The Effect of Intentional Weight Loss on Fracture Risk in Persons With Diabetes: Results From the Look AHEAD Randomized Clinical Trial

Abstract

Intentional weight loss is an important treatment option for overweight persons with type 2 diabetes mellitus (DM), but the effects on long term fracture risk are not known. The purpose of this Look AHEAD analysis was to evaluate whether long term intentional weight loss would increase fracture risk in overweight or obese persons with DM. Look AHEAD is a multicenter, randomized clinical trial. Recruitment began in August 2001 and follow-up continued for a median of 11.3 years at 16 academic centers. 5145 persons aged 45 – 76 with DM were randomized to either an intensive lifestyle intervention (ILI) with reduced calorie consumption and increased physical activity designed to achieve and maintain ≥7% weight loss or to diabetes support and education intervention (DSE). Incident fractures were ascertained every 6 months by self-report and confirmed with central adjudication of medical records. The baseline mean age of participants was 59 years, 60% were women, 63% were Caucasian, and the mean BMI was 36 kg/m2. Weight loss over the intervention period (median 9.6 years) was 6.0% in ILI and 3.5% in DSE. 731 participants had a confirmed incident fracture (358 in DSE v. 373 in ILI). There were no statistically significant differences in incident total or hip fracture rates between the ILI and DSE groups. However, compared to the DSE group, the ILI group had a statistically significant 39% increased risk of a frailty fracture (HR = 1.39, 95% CI 1.02, 1.89). An intensive lifestyle intervention resulting in long term weight loss in overweight/obese adults with DM was not associated with an overall increased risk of incident fracture but may be associated with an increased risk of frailty fracture. When intentional weight loss is planned, consideration of bone preservation and fracture prevention is warranted.

Effect of Exercise Modality During Weight Loss on Bone Health in Older Adults With Obesity and Cardiovascular Disease or Metabolic Syndrome: A Randomized Controlled Trial

“…(7) Importantly, newly published results from the Look AHEAD study (the only RCT, to our knowledge, which has examined the effect of long term intentional weight loss on fracture incidence in overweight and obese adults) confirms that 6–9% weight loss achieved and maintained over nearly a decade increases frailty fracture by 39%, (58) with concomitant loss in BMD (59,60) -although it is worth noting that overall fracture incidence was the same for those randomized to weight loss versus education control. While it remains to be determined if or how strongly clinicians should counsel older patients with obesity about the impact of intentional weight loss on skeletal health, (5) results from this study, and others, (31,32,61) point toward a recommendation to couple resistance training with dietary induced weight loss to optimize the musculoskeletal response.…”

Effect of Aerobic or Resistance Exercise, or Both, on Bone Mineral Density and Bone Metabolism in Obese Older Adults While Dieting: A Randomized Controlled Trial

“…The continued increasing prevalence of obesity in older adults in the US and other more developed countries is a major public health concern exacerbated by the age‐related decline in physical function that results in frailty, decrease in quality of life, and increase in nursing home admissions . However, the appropriate treatment approach for obesity in older adults remains controversial because of the apprehension that weight loss may potentially worsen the age‐related decline in muscle mass and also bone mass that could increase the risk for fractures . Therefore, it has been recommended that weight loss therapy in older adults should include an intervention such as regular exercise to prevent bone and muscle loss …”

Impact of Body Weight Dynamics Following Intentional Weight Loss on Fracture Risk: Results from The Action for Health in Diabetes Study

“…The study was approved by local Institutional Review Boards and all participants provided informed consent. Details on the study design and baseline characteristics have previously been published, along with treatment effects on BMD and fracture . The primary analysis of this work includes 1885 (of 2570) Intensive Lifestyle Intervention (ILI) participants who were successful at losing any weight during the first year of the study ( n = 2290) and had at least two follow‐up weights (excluded n = 301), no fractures prior to year 4 (excluded n = 77), and non‐missing covariate data (excluded n = 27).…”

“…Overweight or obese individuals with diabetes are often prescribed weight loss to improve glycemic control, yet weight loss may further augment fracture risk . Indeed, recent results from the Look AHEAD study suggest 6% to 9% weight loss achieved and maintained over nearly a decade is associated with significantly reduced bone mineral density (BMD) and increased risk of hip, pelvis, and upper arm fracture . Data also suggest that bone mass is not recovered when lost weight is regained, raising concern about the long‐term impact of repeated weight loss attempts on bone health.…”

“…(3) Indeed, recent results from the Look AHEAD study suggest 6% to 9% weight loss achieved and maintained over nearly a decade is associated with significantly reduced bone mineral density (BMD) (4,5) and increased risk of hip, pelvis, and upper arm fracture. (6) Data also suggest that bone mass is not recovered when lost weight is regained, (7,8) raising concern about the long-term impact of repeated weight loss attempts on bone health. Given the well-known recidivism of obesity, (9) surprisingly little is known about the effect of weight regain or weight cycling on incident fracture risk.…”