We hypothesized that the
anabolic action of
parathyroid hormone (PTH) with the anti-catabolic agents
cathepsin K inhibitor and
alendronate differs depending on the remodeling status in the
bone. C57/BL/6J
mice, 8 weeks of age, were subjected to ovariectomized (OVX) or sham
surgery. At 6 weeks after
surgery, the
mice were treated with
cathepsin K inhibitor,
alendronate, or a vehicle (daily, for 8 weeks), with or without PTH (1-34) (5 times/week, for the last 4 weeks). We assessed the
bone chemical markers of the serum and
urine,
bone mineral density (BMD), histomorphomery in the primary and secondary spongiosa of the
proximal tibia after
fluorescence labeling,
primary cell culture, and
mRNA expressions in
bone marrow cells.
Cathepsin K inhibitor and
alendronate significantly increased the BMD and the
bone volume of the primary and secondary spongiosa, with a reduction of the
urinary C-telopeptide of
type I collagen that was increased by OVX, respectively.
Cathepsin K inhibitor augmented the
anabolic action of PTH on the BMD and
bone volume at both the primary and secondary spongiosa, while
alendronate had the same effect on the BMD and
bone volume only at the primary spongiosa.
Cathepsin K inhibitor did not decrease serum
osteocalcin with or without PTH, while
alendronate did decrease it.
Cathepsin K inhibitor did not decrease the values of
osteoclast number or
bone formation rate with or without PTH, while
alendronate decreased those values and increased
osteoclast apoptosis. The combination of PTH and
cathepsin K inhibitor increased alkaline phosphatase-positive CFU-f formation and c-fos, osterix, and
osteocalcin mRNA expressions of
bone marrow cells as well as PTH alone, while the combination of PTH and
alendronate decreased those values. This study demonstrated that
alendronate enhances the
anabolic action of PTH at the primary spongiosa, but blunts it in the remodeling
trabecular bone, while
cathepsin K inhibitor enhances the action at both sites in OVX
mice. In conclusion, the
anabolic action of intermittent PTH in combination with
cathepsin K inhibitor or
alendronate differs depending on the remodeling status of
bone in OVX
mice.
