High Vitamin D Intake Improves Bone Health in Obesity

Abstract

The impact of obesity on bone health remains controversial. Obesity is often considered “beneficial” to bone health because high body weight imposes a large mechanical load on weight‐bearing bones leading to increased bone mass and strength to accommodate such a load. The mechanical implications and hormonal effects of obesity on the growing, forming bone can be different from those effects on the mature bone. The active form of vitamin D, 1,25‐dihydroxyvitamin D3 (1,25(OH)2D3) is the hormonal regulator of bone formation, mineralization and remodeling, and low vitamin D status is routinely observed in obesity. We hypothesized that (1) an increased body weight is detrimental to the growing bone due to its high rate of formation and low level of mineralization and that (2) regulation of bone mineral (Ca and P) and matrix (collagen) status via the vitamin D endocrine system is impaired in obesity because of secondary vitamin D insufficiency. The aim of this study was to examine the effects of the increased vitamin D3 intake, alone and in combination with increased calcium intake, on the bone status in a diet‐induced obesity (DIO) mouse model. Male mice were fed for 10 weeks a high‐fat diet (DIO) containing high levels of vitamin D3 (10,000 IU/kg vs. 1,000 IU/kg in control), calcium (1.2% vs. 0.55% in control), or vitamin D3 plus calcium (10,000 IU/kg D3 plus 1.2% Ca vs. 1,000 IU/kg D3 plus 0.55% Ca). Bone weight, specific gravity, mineral (Ca and P) and collagen (hydroxyproline) content were measured in the femur and the tibia. Regulators of Ca2+ metabolism and markers of bone status (parathyroid hormone (PTH), 25‐hydroxyvitamin D (25(OH)D), 1,25(OH)2D3, and osteocalcin) were measured in blood plasma. DIO mice had a lower bone mineral (Ca and P) content and relative bone weight compared to the normal control; the collagen content was not changed. DIO was accompanied by a decrease in 25(OH)D and 1,25(OH)2D3 concentrations, whereas PTH and osteocalcin concentrations were increased. High vitamin D3 and calcium intakes significantly increased bone Ca and P content and relative bone weight in DIO mice, which was accompanied by an increase in 1,25(OH)2D3 concentration and a decrease in PTH and osteocalcin concentrations in blood. DIO mice were characterized by obese phenotype, elevated blood glucose and impaired glucose tolerance, increased insulin and decreased adiponectin concentrations in blood, and a decreased level of adipocyte apoptosis in adipose tissue. DIO mice fed diet with high vitamin D3 and increased calcium content demonstrated significantly improved blood markers related to vitamin D status and adiposity as well as a decreased weight of white adipose tissue depots due to increased level of adipocyte apoptosis. The major results of the present study indicate that high vitamin D and calcium intake is effective in increasing mineral content in the growing bone of obese mice and that the hormonal mechanism of this effect involves the vitamin D – PTH axis. The findings obtained strongly imply that increasing vitamin D and calcium intakes may contribute to prevention of “obesity” of bone and obesity‐related causes contributing to obese bone (diabetes mellitus, secondary hyperparathyroidism and vitamin D insufficiency).Support or Funding InformationSupported by USDA SD00H533.