubMedCrossRef
23.
• Korkalainen M, Kallio E, Olkku A, Nelo K, Ilvesaro J, Tuukkanen J, Mahonen A, Viluksela M. Dioxins interfere with differentiation of osteoblasts and osteoclasts. Bone 2009;44(6):1134–42. This paper shows that OCN and ALP are lower in arylhydrocarbon knockout mice, thus suggesting a role in the normal development of bone cells.PubMedCrossRef
24.
Lian JB, Stein GS. The developmental stages of osteoblast growth and differentiation exhibit selective responses of genes to growth factors (TGF beta 1) and hormones (vitamin D and glucocorticoids). J Oral Implantol. 1993;19(2):95–105. discussion 136–107.PubMed
25.
Stein GS, Lian JB. Molecular mechanisms mediating proliferation/differentiation interrelationships during progressive development of the osteoblast phenotype. Endocr Rev. 1993;14(4):424–42.PubMed
26.
• Wejheden C, Brunnberg S, Larsson S, Lind PM, Andersson G, Hanberg A. Transgenic mice with a constitutively active aryl hydrocarbon receptor display a gender-specific bone phenotype. Toxicol Sci. 2010;114(1):48–58. This paper shows that in vivo measures reflecting osteoclast activity are increased in female mice with a CA-AhR.PubMedCrossRef
27.
Singh SU, Casper RF, Fritz PC, Sukhu B, Ganss B, Girard Jr B, et al. Inhibition of dioxin effects on bone formation in vitro by a newly described aryl hydrocarbon receptor antagonist, resveratrol. J Endocrinol. 2000;167(1):183–95.PubMedCrossRef
28.
• Voronov I, Li K, Tenenbaum HC, Manolson MF. Benzo[a]pyrene inhibits osteoclastogenesis by affecting RANKL-induced activation of NF-kappaB. Biochem Pharmacol. 2008;75(10):2034–44. This paper explores the mechanism of action of carcinogens on osteoclasts, demonstrating that they suppress osteoclastogenesis.PubMedCrossRef
29.
Naruse M, Otsuka E, Ishihara Y, Miyagawa-Tomita S, Hagiwara H. Inhibition of osteoclast formation by 3-methylcholanthrene, a ligand for arylhydrocarbon receptor: suppression of osteoclast differentiation factor in osteogenic cells. Biochem Pharmacol. 2004;67(1):119–27.PubMedCrossRef
30.
Lees RL, Sabharwal VK, Heersche JN. Resorptive state and cell size influence intracellular pH regulation in rabbit osteoclasts cultured on collagen-hydroxyapatite films. Bone. 2001;28(2):187–94.PubMedCrossRef
31.
•• Wong PK, Christie JJ, Wark JD. The effects of smoking on bone health. Clin Sci (Lond) 2007;113(5):233–41. This is an excellent review detailing many clinical studies on smoking and bone loss.CrossRef
32.
Bruno RD, Njar VC. Targeting cytochrome P450 enzymes: a new approach in anti-cancer drug development. Bioorg Med Chem. 2007;15(15):5047–60.PubMedCrossRef
33.
Tsuchiya Y, Nakajima M, Yokoi T. Cytochrome P450-mediated metabolism of estrogens and its regulation in human. Cancer Lett. 2005;227(2):115–24.PubMedCrossRef
34.
Safe S, Wang F, Porter W, Duan R, McDougal A. Ah receptor agonists as endocrine disruptors: antiestrogenic activity and mechanisms. Toxicol Lett. 1998;102–103:343–7.PubMedCrossRef
35.
Boverhof DR, Kwekel JC, Humes DG, Burgoon LD, Zacharewski TR. Dioxin induces an estrogen-like, estrogen receptor-dependent gene expression response in the murine uterus. Mol Pharmacol. 2006;69(5):1599–606.PubMedCrossRef
36.
Rapuri PB, Gallagher JC, Balhorn KE, Ryschon KL. Smoking and bone metabolism in elderly women. Bone. 2000;27(3):429–36.PubMedCrossRef
Metadata
Title
The Effects of Smoke Carcinogens on Bone
Authors
Carol Yan
Narayan G. Avadhani
Jameel Iqbal
Publication date
01-12-2011
Publisher
Current Science Inc.
Published in
Current Osteoporosis Reports / Issue 4/2011
Print ISSN: 1544-1873
Electronic ISSN: 1544-2241
DOI
https://doi.org/10.1007/s11914-011-0068-x

Other articles of this Issue 4/2011

Current Osteoporosis Reports 4/2011 Go to the issue

Pediatrics and Skeletal Development (Craig Langman and Maria Luisa Bianchi, Section Editors)

Bone Development in the Fetus and Neonate: Role of the Calciotropic Hormones

Epidemiology and Pathophysiology (Mone Zaidi and Jeffrey I. Mechanick, Section Editors)

Events in Articular Chondrocytes with Aging

Epidemiology and Pathophysiology (Mone Zaidi and Jeffrey I. Mechanick, Section Editors)

Anti-Cancer Actions of Denosumab

Epidemiology and Pathophysiology (Mone Zaidi and Jeffrey I. Mechanick, Section Editors)

Vitamin D in the Persian Gulf: Integrative Physiology and Socioeconomic Factors

Epidemiology and Pathophysiology (Mone Zaidi and Jeffrey I. Mechanick, Section Editors)

Stem Cell Interactions in a Bone Marrow Niche

Pediatrics and Skeletal Development (Craig Langman and Maria Luisa Bianchi, Section Editors)

Rickets