Bone mineral density, body height, and vitamin D receptor gene polymorphism in middle-aged men.

BACKGROUND: Polymorphisms of the vitamin D receptor (VDR) gene have been suggested to account for some of the genetic variation in bone mass. However, the relationship has been controversial. It has been suggested that environmental factors such as physical activity may be one of the many reasons for this controversy.AIM. We investigated the possible interactions of VDR gene polymorphisms and low to moderate intensity exercise on bone mineral density (BMD) in a four-year controlled, randomized intervention trial in 140 middle-aged Finnish men. METHOD: The TaqI, FokI, and ApaI restriction fragment length polymorphism (RFLP)-markers of the VDR gene were evaluated. BMDs of the lumbar spine (L2-L4), femoral neck, and total proximal femur were measured with dual-energy X-ray absorptiometry (DXA). In addition, the relations of the VDR gene polymorphism with bone turnover markers (serum tartrate-resistant acid phosphatase (TRAP) 5b activity and serum osteocalcin concentration) were evaluated. RESULTS: At the randomization, the subjects with the VDR TaqI Tt or tt genotype had a greater body height than the subjects with TT genotype (P=0.001). In addition, the association of VDR TaqI polymorphism with femoral BMD was found. The Tt or tt genotype associated with higher femoral neck values than the TT genotype (P=0.003) at randomization. After adjusting the femoral neck for body height, the association remained (P=0.021). We did not find any association between VDR gene polymorphism and bone turnover markers or any interactions of VDR gene polymorphisms and exercise on BMD. CONCLUSIONS: The TaqI polymorphism may be associated with body height and femoral neck BMD values. The present findings also suggest that the VDR polymorphisms do not modify the effect of regular aerobic exercise on BMD. However, more randomized controlled exercise trials are needed to investigate the role of exercise intensity on VDR gene polymorphisms, and the role of VDR gene polymorphisms on BMD.

Adenovirus-mediated VEGF-A gene transfer induces bone formation in vivo.

Osteoporosis is a major problem in elderly population. We tested the hypothesis whether vascular endothelial growth factor (VEGF-A) gene transfer is an appropriate way to enhance bone formation and recruitment of osteoblasts in vivo. Adenovirus vectors containing VEGF-A or lacZ cDNAs (1.4x10(10) pfu) were injected locally into right distal femurs of New Zealand White rabbits. Saline was injected into all contralateral distal femurs. One and three weeks after the gene transfers femurs were collected for analyses. X-Gal staining showed that up to 20% of the bone marrow cells were transfected although gene transfer also resulted in biodistribution of the vector and expression of the transgene in liver and spleen. Trabecular bone hard tissue histomorphometry of the distal femurs was performed to analyze the effect of gene transfer on bone turnover. When compared with unilateral lacZ transfected trabecular bone at one-week and three-week time points, VEGF-A gene transfer significantly increased bone formation parameters, such as osteoblast number, osteoid volume, and bone volume. Also, bone resorption surface was greatly reduced. It is concluded that injection of adenovirus vector can transfect bone marrow cells in vivo with a relatively high efficiency. Our results suggest that adenovirus-mediated VEGF-A gene transfer induces bone formation via increasing osteoblast activity and may be useful for the treatment of osteoporosis and other diseases that require efficient osteogenic therapy.