**8. Soy and osteoporosis**

Just as OA greatly affects women more so than men, osteoporosis is a particularly concerning problem for the aging female population. Because intestinal cells contain ER, and because estrogen enhances calcium transport [104], it stands to reason that phytoestrogens like soy may increase intestinal calcium transport. There have been multiple studies researching intestinal transport of calcium and soy, as well as the effect of soy on animal models of osteoporosis, and human studies. A study by our lab in 2001 [104] confirmed that not only does ovariectomy decrease rates of calcium transport, but that soy isoflavones in soy protein promoted calcium absorption in a manner analogous to estrogen without any of the side effects/risk. Pawlowski et al. [105] also found that soy isoflavones were effective in increasing calcium retention in bone, and Arjmandi et al. [84] found that women not on hormone replacement therapy who supplemented soy protein experienced reduced urinary calcium excretion.

Animal studies have yielded positive results for isoflavone's bone sparing properties. A 1998 study [106] by our lab compared casein protein and soy protein in ovariectomized (OVX) rats, and found that soy protein with higher levels of isoflavones spared the femoral bone density decreases brought about by ovariectomy. Our 2006 study [107] found that soy positively affected tibial architectural properties of OVX rats, including trabecular thickness, separation, and number

without preserving BMD. Another study by our lab [108] found that soy protein with or without isoflavones did not preserve BMD in a male rat model of osteoporosis, but did positively affect the biomechanical properties of bone including yield and ultimate force which are measures of elasticity and plasticity in bone. Multiple other studies have concluded that any bone sparing effects of soy consumption are likely due to soy isoflavone content, which increases bone formation and improves the architectural properties of bone [109–112].

Interestingly, while animal studies have been promising for moderate prevention of bone loss, a 2-year Thai study [113] found that soy isoflavones did not significantly reduce bone loss. Similarly, a 3-year study [114] that gave postmenopausal women soy isoflavones did not find significant bone sparing effects, except for the femoral neck which was still only modestly affected by supplementation. The same lab then evaluated the safety of soy isoflavone supplementation by evaluating effects on hormones, endometrial thickness, and any adverse events, finding no negative evidence of treatment effect on this population, once again indicating that soy supplementation is safe. Wong et al. [115] found that 120 mg of soy isoflavones did reduce whole body BMD loss, but did not positively affect common female fracture sites. Studies by our lab [96, 116], and others [117], generally find that soy supplementation for the treatment of osteoporosis generally has little to no effect on BMD, but may still positively affect bone metabolism as well as bone quality.
