Exposure to Flaxseed and its Purified Lignan Reduces Bone Strength in Young but Not Older Male Rats

Abstract

Flaxseed is the richest source of the plant lignan secoisolariciresinol diglycoside (SDG), which is converted to the two major mammalian lignans, enterodiol (ED) and enterolactone (EL), by colonic bacteria. Because both ED and EL can produce biological effects similar to estrogen, exposure to lignans during early stages of development may adversely alter the normal development of bone in males since bone is a hormone-sensitive tissue. To determine whether early exposure to flaxseed or its lignan compromised the acquisition of bone mass or reduced bone strength, male offspring were exposed to one of three diets during lactation only (birth through postnatal day [PND] 21) via mother's milk or continuously from the start of lactation through to adolescence (PND 50) or young adulthood (PND 132). The diets were a basal diet (BD) that was devoid of phytoestrogens, BD containing 10% flaxseed, or BD containing the equivalent quantity of SDG present in a 10% flaxseed diet. To assess bone quantity, the bone mineral content (BMC) and bone mineral density (BMD) of femurs were assessed by dual-energy x-ray absorptiometry. Since the biomechanical properties of bone are indicators of the microarchitecture and thus bone quality, the biomechanical strength of femurs was assessed by three-point bending. At PND 50, ultimate bending stress and Young's modulus, measures of bone strength, were reduced among rats that received the 10% flaxseed diet from PND 0 through PND 50, while there were no marked differences in bone size, BMC, or BMD among groups. Interestingly, this effect does not appear to be due to the lignan in flaxseed, as continuous exposure to the diet containing the equivalent quantity of lignan (10 S diet) did not alter any measures of bone strength. In contrast to PND 50, bone strength did not differ among groups at PND 132, indicating that the compromise in bone strength was not sustained into early adulthood. Bone size, BMC, and BMD continued to be similar among treatment groups at PND 132. In conclusion, exposing male rats to a diet containing 10% flaxseed or an equivalent quantity of lignan either during lactation only or through to early adulthood is safe with respect to bone health, as measures of bone mass and strength were similar to control rats.