Deviations from the ideal body weight have long been found to be associated with higher risks for various diseases. Both underweight and overweight are tied to co-morbidities. Obesity is positively associated with many chronic disorders such as hypertension, dyslipidemia, type 2 diabetes mellitus, coronary heart disease, and certain cancers. Interestingly, some studies found that high body mass index (BMI) does not have an effect on total mortality in people who keep a healthy lifestyle [1]. Furthermore, while abdominal adiposity is a definite marker of risk, BMI values higher than 25 kg/m2 were shown to actually be protective, whereas BMI < 18.5 kg/m2 significantly increased mortality risk in middle-aged women [2]. Low body weight does not catch much public attention, since it is usually considered the result of improper eating habits or severe, chronic illnesses. In contrast, great efforts have always been made to fight obesity, ‘the disease of the modern world’. Unfortunately, drug therapies for obesity were found either ineffective or unsafe, and therefore, healthy diet and physical activity remain the basis for any intervention. To lose weight is simple, since all it takes is to eat less. This is why short-term weight loss programs do succeed. The major problem is how to maintain the weight achieved for a longer term, and this is where most people fail. But during this ‘zig-zag’ when weight is lost and then regained, some metabolic alterations that accompany this course may not be reversible.

Two recent, small-scale studies reported on the effects of bi-directional weight changes (initially losing, then regaining weight) on bone parameters [3,4]. In the first study [3], 23 postmenopausal women completed a 6-month, exercise-based, weight loss program and were followed until month 18. Dual-energy X-ray absorptiometry (BMD) was performed at baseline, 6, and 18 months. At baseline, subjects were aged 56.8 ± 5.4 years (mean ± standard deviation), 10 years postmenopausal, and their mean BMI was 29.6 kg/m2. They lost mean 3.9 kg during the weight loss intervention and during follow-up they regained 2.9 kg. Six months of weight loss resulted in a significant decrease in mean lumbar spine (LS) (-1.7%; p = 0.002) and hip (-0.04%; p = 0.03) BMD that was accompanied by an increase in a biomarker of bone resorption (CTX). However, weight regain was not associated with increased bone density (mean LS BMD 0.05%; p = 0.15, mean hip BMD -0.60%; p = 0.81) or decreased bone resorption.

In the second study, 24 obese or overweight women (BMI 25.8–42.5 kg/m2) with at least two risk factors for the metabolic syndrome participated in a12-month study that examined the effects of prescribed weight loss and regain on bone turnover and on BMD [4]. During the first 6 months, participants lost ~ 10% of their initial body weight via energy restriction and supervised aerobic exercise. Then they regained about 50% of the lost weight. Results were very similar to those of the previous study, with bone loss during the first phase, but no change was recorded when the weight partially increased during the second phase of the study. Also, an increase in bone markers (osteocalcin and CTX) was not reversed following weight regain. 

A decade ago, Fogelholm and colleagues investigated the same clinical scenario in 74 premenopausal women with mean BMI of 34 kg/m2 [5]. Three-month weight reduction with a very-low-energy diet led to mean weight loss of 13.2 kg, accompanied by decreased lumbar, trochanteric and radial BMD (p < 0.05). Later on, an average 62% of the weight loss was regained but, despite that, at the end of the study (month 36), lumbar and femoral neck BMD were still lower than initially (p < 0.05).

Amos Pines
Department of Medicine ‘T’, Ichilov Hospital, Tel-Aviv, Israel

References
1. Matheson EM, King DE, Everett CJ. Healthy lifestyle habits and mortality in overweight and obese individuals. J Am Board Fam Med 2012;25:9–15.
http://www.ncbi.nlm.nih.gov/pubmed/22218619
2. Tice JA, Kanaya A, Hue T, et al. Risk factors for mortality in middle-aged women. Arch Intern Med 2006;166:2469–77.
http://www.ncbi.nlm.nih.gov/pubmed/17159012
3. 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;19:2345–50.
http://www.ncbi.nlm.nih.gov/pubmed/21852813
4. Hinton PS, Rector RS, Linden MA, et al. Weight-loss-associated changes in bone mineral density and bone turnover after partial weight regain with or without aerobic exercise in obese women. Eur J Clin Nutr 2011 Dec 21. Epub ahead of print.
http://www.ncbi.nlm.nih.gov/pubmed/22190134
5. Fogelholm GM, Sievänen HT, Kukkonen-Harjula TK, Pasanen ME. Bone mineral density during reduction, maintenance and regain of body weight in premenopausal, obese women. Osteoporos Int 2001;12:199–206.
http://www.ncbi.nlm.nih.gov/pubmed/11315238
6. Forsmo S, Langhammer A, Schei B. Past and current weight change and forearm bone loss in middle-aged women: the Nord-Trøndelag Health Study, Norway. Menopause 2009;16:1197–204.
http://www.ncbi.nlm.nih.gov/pubmed/19455067
7. De Laet C, Kanis JA, Odén A, et al. Body mass index as a predictor of fracture risk: a meta-analysis. Osteoporos Int 2005;16:1330–8.
http://www.ncbi.nlm.nih.gov/pubmed/15928804
8. Siris ES, Baim S, Nattiv A. Primary care use of FRAX: absolute fracture risk assessment in postmenopausal women and older men. Postgrad Med 2010;122:82–90.
http://www.ncbi.nlm.nih.gov/pubmed/20107292
9. Black DM, Steinbuch M, Palermo L, et al. An assessment tool for predicting fracture risk in postmenopausal women. Osteoporos Int 2001;12:519–28.
http://www.ncbi.nlm.nih.gov/pubmed/11527048
10. Teng K. Premenopausal osteoporosis, an overlooked consequence of anorexia nervosa. Cleve Clin J Med 2011;78:50–8.
http://www.ncbi.nlm.nih.gov/pubmed/21199907
11. Mehler PS, Cleary BS, Gaudiani JL. Osteoporosis in anorexia nervosa. Eat Disord 2011;19:194–202.
http://www.ncbi.nlm.nih.gov/pubmed/21360368
12. Bales CW, Buhr G. Is obesity bad for older persons? A systematic review of the pros and cons of weight reduction in later life. J Am Med Dir Assoc 2008;9:302–12.
http://www.ncbi.nlm.nih.gov/pubmed/18519110