Temporal expression of the anabolic action of PTH in cancellous bone of ovariectomized rats

Abstract

When administered intermittently, parathyroid hormone (PTH) is a potent anabolic agent in both human and animal bone. To improve our understanding of this anabolic effect, we have examined the time course of PTH 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 μg/kg/d of rat PTH (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 skeletal histomorphometry of the proximal tibia and mechanical strength of the 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 μm³/μm²/d), as determined by an increase 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 μm/d). The largest increments in these variables reflecting bone formation 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 μm) without a corresponding increment in trabecular number (Tb.N) (3.65 ± 0.17 to 3.55 ± 0.26). Extensive tetracycline labels were visualized on the surface of trabecular rod‐like and plate‐like structures. A small transient, though not statistically significant, increase occurred in both eroded surface and urinary pyridinoline 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 Ovx 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 treatment of Ovx rats elicited an immediate increase of bone formation activity by the existing osteoblasts, 2) the increase of Cn‐BV/TV after PTH administration resulted primarily from an increase in Tb.Th, and 3) improved mechanical strength after PTH treatment can be achieved by increases in Tb.Th without an increase in Tb.N.