Eldecalcitol and calcitriol stimulates 'bone minimodeling,' focal bone formation without prior bone resorption, in rat trabecular bone

Vitamin D is known as a potent stimulator of bone resorption. The active form of vitamin D3, calcitriol (1α,25-dihydroxyvitamin D3), stimulates release of calcium (Ca) from bone in ex vivo organ culture, and treatment with large amounts of an active vitamin D3 analog induces hypercalcemia and bone resorption in mice in vivo. Calcitriol strongly induces both receptor activator of NF-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) in osteoblasts in vitro. On the other hand, it has been reported that active vitamin D3 inhibits bone resorption in various experimental animal models. We previously showed that eldecalcitol [1α,25-dihydroxy-2β-(3-hydroxy-propyloxy)vitamin D3; ED-71] suppresses bone resorption and increases bone mineral density (BMD) to a greater extent than alfacalcidol (1α-hydroxyvitamin D3) in ovariectomized (OVX) rats in vivo. To elucidate the histological events that follow administration of eldecalcitol compared to calcitriol, OVX rats were given either vehicle, eldecalcitol (10, 30, or 90ng/kg), or calcitriol (33.3, 100, 300, or 900ng/kg), and sham-operated control Animals were given vehicle, 5-times per week for 12 weeks. The lumbar spine and femur were removed and processed for bone mineral density (BMD) assessments and the femur for histomorphometrical analyzes. Both eldecalcitol and calcitriol increased the lumbar and femoral BMD in a dose dependent manner. Bone histomorphometry revealed that osteoclast surface (Oc.S/BS) and eroded surface (ES/BS) were dose-dependently suppressed in the trabecular region of the femur. Both calcitriol and eldecalcitol dose-dependently stimulated focal bone formation that started without prior bone resorption, a process known as bone minimodeling. Both reduction of bone resorption and stimulation of focal bone formation were more clearly observed in the eldecalcitol-treated rats than in the calcitriol-treated rats. Taken together, these findings suggest that eldecalcitol is a more potent vitamin D3 analog that stimulates focal bone formation (minimodeling) and suppresses bone resorption more strongly than does calcitriol. This article is part of a Special Issue entitled 'Vitamin D Workshop'.