The Effect of Chronic Nicotine Administration on Bone Mineral Content and Bone Strength in Normal and Castrated Male Rats

Abstract

Tobacco, containing nicotine as the principal pharmacologically active chemical, has been identified as being a risk factor for the development of osteoporosis. Thirty-two male Wistar rats of two months of age were castrated or sham operated to evaluate the effects of long-term administration (four months) of nicotine in drinking water (9.0 mg/kg/day). The presence of cotinine in urine confirmed successful delivery of nicotine. The bones were tested mechanically by a three point bending test in a Mini Bionix (MTA) testing system. The bones from castrated rats were characterized by a reduction in bone density as well as ash, calcium and phosphate content. Castration significantly altered mechanical properties of bone (9%) and femoral cortical thickness. When intact rats were treated with a high dose of nicotine, nicotine had negative effect on tibial bone density as well as ash, calcium, phosphate content and significantly altered the mechanical properties of bone (12%) and femoral cortical thickness compared to intact animals. Nicotine itself does not exert any anti-androgenic effect and does not produce changes in the weight of seminal vesicles. Nicotine-induced bone loss is associated with high bone turnover in the male rats as expressed by increased TrACP and B-ALP. When castrated rats were treated with the high dose of nicotine the changes in bone density resulting from castration were not further potentiated. These results document the efficacy of nicotine at high doses to cause bone loss and loss of bone mechanical strength in intact rats. The results of the present study may be interpreted as supporting the hypothesis of nicotine as a risk factor for osteoporosis.

Key words

nicotine - bone mineral density - bone strength - male rats

References

• 1 Jensen CF. Osteoporosis of the slender smoker revisited by epidemiologic approach.  Eur J Clin Invest. 1986;  16 239-243
• 2 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;  315 841-846
• 3 Hoidrup S, Prescott E, Sorensen TI, Gottchau A, Lauritzen JB, Schroll M, Gronbaek M. Tobacco smoking and risk of hip fracture in men and women.  Int J Epidemiol. 2000;  29 253-259
• 4 Slemenda CW, Hui SL, Longscope C. Cigarette smoking obesity and bone mass.  J Bone Miner Res. 1989;  4 737-741
• 5 Van Voorhis B, Dawson JD, Stovall DW, Sparks AET, Syrop CH. The effects of smoking on ovarian function and fertility during assisted reproductive cycles.  Obstet Gynecol. 1996;  88 785-791
• 6 Baron JA, Vecchia C, Levi F. The antiestrogenic effect of cigarette smoke in women.  Am J Obstet Gynecol. 1990;  162 502-514
• 7 Tanko LB, Christiansen C. An update on the antiestrogenic effect of smoking: a literature review with implications for researchers and practitioners.  Menopause. 2004;  11 104-109
• 8 Casper RF, Quesne M, Rogers JM, Shirota T, Joliver A, Milgrom E, Savouret JF. Resveratrol has antagonist activity on the acryl hydrocarbon receptor: implication for prevention of dioxin toxicity.  Mol Pharmacol. 1999;  56 784-790
• 9 Lee IL, Lee JSC, Waldman SD, Casper RF, Grynpas MD. Polycyclic aromatic hydrocarbons present in cigarette smoke cause bone loss in an ovariectomized rat model.  Bone. 2002;  30 917-923
• 10 Egger P, Duggleby S, Hobbs R, Fall C, Copper C. Cigarette smoking and bone mineral density in the elderly.  J Epidemiol Community Health. 1996;  50 47-50
• 11 Akhter MP, Iwaniec UT, Haynatzki GR, Fung YK, Cullen DM, Recker RR. Effects of nicotine on bone mass and strength in aged female rats.  J Orthop Res. 2003;  21 14-19
• 12 Broulik PD, Jarab J. The effect of chronic nicotine administration on bone mineral content in mice.  Horm Metab Res. 1993;  25 219-221
• 13 Jarvis MJ, Tunstall-Pedoe H, Feyerabend C, Vesey C. Comparison of tests used to distinguish smokers from nonsmokers.  Am J Public Health. 1987;  77 1435-1439
• 14 Kalu DN, Hardin RR, Ceckerham R. Evaluation of the pathogenesis of skeletal changes in ovariectomized rats.  Endocrinology. 1994;  115 507-511
• 15 Deyhim F, Garica K, Lopez E, Gonzales J, Ino S, Garcia M, Patil BS. Citrus juice modulates bone strength in male senescent rat model of osteoporosis.  Nutrition. 2006;  22 559-563
• 16 Gitelman H. An improved automated procedure for the determination of calcium in biological specimens.  Anal Biochem. 1967;  18 521-531
• 17 Kraml J. A semiautomated determination of phospholipids.  Clin Chim Acta. 1966;  13 442-448
• 18 Štìpán JJ, Šilinková-Málková E, Havránek T, Formánková J, Zichová J, Lachmanová J, Straková M, Broulik P, Pacovský V. Relationship of plasma tartrate-resistant acid phosphatase to the bone isoenzyme of serum alkaline phosphatase in hyperpathyrodism.  Clin Chim Acta. 1983;  133 189-200
• 19 Moss D. A simplified heat-inactivation method for investigation alkaline phosphatase isoenzymes in serum.  Clin Chim Acta. 1975;  61 63-71
• 20 Beall PT, Misra LK, Young RL, Spjut HJ, Evans HJ, Le Blame A. Clomiphene protects against osteoporosis in the mature ovariectomized rat.  Calcif Tissue Int. 1984;  36 123-125
• 21 Vanderschueren DE, Vautterck AMH, Suiker WJ, Wisser LPC, Schot R, Bouillon R. Bone and mineral me olism in aged male rats. Short and long term effects of androgen deficiency.  Endocrinology. 1992;  130 2906-2916
• 22 Turner CH, Burr DB. Basic biomechanical measurements of bone: A tutorial.  Bone. 1993;  14 595-608
• 23 Broulik PD, Rosenkrancová J, Růžička P, Sedláek R. Effect of alendronate administration on bone mineral density and bone strength in castrated rats.  Horm Metab Res. 2005;  37 414-418
• 24 Růžička R, Michálek J, Rosenkrancová J, Sedláek R. Cross section parameters acquisition from digital images. Prague, Proceedings of workshop 2002.  Prague CTU. 2002;  B 910-911
• 25 Duncan D. Multiple range and multiple F test.  Biometrics. 1955;  11 1-4
• 26 Benowitz NL, Kuyt F, Jacob P, Jones RT, Osman AL. Cotinine disposition and effects.  Clin Pharmacol Ther. 1983;  34 604-611
• 27 Ott SM. Fractures after long term alendronate therapy.  J Clin Endocrinol Metab. 2001;  86 1835-1842
• 28 Iwaniec UT, Haynatzki GR, Fung YK, Akhter MP, Haven MC, Cullen DM. Effects of nicotine on bone and calciotropic hormones in aged ovariectomized rats.  J Musculoskelet Neuronal Interact. 2002;  2 469-478
• 29 Iwaniec UT, Fung YK, Akhter MP, haven MC, Nespor S, Haynatzki GR, Cullen DM. Effects of nicotine on bone mass, turnover and strength in adult female Rats.  Calcif Tissue Int. 2001;  68 358-364
• 30 Liu XD, Zhu YK, Umino T, Spurzem JR, Romberger DJ, Wang H, Reed E, Rennard SI. Cigarette smoke inhibits osteogenic differentiation and proliferation of human osteoprogenitor cells in monolayer and three-dimensional collagen gel culture.  J Lab Clin Med. 2001;  137 208-219
• 31 Fung YK, Iwaniec U, Cullen DM, Akhter MP, Haven MC, Timmins P. Long-term effects of nicotine on bone and calciotropic hormones in adult female rats.  Pharmacol Toxicol. 1999;  85 181-187
• 32 Ramp WK, Lenz RJ, Galvin JS. Nicotine inhibits collagen synthesis and alkaline phosphatase activity but stimulate DNA synthesis in osteoblast-like cells.  Proc Soc Exp Biol Med. 1991;  197 36-42
• 33 Rapuri PB, Gallagher JC, Balhorn KE, Ryschon KL. Smoking and bone metabolism in elderly women.  Bone. 2000;  3 429-436
• 34 Akmal M, Kesani A, Anand B, Singh A, Wiseman M, Goodship A. Effect of nicotine on spinal disc cells: a cellular mechanism for disc degeneration.  Spine. 2004;  29 568-575

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