Comparison of the Abilities of Human Parathyroid Hormone (hPTH)-(1-34) and [Leu²⁷]-cyclo(Glu²²-Lys²⁶)-hPTH-(1-31)NH₂ to Stimulate Femoral Trabecular Bone Growth in Ovariectomized Rats

Abstract.

hPTH-(1-31)NH₂, so far the smallest of the potently anabolic N-terminal fragments of the human parathyroid hormone, stimulates trabecular growth in the distal femurs of ovariectomized (OVX) rats as strongly as hPTH-(1-34) when injected at a high daily dose such as 1 nmol/100 g of body weight, but it is only about 70% as effective as hPTH-(1-34) when injected at the suboptimal 0.6 nmol/100 g of body weight. A lactam derivative of hPTH-(1-31)-NH₂, [Leu²⁷]-cyclo(Glu²²-Lys²⁶)-hPTH-(1-31)NH₂, is a much more effective stimulator of adenylyl cyclase in ROS 17/2 rat osteoblast-like cells and a significantly more effective stimulator of femoral trabecular growth in OVX rats than hPTH-(1-31)NH₂. We have now shown that [Leu²⁷]-cyclo(Glu²²-Lys²⁶)-hPTH-(1-31)NH₂ prevents the OVX-induced loss of femoral trabeculae significantly more effectively than hPTH-(1-34) and stimulates the thickening of the trabeculae remaining in severely depleted femoral trabecular bone of OVX rats as effectively as hPTH-(1-34) when injected at 0.6 nmol/100 g of body weight.