Combination therapy with low-dose teriparatide and zoledronate contributes to fracture healing on rat femoral fracture model
Abstract Background Delay in fracture healing or non-union can be devastating complication. Recent studies have reported that teriparatide (TP) demonstrated effectively on callus formation and mechanical strength and zoledronate (ZA) increased the callus size and resistance at the fracture site in r...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-10-01
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| Series: | Journal of Orthopaedic Surgery and Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13018-018-0917-8 |
| _version_ | 1798043244302434304 |
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| author | Yuta Tsubouchi Shinichi Ikeda Masashi Kataoka Hiroshi Tsumura |
| author_facet | Yuta Tsubouchi Shinichi Ikeda Masashi Kataoka Hiroshi Tsumura |
| author_sort | Yuta Tsubouchi |
| collection | DOAJ |
| description | Abstract Background Delay in fracture healing or non-union can be devastating complication. Recent studies have reported that teriparatide (TP) demonstrated effectively on callus formation and mechanical strength and zoledronate (ZA) increased the callus size and resistance at the fracture site in rat fracture model. In this study, the effects of combination therapy with low dose TP and ZA on fracture healing was evaluated. Methods From 1 week post-operation, TP (5 times a week administration) and ZA (0.1 mg/kg single administration) were administered by dividing the rats into the following five groups: TP 1 μg group {T(1): TP 1 μg/kg}, ZA group (ZA:0.1 mg/kg), TP1 μg+ZA group {T(1)+ZA: TP 1 μg/kg+ZA}, TP 10 μg+ZA group {T(10)+ZA: TP 10 μg/kg + ZA}, and control group (C: administered saline). Rt femurs were excised 7 weeks after the surgery; bone fusions were evaluated with soft X-ray images on a 4-point scale. And the histopathological examination was performed in demineralized and non-demineralized specimens. Furthermore, the Radiographic Union Scale was conducted in all specimens. Results About the bone fusions rates, C, T(1), ZA, T(1)+ZA, and T(10)+ZA groups demonstrated 20.0%, 55.6%, 70.0%, 70.0%, and 80.0%, respectively, and with 4-point scale, each group was 0.50, 1.56, 2.00, 2.60, and 2.80 points, respectively. The callus volume was significantly increased to 16.66 mm2 and 17.75 mm2 in the T(1)+ZA and T(10)+ZA groups, respectively, while 10.65 mm2 (p < 0.05) in the C group. Furthermore, the callus area in the T(10)+ZA group was also observed to have significantly increased to 78.78%, compared with 54.63% and 44.11% in the C and T(1)+ZA groups, respectively (p < 0.01). Histopathologically, cartilage tissue and immature callus formation were observed at the bone junction in the C group; however, the osseous bridge formation of mature callus was observed in the ZA, T(1)+ZA, and T(10)+ZA groups. Conclusion It is suggested that administration of low dose TP and ZA in combination may lead to the treatment of delayed union of fracture. We hope the combination treatment may become one of new therapeutic strategy. |
| first_indexed | 2024-04-11T22:46:40Z |
| format | Article |
| id | doaj.art-e48a13fae1b04ed483ff452e93145a91 |
| institution | Directory Open Access Journal |
| issn | 1749-799X |
| language | English |
| last_indexed | 2024-04-11T22:46:40Z |
| publishDate | 2018-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Orthopaedic Surgery and Research |
| spelling | doaj.art-e48a13fae1b04ed483ff452e93145a912022-12-22T03:58:45ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2018-10-011311710.1186/s13018-018-0917-8Combination therapy with low-dose teriparatide and zoledronate contributes to fracture healing on rat femoral fracture modelYuta Tsubouchi0Shinichi Ikeda1Masashi Kataoka2Hiroshi Tsumura3Oita University Hospital Rehabilitation Center, Oita UniversityDepartment of Rehabilitation Medicine, Faculty of Medicine, Oita UniversityPhysical Therapy Course of Study, Faculty of Welfare and Health Sciences, Oita UniversityDepartment of Orthopaedic Surgery, Faculty of Medicine, Oita UniversityAbstract Background Delay in fracture healing or non-union can be devastating complication. Recent studies have reported that teriparatide (TP) demonstrated effectively on callus formation and mechanical strength and zoledronate (ZA) increased the callus size and resistance at the fracture site in rat fracture model. In this study, the effects of combination therapy with low dose TP and ZA on fracture healing was evaluated. Methods From 1 week post-operation, TP (5 times a week administration) and ZA (0.1 mg/kg single administration) were administered by dividing the rats into the following five groups: TP 1 μg group {T(1): TP 1 μg/kg}, ZA group (ZA:0.1 mg/kg), TP1 μg+ZA group {T(1)+ZA: TP 1 μg/kg+ZA}, TP 10 μg+ZA group {T(10)+ZA: TP 10 μg/kg + ZA}, and control group (C: administered saline). Rt femurs were excised 7 weeks after the surgery; bone fusions were evaluated with soft X-ray images on a 4-point scale. And the histopathological examination was performed in demineralized and non-demineralized specimens. Furthermore, the Radiographic Union Scale was conducted in all specimens. Results About the bone fusions rates, C, T(1), ZA, T(1)+ZA, and T(10)+ZA groups demonstrated 20.0%, 55.6%, 70.0%, 70.0%, and 80.0%, respectively, and with 4-point scale, each group was 0.50, 1.56, 2.00, 2.60, and 2.80 points, respectively. The callus volume was significantly increased to 16.66 mm2 and 17.75 mm2 in the T(1)+ZA and T(10)+ZA groups, respectively, while 10.65 mm2 (p < 0.05) in the C group. Furthermore, the callus area in the T(10)+ZA group was also observed to have significantly increased to 78.78%, compared with 54.63% and 44.11% in the C and T(1)+ZA groups, respectively (p < 0.01). Histopathologically, cartilage tissue and immature callus formation were observed at the bone junction in the C group; however, the osseous bridge formation of mature callus was observed in the ZA, T(1)+ZA, and T(10)+ZA groups. Conclusion It is suggested that administration of low dose TP and ZA in combination may lead to the treatment of delayed union of fracture. We hope the combination treatment may become one of new therapeutic strategy.http://link.springer.com/article/10.1186/s13018-018-0917-8Fracture healingTeriparatideZoledronate |
| spellingShingle | Yuta Tsubouchi Shinichi Ikeda Masashi Kataoka Hiroshi Tsumura Combination therapy with low-dose teriparatide and zoledronate contributes to fracture healing on rat femoral fracture model Journal of Orthopaedic Surgery and Research Fracture healing Teriparatide Zoledronate |
| title | Combination therapy with low-dose teriparatide and zoledronate contributes to fracture healing on rat femoral fracture model |
| title_full | Combination therapy with low-dose teriparatide and zoledronate contributes to fracture healing on rat femoral fracture model |
| title_fullStr | Combination therapy with low-dose teriparatide and zoledronate contributes to fracture healing on rat femoral fracture model |
| title_full_unstemmed | Combination therapy with low-dose teriparatide and zoledronate contributes to fracture healing on rat femoral fracture model |
| title_short | Combination therapy with low-dose teriparatide and zoledronate contributes to fracture healing on rat femoral fracture model |
| title_sort | combination therapy with low dose teriparatide and zoledronate contributes to fracture healing on rat femoral fracture model |
| topic | Fracture healing Teriparatide Zoledronate |
| url | http://link.springer.com/article/10.1186/s13018-018-0917-8 |
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