Rapid Transition from a High-Fat, High-Fructose to a Low-Fat, Low-Fructose Diet Reverses Gains in Bone Mass and Strength

ABSTRACT Purpose Obesity is thought to negatively impact bone quality and strength despite improving bone mineral density. We hypothesized that 1) continuous consumption of a high-fat, high-sugar (HFS) diet would impair bone quality and strength, and 2) a change from an HFS diet to a low-fat, low-sugar (LFS) would reverse HFS-induced impairments to bone quality and strength. Methods Six-week-old male C57Bl/6 mice ( n = 10/group) with access to a running wheel were randomized to an LFS diet or an HFS diet with simulated sugar-sweetened beverages (20% fructose in place of regular drinking water) for 13 wk. HFS mice were subsequently randomized to continuing HFS feeding (HFS/HFS) or transition to the LFS diet (HFS/LFS) for four additional weeks. Results HFS/HFS mice exhibited superior femoral cancellous microarchitecture (i.e., greater BV/TV, Tb.N, Tb.Th, and decreased Tb.Sp) and cortical bone geometry (i.e., lower Ct.CSA and pMOI) compared with all other groups. At the femoral mid-diaphysis, structural, but not material, mechanical properties were greatest in HFS/HFS mice. However, HFS/HFS exhibited greater femoral neck strength only when compared with mice assigned to diet transition (HFS/LFS). Osteoclast surface and the percentage of osteocytes staining positive for interferon-gamma were greater in HFS/LFS mice, consistent with reduced cancellous microarchitecture postdiet transition. Conclusions HFS feeding enhanced bone anabolism and structural, but not material, mechanical properties in exercising mice. A change from an HFS to LFS diet returned the bone structure to that of continuously LFS-fed mice while compromising strength. Our results indicate rapid weight loss from obese states should be performed with caution to prevent bone fragility. A deeper analysis into the altered bone phenotype in diet-induced obesity from a metabolic standpoint is needed.