Parathyroid hormone and growth hormone have additive or synergetic effect when used as intervention treatment in ovariectomized rats with establishedosteopenia

The severely osteoporotic human skeleton is characterized by thin cortices and a very fragile cancellous framework. To increase the biomechanical comp etence of such a skeleton, powerful anabolic agents are needed. The aim of the present study was to compare the effect of parathyroid hormone (PTH), g rowth hormone (GH) and combination treatment with PTH and GH in an aged, ra t model with established osteopenia. Furthermore, envelope- and site-specif ic effects of the two agents are described, Twelve-month-old virgin F334 ra ts were divided into sis groups with 11 animals per group: (1) baseline; (2 ) sham-operated + solvent vehicle (s.v.) (sham); (3) ovariectomized + s.v. (ovx); (4) ovx + GH 2.5 mg/kg body weight per day; (5) ovx + PTH 80 mu g/kg body weight per day; and (6) ovx + GH and PTH treatment, Group 1 were kill ed to establish baseline values. Groups 2 (sham) and 3 (ovx) were killed af ter 24 weeks. Groups 4, 5, and 6 were allowed to develop osteopenia for 16 weeks before treatment was initiated. Treatment was given for a period of 8 weeks, The effects of GH, PTH, and GH + PTH cotherapy were measured by bio mechanical testing at four different skeletal sites: lumbar vertebra; femor al diaphysis; femoral neck; and distal femoral metaphysis. In addition, sta tic histomorphometry was performed at the middiaphyseal region. Ovx induced a loss of bone strength at all sites, but this was significant only at the femoral diaphysis and distal metaphysis, GH could reverse the loss of stre ngth at the diaphysis, but not at the metaphysis. PTH, on the other hand, r eversed the loss of strength to values significantly over ovx at all four s ites. At the metaphysis, PTH monotherapy increased strength to above sham l evels. However, GH + PTH cotherapy showed additive or synergistic effects a t the four tested sites, leading to strength values significantly over sham at all these sites. Static histomorphometry showed that GH exerted its mai n effect on the periosteal envelope and PTH on the endocortical envelope; f or this reason, the GH + PTH combination treatment had an additive or syner gistic effect. We conclude that GH and PTH have a very pronounced anabolic effect when given in cotherapy, Therefore, this treatment regime seems prom ising in the clinical situation for management of patients with severe, est ablished osteoporosis. (Bone 26:643-651; 2000) (C) 2000 by Elsevier Science Inc. All rights reserved.