Abstract
Long chain polyunsaturated fatty acids (LCPUFAs) are involved in the regulation of bone metabolism. Increased dietary consumption of n-3, and possibly some n-6, LCPUFAs may limit postmenopausal bone loss. The aim of this study was to determine the effects on bone of specific fatty acids within the n-3 and n-6 LCPUFA families in ovariectomized (OVX) rats. Rats were OVX or sham-operated and fed either a control diet (OVX and sham) or a diet supplemented with 0.5 g/kg body weight/day of γ-linolenic (GLA), eicosapentaenoic (EPA), docosahexaenoic (DHA) ethyl esters or a mixture of all three (MIX) for 16 weeks. Bone mineral content (BMC), area, and density and plasma concentrations of insulin-like growth factor-I, vitamin D, selected biochemical markers of bone metabolism, and parathyroid hormone (PTH) were determined. The OVX-induced decrease in lumbar spine BMC was significantly attenuated by DHA but not by EPA or GLA supplementation or supplementation with a mixture of all three LCPUFAs. Endosteal circumferences of tibiae were significantly greater in DHA and EPA compared to OVX. Plasma C-terminal telopeptide of type I collagen and osteocalcin concentrations were not significantly different in the DHA group compared to OVX. Femur BMC decreased by a significantly greater amount in GLA than OVX, and final plasma PTH concentrations were significantly higher in GLA compared to all other groups. In conclusion, DHA ameliorated OVX-induced bone mineral loss. GLA exacerbated post-OVX bone mineral loss, possibly as a result of PTH-induced bone catabolism.
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References
Kruger M, Horrobin D (1997) Calcium metabolism, osteoporosis and essential fatty acids. A review. Prog Lipid Res 36:131–151
Watkins B, Seifert M (1996) Food lipids and bone health. In: McDonald R, Min D (eds) Food lipids and health. Marcel Dekker, New York
Das UN (2000) Essential fatty acids and osteoporosis. Nutrition 16:386–390
Raisz LG, Pilbeam CC, Fall PM (1993) Prostaglandins—mechanisms of action and regulation of production in bone. Osteoporos Int 3:S136–S140
Conconi MT, Tommasini M, Baiguera S, De Coppi P, Parnigotto PP, Nussdorfer GG (2002) Effects of prostaglandins E1 and E2 on the growth and differentiation of osteoblast-like cells cultured in vitro. Int J Mol Med 10:451–456
Yoshiko Y, Gonsalves P, Hiyama S, Uchida T, Maeda N, Aubin JE (2003) Activation of prostaglandin E receptor EP2 during the osteoprogenitor proliferation-differentiation transition is the major pathway mediating the anabolic effects of PGE2 on osteoblast development in rat calvaria cell cultures. Bone 32:S139–S139
Collins DA, Chambers TJ (1991) Effect of prostaglandins E1, E2, and F2α on osteoclast formation in mouse bone-marrow cultures. J Bone Miner Res 6:157–164
Ono K, Kaneko H, Choudhary S, Pilbeam CC, Lorenzo JA, Akatsu T, Kugai N, Raisz LG (2005) Biphasic effect of prostaglandin E2 on osteoclast formation in spleen cell cultures: role of the EP2 receptor. J Bone Miner Res 20:23–29
Yun AJ, Lee PY (2004) Maladaptation of the link between inflammation and bone turnover may be a key determinant of osteoporosis. Med Hypotheses 63:532–537
Teitelbaum SL (2004) Postmenopausal osteoporosis, T cells, and immune dysfunction. Proc Natl Acad Sci USA 101:16711–16712
Johnson MM, Swan DD, Surette ME, Stegner J, Chilton T, Fonteh AN, Chilton FH (1997) Dietary supplementation with gamma-linolenic acid alters fatty acid content and eicosanoid production in healthy humans. J Nutr 127:1435–1444
Miller CC, Tang W, Ziboh VA, Fletcher MP (1991) Dietary supplementation with ethyl-ester concentrates of fish oil (n-3) and borage oil (n-6) polyunsaturated fatty-acids induces epidermal generation of local putative antiinflammatory metabolites. J Invest Dermatol 96:98–103
Kumar GS, Das UN, Kumar KV, Madhavi N, Das NP, Tan BKH (1992) Effect of n-6 and n-3 fatty-acids on the proliferation of human-lymphocytes and their secretion of TNF-alpha and IL-2 invitro. Nutr Res 12:815–823
Furse RK, Rossetti RG, Zurier RB (2001) Gamma-linolenic acid, an unsaturated fatty acid with anti-inflammatory properties, blocks amplification of IL-1 beta production by human monocytes. J Immunol 167:490–496
Furse RK, Rossetti RG, Seiler CM, Zurier RB (2002) Oral administration of gamma-linolenic acid, an unsaturated fatty acid with anti-inflammatory properties, modulates interleukin-10 production by human monocytes. J Clin Immunol 22:83–91
Decaterina R, Cybulsky MI, Clinton SK, Gimbrone MA, Libby P (1994) The omega-3-fatty-acid docosahexaenoate reduces cytokine-induced expression of proatherogenic and proinflammatory proteins in human endothelial-cells. Arterioscler Thromb 14:1829–1836
Soyland E, Lea T, Sandstad B, Drevon A (1994) Dietary supplementation with very long-chain n-3 fatty-acids in man decreases expression of the interleukin-2 receptor (Cd25) on mitogen-stimulated lymphocytes from patients with inflammatory skin diseases. Eur J Clin Invest 24:236–242
Danno K, Ikai K, Imamura S (1993) Antiinflammatory effects of eicosapentaenoic acid on experimental skin inflammation models. Arch Dermatol Res 285:432–435
Robinson DR, Xu LL, Tateno S, Guo MY, Colvin RB (1993) Suppression of autoimmune-disease by dietary n-3 fatty-acids. J Lipid Res 34:1435–1444
Weiss LA, Barrett-Connor E, von Muhlen D (2005) Ratio of n-6 to n-3 fatty acids and bone mineral density in older adults: the Rancho Bernardo Study. Am J Clin Nutr 81:934–938
Kruger M, Coetzer H, de Winter R, Claassen N (1995) Eicosapentaenoic acid and docosahexaenoic acid supplementation increases calcium balance. Nutr Res 15:211–219
Kruger M, Claassen N, Schlemmer C, Coetzer H (1999) Essential fatty acid supplementation: effect on oestrogen deficiency induced bone loss in the female rat. Calcif Tissue Int 64:63
Weiler HA (2000) Dietary supplementation of arachidonic acid is associated with higher whole body weight and bone mineral density in growing pigs. Pediatr Res 47:692–697
Kruger M, Coetzer H, de Winter R, Gericke G, van Papendorp D (1998) Calcium, gamma-linolenic acid and eicosapentaenoic acid supplementation in senile osteoporosis. Aging Clin Exp Res 10:385–394
Claassen N, Coetzer H, Steinmann C, Kruger M (1995) The effect of different n-6/n-3 essential fatty acid ratios on calcium balance and bone in rats. Prostaglandins Leukot Essent Fatty Acids 53:13–19
Claassen N, Potgieter HC, Seppa M, Vermaak WJH, Coetzer H, Vanpapendorp DH, Kruger MC (1995) Supplemented gamma-linolenic acid and eicosapentaenoic acid influence bone status in young male rats—effects on free urinary collagen cross-links, total urinary hydroxyproline, and bone calcium content. Bone 16:S385–S392
Watkins BA, Shen CL, Allen KGD, Seifert MF (1996) Dietary (n-3) and (n-6) polyunsaturates and acetylsalicylic acid alter ex vivo PGE2 biosynthesis, tissue IGF-I levels, and bone morphometry in chicks. J Bone Miner Res 11:1321–1332
Poulsen RC, Kruger MC (2006) Detrimental effect of eicosapentaenoic acid supplementation on bone following ovariectomy in rats. Prostaglandins Leukot Essent Fatty Acids 75:419–427
Gnudi SRG, Mongiorgi R, Fini M, Zati A, Figus E, Monti S, Ripamonti C (1993) Evaluation of an experimental model of osteoporosis induced in the female rat through ovariectomy. Boll Soc Ital Biol Sper 69:453–460
Kruger MC, Schollum LM (2005) Is docosahexaenoic acid more effective than eicosapentaenoic acid for increasing calcium bioavailability? Prostaglandins Leukot Essent Fatty Acids 73:327–334
Schlemmer C, Coetzer H, Claassen N, Kruger M (1999) Oestrogen and essential fatty acid supplementation corrects bone loss due to ovariectomy in the female Sprague Dawley rat. Prostaglandins Leukot Essent Fatty Acids 61:381–390
Baggio B, Budakovic A, Nassuato MA, Vezzoli G, Manzato E, Luisetto G, Zaninotto M (2000) Plasma phospholipid arachidonic acid content and calcium metabolism in idiopathic calcium nephrolithiasis. Kidney Int 58:1278–1284
Shen C-L, Yeh J, Rasty J, Li Y, Watkins B (2006) Protective effect of dietary long-chain n-3 polyunsaturated fatty acids on bone loss in gonad-intact middle-aged male rats. Br J Nutr 95:462–468
National Research Council (1995) Nutrient requirements of laboratory animals, 4th rev ed. National Academy Press, Washington DC
Rahman M, Bhattacharya A, Banu J, Fernandes G (2005) Reduced bone loss by docosahexaenoic acid (DHA) than eicosapentaenoic acid (EPA) in ovariectomised mice. J Bone Miner Res 20:S127
Li Y, Reinwald S, Seifert M, Watkins B (2003) Dietary docosahexaenoic acid supplementation maintains bone mass in ovariectomised rats. Exp Biol Abstracts B321:188.110
Watkins BA, Li Y, Seifert MF (2006) Dietary ratio of n-6/n-3 PUFAs and docosahexaenoic acid: actions on bone mineral and serum biomarkers in ovariectomized rats. J Nutr Biochem 17:282–289
Andersson S, Holmberg I, Wikvall K (1983) 25-Hydroxylation of C27-steroids and vitamin D3 by a constitutive cytochrome P-450 from rat liver microsomes. J Biol Chem 258:6777–6781
Roborgh JR, de Man TJ (1960) The hypercalcemic activity of dihydrotachysterol2 and dihydrotachysterol3 and of the vitamins D2 and D3 after intravenous injection of the aqueous preparations. II: Comparative experiments on rats. Biochem Pharmacol 3:277–282
Nakane M, Fey TA, Dixon DB, Ma JL, Brune ME, Li YC, Wu-Wong JR (2006) Differential effects of vitamin D analogs on bone formation and resorption. J Steroid Biochem Mol Biol 98:72–77
Sakaguchi K, Morita I, Murota S (1994) Eicosapentaenoic acid inhibits bone loss due to ovariectomy in rats. Prostaglandins Leukot Essent Fatty Acids 50:81–84
Leonard F, Haag M, Kruger M (2001) Modulation of intestinal vitamin D receptor availability and calcium ATPase activity by essential fatty acids. Prostaglandins Leukot Essent Fatty Acids 64:147–150
Brandi M, Fitzpatrick L, Coon H, Aurbach G (1986) Bovine parathyroid cells: cultures maintained for more than 140 population doublings. Proc Natl Acad Sci USA 83:1709–1713
Shemerdiak W, Kukreja S, Johnson P (1981) Effect of prostaglandin E1, E2 or indomethacin on serum parathyroid hormone and calcitonin in the rat. Prostaglandins Med 6:641–645
Qin L, Raggatt LJ, Partridge NC (2004) Parathyroid hormone: a double-edged sword for bone metabolism. Trends Endocrinol Metab 15:60–65
Ishizuya T, Yokose S, Hori M, Noda T, Suda T, Yoshiki S, Yamaguchi A (1997) Parathyroid hormone exerts disparate effects on osteoblast differentiation depending on exposure time in rat osteoblastic cells. J Clin Invest 99:2961–2970
Acknowledgments
This study was funded by Fonterra Brands Ltd., New Zealand. R. C. P. was the recipient of a TAD scholarship from the Tertiary Education Commission, New Zealand.
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Poulsen, R.C., Firth, E.C., Rogers, C.W. et al. Specific Effects of γ-Linolenic, Eicosapentaenoic, and Docosahexaenoic Ethyl Esters on Bone Post-ovariectomy in Rats. Calcif Tissue Int 81, 459–471 (2007). https://doi.org/10.1007/s00223-007-9080-7
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DOI: https://doi.org/10.1007/s00223-007-9080-7