Bone is a dynamic tissue undergoing continuous renewal through a remodelling process that combines the removal of old tissue by osteoclasts and the production of new tissue by osteoblasts. The remodelling process is the result of interactions between these cells and other molecular agents including hormones, growth factors and cytokines. Changes in the remodelling process are the basis of metabolic bone diseases.

Among these, the most important is osteoporosis. This is characterised by low bone mass and microstructural deterioration of bone, leading to fragility and an increased risk of fractures. Osteoporosis mainly affects women in menopause and is caused by oestrogen deficiency. In its dormant state, this disease is found in about 25% of menopausal women. It has been shown that 50-year- old women with osteoporosis have a 40% greater chance of exper – iencing fractures of the hip, spine or forearm during the remainder of their lives 1 Cummings SR, Melton LJ. Epidemiology and outcomes of osteoporotic fractures. Lancet. 2002; 359:1761-7. . This occurs because bone remodelling becomes more active during the postmenopausal period but resorption is not adequately counter- balanced by the formation of new bone 2 Garnero P, Sornay-Rendu E, Chapuy MC, Delmas PD. Increased bone turnover in late post- menopausal women is a major determinant of osteoporosis. J Bone Miner Res. 1996; 11:337-49. . One of the factors implicated in the pathogenesis of osteoporosis is oxidative stress 3 Syed FA, Ng AC. The pathophysiology of the aging skeleton. Curr Osteoporos Rep. 2010; 8:235-40. . Animal studies and epidemiological studies in women with osteoporosis indicate that oxidative stress markers are increased in this disease while plasma and bone tissue antioxidant activities are reduced 4 Zhang YB, Zhong ZM, Hou G, et al. Involvement of oxidative stress in age-related bone loss. J Surg Res. 2011; 169:e37-42. 5
Maggio D, Barabani M, Pierandrei M, et al. Marked decrease in plasma antioxidants in aged osteoporotic women: results of a cross-sectional study. J Clin Endocrinol Metab. 2003; 88:1523-7.
. Oxidative stress acts mainly on osteoclasts. Hydrogen peroxide (H2O2) produced by endothelial cells in close contact with osteoclasts and the H2O2 formed by the latter is involved in their formation, differentiation and motility while also enhancing their activity and bone resorption 6 Rao LG. Will tomatoes prevent osteoporosis? Endocrinology Rounds 2005; 5(2). 7 Banfi G, Iorio EL, Corsi MM. Oxidative stress, free radicals and bone remodeling. Clin Chem Lab Med. 2008;46: 1550-5. . Tartrate-resistant acid phosphatase (TRAP) located on the surface of osteoclasts reacts with H2O2 and produces reactive oxygen species (ROSs) that are highly destructive to collagen and other proteins, resulting in bone resorption 8 Halleen JM, R├ñis├ñnen S, Salo JJ, et al. Intracellular fragmentation of bone resorption products by reactive oxygen species generated by osteoclastic tartrate-resistant acid phos- phatase. J Biol Chem. 1999; 274:22907-10. . Little is known about the role of oxidative stress and osteoblasts, but there is evidence that in these cells the ROSs cause cell death and reduction of alkaline phosphatase 9 Liu H-C, Cheng R-M, Lin F-H, Fang H-W. Sintered beta-dicalcium phosphate particles in- duce intracellular reactive oxygen species in rat osteoblasts. Biomed Eng Appl Basis Commun 1999; 11:259-64. . As previously mentioned, during the postmenopausal period, the oxidative stress that occurs in bone tissue is essentially due to a deficiency of oestrogens, which inhibit ROS production as well as displaying direct antioxidant properties 10 Berger CE, Horrocks BR, Datta HK. Direct non-genomic effect of steroid hormones on su- peroxide generation in the bone resorbing osteoclasts. Molecular and Cellular Endocrinology 1999; 149:53-59. 11 Wagner AH, Schroeter MR, Hecker M. 17╬▓-estradiol inhibition of NADPH oxidase expres- sion in human endothelial cells. FASEB J 2001; 15:2121-30. 12 Clarke R, Leonessa F, Welch JN, Skaar TC. Cellular and molecular pharmacology of antie- strogen action and resistance. Pharmacol Rev 2001; 53:25-71. . In this context, certain studies have shown a potential protective role for lycopene within bone tissue in postmenopausal women. It should firstly be stressed that lycopene inhibits both osteoclast formation and their production of ROS, while acting as a promoter of cell proliferation within the osteoblast compartment 13 Rao LG, Krishnadev N, Banasikowska K, Rao AV. Lycopene I ÔÇô Effect on osteoclasts: lycopene inhibits basal and parathyroid hormone-stimulated osteoclast formation and mineral re- sorption mediated by reactive oxygen species in rat bone marrow cultures. J Med Food 2003; 6:69-78. 14 Kim L, Rao AV, Rao LG.Lycopene II – Effect on osteoblasts: the caroteroid lycopene stimulates cell proliferation and alkaline phosphatase activity of SaOS-2 cells. J Med Food 2003; 6:79-86. . Epidemiological studies have shown that women with postmenopausal osteoporosis have lower plasma lycopene levels than those with – out such a change in bone metabolism 15 Yang Z, Zhang Z, Penniston KL, et al. Serum carotenoid concentrations in post- menopausal wo-men from the United States with and without osteoporosis. Int J Vitam Nutr Res. 2008; 78:105-11. . On the other hand, it was shown very recently that lycopene supplementation in postmenopausal women increases plasma levels of lycopene and at the same time significantly reduces bone resorption markers16 Mackinnon ES, Rao AV, Josse RG, Rao LG. Supplementation with the antioxidant lycopene significantly decreases oxidative stress parameters and the bone resorption marker N-telopep- tide of type I collagen in postmenopausal women. Osteoporos Int. 2011; 22:1091-101. (Figure 7)

while a restriction brings about the opposite effect 17
Mackinnon ES, Rao AV, Rao LG. Dietary restriction of lycopene for a period of one month resulted in significantly increased biomarkers of oxidative stress and bone resorption in post- menopausal women. J Nutr Health Aging. 2011; 15:133-8.
. In the long term, the beneficial effect of lycopene on bone tissue is evidenced by a significant reduction in hip fractures and non- vertebral fractures, as indicated by data from the Framingham Osteo porosis Study 18 Sahni S, Hannan MT, Blumberg J, et al. Protective effect of total carotenoid and lycopene intake on the risk of hip fracture: a 17-year follow-up from the Framingham Osteoporosis Study. J Bone Miner Res. 2009; 24:1086-94. .


References   [ + ]

1. Cummings SR, Melton LJ. Epidemiology and outcomes of osteoporotic fractures. Lancet. 2002; 359:1761-7.
2. Garnero P, Sornay-Rendu E, Chapuy MC, Delmas PD. Increased bone turnover in late post- menopausal women is a major determinant of osteoporosis. J Bone Miner Res. 1996; 11:337-49.
3. Syed FA, Ng AC. The pathophysiology of the aging skeleton. Curr Osteoporos Rep. 2010; 8:235-40.
4. Zhang YB, Zhong ZM, Hou G, et al. Involvement of oxidative stress in age-related bone loss. J Surg Res. 2011; 169:e37-42.
5.
Maggio D, Barabani M, Pierandrei M, et al. Marked decrease in plasma antioxidants in aged osteoporotic women: results of a cross-sectional study. J Clin Endocrinol Metab. 2003; 88:1523-7.
6. Rao LG. Will tomatoes prevent osteoporosis? Endocrinology Rounds 2005; 5(2).
7. Banfi G, Iorio EL, Corsi MM. Oxidative stress, free radicals and bone remodeling. Clin Chem Lab Med. 2008;46: 1550-5.
8. Halleen JM, Räisänen S, Salo JJ, et al. Intracellular fragmentation of bone resorption products by reactive oxygen species generated by osteoclastic tartrate-resistant acid phos- phatase. J Biol Chem. 1999; 274:22907-10.
9. Liu H-C, Cheng R-M, Lin F-H, Fang H-W. Sintered beta-dicalcium phosphate particles in- duce intracellular reactive oxygen species in rat osteoblasts. Biomed Eng Appl Basis Commun 1999; 11:259-64.
10. Berger CE, Horrocks BR, Datta HK. Direct non-genomic effect of steroid hormones on su- peroxide generation in the bone resorbing osteoclasts. Molecular and Cellular Endocrinology 1999; 149:53-59.
11. Wagner AH, Schroeter MR, Hecker M. 17╬▓-estradiol inhibition of NADPH oxidase expres- sion in human endothelial cells. FASEB J 2001; 15:2121-30.
12. Clarke R, Leonessa F, Welch JN, Skaar TC. Cellular and molecular pharmacology of antie- strogen action and resistance. Pharmacol Rev 2001; 53:25-71.
13. Rao LG, Krishnadev N, Banasikowska K, Rao AV. Lycopene I ÔÇô Effect on osteoclasts: lycopene inhibits basal and parathyroid hormone-stimulated osteoclast formation and mineral re- sorption mediated by reactive oxygen species in rat bone marrow cultures. J Med Food 2003; 6:69-78.
14. Kim L, Rao AV, Rao LG.Lycopene II – Effect on osteoblasts: the caroteroid lycopene stimulates cell proliferation and alkaline phosphatase activity of SaOS-2 cells. J Med Food 2003; 6:79-86.
15. Yang Z, Zhang Z, Penniston KL, et al. Serum carotenoid concentrations in post- menopausal wo-men from the United States with and without osteoporosis. Int J Vitam Nutr Res. 2008; 78:105-11.
16. Mackinnon ES, Rao AV, Josse RG, Rao LG. Supplementation with the antioxidant lycopene significantly decreases oxidative stress parameters and the bone resorption marker N-telopep- tide of type I collagen in postmenopausal women. Osteoporos Int. 2011; 22:1091-101.
17.
Mackinnon ES, Rao AV, Rao LG. Dietary restriction of lycopene for a period of one month resulted in significantly increased biomarkers of oxidative stress and bone resorption in post- menopausal women. J Nutr Health Aging. 2011; 15:133-8.
18. Sahni S, Hannan MT, Blumberg J, et al. Protective effect of total carotenoid and lycopene intake on the risk of hip fracture: a 17-year follow-up from the Framingham Osteoporosis Study. J Bone Miner Res. 2009; 24:1086-94.