Physical activity and soy protein isolate (SPI) augmentation have been reported to be
beneficial for bone health. We hypothesized that combining voluntary running and SPI
intake would alleviate detrimental changes in bone induced by a high-fat diet. A 2 × 2 × 2
experiment was designed with diets containing 16% or 45% of energy as corn oil and 20% SPI
or casein fed to sedentary or running male C57BL/6 mice for 14 weeks. Distal femurs were
assessed for microstructural changes. The high-fat diet significantly decreased trabecular
number (Tb.N) and bone mineral density (BMD) and increased trabecular separation (Tb.Sp).
Soy protein instead of casein, regardless of fat content, in the diet significantly increased
bone volume fraction, Tb.N, connectivity density, and BMD and decreased Tb.Sp. Voluntary
running, regardless of fat content, significantly decreased bone volume fraction, Tb.N,
connectivity density, and BMD and increased Tb.Sp. The high-fat diet significantly
decreased osteocalcin and increased tartrate-resistant acid phosphatase 5b (TRAP 5b)
concentrations in plasma. Plasma concentrations of osteocalcin were increased by both SPI
and running. Running alleviated the increase in TRAP 5b induced by the high-fat diet. These
findings demonstrate that a high-fat diet is deleterious, and SPI is beneficial to trabecular
bone properties. The deleterious effect of voluntary running on trabecular structural