Mediterranean Diet, Physical Activity, and Bone Health in Older Adults: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Understanding the effects of diet and physical activity on bone health may help to mitigate concomitant weight loss- and age-related bone deterioration. Objective: To evaluate the effects of a weight-loss lifestyle intervention on bone mineral density (BMD), bone mineral content (BMC), and low BMD prevalence. Design, Setting, and Participants: The 3-year, parallel-group Prevención con Dieta Mediterránea-Plus (PREDIMED-Plus) randomized clinical trial was conducted at recruiting centers in Spain from October 2013 to December 2016. Men and women (aged 55-75 years) with metabolic syndrome and overweight or obesity, as well as access to dual-energy x-ray absorptiometry (DXA) (from 4 centers in Navarra, Mallorca, Reus, and León), were included in this prespecified secondary analysis. The analysis was conducted from September 1 to October 30, 2024. Intervention: Participants were randomly allocated (1:1) to the intervention or the control. The intervention group followed an energy-reduced Mediterranean diet and increased physical activity, whereas the control group was advised to follow an ad libitum Mediterranean diet with no physical activity promotion. Main Outcomes and Measures: BMD (total femur, lumbar spine [L1-L4], and femoral trochanter) and total BMC were measured using DXA at baseline and at 1 and 3 years of follow-up. T scores from BMD variables were determined, and osteopenia or osteoporosis status was defined as low BMD. Linear and logistic 2-level mixed models were used for main analyses including participants lost to follow-up. Intention-to-treat analysis, completers case analysis, and sensitivity analysis were additionally performed. Results: This study included 924 older adults (mean [SD] age, 65.1 [5.0] years; 454 women [49.1%] and 470 men [50.9%]). Significant differences in mean changes between groups were observed, with an overall 3-year intervention increase in the intervention group (n = 460) compared with the control group (n = 464) in lumbar spine (L1-L4) BMD (between-group differences, -0.1 [95% CI, -0.8 to 0.8] g/cm2 after 1 year and 0.9 [95% CI, 0.1-1.8] g/cm2 after 3 years; overall P = .05). This protective association was observed for women (between-group differences, -0.1 [95% CI, -1.3 to 1.1] g/cm2 after 1 year and 1.8 [95% CI, 0.6-2.9] g/cm2 after 3 years; overall P = .005) but not for men. No overall 3-year intervention effect on total BMC and low BMD prevalence was observed. Conclusions and Relevance: In the PREDIMED-Plus trial, an energy-reduced Mediterranean diet and physical activity lifestyle intervention mitigated weight loss- and age-related BMD decline among older women with metabolic syndrome compared with conventional ad libitum Mediterranean diet recommendations. Weight-loss lifestyle interventions with longer follow-up are warranted in the future to confirm these results in relation to bone health. Trial Registration: ISRCTN Registry Identifier: ISRCTN89898870.