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Combined treatment with alendronate and Drynaria rhizome extracts

Effect on fracture healing in osteoporotic rats

Kombinationstherapie mit Alendronat und Drynaria-rhizome-Extrakt

Effekt auf die Frakturheilung bei osteoporotischen Ratten

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Abstract

The effects of both alendronate (ALN) and Drynaria rhizome extracts (DRE) alone could promote bone healing in osteoporotic fractures but there are no reports about the combined use of ALN and DRE for promotion of bone healing of fractures in osteoporotic settings. This study investigated the effects of ALN plus DRE on fractures in osteopenic rats. Osteopenic rats underwent unilateral transverse osteotomy on the femur fixed by a sterilized Kirschner wire 2 weeks after intragastric administration of retinoic acid (80 mg/kg body weight/day). Subsequently, the animals were randomly divided into four groups: control, ALN, DRE and ALN + DRE. All rats from groups ALN, DRE and ALN + DRE received ALN (40 mg/kg, weekly), DRE (90 mg/kg/day), or both for 2, 4 and 6 weeks. The results of our study indicated that all treatment promoted fracture healing and callus formation compared to controls but ALN + DRE treatment showed significantly stronger effects than ALN or DRE alone in histological, X‑ray and biomechanical tests. These results seem to indicate that combined treatment with ALN and DRE has an additive effect on fracture healing and callus formation in osteoporotic rats.

Zusammenfassung

Die Auswirkungen von sowohl Alendronat (ALN) als auch Drynaria-rhizome-Extrakten (DRE) als Einzeltherapie fördern die Knochenheilung von osteoporotischen Frakturen, jedoch existieren keine Berichte über die kombinierte Anwendung von ALN und DRE zur Förderung der Knochenheilung bei Frakturen osteoporotischen Ursprungs. Diese Studie untersuchte die Auswirkungen von ALN plus DRE auf Frakturen bei Ratten mit Osteoporose. Bei osteoporotischen Ratten erfolgte 2 Wochen nach einer intragastralen Gabe von Retinsäure (80 mg/kg Körpergewicht/Tag) eine unilaterale tranversale Osteotomie des Femurs, der mit einem Kirschner-Draht fixiert wurde. Anschließend wurden die Tiere randomisiert in 4 Gruppen eingeteilt: Kontrollgruppe, ALN, DRE und ALN + DRE. Alle Ratten der Gruppen ALN, DRE und ALN + DRE erhielten ALN (40 mg/kg, wöchentlich), DRE (90 mg/kg/Tag) oder beides für 2, 4 und 6 Wochen. Die Ergebnisse unserer Studie deuteten darauf hin, dass alle Behandlungen im Vergleich zur Kontrollgruppe die Frakturheilung und Kallusbildung förderten, wobei die Therapie mit ALN + DRE in histologischen, radiologischen und biomechanischen Untersuchungen signifikant stärkere Auswirkungen zeigte als ALN oder DRE alleine. Diese Ergebnisse scheinen darauf hinzuweisen, dass eine Kombinationstherapie mit ALN und DRE einen zusätzlichen Effekt auf die Frakturheilung und Kallusbildung bei osteoporotischen Ratten hat.

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References

  1. Arantes HP, Gimeno SG, Chiang AY, Bilezikian JP, Lazaretticastro M (2016) Incidence of vertebral fractures in calcium and vitamin D‑supplemented postmenopausal Brazilian women with osteopenia or osteoporosis: data from arzoxifene generations trial. Arch Endocrinol Metab 60(1):54–59

    Article  PubMed  Google Scholar 

  2. Wright NC, Looker AC, Saag KG, Curtis JR, Delzell ES, Randall S, Dawson-Hughes B (2014) The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res 29(11):2520–2526. https://doi.org/10.1002/jbmr.2269

    Article  PubMed  Google Scholar 

  3. Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King A, Tosteson A (2007) Incidence and economic burden of osteoporosis-related fractures in the United States, 2005–2025. J Bone Miner Res 22(3):465–475. https://doi.org/10.1359/jbmr.061113

    Article  PubMed  Google Scholar 

  4. Hannan EL, Magaziner J, Wang JJ, Eastwood EA, Silberzweig SB, Gilbert M, Morrison RS, McLaughlin MA, Orosz GM, Siu AL (2001) Mortality and locomotion 6 months after hospitalization for hip fracture: risk factors and risk-adjusted hospital outcomes. JAMA 285(21):2736–2742

    Article  CAS  PubMed  Google Scholar 

  5. Roux C, Wyman A, Hooven FH, Gehlbach SH, Adachi JD, Chapurlat RD, Compston JE, Cooper C, Diez-Perez A, Greenspan SL, Lacroix AZ, Netelenbos JC, Pfeilschifter J, Rossini M, Saag KG, Sambrook PN, Silverman S, Siris ES, Watts NB, Boonen S, GLOW investigators (2012) Burden of non-hip, non-vertebral fractures on quality of life in postmenopausal women: the Global Longitudinal study of Osteoporosis in Women (GLOW). Osteoporos Int 23(12):2863–2871. https://doi.org/10.1007/s00198-012-1935-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Mccann RM, Colleary G, Geddis C, Clarke SA, Jordan GR, Dickson GR (2008) Effect of osteoporosis on bone mineral density and fracture repair in a rat femoral fracture model. J Orthop Res 26(3):384–393

    Article  PubMed  Google Scholar 

  7. Hao YJ, Zhang G, Wang YS, Qin L, Hung WY, Leung K, Pei FX (2007) Changes of microstructure and mineralized tissue in the middle and late phase of osteoporotic fracture healing in rats. Bone 41(4):631–638. https://doi.org/10.1016/j.bone.2007.06.006

    Article  PubMed  Google Scholar 

  8. Reszka AA, Rodan GA (1998) Mechanisms of action of bisphosphonates. Annu Rev Pharmacol Toxicol 38(1):375–388

    Article  Google Scholar 

  9. Uchiyama S, Itsubo T, Nakamura K, Fujinaga Y, Sato N, Imaeda T, Kadoya M, Kato H (2013) Effect of early administration of alendronate after surgery for distal radial fragility fracture on radiological fracture healing time. Bone Joint J 95-B(11):1544–1550. https://doi.org/10.1302/0301-620X.95B11.31652

    Article  CAS  PubMed  Google Scholar 

  10. van der Poest CE, Patka P, Vandormael K, Haarman H, Lips P (2000) The effect of alendronate on bone mass after distal forearm fracture. J Bone Miner Res 15(3):586–593. https://doi.org/10.1359/jbmr.2000.15.3.586

    Article  Google Scholar 

  11. Adolphson P, Abbaszadegan H, Bodén H, Salemyr M, Henriques T (2000) Clodronate increases mineralization of callus after Colles’ fracture: a randomized, double-blind, placebo-controlled, prospective trial in 32 patients. Acta Orthop Scand 71(2):195–200

    Article  CAS  PubMed  Google Scholar 

  12. Li H, Miyahara T, Tezuka Y, Namba T, Suzuki T, Dowaki R, Watanabe M, Nemoto N, Tonami S, Seto H (1999) The effect of kampo formulae on bone resorption in vitro and in vivo. II. Detailed study of berberine. Biol Pharm Bull 22(4):391–396

    Article  CAS  PubMed  Google Scholar 

  13. Jeong JC, Kang SC, Jeong CW, Kim HM, Lee YC, Chang YC, Kim CH (2003) Inhibition of drynariae rhizoma extracts on bone resorption mediated by processing of cathepsin K in cultured mouse osteoclasts. Int Immunopharmacol 3(12):1685–1697

    Article  CAS  PubMed  Google Scholar 

  14. Liu RH, Kang X, Xu LP, Nian HL, Yang XW, Shi HT, Wang XJ (2015) Effects of the combined extracts of herba epimedii and fructus ligustri lucidi on bone mineral content and bone turnover in osteoporotic rats. BMC Complement Altern Med 15(1):1–8

    Article  CAS  Google Scholar 

  15. Ling-jie F, Ting-ting T, Yong-qiang H, Ke-rong D (2013) Long-term effects of alendronate on fracture healing and bone remodeling of femoral shaft in ovariectomized rats. Acta Pharmacol Sin 34(3):387–392

    Article  CAS  Google Scholar 

  16. Hao Y, Ma Y, Wang X, Jin F, Ge S (2012) Short-term muscle atrophy caused by botulinum toxin-A local injection impairs fracture healing in the rat femur. J Orthop Res 30(4):574–580

    Article  CAS  PubMed  Google Scholar 

  17. Comelekoglu U, Bagis S, Yalin S, Ogenler O, Yildiz A, Sahin NO, Oguz I, Hatungil R (2007) Biomechanical evaluation in osteoporosis: ovariectomized rat model. Clin Rheumatol 26(3):380–384. https://doi.org/10.1007/s10067-006-0367-2

    Article  PubMed  Google Scholar 

  18. Manolagas SC (2000) Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev 21(2):115–137

    CAS  PubMed  Google Scholar 

  19. Dempster DW (2002) The impact of bone turnover and bone-active agents on bone quality: focus on the hip. Osteoporos Int 13(13):349–352

    Article  CAS  PubMed  Google Scholar 

  20. Tao ZS, Qiang Z, Tu KK, Huang ZL, Xu HM, Sun T, Lv YX, Cui W, Yang L (2015) Treatment study of distal femur for parathyroid hormone (1–34) and beta-tricalcium phosphate on bone formation in critical size defects in rats. J Biomater Appl 30(4):484–491. https://doi.org/10.1177/0885328215592854

    Article  CAS  PubMed  Google Scholar 

  21. Moazzaz P, Gupta MC, Gilotra MM, Gilotra MN, Maitra S, Theerajunyaporn T, Chen JL, Reddi AH, Martin RB (2005) Estrogen-dependent actions of bone morphogenetic protein-7 on spine fusion in rats. Spine 30(15):1706–1711

    Article  PubMed  Google Scholar 

  22. Hochberg MC, Greenspan S, Wasnich RD, Miller P, Thompson DE, Ross PD (2002) Changes in bone density and turnover explain the reductions in incidence of nonvertebral fractures that occur during treatment with antiresorptive agents. J Clin Endocrinol Metab 87(4):1586–1592

    Article  CAS  PubMed  Google Scholar 

  23. Wasnich RD, Miller PD (2000) Antifracture efficacy of antiresorptive agents are related to changes in bone density. J Clin Endocrinol Metab 85(1):231–236

    Article  CAS  PubMed  Google Scholar 

  24. Wong RW, Rabie B, Bendeus M, Hägg U (2007) The effects of rhizoma curculiginis and rhizoma drynariae extracts on bones. Chin Med 2(1):1–7

    Article  Google Scholar 

  25. Jeong JC, Lee BT, Yoon CH, Kim HM, Kim CH (2005) Effects of drynariae rhizoma on the proliferation of human bone cells and the immunomodulatory activity. Pharmacol Res 51(2):125–136

    Article  PubMed  Google Scholar 

  26. Chen LL, Lei LH, Ding PH, Tang Q, Wu YM (2011) Osteogenic effect of frynariae rhizoma extracts and Naringin on MC3T3-E1 cells and an induced rat alveolar bone resorption model. Arch Oral Biol 56(56):1655–1662

    Article  CAS  PubMed  Google Scholar 

  27. Jeong JC, Lee JW, Yoon CH, Lee YC, Chung KH, Kim MG, Kim CH (2005) Stimulative effects of drynariae rhizoma extracts on the proliferation and differentiation of osteoblastic MC3T3-E1 cells. J Ethnopharmacol 96(3):489–495

    Article  PubMed  Google Scholar 

  28. Schindeler A, Mcdonald MM, Bokko P, Little DG (2008) Bone remodeling during fracture repair: the cellular picture. Semin Cell Dev Biol 19(5):459–466

    Article  CAS  PubMed  Google Scholar 

  29. Hanna S, Jasmin L, Epari DR, Petra S, Christine E, Sarah M, Hermann B, Haas NP, Duda GN (2006) Osteoclastic activity begins early and increases over the course of bone healing. Bone 38(4):547–554

    Article  Google Scholar 

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Funding

This work was funded by a research grant to Zhejiang Province Medicine and Health Research Project (No. 2016KYB196), Zhejiang Chinese Medicine Bureau Research Project (No. 2016ZA140), Science Technology Department of Zhejiang Province Research Project (No. 2017C37125) and Key Project of Natural Science Research for Colleges and universities of Anhui Province Project (No.KJ2017A266).

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Authors and Affiliations

  1. Department of Orthopedics, The Second Affiliated Hospital, Yuying Children’s Hospital of Wenzhou Medical University, 109 Xueyuan Road, 32500, Wenzhou, Zhejiang, China

    Long Chen Ph.D & Kailiang Zhou MD

  2. Department of Traumatic Orthopedics, Shandong Provincial Hospital, Shandong University, 324 Jin Fifth Wei Seventh Road, 250021, Jinan, Shandong, China

    Long Chen Ph.D & Dong-Sheng Zhou Ph.D

  3. Department of Traumatic Orthopedics, The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, No. 2, Zhe shan Xi Road, 241001, Wuhu, Anhui, China

    Zhou-Shan Tao MD

  4. Department of Surgery, The Second Affiliated Hospital, Yuying Children’s Hospital of Wenzhou Medical University, 109 Xueyuan Road, 32500, Wenzhou, Zhejiang, China

    Hui Chen MD

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  1. Long Chen Ph.D
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  2. Zhou-Shan Tao MD
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Correspondence to Dong-Sheng Zhou Ph.D.

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Conflict of interest

L. Chen, Z.-S. Tao, H. Chen, K. Zhou and D.-S. Zhou declare that they have no competing interests.

All animal experiments were conducted in accordance with international standards on animal welfare as well as being compliant with the Animal Research Committee of the university.

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Long Chen and Zhou-Shan Tao are co-authors and contributed equally to this work.

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Chen, L., Tao, ZS., Chen, H. et al. Combined treatment with alendronate and Drynaria rhizome extracts. Z Gerontol Geriat 51, 875–881 (2018). https://doi.org/10.1007/s00391-017-1326-z

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  • DOI: https://doi.org/10.1007/s00391-017-1326-z

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