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Teriparatide and pelvic fracture healing: a phase 2 randomized controlled trial

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Abstract

Summary

Pelvic fracture patients were randomized to blinded daily subcutaneous teriparatide (TPTD) or placebo to assess healing and functional outcomes over 3 months. With TPTD, there was no evidence of improved healing by CT or pain reduction; however, physical performance improved with TPTD but not placebo (group difference p < 0.03).

Introduction

To determine if teriparatide (20 μg/day; TPTD) results in improved radiologic healing, reduced pain, and improved functional outcome vs placebo over 3 months in pelvic fracture patients.

Methods

This randomized, placebo-controlled study enrolled 35 patients (women and men >50 years old) within 4 weeks of pelvic fracture and evaluated the effect of blinded TPTD vs placebo over 3 months on fracture healing. Fracture healing from CT images at 0 and 3 months was assessed as cortical bridging using a 5-point scale. The numeric rating scale (NRS) for pain was administered monthly. Physical performance was assessed monthly by Continuous Summary Physical Performance Score (based on 4 m walk speed, timed repeated chair stands, and balance) and the Timed Up and Go (TUG) test.

Results

The mean age was 82, and >80% were female. The intention to treat analysis showed no group difference in cortical bridging score, and 50% of fractures in TPTD-treated and 53% of fractures in placebo-treated patients were healed at 3 months, unchanged after adjustment for age, sacral fracture, and fracture displacement. Median pain score dropped significantly in both groups with no group differences. Both CSPPS and TUG improved in the teriparatide group, whereas there was no improvement in the placebo group (group difference p < 0.03 for CSPPS at 2 and 3 months).

Conclusion

In this small randomized, blinded study, there was no improvement in radiographic healing (CT at 3 months) or pain with TPTD vs placebo; however, there was improved physical performance in TPTD-treated subjects that was not evident in the placebo group.

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References

  1. Kannus P, Palvanen M, Niemi S, Parkkari J, Järvinen M (2000) Epidemiology of osteoporotic pelvic fractures in elderly people in Finland: sharp increase in 1970–1997 and alarming projections for the new millennium. Osteoporos Int 11:443–448. https://doi.org/10.1007/s001980070112

    Article  CAS  PubMed  Google Scholar 

  2. Rinne PP, Laitinen MK, Kannus P, Mattila VM (2020) The incidence of pelvic fractures and related surgery in the Finnish adult population: a nationwide study of 33,469 patients between 1997 and 2014. 91:587-92

  3. Hansen D, Bazell C, Pelizzari P, Pyenson B (2019) Medicare cost of osteoporotic fractures. The clinical and cost burden of an important consequence of osteoporosis. Milliman, Inc on behalf of National Osteoporosis Foundation

  4. Alnaib M, Waters SS, Shanshal YY, Caplan NN, Jones SS, St Clair Gibson A, Kader DD (2012) Combined pubic rami and sacral osteoporotic fractures: a prospective study. J Orthop Trauma 13:97–103. https://doi.org/10.1007/s10195-012-0182-2

    Article  CAS  Google Scholar 

  5. Krappinger D, Kammerlander C, Hak D, Blauth M (2010) Low-energy osteoporotic pelvic fractures. Arch Orthop Trauma Surg 130:1167–1175. https://doi.org/10.1007/s00402-010-1108-1

    Article  PubMed  Google Scholar 

  6. Prieto-Alhambra D, Avilés FF, Judge A, Van Staa TT, Nogués X, Arden NK, Díez-Pérez A, Cooper C, Javaid MK (2012) Burden of pelvis fracture: a population-based study of incidence, hospitalisation and mortality. Osteoporos Int 23

  7. Pike C, Birnbaum HG, Schiller M, Sharma H, Burge R, Edgell ET (2010) Direct and indirect costs of non-vertebral fracture patients with osteoporosis in the US. Pharmacoeconomics 28:395–409. https://doi.org/10.2165/11531040-000000000-00000

    Article  PubMed  Google Scholar 

  8. Smith CT, Barton DW, Piple AS, Carmouche JJ (2021) Pelvic fragility fractures: an opportunity to improve the undertreatment of osteoporosis. J Bone Joint Surg Am 103:213–218. https://doi.org/10.2106/JBJS.20.00738

    Article  PubMed  Google Scholar 

  9. Ellegaard M, Jørgensen NR, Schwartz P (2010) Parathyroid hormone and bone healing. Calcif Tissue Int 87:1–13. https://doi.org/10.1007/s00223-010-9360-5

    Article  CAS  PubMed  Google Scholar 

  10. 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 90:343–353. https://doi.org/10.1007/s00223-012-9587-4

    Article  CAS  PubMed  Google Scholar 

  11. Murphy CM, Schindeler A, Cantrill LC, Mikulec K, Peacock L, Little DG PTH(1-34) Treatment increases bisphosphonate turnover in fracture repair in rats. J Bone Miner Res 30:1022–1029. https://doi.org/10.1002/jbmr.2424

  12. Pietrogrande L, Raimondo E (2013) Teriparatide in the treatment of non-unions: scientific and clinical evidences. Injury 44:54–S57. https://doi.org/10.1016/S0020-1383(13)70013-5

    Article  Google Scholar 

  13. 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 25:404–414. https://doi.org/10.1359/jbmr.090731

    Article  CAS  PubMed  Google Scholar 

  14. Ohtori S, Inoue G, Orita S, Yamauchi K, Eguchi Y, Ochiai N, Kishida S, Kuniyoshi K, Aoki Y, Nakamura J, Ishikawa T, Miyagi M, Kamoda H, Suzuki M, Kubota G, Sakuma Y, Oikawa Y, Inage K, Sainoh T, Takaso M, Ozawa T, Takahashi K, Toyone T (2012) Teriparatide accelerates lumbar posterolateral fusion in women with postmenopausal osteoporosis: prospective study. Spine (Phila Pa 1976) 37:1464

    Article  Google Scholar 

  15. Malouf-Sierra J, Tarantino U, García-Hernández PA, Corradini C, Overgaard S, Stepan JJ, Borris L, Lespessailles E, Frihagen F, Papavasiliou K, Petto H, Aspenberg P, Caeiro JR, Marin F (2017) Effect of teriparatide or risedronate 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. https://doi.org/10.1002/jbmr.3067

    Article  CAS  PubMed  Google Scholar 

  16. 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 93:1583–1587. https://doi.org/10.2106/JBJS.J.01379

    Article  PubMed  Google Scholar 

  17. Eastman K, Gerlach M, Piec I, Greeves J, Fraser W (2021) Effectiveness of parathyroid hormone (PTH) analogues on fracture healing: a meta-analysis. Osteoporos Int DOI. https://doi.org/10.1007/s00198-021-05847-0

  18. Moon NH, Jang JH, Shin WC, Jung SJ (2020) Effects of teriparatide on treatment outcomes in osteoporotic hip and pelvic bone fractures: meta-analysis and systematic review of randomized controlled trials. Hip & pelvis 32:182–191. https://doi.org/10.5371/hp.2020.32.4.182

    Article  Google Scholar 

  19. Han S, Wen S, Zhao Q, Huang H, Wang H, Cong Y, Shang K, Ke C, Zhuang Y, Zhang B (2020) The efficacy of teriparatide in improving fracture healing in hip fractures: a systematic review and meta-analysis. Biomed Res Int 2020:1–10

    Google Scholar 

  20. 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:e0168691. https://doi.org/10.1371/journal.pone.0168691

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Litrenta J, Tornetta P 3rd, Mehta S, Jones C, OʼToole RV, Bhandari M, Kottmeier S, Ostrum R, Egol K, Ricci W, Schemitsch E, Horwitz D (2015) Determination of radiographic healing: an assessment of consistency using RUST and modified RUST in metadiaphyseal fractures. J Orthop Trauma 29:516–520. https://doi.org/10.1097/BOT.0000000000000390

    Article  PubMed  Google Scholar 

  22. Fisher JS, Kazam JJ, Fufa D, Bartolotta RJ (2019) Radiologic evaluation of fracture healing. Skelet Radiol 48:349–361. https://doi.org/10.1007/s00256-018-3051-0

    Article  Google Scholar 

  23. Jensen MP, Karoly P (2001) Self-report scales and procedures for assessing pain in adults, In Turk DC, Melzack R (eds) (2001) Handbook of pain assessment (2nd ed). The Guilford Press, New York, NY, pp 15–34.

  24. Butler PV (1997) Linear analogue self-assessment and procrustean measurement: a critical review of visual analogue scaling in pain assessment. J Clin Psychol Med Settings 4:111–129

    Article  Google Scholar 

  25. Ostelo RWJG, Deyo RA, Stratford P, Waddell G, Croft P, Von Korff M, Bouter LM, de Vet HC (2008) Interpreting change scores for pain and functional status in low back pain: towards international consensus regarding minimal important change. Spine (Phila Pa 1976) 33:90–94. https://doi.org/10.1097/BRS.0b013e31815e3a10

    Article  Google Scholar 

  26. Guralnik JM, Simonsick EM, Ferrucci L, Glynn RJ, Berkman LF, Blazer DG, Scherr PA, Wallace RB (1994) A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol 49:85–M94. https://doi.org/10.1093/geronj/49.2.m85

    Article  Google Scholar 

  27. Ferrucci L, Simonsick EM, Salive ME, Wallace RB (1995) Lower-extremity function in persons over the age of 70 years as a predictor of subsequent disability. N Engl J Med 332:556–561. https://doi.org/10.1056/NEJM199503023320902

    Article  PubMed  Google Scholar 

  28. Guralnik JM, Seeman TE, Tinetti ME, Nevitt MC, Berkman LF (1994) Validation and use of performance measures of functioning in a non-disabled older population: MacArthur studies of successful aging. Aging (Milano) 6:410–419. https://doi.org/10.1007/BF03324272

    Article  CAS  Google Scholar 

  29. Ostir GV, Volpato S, Fried LP, Chaves P, Guralnik JM (2002) Reliability and sensitivity to change assessed for a summary measure of lower body function: results from the Women’s Health and Aging Study. J Clin Epidemiol 55:916–921. https://doi.org/10.1016/s0895-4356(02)00436-5

    Article  PubMed  Google Scholar 

  30. Onder G, Penninx BWJH, Lapuerta P, Fried LP, Ostir GV, Guralnik JM, Pahor M (2002) Change in physical performance over time in older women: the Women’s Health and Aging Study. J Gerontol A Biol Sci Med Sci 57:289–M293. https://doi.org/10.1093/gerona/57.5.m289

    Article  Google Scholar 

  31. Nieves JW, Zion M, Pahor M, Bernabei R, Gussekloo J, Simon H, Park J, Li T, Lapuerta P, Williams GR (2005) Evaluation of continuous summary physical performance scores (CSPPS) in an elderly cohort. Aging Clin Exp Res 17:193–200. https://doi.org/10.1007/BF03324596

    Article  PubMed  Google Scholar 

  32. Nieves JW, Li T, Zion M, Gussekloo J, Pahor M, Bernabei R, Simon H, Williams GR, Lapuerta P (2007) The clinically meaningful change in physical performance scores in an elderly. Cohort 19:484–491. https://doi.org/10.1007/BF03324735

    Article  Google Scholar 

  33. Podsiadlo D, Richardson S (1991) The timed “Up & Go”: a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc 39:142–148. https://doi.org/10.1111/j.1532-5415.1991.tb01616.x

    Article  CAS  PubMed  Google Scholar 

  34. Larsson BAM, Johansson L, Johansson H, Axelsson KF, Harvey N, Vandenput L, Magnusson P, McCloskey E, Liu E, Kanis JA, Sundh D, Lorentzon M (2021) The timed up and go test predicts fracture risk in older women independently of clinical risk factors and bone mineral density. Osteoporos Int 32:75–84. https://doi.org/10.1007/s00198-020-05681-w

    Article  CAS  PubMed  Google Scholar 

  35. Hachisuka K, Ogata H, Ohkuma H, Tanaka S, Dozono K (1997) Test-retest and inter-method reliability of the self-rating Barthel Index. Clin Rehabil 11:28–35. https://doi.org/10.1177/026921559701100105

    Article  CAS  PubMed  Google Scholar 

  36. Stewart AL, Hays RD, Ware JE Jr (1988) The MOS short-form general health survey. Reliability and validity in a patient population. Med Care 26:724–735. https://doi.org/10.1097/00005650-198807000-00007

    Article  CAS  PubMed  Google Scholar 

  37. Ware JE Jr, Sherbourne CD (1992) The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 30:473–483

    Article  Google Scholar 

  38. Pirie W (1983) Jonckheere Tests for Ordered Alternatives, In Kotz S, Johnson NL and Read CB (eds) (1983) Encyclopedia of statistical sciences. John Wiley & Sons, New York, pp 315–318.

  39. Morshed S, Corrales L, Genant H, Miclau T 3rd (2008) Outcome assessment in clinical trials of fracture-healing. J Bone Joint Surg Am 90(Suppl 1):62–67. https://doi.org/10.2106/JBJS.G.01556

    Article  PubMed  Google Scholar 

  40. Bhandari M, Guyatt GH, Swiontkowski MF, Tornetta P 3rd, Sprague S, Schemitsch EH (2002) A lack of consensus in the assessment of fracture healing among orthopaedic surgeons. J Orthop Trauma 16:562–566. https://doi.org/10.1097/00005131-200209000-00004

    Article  PubMed  Google Scholar 

  41. Kooistra BW, Dijkman BG, Busse JW, Sprague S, Schemitsch EH, Bhandari M (2010) The radiographic union scale in tibial fractures: reliability and validity. J Orthop Trauma 24(Suppl 1):S81–S86. https://doi.org/10.1097/BOT.0b013e3181ca3fd1

    Article  PubMed  Google Scholar 

  42. Huang T, Yang T, Huang K, Peng K, Lee MS (2015) Hsu RW (2015) Effect of teriparatide on unstable pertrochanteric fractures. Biomed Res Int 2015:1–8. https://doi.org/10.1155/2015/568390

    Article  CAS  Google Scholar 

  43. 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. https://doi.org/10.1016/j.bonr.2019.100217

    Article  PubMed  PubMed Central  Google Scholar 

  44. Johansson T (2016) PTH 1-34 (teriparatide) may not improve healing in proximal humerus fractures. A randomized, controlled study of 40 patients. Acta Orthop 87:9–82. https://doi.org/10.3109/17453674.2015.1073050

    Article  Google Scholar 

  45. Aspenberg P, Johansson T (2010) Teriparatide improves early callus formation in distal radial fractures. Acta Orthop 81:234–236. https://doi.org/10.3109/17453671003761946

    Article  PubMed  PubMed Central  Google Scholar 

  46. Rommens PM, Wagner D, Hofmann A (2017) Fragility fractures of the pelvis. JBJS Reviews 5. https://doi.org/10.2106/JBJS.RVW.16.00057

  47. 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 474:1234–1244. https://doi.org/10.1007/s11999-015-4669-z

    Article  PubMed  PubMed Central  Google Scholar 

  48. Chesser TJS, Fox R, Harding K, Halliday R, Barnfield S, Willett K, Lamb S, Yau C, Javaid MK, Gray AC, Young J, Taylor H, Shah K, Greenwood R (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:840–845. https://doi.org/10.1302/0301-620X.98B6.36794

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This study was operated under IND 126129 and registered as Clinicaltrials.gov identifier: NCT02972424. Experimental TPTD and placebo were provided by Eli Lilly; they had no input into the conduct of the trial, interpretation of the results, or the writing of the manuscript. We would like to thank our data manager, Kelly Halvorsen, and Research Pharmacist Patti Dempster. We would also like to thank our internal safety officer, Dr. Emily Stein, and our NIAMS and NCR appointed DSMB members for their support during this trial.

Funding

Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number U01AR069869. This study was partially supported by the Clinical and Translational Science Center at Weill Cornell Medicine, NIH/NCATS Grant # UL1TR002384. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Correspondence to J.W. Nieves.

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Conflicts of interest

JN has received study drug for an NIH trial from Eli Lilly and Radius. FC consults for Amgen and Radius, received lecture fees from Amgen and Radius, and received grant support from Eli Lilly and Amgen. JL consults for Mesentech, Radius Health, Terumo BCT, Kuras, and ON Foundation and received grant support from Merck and Novartis. DM, MR, IH, RB, ML, JJK, and JR have nothing to declare. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Nieves, ., Cosman, F., McMahon, . et al. Teriparatide and pelvic fracture healing: a phase 2 randomized controlled trial. Osteoporos Int 33, 239–250 (2022). https://doi.org/10.1007/s00198-021-06065-4

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