The experimental work characterizing the anabolic effect of parathyroid hor
mone (PTH) in bone has been performed in nonmurine ovariectomized (OVX) ani
mals, mainly rats. A major drawback of these animal models is their inacces
sibility to genetic manipulations such as gene knockout and overexpression.
Therefore, this study on PTH anabolic activity was carried out in OVX mice
that can be manipulated genetically in future studies. Adult Swiss-Webster
mice were OVX, and after the fifth postoperative week were treated intermi
ttently with human PTH(1-34) [hPTH(1-34)] or vehicle for 4 weeks. Femoral b
ones were evaluated by microcomputed tomography (mu CT) followed by histomo
rphometry. A tight correlation was observed between trabecular density (BV/
TV) determinations made by both methods. The BV/TV showed >60% loss in the
distal metaphysis in 5-week and 9-week post-OVX, non-PTH-treated animals. P
TH induced a similar to 35% recovery of this loss and a similar to 40% reve
rsal of the associated decreases in trabecular number (Tb.N) and connectivi
ty. PTH also caused a shift from single to double calcein-labeled trabecula
r surfaces, a significant enhancement in the mineralizing perimeter and a r
espective 2- and Mold stimulation of the mineral appositional rate (MAR) an
d bone formation rate (BFR). Diaphyseal endosteal cortical MAR and thicknes
s also were increased with a high correlation between these parameters. The
se data show that OVX osteoporotic mice respond to PTH by increased osteobl
ast activity and the consequent restoration of trabecular network. The Swis
s-Webster mouse model will be useful in future studies investigating molecu
lar mechanisms involved in the pathogenesis and treatment of osteoporosis,
including the mechanisms of action of known and future bone antiresorptive
and anabolic agents.