Background

Nutritional weight-loss interventions are known to reduce bone mineral density (BMD), which can be prevented by adding (resistance) exercise training. However, this combined effect is not well studied in non-obese adults. In addition, the association between biomarkers and metabolite-based composite health markers with changes in BMD in such an intervention has not been studied as thoroughly.

Objective

The aims of the current study were to investigate the effect of a combined nutritional and activity lifestyle intervention on lumbar spine and total body BMD in healthy middle-aged to older adults, and to relate these effects to a selection of immune-metabolic biomarkers, muscle mass and fat mass measurements, and two composite metabolite-based health scores.

Methods

In this ancillary study of the single-arm Growing Old TOgether (GOTO) trial (trial registration number GOTNL3301 [https://onderzoekmetmensen.nl/nl/trial/27183], NL-OMON27183), 134 participants (mean age 62.9 years, 49% female) undertook a 13-week lifestyle modification, incorporating 12.5% caloric restriction and 12.5% increase in physical activity. The impact on lumbar spine and total body BMD was evaluated using dual-energy X-ray absorptiometry (DEXA). The intervention effect on BMD was related to changes in immune-metabolic biomarkers and two metabolite-based immune-metabolic health scores.

Results

The trial significantly reduced bodyweight with 3.3 and 3.4 kg, consisting of 1.4 and 1.1 kg lean mass, in males (fdr < 0.001) and females (fdr < 0.001), respectively. Lean mass reduced by 1.4 kg in males (fdr < 0.001) and 1.1 kg in females (fdr < 0.001), whereas total body fat% reduced significantly with -1.5% (fdr < 0.001) in males and -1.5% (fdr < 0.001) in females. In males, lumbar spine BMD increased with 3.0% (fdr < 0.001) and total body BMD with 0.7% (fdr = 0.002). In females, the lumbar spine BMD had a trend in the upwards direction (1.2%, fdr = 0.09) and the total body BMD remained stable (0.4%, fdr = 0.07). In males, the increase in lumbar spine BMD was significantly associated with decreased weight (fdr = 0.001) and with decreased body and trunk fat% (fdr = 0.001, fdr = 0.001) and improved immune-metabolic health (fdr = 0.02). Males with higher BMD but a poor metabolite-based health score at baseline had a stronger increase in lumbar spine BMD (fdr = 0.03).

Conclusions

A combined nutritional and activity lifestyle intervention significantly improved BMD of males with good bone health at baseline while at the same time improving metabolic health. Nutritional weight-loss interventions may not harm BMD when combined with exercise.

© 2026 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.