COMPARISON OF THE ABILITIES OF HUMAN PARATHYROID-HORMONE (HPTH)-(1-34) AND [LEU(27)]-CYCLO(GLU(22)-LYS(26))-HPTH-(L-31)NH2 TO STIMULATE FEMORAL TRABECULAR BONE-GROWTH IN OVARIECTOMIZED RATS

hPTH-(1-31)NH2, so far the smallest of the potently anabolic N-termina l fragments of the human parathyroid hormone, stimulates trabecular gr owth 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 o f body weight, but it is only about 70% as effective as hPTH-(1-34) wh en injected at the suboptimal 0.6 nmol/100 g of body weight. A lactam derivative of hPTH-(1-31)NH,, [Leu(27)]-cyclo(Glu(22)-Lys(26))-hPTH-(1 -31)NH2, is a much more effective stimulator of adenylyl cyclase in RO S 17/2 rat osteoblast-like cells and a significantly more effective st imulator of femoral trabecular growth in OVX rats than hPTH-(1-31)NH2. We have now shown that [Leu(27)]-cyclo(Glu(22)-Lys(26))-hPTH-(1-31)NH 2 prevents the OVX-induced loss of femoral trabeculae significantly mo re effectively than hPTH-(1-34) and stimulates the thickening of the t rabeculae remaining in severely depleted femoral trabecular bone of OV X rats as effectively as hPTH-(1-34) when injected at 0.6 nmol/100 g o f body weight.