Alfacalcidol-stimulated focal bone formation on the cancellous surface and increased bone formation on the periosteal surface of the lumbar vertebrae of adult female rats.
OBJECTIVE
To investigate the skeletal effects of alfacalcidol alone or in combination with exercise in intact adult female rats.


METHODS
Seventy-four 8.5-month-old rats were orally administered 0, 0.005, 0.025, 0.05 or 0.1 microg/kg of alfacalcidol for 12 weeks, alone or in combination with exercise. Cancellous bone histomorphometric measurements were performed on the second lumbar vertebra.


RESULTS
At 0.05 and 0.1 microg/kg, alfacalcidol caused a significant increase in cancellous bone volume, accompanied by an increase in trabecular architecture. Percent eroded surface, bone resorption and formation were suppressed by alfacalcidol treatment. However, mineral apposition rate was significantly increased, indicating osteoblast activity was increased. A positive balance between bone formation and resorption was observed in the rats treated with the highest dose of alfacalcidol. Alfacalcidol induced a unique bone formation site ("bouton") on the cancellous surface. These boutons connected adjacent trabeculae and increased trabecular thickness. They exhibited both smooth and scalloped cement lines, suggesting that they were formed by minimodeling- and remodeling-based bone formation. Furthermore, alfacalcidol at 0.1 microg/kg increased periosteal bone formation of the lumbar transverse processes. Bipedal stance exercise alone did not have an effect on bone balance and bone turnover. There were no interactions between alfacalcidol and bipedal stance exercise except for a decrease in bone resorption.


CONCLUSIONS
Alfacalcidol exhibited both anti-catabolic and anabolic effects on bone in intact female rats. The effect of combined treatment with alfacalcidol and bipedal stance exercise was no better than that of alfacalcidol alone.
Chen
HaiYan
H
Division of Radiobiology, University of Utah, Salt Lake City, UT, USA.
Tian
XiaoYan
X
Liu
XiaoQing
X
Setterberg
Rebecca B
RB
Li
Mei
M
Jee
Webster S S
WS
D000284:Administration, Oral; D000375:Aging / Q000502:physiology; D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001862:Bone Resorption / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D002118:Calcium / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006887:Hydroxycholecalciferols / Q000494:pharmacology*; D008159:Lumbar Vertebrae / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D010521:Periosteum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010758:Phosphorus / Q000097:blood; D010805:Physical Conditioning, Animal / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley
D050071:Bone Density Conservation Agents; D006887:Hydroxycholecalciferols; D010758:Phosphorus; D002118:Calcium; C008088:alfacalcidol