ARS | Publication request: Osteoprotective Effect of Alfacalcidol in Female Rats with Systemic Chronic Inflammation

Submitted to: Endocrine Society Meeting
Publication Type: Abstract Only
Publication Acceptance Date: March 10, 2010
Publication Date: July 25, 2010
Citation: Shen, C., Cao, J.J., Yeh, J.K. 2010. Osteoprotective Effect of Alfacalcidol in Female Rats with Systemic Chronic Inflammation. [abstract] Endocrine Society Meeting. 31(3):S1065.

Technical Abstract: Studies have shown that alfacalcidol (a hydroxylated form of vitamin D) mitigates glucocorticoid-induced bone loss. This study was undertaken to explore the mechanism and bone microarchitecture of alfacalcidol in rats with systemic chronic inflammation. Thirty female rats (3-month-old) assigned to 3 groups (n=10/group), placebo administration, lipopolysaccharide (LPS) administration, and LPS+alfacalcidol (0.05 ug/kg alfacalcidol orally, 5x/week) for 12 weeks. Efficacy was evaluated in femur and tibia by dual-energy X-ray absorptiometry and histomorphometric analysis, respectively. The femoral bone strength was assessed by 3-point bending test. Bone formation biomarker (osteocalcin) and resorption biomarker (tartrate resistant acid phosphatase, TRAP) were determined by respective kits. Expression of tumor necrosis factor-alpha(TNF-alpha) in proximal tibia was evaluated by immunohistochemistry. Data were analyzed by one-way ANOVA followed by post hoc test. LPS administration resulted in lower values for bone mineral density and strength of femur, and bone volume, trabecular number and thickness in proximal tibia, but higher values for TRAP, trabecular separation and osteoclast number in proximal tibia, bone formation rate at proximal tibia and periosteal bone, eroded surface at tibial shaft, and TNF-alpha expression in proximal tibia. In contrast to these negative impacts of LPS in bone, oral administration of alfacalcidol significantly increased bone mineral density and strength of femur, bone volume, trabecular number and thickness in proximal tibia, while suppressed TRAP, trabecular separation and osteoclast number in proximal tibia, bone formation rate at proximal tibia and periosteal bone, erosion surface at tibial shaft, and TNF-alpha expression in proximal tibia. Neither LPS nor alfacalcidol affected the femoral total area, osteocalcin, and endocortical mineral apposition rate and bone formation rate at tibia shaft. This study demonstrates that alfacalcidol administrated to female rats for 12 weeks protects bone microarchitecture due to chronic inflammation. Such an osteo-protective role of alfacalcidol may be attributed to a decrease in inflammatory mediator, TNF-alpha. This study suggests a potentially significant prophylactic role of alfacalcidol in bone health of women with systemic chronic inflammation-induced bone loss.