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Maintenance of increased bone mass after recombinant human parathyroid hormone (1-84) with sequential zoledronate treatment in ovariectomized rats.
J Bone Miner Res. 2004 Jun; 19(6):931-7.JB

Abstract

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 microg/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rats (SHAM; n = 6), (3) OVX rats with PTH maintenance (PTH-M; n = 6), (4) OVX rats treated with PTH and then PTH was withdrawn (PTH-W; n = 6), (5) PTH-treated OVX rats treated with 17beta-estradiol (PTH-E; 10 microg/day SC, 5 days/week; n = 6), and (6) PTH-treated OVX rats treated with zoledronate (PTH-Z; 12.5 microg/kg SC weekly; n = 6). BMD of the right femora was measured by DXA. microCT 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 approximately 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 (17beta-estradiol versus zoledronate). The zoledronate after rhPTH(1-84) as a sequential regimen was quite consistently effective.

Authors+Show Affiliations

Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15125792

Citation

Rhee, Yumie, et al. "Maintenance of Increased Bone Mass After Recombinant Human Parathyroid Hormone (1-84) With Sequential Zoledronate Treatment in Ovariectomized Rats." Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, vol. 19, no. 6, 2004, pp. 931-7.
Rhee Y, Won YY, Baek MH, et al. Maintenance of increased bone mass after recombinant human parathyroid hormone (1-84) with sequential zoledronate treatment in ovariectomized rats. J Bone Miner Res. 2004;19(6):931-7.
Rhee, Y., Won, Y. Y., Baek, M. H., & Lim, S. K. (2004). Maintenance of increased bone mass after recombinant human parathyroid hormone (1-84) with sequential zoledronate treatment in ovariectomized rats. Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, 19(6), 931-7.
Rhee Y, et al. Maintenance of Increased Bone Mass After Recombinant Human Parathyroid Hormone (1-84) With Sequential Zoledronate Treatment in Ovariectomized Rats. J Bone Miner Res. 2004;19(6):931-7. PubMed PMID: 15125792.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Maintenance of increased bone mass after recombinant human parathyroid hormone (1-84) with sequential zoledronate treatment in ovariectomized rats. AU - Rhee,Yumie, AU - Won,Ye-Yeon, AU - Baek,Myong-Hyun, AU - Lim,Sung-Kil, Y1 - 2004/01/19/ PY - 2003/08/25/received PY - 2003/11/24/revised PY - 2004/01/16/accepted PY - 2004/5/6/pubmed PY - 2005/2/25/medline PY - 2004/5/6/entrez SP - 931 EP - 7 JF - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JO - J Bone Miner Res VL - 19 IS - 6 N2 - UNLABELLED: 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 microg/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 17beta-estradiol (PTH-E; 10 microg/day SC, 5 days/week; n = 6), and (6) PTH-treated OVX rats treated with zoledronate (PTH-Z; 12.5 microg/kg SC weekly; n = 6). BMD of the right femora was measured by DXA. microCT 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 approximately 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 (17beta-estradiol versus zoledronate). The zoledronate after rhPTH(1-84) as a sequential regimen was quite consistently effective. SN - 0884-0431 UR - https://www.unboundmedicine.com/medline/citation/15125792/Maintenance_of_increased_bone_mass_after_recombinant_human_parathyroid_hormone__1_84__with_sequential_zoledronate_treatment_in_ovariectomized_rats_ L2 - https://doi.org/10.1359/JBMR.040123 DB - PRIME DP - Unbound Medicine ER -