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Bogaards FA, Groenendijk I, […], Slagboom PE | 17-04-2026 | 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.
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.
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.
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).
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.
Bogaards FA, Groenendijk I, Gehrmann T, Beekman M, Lakenberg N, Suchiman HED, de Groot LCPGM, Reinders MJT, Slagboom PE. J Cachexia Sarcopenia Muscle. 2026 Apr;17(2):e70226. doi: 10.1002/jcsm.70226
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