Part of these results was presented in abstract form as a plenary poster at the 24th Annual Meeting of the American Society for Bone and Mineral Research, San Antonio, Texas, September 20-24, 2002.
Maintenance of Increased Bone Mass After Recombinant Human Parathyroid Hormone (1-84) With Sequential Zoledronate Treatment in Ovariectomized Rats†
Article first published online: 19 JAN 2004
Copyright © 2004 ASBMR
Journal of Bone and Mineral Research
Volume 19, Issue 6, pages 931–937, June 2004
How to Cite
Rhee, Y., Won, Y.-Y., Baek, M.-H. and Lim, S.-K. (2004), Maintenance of Increased Bone Mass After Recombinant Human Parathyroid Hormone (1-84) With Sequential Zoledronate Treatment in Ovariectomized Rats. J Bone Miner Res, 19: 931–937. doi: 10.1359/JBMR.040123
The authors have no conflict of interest
- Issue published online: 2 DEC 2009
- Article first published online: 19 JAN 2004
- Manuscript Accepted: 16 JAN 2004
- Manuscript Revised: 24 NOV 2003
- Manuscript Received: 25 AUG 2003
- sequential therapy;
- recombinant human parathyroid hormone (1-84);
The concept of lose, restore, maintain (LRM) for reversing existing osteoporosis was tested in rats. The withdrawal of PTH results in the loss of the acquired bone mass, but sequential therapy with zoledronate quite effectively maintained the PTH(1-84)-acquired bone quantity and quality.
Introduction: Because antiresorptive agents against osteoporosis are presently quite limited, strong anabolic agents such as human parathyroid hormone (hPTH) are quite helpful. However, because hPTH(1-34) is available only through injection and has a critical side effect of causing bone tumors during life-long administration in the rat, it would be practical to use PTH for the shortest possible duration to obtain the maximal effect. To determine the effectiveness of the osteoporosis-reversing concept of lose, restore, and maintain (LRM), recombinant hPTH(1-84) [rhPTH(1-84)] and the respective antiresorptive agents were sequentially studied.
Materials and Methods: Thirty-six, 20-week-old Sprague-Dawley rats were used. Treatment started at the 25th week after ovariectomy, which was performed at 20 weeks of age, with 5 weeks of rhPTH(1-84) 100 μg/kg/day, 5 days/week, followed by the respective sequential therapies for 5 weeks as follows: (1) ovariectomized rats (OVX; n = 6), (2) sham-operated rats (SHAM; n = 6), (3) OVX rats with PTH maintenance (PTH-M; n = 6), (4) OVX rats treated with PTH and then PTH was withdrawn (PTH-W; n = 6), (5) PTH-treated OVX rats treated with 17β-estradiol (PTH-E; 10 μg/day SC, 5 days/week; n = 6), and (6) PTH-treated OVX rats treated with zoledronate (PTH-Z; 12.5 μg/kg SC weekly; n = 6). BMD of the right femora was measured by DXA. μCT was used to measure the structural parameters of the second lumbar vertebrae. Three-point bending test of the femora and compressive tests of vertebrae were also performed.
Results: Bone quantity data showed that the BMD and most of the microstructural parameters were significantly higher in the PTH-M and PTH-Z groups than in the OVX and PTH-W groups (p < 0.05). Measurement of the cortical thickness revealed that only the PTH-M group showed a significant increase (p = 0.001). The ultimate force (Fu) at the midshaft of the femora was similar in the treated groups and stronger than in the OVX group (p < 0.05). However, in the vertebrae, the Fu of the PTH-M and PTH-Z groups was significantly higher, by ∼44-47%, than in the OVX and PTH-E groups and showed a higher tendency than in the PTH-W group.
Conclusion: PTH withdrawal resulted in the loss of acquired BMD, and sequential therapy with antiresorptives prevented further loss (17β-estradiol versus zoledronate). The zoledronate after rhPTH(1-84) as a sequential regimen was quite consistently effective.