Sex Differences in Bone Loss With Weight Loss in the Pounds Lost Trial: Evaluation of Mechanisms
Siegel, Molly Riordan
MetadataShow full item record
CitationSiegel, Molly Riordan. 2016. Sex Differences in Bone Loss With Weight Loss in the Pounds Lost Trial: Evaluation of Mechanisms. Doctoral dissertation, Harvard Medical School.
AbstractPurpose: Obesity is an increasingly prevalent health concern, and according to the CDC, over 2/3 of Americans are overweight or obese. While weight loss has been shown to prevent the medical complications of obesity, it is important to understand potential risks of weight loss in overweight patients. Loss of bone mass is a known complication of weight loss and increases patients’ risk of osteoporosis and fracture(s). Minimizing bone loss should thus be a goal of weight loss treatment. In the POUNDS LOST trial, 811 obese and overweight individuals were randomized to 1 of 4 diets varying in macronutrient content and followed for two years. While participants lost similar amounts of weight across the four diets, females lost BMD at the spine (LS) and femoral neck (FN) while males gained BMD at the LS. The purpose of this study was to understand mechanisms by which females lost BMD with weight loss and males did not.
Methods: In 231 POUNDS LOST participants we analyzed biomarkers of bone turnover (osteocalcin, C-telopeptide), sclerostin, adipokines (leptin, adiponectin), and calcium homeostasis (calcium, 25-OH Vitamin D, PTH) at baseline and after 2 years of weight loss. Multivariate analyses correlated the 2-year changes in these biomarkers with changes in LS BMD and with visceral adipose tissue and evaluated whether there were sex differences in these interactions.
Results: Males lost more weight than females, though the weight change was not different between sexes once adjusted for baseline weight. Change in C-telopeptide was associated with a change in BMD in pre- and post-menopausal females; change in C-telopeptide explained 42 percent of the change in BMD in pre-menopausal females and 9 percent of the change in BMD in post-menopausal females; there was not an association between change in C-telopeptide and change in BMD in males. Males had significantly lower levels of sclerostin at month 24 than pre-and post-menopausal females (1100 pg/mL in males, 1131 pg/mL pre-menopausal females, 1269 post-menopausal females), but sclerostin was not correlated with degree of weight lost or change in BMD. There were no sex differences in the relationship between sclerostin and BMD. There were sex differences in the change in leptin with weight loss (males change -.62 ln ng/mL; pre-menopausal females +0.17 ln ng/mL; post-menopausal females change +0.04 ln ng/mL). There were also sex differences in the relationship of change in leptin to change in BMD. In males, decreases in leptin were associated with an increase in BMD; decrease in leptin accounted for 3.6 percent of the increase in BMD. This relationship was not seen in pre-menopausal females or post-menopausal females. All groups had low vitamin D levels (<30ng/mL)at baseline. There was a relationship between change in vitamin D and change in BMD; however, there were no sex differences in change in vitamin D and change in BMD. There were sex differences in the change in parathyroid hormone with weight loss (males decreased -0.1 pg/mL; pre-menopausal females increased 27.2 pg/mL; post-menopausal females increased 6.3 pg/mL). Change in parathyroid hormone was not associated with a change in BMD, and there were not sex differences in the relationship between change in parathyroid hormone and change in BMD.
Conclusions: Sex differences in bone loss with weight loss may be explained by increased bone resorption as indicated by the biomarker c-telopeptide. The sex differences are seen in both pre- and post-menopausal females, though they are more significant in premenopausal females. Lower leptin levels may have a protective effect on bone in males with weight loss. Vitamin D levels may be low in obese and overweight individuals, and changes to vitamin D are associated with change in BMD in both males and females. Ongoing studies are examining in this cohort whether there are sex differences in the relationships between changes in body composition (fat, BMD and lean tissue) and adipokines and measures of calcium homeostasis.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:40620254