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American Journal of Clinical Nutrition, Vol. 72, No. 3, 679-680, September 2000
© 2000 American Society for Clinical Nutrition


Editorials

Provocative relation between soy and bone maintenance1,2

John W Erdman, Jr, Rachel J Stillman and Richard A Boileau

1 From the Division of Nutritional Sciences, University of Illinios, Urbana.

See corresponding article on page844.

2 Address reprint requests to JW Erdman Jr, Division of Nutritional Sciences, University of Illinois, 449 Bevier Hall, 905 S Goodwin Avenue, Urbana, IL 61801. E-mail: j-erdman{at}uiuc.edu.

There has been a substantial increase in research on the potential health aspects of soy protein and soy phytoestrogens since the publication of the Proceedings of the First International Symposium on the Role of Soy in Preventing and Treating Chronic Disease in 1995 (1). The data showing a significant reduction in serum cholesterol with soy protein consumption were strong enough that in October 1999 the Food and Drug Administration approved a health claim for food labels on products that contain >=6.25 g soy protein/serving. Other soy and health relations are less clear.

The effects of soy and soy phytoestrogens on bone maintenance are under active evaluation. Trials with ovariectomized rats suggested that soy with isoflavones compared with ethanol-washed soy (essentially devoid of isoflavones) prevents the bone loss associated with the reduction of endogenous estrogen that occurs with menopause (2). In contrast, supplementation of surgically postmenopausal cynomolgus monkeys with conjugated equine estrogens prevented bone loss, but soy did not (3).

In the first published human trial, we found that supplementing postmenopausal woman for 6 mo with 40 g soy protein/d containing 90 but not 45 mg isoflavones/d (aglycone units) significantly increased bone mineral content (BMC) and bone mineral density (BMD) of the lumbar spine but not of other bone sites (4). In this issue of the Journal, Alekel et al (5) give the results of a second 6-mo feeding trial with soy that specifically evaluated the effects of soy with isoflavones (80 mg/d) and with isoflavones reduced to 4.4 mg/d on bone sparing in perimenopausal women. Although there were some differences between the trials (Table 1Go), Alekel et al also found that soy with high amounts of isoflavones attenuated bone loss from the lumbar spine. The only other report of a feeding trial was an abstract from Gallagher et al (6). In that trial, no effect was found on spine or femur BMD of postmenopausal woman supplemented with soy with 3 different amounts of isoflavones after 9 mo.


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TABLE 1.. Comparison of studies by Alekel et al and Potter et al1
 
As noted by Alekel et al (5), 24 wk is a short time for a dietary study of bone loss because the bone remodeling cycle ranges up to 80 wk in length (7). It would be premature to assume that soy with isoflavones has a significant long-term bone-sparing effect or that soy reduces bone fractures of the spine. Studies of 2 or 3 y in length are necessary to test for long-term bone-sparing effects. However, these 2 published studies along with results from trials with ipriflavone (8), a synthetic isoflavone, on vertebral bone loss provide strong support for longer studies. It is interesting that one of the metabolites of ipriflavone is daidzein, one of the isoflavones in soy (9).

Note that the spine was the bone site affected by soy with isoflavones (Table 1Go). Results from the Postmenopausal Estrogen/Progestin Interventions Trial (10) showed a greater responsiveness to various estrogen treatments in the spine than in the hip. Duan et al (11) suggested that hormone replacement therapy may be a more effective means of reducing the risk of spine than of hip fractures. Trabecular bone is known to have a higher turnover rate than does cortical bone. Thus, the lumbar spine, which is relatively high in trabecular bone, should be more sensitive to compounds that are thought to affect remodeling, such as estrogens and phytoestrogens.

In a recent editorial focused on the potential role of soy phytoestrogens in postmenopausal women, Clarkson (3) concluded that the effects of soy or phytoestrogen supplements on postmenopausal bone loss were uncertain. Messina (9) labeled the relation between isoflavones and bone health as "provocative." We feel that the positive effects in these 2 trials warrant further long-term studies. It would be a great benefit to peri- and postmenopausal woman if soy with isoflavones alone or with other therapy were shown to attenuate bone loss in the spine, providing these women with an alternative approach to hormone therapy for maintaining bone.

REFERENCES

  1. Messina M, Erdman JW Jr. First International Symposium on the Role of Soy in Preventing and Treating Chronic Disease. J Nutr 1995;125(suppl):567S–808S.
  2. Arjmandi BH, Getlinger MJ, Goyal NV, et al. Role of soy protein with normal or reduced isoflavone content in reversing bone loss induced by ovarian deficiency in rats. Am J Clin Nutr 1998;68(suppl): 1358S–63S.[Abstract]
  3. Clarkson TB. Soy phytoestrogens: what will be their role in postmenopausal hormone replacement therapy? Menopause 2000;7:71–5.[Medline]
  4. Potter SM, Baum JA, Teng H, Stillman, RJ, Shay NF, Erdman JW Jr. Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. Am J Clin Nutr 1998; 68(suppl):1375S–9S.[Abstract]
  5. Alekel DL, St Germain A, Peterson CT, Hanson KB, Stewart JW, Toshiya T. Isoflavone-rich soy protein isolate attenuates bone loss in the lumbar spine of perimenopausal women. Am J Clin Nutr 2000;72:844–52.[Abstract/Free Full Text]
  6. Gallagher JC, Rafferty K, Haynatzka V, Wilson M. The effect of soy protein on bone metabolism. J Nutr 2000;130:667S (abstr).
  7. Heaney RP. The bone-remodeling transient: implications for the interpretation of clinical studies of bone mass change. J Bone Miner Res 1994;9;1515–23.[Medline]
  8. Ohta H, Kumukai S, Makita K, Masuzawa T, Nozawa S. Effects of 1-year ipriflavone treatment on lumbar bone mineral density and bone metabolic markers in postmenopausal women with low bone mass. Horm Res 1999;51:178–83.[Medline]
  9. Messina MJ. Legumes and soybeans: overview of their nutritional profiles and health effects. Am J Clin Nutr 1999;70(suppl):439S–50S.[Abstract/Free Full Text]
  10. Effects of hormone therapy on bone mineral density: results from the postmenopausal estrogen/progestin interventions (PEPI) trial. The Writing Group for the PEPI. JAMA 1996;276:1389–96.[Abstract/Free Full Text]
  11. Duan Y, Tabensky A, DeLuca V, Seeman E. The benefit of hormone replacement therapy on bone mass is greater at the vertebral body than posterior processes or proximal femur. Bone 1997;21:447–51.[Medline]



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