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A three-year parallel-group trial, known as Prevención con Dieta Mediterránea-Plus (PREDIMED-Plus), details the results of a secondary analysis of a randomized and controlled clinical trial that evaluated the effects of a weight loss lifestyle intervention on bone health among older adults. This trial took place between 2013 and 2016 across 23 centers in Spain, and included 924 older adults (mean age 65) with either overweight or obesity and at least 3 criteria of the metabolic syndrome (but not preexisting cardiovascular disease). The control group was encouraged to follow the Mediterranean diet, but without any energy restrictions or specific recommendations for physical activity. In contrast, the intervention group was prescribed the Mediterranean diet with a 30% calorie reduction, as well as counseling to increase physical activity to at least 150 minutes per week of moderate to vigorous exercise, with specific guidelines (e.g., walking at least 45 minutes per day, six days per week) and behavioral strategies to accomplish these goals. The prespecified primary outcomes were bone mineral density (BMD), total bone mineral content (BMC), and low BMD prevalence.
After 3 years, people in the intervention group lost 3% of their total body weight compared to 0.7% in the control group, with a between-group significant difference of 2.2 kg. Over this period, there was a significant protective effect on the lumbar spine BMD, with the control group having a mean change of -0.1 g/cm2 compared to baseline vs. an increase of 0.9 g/cm2 in the intervention group overall. This protection was not observed among men; however, among women, the difference between groups was even larger (1.8 g/cm² at 3 years), with women in the control group experiencing a decrease of 1.3 g/cm² compared to an increase of 0.4 g/cm² among women in the intervention group. No significant differences were observed at other sites (total femur, femoral trochanter), or in the prevalence of low BMD. However, in a multivariate intention-to-treat analysis, the protective effect on the lumbar spine BMD among women was even larger (between-group difference of 2.2 g/cm2), and a protective effect on the total femur BMD was also observed (mean difference of 1.0 g/cm2).
This is quite an important finding. For context, the rate of overweight and obesity has grown in all age groups, including among older adults, and the health and longevity benefits of weight loss are many. However, weight loss has been associated with bone loss and increased fracture risk in both observational and controlled trials, particularly when not paired with physical activity, so the risk to bone health in older populations on energy-restrictive diets is uncertain. It's also worth noting that BMD and fracture risk are not equivalent. For example, a number of studies have shown an association between obesity and higher BMD, possibly due to additional mechanical loading on the bone. Despite this, more recent studies suggest that obesity is associated with an increased risk for fracture and does not have a protective effect.
The largest meta-analysis to date, published in the Journal of Bone and Mineral Research, included 63 cohorts and 16 million person-years, and found that although a low body mass index (BMI) is associated with a greater fracture risk, after adjusting for (femoral neck) BMD, a higher BMI is also associated with a greater fracture risk. For instance, obesity II (BMI ≥ 35.0 kg/m2) is associated with a 24% higher risk for hip fracture among women (vs. normal BMI) and a 70% higher risk among men. Similarly, a 2023 meta-analysis published in the Annals of Medicine, which included nearly 700,000 postmenopausal women, found that obesity was associated with an 18% higher risk for all-cause and vertebral fractures (but a lower risk for pelvic fractures).
Even though obesity itself has been associated with a protective effect on bone BMD, it’s not clear whether this translates to a protective effect on fracture risk. Yet weight loss interventions that involve energy restriction may cause high turnover bone loss, with uncertain outcomes on fracture risk. Previous studies suggest that physical activity can mitigate some, but not all, of the bone loss that occurs with diet-induced weight loss
This recent study shows that at least the bone loss associated with an energy-restrictive Mediterranean diet can be partly mitigated by physical activity. Additionally, it’s important to note that the control group was encouraged to follow a Mediterranean diet that was not necessarily energy-restrictive, and yet they still lost bone mass over the 3-year period. The Mediterranean diet itself is an anti-inflammatory diet, and may have had bone-protective effects compared to a more standard diet, possibly masking a more protective effect. It’s plausible that the energy-restrictive Mediterranean diet, coupled with physical activity, prevents not only the bone loss associated with energy restriction but also, to some degree, the bone loss that may normally occur.
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