INTERACTION OF FLAXSEED AND LOW DOSE ESTROGEN ON BONE METABOLISM IN THE OVARIECTOMIZED RAT MODEL OF POSTMENOPAUSAL OSTEOPOROSIS

 

Sandra M. Sacco1, Jessica M.Y. Jiang1, Sandra Reza-López1, David W.L. Ma1,2, Lilian U. Thompson1, Wendy E. Ward1

1Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; 2Department of Human Health & Nutritional Sciences, College of Biological Science, University of Guelph, Ontario, Canada

 

ABSTRACT

Flaxseed (FS) is a rich source of lignans and alpha-linolenic acid (ALA), components that may modulate bone metabolism.  Many postmenopausal women consume complementary health products such as FS in addition to pharmacological agents such as estrogen replacement therapy (E2) for additional support for menopausal-related symptoms such as hot flushes and bone loss.  However, little is known about the therapeutic potential of FS in postmenopausal osteoporosis or its potential interaction with E2, particularly low dose E2 which may have lesser adverse effects than standard doses of estrogen.  The study objectives were to determine the effects of 10% dietary FS, low dose E2 and their combination on (a) bone mineral density (BMD); (b) biomechanical bone strength, a surrogate measure of fracture risk; and (c) bone fatty acid composition in an ovariectomized (ovx) rat model of postmenopausal osteoporosis. Ovx rats were fed a basal diet and treated with: 1) 10% ground FS; 2) E2 implant; 3) 10% FS + E2; or 4) no treatment (negative control) for 12 weeks.  A sham-operated group was included as a positive control.  The estrogen pellet mimicked low-dose estrogen that is currently prescribed to postmenopausal women.  At the end of the 12 week intervention, bone mineral density (BMD), biomechanical bone strength, and fatty acid composition were measured at multiple skeletal sites. Compared to either treatment alone, FS + E2 resulted in the highest BMD and peak load at the lumbar vertebrae with no effect on bone mineral or strength in long bones.  Both the lumbar vertebrae and tibias were responsive to changes in dietary fat as FS and FS + E2 resulted in significantly higher relative levels of ALA and eicosapentaenoic acid, and lower relative levels of linoleic acid, arachidonic acid and n-6/n-3 ratio compared to all other groups.  Thus, FS combined with low dose E2 provides the greatest protection against ovariectomy-induced bone loss compared to either treatment alone. This benefit is site-specific to vertebrae with no benefit to long bones. This study demonstrates that FS, rich in ALA, alters fatty acid composition in rat bones.