The effects of recombinant human parathyroid hormone, rhPTH(1-84), on bone mass in undernourished rats

Abstract

Energy intake restriction reduces bone formation both in protein-energy malnourished children and in undernourished rats, and such conditions might cause partial or irreversible bone loss. Because the use of anti-resorptive agents in this situation is seemingly limited, we examined the effect of the anabolic agent, recombinant human parathyroid hormone (rhPTH(1-84)), on bones in undernourished conditions. First, the osteopenic changes of rat bones with 40% restricted diet for 4 weeks were confirmed. Subsequently, another set of the rats were randomized into four groups and studied for 8 weeks: the freely fed group (control group); the restricted diet, then freely fed group (restriction-ad libitum group); the restricted diet-vehicle-treated group (restriction-vehicle group); and the restricted diet-PTH-treated group (restriction-PTH group). In the restriction-vehicle group, total femoral bone mineral density (BMD) was lower and femoral length was shorter than the control group by 15.4% and 8.1% respectively (P<0.05). In the restriction-ad libitum group, these parameters recovered fully to those of the control group. In the case of intermittent PTH treatment in the persistent undernourished state, the BMD of total femur caught up with those of the control or the restriction-ad libitum group. However, the femoral length remained shorter than those of the other groups. Serum osteocalcin was significantly reduced in continuously undernourished rats, whereas it was elevated in the restriction-PTH group. In conclusion, BMD of total femur was low in undernourished rats. However, it increased after re-feeding ad libitum or intermittent PTH treatment. We suggest that rhPTH(1-84) may be a possible therapeutic agent for ongoing bone loss, especially in patients in a chronically undernourished condition.