Menopause Live (21 November, 2011) from IMS

Villalon and colleagues report a study of the effect of weight loss and weight regain on bone mineral density (BMD) in postmenopausal overweight or obese women [1]. They measured BMD and body composition by dual-energy X-ray absorptiometry, biochemical markers of bone formation and resorption, and aerobic power by spirometry (VO2 peak). They found that weight loss over a 6-month period results in significant loss of bone from the lumbar spine and hip. Subsequent weight regain over a 12-month period did not produce any increase in BMD. They conclude that weight maintenance and fitness may be a better strategy than weight reduction for bone and metabolic health.

Comment
This study has many limitations and drawbacks. First, the authors are using data drawn solely from the placebo arm of a prospective, randomized trial, which was presumably not a pre-planned part of their original study design. Thus, the study is uncontrolled with regard to weight loss and weight regain in this placebo group, as there are no matched weight-steady women for comparison. Second, the numbers involved are extremely small, 23 women. They then split them into subgroups according to being above or below the median weight loss over the 6-month period, resulting in even smaller numbers. Third, two different densitometers were used and the results between them may not be strictly comparable, even though each individual was measured only on one system. The weight reduction was achieved by a supervised endurance exercise program. No mention is made of their diet and whether this changed during the study. Furthermore, no mention is made whether or not the participants continued with any unsupervised exercise during the 12-month follow-up. The median weight loss achieved was 3.9 kg, but there was quite a wide range of values. Body composition measurements showed that this weight loss was due to a significant decrease in fat mass with no change in fat-free mass. This was associated with significant loss of BMD, but these changes were small in the lumbar spine (-1.7%) and negligible in the hip (-0.04%). The authors state that this was accompanied by an increase in a marker of bone resorption (CTX), but this was not statistically significant. There was a significant decrease in a bone formation marker (bone ALP) but this decrease of -0.7% would appear biologically meaningless. During the 12-month follow-up there was a significant increase in fat mass, with again no change in fat-free mass. There were no significant changes in the BMD or bone biochemical markers during the follow-up. 

It is impossible to draw any meaningful conclusions from this study. The association between lean body mass and bone has long been known [2], but the association between fat mass and bone is more controversial [3-5]. However, it seems likely that increased fat mass has a positive effect on the skeleton, not only through load bearing but also through production of factors that influence bone such as estrogens and adipocytokines [6]. Whether weight loss has a meaningful adverse effect on bone mass and fracture risk remains to be determined. Of much more importance is the association between obesity and increased risk for cardiovascular disease [7] and for breast cancer [8]. Thus, weight normalization should always be encouraged, irrespective of any minor deleterious effect on the skeleton.

John Stevenson
National Heart & Lung Institute, Imperial College London, Royal Brompton Hospital, London, UK

References
1. Villalon KL, Gozansky WS, Van Pelt RE, et al. A losing battle: weight regain does not restore weight loss-induced bone loss in postmenopausal women. Obesity 2011; Aug 18. Epub ahead of print
http://www.ncbi.nlm.nih.gov/pubmed/21852813
2. Stevenson JC, Banks LM, Spinks TJ, et al. Regional and total skeletal measurements in the early postmenopause. J Clin Invest 1987;80:258-62
http://www.ncbi.nlm.nih.gov/pubmed/3597775
3. Yoo HJ, Park MS, Yang SJ, et al. The differential relationship between fat mass and bone mineral density by gender and menopausal status. J Bone Miner Metab 2011; Jun 7. Epub ahead of print
http://www.ncbi.nlm.nih.gov/pubmed/21644057
4. El Hage R, Jacob C, Moussa E, Baddoura R. Relative importance of lean mass and fat mass on bone mineral density in a group of Lebanese postmenopausal women. J Clin Densitom 2011;14:326-31
http://www.ncbi.nlm.nih.gov/pubmed/21600821
5. Saarelainen J, Honkanen R, Tupperainen M, Jurvelin JS, Niskanen L. Body fat distribution is associated with lumbar spine bone density independently of body weight in postmenopausal women. Maturitas 2011;69:86-90
http://www.ncbi.nlm.nih.gov/pubmed/21388758
6. Reid IR. Relationships between fat and bone. Osteoporosis Int 2008;19:595-606
http://www.ncbi.nlm.nih.gov/pubmed/17965817
7. Van Pelt RE, Evans EM, Schechtman KB, Ehsani AA, Kohrt WM. Contributions of total and regional fat mass to risk of cardiovascular disease in older women. Am J Physiol Endocrinol Metab 2002;282:E1023-8
http://www.ncbi.nlm.nih.gov/pubmed/11934666
8. Krebs EE, Taylor BC, Cauley JA, Stone KL, Bowman PJ, Ensrud KE. Measures of adiposity and risk of breast cancer in older postmenopausal women. J Am Geriatr Soc 2006;54:63-9
http://www.ncbi.nlm.nih.gov/pubmed/16420199