Effect of combined humanPTH(1-34) and calcitonin treatment in ovariectomized rats.
We examined the combined effects of human parathyroid hormone 1-34 (hPTH) and elcatonin (ECT: a synthetic derivative of eel calcitonin) to prevent loss of bone mass, architecture and strength in ovariectomized (OVX) rats. Fifty-four female rats (aged 13 weeks) were assigned to one of nine groups: Sham (fake surgery performed), OVX, ECT (15 U/kg administered), PTH5, PTH10 and PTH20 (5, 10 or 20 microg/kg administered), and E+PTH5, E+PTH10 and E+PTH20 (15 U/kg of ECT and 5, 10 or 20 microg/kg of hPTH administered). The drug or vehicle was subcutaneously administered three times a week for 12 weeks. The femurs were removed at the completion of the experiment. The right distal femoral metaphysis was used for measuring bone mineral density (BMD), analyzing trabecular bone structure by micro-computed tomography (microCT), and conducting the bone strength test, and the left femur was used for histomorphometric analysis. Trabecular bone volume (BV/TV) and other bone mass parameters were greater in the ECT and PTH groups than in the OVX group. The number of nodes (N.Nd/TV) and trabecular number (Tb.N) were significantly greater in the ECT group, and trabecular thickness (Tb.Th) and trabecular bone pattern factor (TBPf) were significantly greater in the PTH group. These results indicate that these drugs preserve the bone architecture by different means. Analysis by means of microCT revealed that BV/TV, Tb.N, fractal D and N.Nd/TV were significantly greater in the E+PTH groups than in the PTH groups at each concentration. Trabecular separation (Tb.Sp) was significantly lower in the E+PTH5 and E+PTH10 groups than in the respective PTH5 and PTH10 groups. When the maximum load was applied in a compression test on the distal femur, the E+PTH groups had higher values than the PTH groups, however, the three point bending strength of the diaphysis of femur in the E+PTH10 and E+PTH20 groups tended to be low compared to those in the PTH10 and PTH20 groups. These results indicate that combination therapy using PTH and ECT preserves the trabecular microarchitecture better than single-drug therapy using ECT or PTH in OVX rats, however, it is necessary to optimize the calcitonin (CT) dosage and administration in order to achieve the optimal combined effect of PTH and CT.
Washimi
Yuki
Y
Department of Orthopedic Surgery, Ichinomiya West Hospital, 89-1 Origuchinishi, Ichinomiya Aichi, Japan. washimi@anzu.or.jp
Ito
Masato
M
Morishima
Yosuke
Y
Taguma
Kanako
K
Ojima
Yoshihide
Y
Uzawa
Toyonobu
T
Hori
Masayuki
M
D000818:Animals; D001835:Body Weight; D015519:Bone Density; D001862:Bone Resorption / Q000188:drug therapy*; D002116:Calcitonin / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D010052:Ovariectomy; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D010281:Parathyroid Hormone; D002116:Calcitonin