TEMPORAL EXPRESSION OF THE ANABOLIC ACTION OF PTH IN CANCELLOUS BONE OF OVARIECTOMIZED RATS

When administered intermittently, parathyroid hormone (PTH) is a poten t anabolic agent in both human and animal bone, To improve our underst anding of this anabolic effect, we have examined the time course of PT H action in an established animal model of estrogen deficiency-induced bone loss: the ovariectomized rat, Animals were ovariectomized (Ovx) and allowed to lose bone for 6 weeks. A dose of 20 mu g/kg/d of rat PT H (1-34) was administered s.c., 6 days each week for periods of 1, 2, 3, 4, 6 and 8 weeks, Animals,were sacrificed for evaluation of skeleta l histomorphometry of the proximal tibia and mechanical strength of th e cancellous bone in the marrow cavity of the distal femur, Cancellous bone volume (Cn-BV/TV) increased gradually over 8 weeks of treatment (16.8 +/- 1.6 to 24.1 +/- 2.7%) as did the bone formation rate (0.308 +/- 0.054 to 1.659 +/- 0.293 mu m(3)/mu m(2)/d), as determined by an i ncrease in both total mineralization surface (15.5 +/- 2.1 to 42.7 +/- 5.0%) and mineral apposition rate (1.88 +/- 0.20 to 3.55 +/- 0.39 mu m/d), The largest increments in these variables reflecting bone format ion occurred over the first week of treatment, This bone formation was accompanied by an increase in trabecular thickness (Tb.Th) (55.3 +/- 3.4 to 80.5 +/- 5.0 mu m) without a corresponding increment in trabecu lar number (Tb.N) (3.65 +/- 0.17 to 3.55 +/- 0.26), Extensive tetracyc line labels were visualized on the surface of trabecular rod-like and plate-like structures, A small transient, though not statistically sig nificant, increase occurred in both eroded surface and urinary pyridin oline concentration immediately after the onset of PTH administration, Osteocalcin showed a small decrement in the first two weeks after PTH administration, but the levels were elevated when compared with the O vx control in later weeks, Mechanical strength of the cancellous bone also increased significantly with PTH treatment (20.5 +/- 2.4 to 46.1 +/- 10.0 Newtons), Our results showed that: 1) intermittent PTH treatm ent of Ovx rats elicited an immediate increase of bone formation activ ity by the existing osteoblasts, 2) the increase of Cn-BV/TV after PTH administration resulted primarily from an increase in Tb.Th, and 3) i mproved mechanical strength after PTH treatment can be achieved by inc reases in Tb.Th without an increase in Tb.N.