Flaxseed enhances the beneficial effect of low-dose estrogen therapy at reducing bone turnover and preserving bone microarchitecture in ovariectomized rats.

Key Findings:

Younger postmenopausal women may safely benefit from lower doses of estrogen therapy to protect from bone loss. This study assessed flaxseed, alone or in combination with estrogen therapy, on bone loss. FS+ low-dose estrogen therapy (LD) attenuated OVX-induced bone turnover exhibited by the lower serum TRAP-5beta, CTX, and osteocalcin compared with the NEG group that was OVX but received no intervention. FS+LD may protect against OVX-induced bone loss and deterioration of bone tissue through modulation of bone cell numbers and bone cell activities. A greater preservation of LV structure was observed. FS enhanced the protective effect of LD on trabecular microarchitecture in the spine. However, markers of bone turnover did not differ between FS+LD and LD. Research is required to determine how FS+LD alters osteoblast and osteoclast activity to result in a greater protection to bone mass, bone microarchitecture and bone strength at the LV.

ABSTRACT:

Our previous research showed greatest protection to vertebral bone mineral density and strength in ovariectomized (OVX) rats when lignan and alpha 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 microg 17 beta-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-5beta (TRAP-5beta)), as well as osteoprotegerin (OPG) and receptor activator of nuclear factor alpha -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-5beta 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. (Authors abstract)