Flaxseed enhances the beneficial effect of low-dose estrogen therapy at reducing bone turnover and preserving bone microarchitecture in ovariectomized rats.
Our previous research showed greatest protection to vertebral bone mineral density and strength in ovariectomized (OVX) rats when lignan- and α-linolenic acid-rich flaxseed (FS) is combined with low-dose estrogen therapy (LD) compared with either treatment alone. This study determined the effects of combined FS+LD on serum and tissue markers of bone turnover and microarchitecture to explain our previous findings. Three-month-old OVX rats were randomized to negative control (NEG), FS, LD or FS+LD for 2 or 12 weeks, meaningful time points for determining effects on markers of bone metabolism and bone structure, respectively. Ground FS was added to the AIN-93M diet (100 g/kg diet) and LD (0.42 μg 17β-estradiol/(kg body weight·day)) was delivered by subcutaneous implant. Sham rats were included as positive control. Bone formation (e.g., osteocalcin), bone resorption (e.g., tartrate-resistant acid phosphatase-5β (TRAP-5β)), as well as osteoprotegerin (OPG) and receptor activator of nuclear factor κ-B ligand (RANKL) were analyzed from the 2-week study by commercial assays (serum) and (or) histology (vertebra). Vertebral bone microarchitecture was measured from the 12-week study using microcomputed tomography. In serum, FS+LD and LD induced lower TRAP-5β and osteocalcin, and higher OPG and OPG/RANKL ratio versus NEG and FS (p < 0.05). In vertebrae, FS+LD induced higher OPG and lower osteocalcin versus NEG (p < 0.01) and did not differ from LD and FS. FS+LD improved bone microarchitecture versus NEG, FS, and LD (p < 0.05). In conclusion, FS+LD protects bone tissue because of a reduction in bone turnover. However, elucidating the distinctive action of FS+LD on bone turnover compared with LD requires further investigation.
a Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON M5S 3E2, Canada.
Sandra M
SM
Sacco
Jianmin
J
Chen
Bernhard
B
Ganss
Lilian U
LU
Thompson
Wendy E
WE
Ward
D000818:Animals; D016723:Bone Remodeling / Q000187:drug effects*; D001842:Bone and Bones / Q000033:anatomy & histology* / Q000187:drug effects* / Q000502:physiology; D004958:Estradiol / Q000008:administration & dosage* / Q000494:pharmacology; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D019597:Flax; D010052:Ovariectomy; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D004967:Estrogens; D004958:Estradiol
bone histology; bone microarchitecture; bone turnover; flaxseed; graine de lin; histologie des os; low-dose estrogen therapy; lumbar vertebra; microarchitecture osseuse; ovariectomized rats; rates ovariectomisées; renouvellement des cellules osseuses; vertèbres lombaires; œstrogénothérapie à faible dose