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Effectiveness of parathyroid hormone (PTH) analogues on fracture healing: a meta-analysis

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Abstract

Summary

This meta-analysis evaluated the evidence for the use of parathyroid hormone (PTH) analogues to improve fracture healing. Eligible studies were prospective randomised controlled trials of adults with acute fractures treated with a PTH analogue. PTH improved functional outcomes but did not affect fracture healing rate or reduce pain.

Purpose

This meta-analysis evaluated the evidence of parathyroid hormone (PTH) analogues in fracture healing. The use of PTH analogues to prevent osteoporotic fractures is well investigated, and studies are emerging on extended indications. One such indication receiving increasing attention is the effect of PTH in fracture healing; however, the overall degree of efficacy remains inconclusive.

Methods

A systematic electronic database search of MEDLINE, EMBASE and the Cochrane Library was conducted for relevant articles in August 2019 with no date restrictions. Randomised controlled trials of adults with acute fractures treated with a PTH analogue were included. PTH was compared with a comparator intervention, placebo or no treatment.

Results

PTH analogue treatment improved functional outcomes in a range of fracture types but did not affect the fracture healing rate or reduce pain. Most trials included in this review were in elderly patients with osteoporosis. There was no evidence that PTH treatment caused harm or impeded fracture healing.

Conclusions

Meta-analysis of published data supports the use of PTH analogues to improve functional outcomes but not fracture healing rate or pain for different fracture types. The evidence for PTH analogue use in fracture healing is less clear in younger, non-osteoporotic patient populations. Trial design was heterogeneous and of limited quality, justifying further original trials.

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Data availability

This study used data already in the public domain, data collection tools will be made available on request to the corresponding author.

Notes

  1. https://www.nice.org.uk/

References

  1. Einhorn TA, Gerstenfeld LC (2015) Fracture healing: mechanisms and interventions. Nat Rev Rheumatol. 11(1):45–54

    Article  PubMed  Google Scholar 

  2. Curtis EM, van der Velde R, Moon RJ, van den Bergh JP, Geusens P, de Vries F et al (2016) Epidemiology of fractures in the United Kingdom 1988-2012: variation with age, sex, geography, ethnicity and socioeconomic status. Bone. 87:19–26

    Article  PubMed  PubMed Central  Google Scholar 

  3. Gormley KJ (2011) Falls prevention and support: translating research, integrating services and promoting the contribution of service users for quality and innovative programmes of care. Int J Older People Nurs. 6(4):307–314

    Article  PubMed  Google Scholar 

  4. England N. NHS Right Care Senario https://www.england.nhs.uk/rightcare/wp-content/uploads/sites/40/2017/02/rightcare-susans-story-full-narrative.pdf2017 [

  5. Fazzalari NL (2011) Bone fracture and bone fracture repair. Osteoporos Int. 22(6):2003–2006

    Article  CAS  PubMed  Google Scholar 

  6. Goldhahn J, Féron JM, Kanis J, Papapoulos S, Reginster JY, Rizzoli R, Dere W, Mitlak B, Tsouderos Y, Boonen S (2012) Implications for fracture healing of current and new osteoporosis treatments: an ESCEO consensus paper. Calcif Tissue Int. 90(5):343–353

    Article  CAS  PubMed  Google Scholar 

  7. Aslan D, Andersen MD, Gede LB, de Franca TK, Jørgensen SR, Schwarz P, Jørgensen NR (2012) Mechanisms for the bone anabolic effect of parathyroid hormone treatment in humans. Scand J Clin Lab Invest. 72(1):14–22

    Article  CAS  PubMed  Google Scholar 

  8. Rubin MR, Bilezikian JP (2003) New anabolic therapies in osteoporosis. Endocrinol Metab Clin North Am. 32(1):285–307

    Article  CAS  PubMed  Google Scholar 

  9. Rubin MR, Bilezikian JP (2003) The anabolic effects of parathyroid hormone therapy. Clin Geriatr Med. 19(2):415–432

    Article  PubMed  Google Scholar 

  10. Dempster DW, Cosman F, Parisien M, Shen V, Lindsay R (1993) Anabolic actions of parathyroid hormone on bone. Endocr Rev. 14(6):690–709

    CAS  PubMed  Google Scholar 

  11. Ito M, Oishi R, Fukunaga M, Sone T, Sugimoto T, Shiraki M, Nishizawa Y, Nakamura T (2014) The effects of once-weekly teriparatide on hip structure and biomechanical properties assessed by CT. Osteoporos Int. 25(3):1163–1172

    Article  CAS  PubMed  Google Scholar 

  12. Varela A, Chouinard L, Lesage E, Smith SY, Hattersley G (2017) One year of abaloparatide, a selective activator of the PTH1 receptor, increased bone formation and bone mass in osteopenic ovariectomized rats without increasing bone resorption. J Bone Miner Res. 32(1):24–33

    Article  CAS  PubMed  Google Scholar 

  13. Komatsubara S, Mori S, Mashiba T, Nonaka K, Seki A, Akiyama T, Miyamoto K, Cao Y, Manabe T, Norimatsu H (2005) Human parathyroid hormone (1-34) accelerates the fracture healing process of woven to lamellar bone replacement and new cortical shell formation in rat femora. Bone. 36(4):678–687

    Article  CAS  PubMed  Google Scholar 

  14. Komrakova M, Krischek C, Wicke M, Sehmisch S, Tezval M, Rohrberg M, Brandsch T, Stuermer KM, Stuermer EK (2011) Influence of intermittent administration of parathyroid hormone on muscle tissue and bone healing in orchiectomized rats or controls. J Endocrinol. 209(1):9–19

    Article  CAS  PubMed  Google Scholar 

  15. Gardner MJ, van der Meulen MC, Carson J, Zelken J, Ricciardi BF, Wright TM et al (2007) Role of parathyroid hormone in the mechanosensitivity of fracture healing. J Orthop Res. 25(11):1474–1480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Li YF, Zhou CC, Li JH, Luo E, Zhu SS, Feng G, Hu J (2012) The effects of combined human parathyroid hormone (1-34) and zoledronic acid treatment on fracture healing in osteoporotic rats. Osteoporos Int. 23(4):1463–1474

    Article  CAS  PubMed  Google Scholar 

  17. Peichl P, Holzer LA, Maier R, Holzer G (2011) Parathyroid hormone 1-84 accelerates fracture-healing in pubic bones of elderly osteoporotic women. J Bone Joint Surg Am. 93(17):1583–1587

    Article  PubMed  Google Scholar 

  18. Aspenberg P, Genant HK, Johansson T, Nino AJ, See K, Krohn K, García-Hernández PA, Recknor CP, Einhorn TA, Dalsky GP, Mitlak BH, Fierlinger A, Lakshmanan MC (2010) Teriparatide for acceleration of fracture repair in humans: a prospective, randomized, double-blind study of 102 postmenopausal women with distal radial fractures. J Bone Miner Res. 25(2):404–414

    Article  CAS  PubMed  Google Scholar 

  19. Greenspan SL, Vujevich K, Britton C, Herradura A, Gruen G, Tarkin I, Siska P, Hamlin B, Perera S (2018) Teriparatide for treatment of patients with bisphosphonate-associated atypical fracture of the femur. Osteoporos Int. 29(2):501–506

    Article  CAS  PubMed  Google Scholar 

  20. Tsuchie H, Miyakoshi N, Kasukawa Y, Nishi T, Abe H, Segawa T, Shimada Y (2016) The effect of teriparatide to alleviate pain and to prevent vertebral collapse after fresh osteoporotic vertebral fracture. J Bone Miner Metab. 34(1):86–91

    Article  CAS  PubMed  Google Scholar 

  21. Im GI, Lee SH (2015) Effect of teriparatide on healing of atypical femoral fractures: a systemic review. J Bone Metab. 22(4):183–189

    Article  PubMed  PubMed Central  Google Scholar 

  22. Zhang D, Potty A, Vyas P, Lane J (2014) The role of recombinant PTH in human fracture healing: a systematic review. J Orthop Trauma. 28(1):57–62

    Article  PubMed  Google Scholar 

  23. Kim SM, Kang KC, Kim JW, Lim SJ, Hahn MH (2017) Current role and application of teriparatide in fracture healing of osteoporotic patients: a systematic review. J Bone Metab. 24(1):65–73

    Article  PubMed  PubMed Central  Google Scholar 

  24. Shi Z, Zhou H, Pan B, Lu L, Liu J, Kang Y, Yao X, Feng S (2016) Effectiveness of teriparatide on fracture healing: a systematic review and meta-analysis. PLoS One. 11(12):e0168691

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Lou S, Lv H, Wang G, Zhang L, Li M, Li Z et al (2016) The effect of teriparatide on fracture healing of osteoporotic patients: a meta-analysis of randomized controlled trials. Biomed Res Int. 2016:6040379

    Article  PubMed  PubMed Central  Google Scholar 

  26. Hong H, Song T, Liu Y, Li J, Jiang Q, Song Q et al (2019) The effectiveness and safety of parathyroid hormone in fracture healing: a meta-analysis. Clinics (Sao Paulo) 74:e800

    Article  Google Scholar 

  27. Shigenobu K, Hashimoto T, Kanayama M, Ohha H, Yamane S (2019) The efficacy of osteoporotic treatment in patients with new spinal vertebral compression fracture pain, ADL, QOL, bone metabolism and fracture-healing - In comparison with weekly teriparatide with bisphosphonate. Bone Rep. 11:100217

    Article  PubMed  PubMed Central  Google Scholar 

  28. Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M et al (2015) Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 4:1

    Article  PubMed  PubMed Central  Google Scholar 

  29. Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I et al (2019) RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 366:l4898

    Article  PubMed  Google Scholar 

  30. Baker A, Young K, Potter J, Madan I. A review of grading systems for evidence-based guidelines produced by medical specialties. Clinical medicine (London, England). 2010;10(4):358-63.

  31. Zhao Y, Xue R, Shi N, Xue Y, Zong Y, Lin W, Pei B, Sun C, Fan R, Jiang Y (2016) Aggravation of spinal cord compromise following new osteoporotic vertebral compression fracture prevented by teriparatide in patients with surgical contraindications. Osteoporos Int. 27(11):3309–3317

    Article  CAS  PubMed  Google Scholar 

  32. Hadji P, Zanchetta JR, Russo L, Recknor CP, Saag KG, McKiernan FE et al (2012) The effect of teriparatide compared with risedronate on reduction of back pain in postmenopausal women with osteoporotic vertebral fractures. Osteoporos Int. 23(8):2141–2150

    Article  CAS  PubMed  Google Scholar 

  33. Malouf-Sierra J, Tarantino U, García-Hernández PA, Corradini C, Overgaard S, Stepan JJ et al (2016) Effect of teriparatide or risedronate in BMD and fracture recovery in elderly patients with a recent pertrochanteric hip fracture: final results of a 78-week randomized clinical trial. J Bone Miner Res. 32:1040–1051

    Article  CAS  Google Scholar 

  34. Chesser TJ, Fox R, Harding K, Halliday R, Barnfield S, Willett K et al (2016) The administration of intermittent parathyroid hormone affects functional recovery from trochanteric fractured neck of femur: a randomised prospective mixed method pilot study. Bone Joint J. 98-B(6):840–845

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Bhandari M, Jin L, See K, Burge R, Gilchrist N, Witvrouw R, Krohn KD, Warner MR, Ahmad QI, Mitlak B (2016) Does teriparatide improve femoral neck fracture healing: results from a randomized placebo-controlled trial. Clin Orthop Relat Res. 474(5):1234–1244

    Article  PubMed  PubMed Central  Google Scholar 

  36. Kanakaris NK, West RM, Giannoudis PV (2015) Enhancement of hip fracture healing in the elderly: Evidence deriving from a pilot randomized trial. Injury. 46(8):1425–1428

    Article  PubMed  Google Scholar 

  37. Almirol EA, Chi LY, Khurana B, Hurwitz S, Bluman EM, Chiodo C, Matzkin E, Baima J, LeBoff MS (2016) Short-term effects of teriparatide versus placebo on bone biomarkers, structure, and fracture healing in women with lower-extremity stress fractures: a pilot study. J Clin Transl Endocrinol. 5:7–14

    PubMed  PubMed Central  Google Scholar 

  38. Johansson T (2016) PTH 1-34 (teriparatide) may not improve healing in proximal humerus fractures. A randomized, controlled study of 40 patients. Acta Orthop. 87(1):79–82

    Article  PubMed  Google Scholar 

  39. Stanciu M, Popa FL. Teriparatide treatment in pelvic fracture. Osteoporos Int (2016) 272016. p. (Suppl 1):S79–S548.

  40. Kastirr I, Radmer S, Andresen R, Schober HC (2016) Osseous consolidation of an aseptic delayed union of a lower leg fracture after parathyroid hormone therapy - a case report. J Clin Diagn Res. 10(7):RD03–RD05

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Yang DH, Hu SY, Meng Y, Tong GJ, Chen JT (2016) Teriparatide for conservative treatment of osteoporotic vertebral fracture: analysis of 12 cases. Nan Fang Yi Ke Da Xue Xue Bao. 36(3):414–418

    PubMed  Google Scholar 

  42. Coppola C, Del Buono A, Maffulli N (2015) Teriparatide in fracture non-unions. Transl Med UniSa. 12:47–53

    CAS  PubMed  Google Scholar 

  43. Kim Y, Tanaka C, Tada H, Kanoe H, Shirai T (2015) Radiographic features of teriparatide-induced healing of femoral fractures. Bone Rep. 3:11–14

    Article  PubMed  PubMed Central  Google Scholar 

  44. Mancilla EE, Brodsky JL, Mehta S, Pignolo RJ, Levine MA (2015) Teriparatide as a systemic treatment for lower extremity nonunion fractures: a case series. Endocr Pract. 21(2):136–142

    Article  PubMed  Google Scholar 

  45. Nozaka K, Shimada Y, Miyakoshi N, Yamada S, Hongo M, Kasukawa Y, Saito H, Kijima H (2014) Combined effect of teriparatide and low-intensity pulsed ultrasound for nonunion: a case report. BMC Res Notes. 7:317

    Article  PubMed  PubMed Central  Google Scholar 

  46. Bednar DA (2013) Teriparatide treatment of a glucocorticoid-associated resorbing nonunion of a type III odontoid process fracture: a case report. J Spinal Disord Tech. 26(8):E319–E322

    Article  PubMed  Google Scholar 

  47. Borges JL (2015) Accelerated fracture healing with teriparatide. Arch Endocrinol Metab. 59(1):89

    Article  PubMed  Google Scholar 

  48. Cortés Franco S, Lorente Muñoz A, Perez Barrero P, Alberdi Viñas J. Surgical failure in patient with cervical fracture and ankylosing spondylitis treated with teriparatide to try to augment consolidation. Acta Neurochirurgica 2013. p. 1955–6.

  49. Tamai K, Takamatsu K, Kazuki K (2013) Successful treatment of nonunion with teriparatide after failed ankle arthrodesis for Charcot arthropathy. Osteoporos Int. 24(10):2729–2732

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Lou S, Lv H, Li Z, Tang P, Wang Y (2018) Parathyroid hormone analogues for fracture healing: protocol for a systematic review and meta-analysis of randomised controlled trials. BMJ Open. 8(1):e019291

    Article  PubMed  PubMed Central  Google Scholar 

  51. Gallagher EJ, Liebman M, Bijur PE (2001) Prospective validation of clinically important changes in pain severity measured on a visual analog scale. Ann Emerg Med. 38(6):633–638

    Article  CAS  PubMed  Google Scholar 

  52. Fredericson M, Bergman AG, Hoffman KL, Dillingham MS (1995) Tibial stress reaction in runners. Correlation of clinical symptoms and scintigraphy with a new magnetic resonance imaging grading system. Am J Sports Med. 23(4):472–481

    Article  CAS  PubMed  Google Scholar 

  53. Gruber R, Koch H, Doll BA, Tegtmeier F, Einhorn TA, Hollinger JO (2006) Fracture healing in the elderly patient. Exp Gerontol. 41(11):1080–1093

    Article  PubMed  Google Scholar 

  54. Gaston MS, Simpson AH (2007) Inhibition of fracture healing. J Bone Joint Surg Br. 89(12):1553–1560

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We would like to thank both Professor Lee Shepstone (Norwich Medical School) and Dr Andoni Toms (Norfolk and Norwich University Hospital), for their help with the statistical and imaging analysis respectively in this meta-analysis.

Funding

This research was funded as part of a Ministry of Defence, UK grant.

Author information

Authors and Affiliations

  1. Norwich Medical School, University of East Anglia, Norwich, UK

    K. Eastman, I. Piec, J. Greeves & W. Fraser

  2. Norfolk and Norwich University Hospital, Norwich, UK

    M. Gerlach

  3. Department of Army Health and Performance Research, Andover, Hampshire, UK

    J. Greeves

Authors
  1. K. Eastman
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  2. M. Gerlach
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  3. I. Piec
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  4. J. Greeves
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  5. W. Fraser
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Corresponding author

Correspondence to K. Eastman.

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Conflicts of interest

Professor William Fraser has received unrestricted research grants, sat on advisory boards and given lectures on behalf of Eli Lilly, NPS and Nycomed. Dr Matt Gerlach, Dr Isabelle Piec, Prof Julie Greeves and Mrs Katharine Eastman have no conflicts of interest.

Ethics approval

This study was not a human or animal experiment so no ethical approval was required.

Consent to participate

This study used data already in the public domain, there was no requirement for consent to be taken.

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This study used data already in the public domain, there was no requirement for consent to be taken.

Code availability

Software used was Review Manager (RevMan) [Computer program]. Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.

RoB 2 tool [Computer program]. Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, Cates CJ, Cheng H-Y, Corbett MS, Eldridge SM, Hernán MA, Hopewell S, Hróbjartsson A, Junqueira DR, Jüni P, Kirkham JJ, Lasserson T, Li T, McAleenan A, Reeves BC, Shepperd S, Shrier I, Stewart LA, Tilling K, White IR, Whiting PF, Higgins JPT. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 2019; 366: l4898.

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Eastman, K., Gerlach, M., Piec, I. et al. Effectiveness of parathyroid hormone (PTH) analogues on fracture healing: a meta-analysis. Osteoporos Int 32, 1531–1546 (2021). https://doi.org/10.1007/s00198-021-05847-0

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