Docosahexaenoic acid and 17 beta-estradiol co-treatment is more effective than 17 beta-estradiol alone in maintaining bone post-ovariectomy

Bone-protective effects of combined treatment with long chain polyunsaturated fatty acids (LCPUFAs) and estrogenic compounds following ovariectomy have previously been reported. Recent evidence suggests the n-3 LCPUFA docosahexaenoic acid (DHA, 22:6n-3) is particularly bone-protective. The aim of this study was to determine whether combined treatment with DHA and estrogenic compounds has a beneficial effect on bone mass in ovariectomized (OVX) rats. Rats were randomized into 9 groups and either ovariectomized (8 groups) or sham-operated (1 group). Using a 2 x 4 factorial design approach, OVX animals received either no estrogenic compound, genistein (20 mg/kg body weight/day), daidzein, (20 mg/kg body weight/day) or 17 beta-estradiol (1 microg/day) with or without DHA (0.5 g/kg body weight/day) for 18 weeks. Bone mineral content (BMC), area (BA), and density (BMD), plasma osteocalcin and IL-6 concentrations, and red blood cell (RBC) fatty acid composition were measured. Femur BMC was significantly greater in animals treated with DHA or 17 beta-estradiol than in ovariectomized controls. Plasma carboxylated osteocalcin was significantly higher in DHA-treated animals and total osteocalcin significantly lower in 17 beta-estradiol-treated animals compared with ovariectomized controls. There were significant interactions between treatment with estrogenic compounds and DHA for femur BMC, plasma IL-6 concentration, and RBC fatty acid composition. Combined treatment with 17beta-estradiol+DHA was more effective than either treatment alone at preserving femur BMC and lowering circulating concentrations of pro-inflammatory IL-6. The percentage of n-3 LCPUFAs in RBCs was significantly greater in animals receiving 17 beta-estradiol+DHA compared with either treatment alone. There was no beneficial effect of combined DHA and phytoestrogen treatment on bone. Results from this study raise the possibility that co-treatment with 17 beta-estradiol and DHA may allow a lower dose of 17 beta-estradiol to be used to provide the same bone-protective effects as when 17 beta-estradiol is administered alone.