Decline in Bone Mass During Weight Loss: A Cause for Concern?

Abstract

C linicians spend countless hours counseling obese patients about weight loss, and the scientific literature is teeming with studies comparing the effectiveness of diets for attaining and maintaining weight loss in the setting of obesity. Among bone and mineral researchers, there is increasing interest in understanding the skeletal effects of both obesity and the weight loss undertaken to treat it. (1,2) However, the treatment of obesity is not the only potential indication for caloric restriction (CR). For years, some individualsmany already at normal weight-have pursued CR with the desire to slow the biological rate of aging and to increase longevity. (3) This potential was explored in the Comprehensive Assessment of Long-term Effects of Reduced Intake of Energy (CALERIE) phase 2 trial, a 2-year randomized controlled trial (RCT) that tested the feasibility, safety, and efficacy of CR in nonobese young and middle-aged adults. Effects on the primary outcomes of resting metabolic rate and core body temperature have been published. (4) In this issue of the Journal of Bone and Mineral Research, Villareal and colleagues (5) report the effects of the CR intervention on bone metabolism and BMD.CALERIE phase 2 enrolled adults 20 to 50 years old with BMI 22 to 28 kg/m 2 , randomizing 218 participants to CR or ad libitum control diets. The CR intervention was designed to produce weight loss during the first year followed by weight maintenance during the second year. The CR group achieved an average 11.7% CR over the 2 years, resulting in a mean weight loss from baseline of 8.4 kg at 12 months (an 11.5% decrease) and 7.5 kg at 24 months (a 10% decrease). Weight change in the control group was negligible. Villareal and colleagues (5) show that spine and proximal femur BMD declined significantly in the CR group, with a 2% decline by 2 years. Markers of bone resorption increased at 6 and 12 months in the CR group, and the bone formation marker bone-specific alkaline phosphatase decreased at 12 and 24 months.Should we be concerned that this decline in bone mass will mean a higher risk of fracture in the future? Or, need we not be concerned because the decline is simply the skeleton's appropriate adaptation to a new, lower body weight? Before attempting to answer these questions, it may be useful to review what we have learned from other human studies about the skeletal effects of weight loss.Most of the published studies addressing weight loss and bone health have examined older adults. Large epidemiologic studies have shown clearly that weight loss is associated with higher fracture risk in older adults, (6)(7)(8)(9)(10)(11)(12)(13)(14) although such studies are generally limited by the possibility that the weight loss was in part the unintentional result of illness that also negatively impacted bone. This potential for confounding prompted the questioning of older women and men in two large prospective cohort studies about weight loss intention. (15,16) Even voluntary weight loss in the setting of overweight or obesity pred...

Effects of obesity treatments on bone mineral density, bone turnover and fracture risk in adults with overweight or obesity

“…In contrast to this finding of hip BMD loss with long-term energy restriction in younger adults, diet-induced weight loss in younger adults -unlike in older adults -has not been associated with similar decreases in BMD despite weight losses of 7%-10% from baseline [90][91][92]. Higher muscle mass and the hormonal profile of younger adults are thought to protect against the negative skeletal effects of diet-induced weight loss [93]. The aforementioned negative effects of long-term energy restriction versus ad libitum intake could thus be attributed to the lower fat free mass of the non-obese younger adults studied in that trial, compared to the higher fat free mass of individuals with overweight or obesity [89].…”

“…Similarly, in a randomized controlled trial in overweight pre-menopausal women, both adequate as well as high calcium intakes were shown to attenuate BMD loss during weight loss [90]. In addition, randomized controlled trials have found that higher protein diets (~86 g/day or 24% of energy intake) confer protection against significant bone loss and may decrease bone turnover during diet-induced weight loss [12,37,93,108]. The benefits of vitamin D supplementation to preserve hip BMD during dietary restriction-induced weight loss have recently been called into question, with the observation that it did not attenuate hip BMD loss in a randomized placebo-controlled trial involving 218 post-menopausal women with vitamin D insufficiency [109].…”

“…There is speculation that bone loss in response to dietinduced weight loss is a normal adaptation to a lighter body [93], akin to the finding that significant reductions in fat free mass are also a normal adaptation to weight loss in adults with overweight or obesity [94]. Furthermore, it has been suggested that while BMD may decline due to diet-induced weight loss, bone quality -as assessed by high resolution magnetic resonance imaging of trabecular bone microarchitecture -does not [95].…”

“…In one of these meta-analyses, resistance training combined with high-impact weight bearing exercises was found to be better at enhancing BMD in postmenopausal women than resistance training alone [101]. Moreover exercise, particularly weight-bearing exercise, has been shown to reduce BMD losses during dietary restriction [93,103]. In addition, exercise-induced weight loss without dietary restriction does not appear to induce the significant decreases in BMD that have been observed with weight loss induced by dietary restriction alone [104].…”

“…In keeping with a role of nutrient depletion in promoting bone loss, BMD loss with obesity treatments can be significantly attenuated or prevented by ensuring adequate dietary (or supplemental) intake of calcium, protein andin the bariatric surgery population -potentially also vitamin D [12,93]. A randomized controlled trial showed that in young adults, preserving normal dietary levels of calcium during moderate energy restriction, with or without exercise, helped to conserve hip and total body BMD during weight loss [91].…”