Journal of Bone and Mineral Metabolism

, Volume 33, Issue 5, pp 553–559 | Cite as

Healing of bisphosphonate-associated atypical femoral fractures in patients with osteoporosis: a comparison between treatment with and without teriparatide

  • Naohisa Miyakoshi
  • Toshiaki Aizawa
  • Satoshi Sasaki
  • Shigeru Ando
  • Shigeto Maekawa
  • Hiroshi Aonuma
  • Hiroyuki Tsuchie
  • Hiroshi Sasaki
  • Yuji Kasukawa
  • Yoichi Shimada
Original Article


Atypical femoral fracture (AFF) often appears with bisphosphonate use. Teriparatide (TPTD) treatment may promote AFF healing, but few controlled or comparative studies have examined the effects of TPTD on healing of bisphosphonate-associated AFF. We retrospectively reviewed the medical records of 45 consecutive AFFs in 34 Japanese patients who had received oral bisphosphonates (alendronate or risedronate) for osteoporosis before AFF and had been followed for ≥12 months (range, 12–90 months). Thirty-seven complete or incomplete AFFs (82 %) were treated surgically and eight incomplete AFFs (18 %) were treated conservatively. Bisphosphonates were stopped at diagnosis. Based on TPTD use after fracture, AFFs were divided into non-TPTD (n = 24) and TPTD (n = 21) groups. Time to fracture-healing and frequency of delayed healing or non-union were compared between groups. Because fracture type (complete or incomplete) differed significantly between groups, only subanalyses for all surgically treated AFFs (complete and incomplete), surgically treated complete AFFs, and conservatively treated incomplete AFFs were performed. In subanalyses for all AFFs treated surgically, mean (± standard deviation) time to fracture healing was significantly better in the TPTD group (5.4 ± 1.5 months) than in the non-TPTD group (8.6 ± 4.7 months; P = 0.012), and the frequency of delayed healing or non-union was significantly lower in the TPTD group than in the non-TPTD group (P = 0.014). Subanalyses for surgically treated complete AFFs yielded similar results, but subanalyses for incomplete AFFs treated conservatively showed no significant differences between groups. TPTD treatment appears to significantly shorten the postoperative time to fracture healing and reduce rates of delayed healing or non-union after bisphosphonate-associated AFF.


Bisphosphonate Bone union Femoral fracture Teriparatide 


Conflict of interest

None of the authors have any conflicts of interest to declare.

Supplementary material

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Supplementary material 1 (TIFF 2829 kb)
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Supplementary material 2 (TIFF 1982 kb)


  1. 1.
    Iwamoto J, Makita K, Sato Y, Takeda T, Matsumoto H (2011) Alendronate is more effective than elcatonin in improving pain and quality of life in postmenopausal women with osteoporosis. Osteoporos Int 22:2735–2742CrossRefPubMedGoogle Scholar
  2. 2.
    Lyles KW, Colón-Emeric CS, Magaziner JS, Adachi JD, Pieper CF et al (2007) Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med 357:1799–1809Google Scholar
  3. 3.
    McClung M, Harris ST, Miller PD, Bauer DC, Davison KS, Dian L, Hanley DA, Kendler DL, Yuen CK, Lewiecki EM (2013) Bisphosphonate therapy for osteoporosis: benefits, risks, and drug holiday. Am J Med 126:13–20CrossRefPubMedGoogle Scholar
  4. 4.
    Shane E, Burr D, Abrahamsen B, Adler RA, Brown TD et al (2014) Atypical subtrochanteric and diaphyseal femoral fractures: second report of a task force of the american society for bone and mineral research. J Bone Miner Res 29:1–23Google Scholar
  5. 5.
    Egol KA, Park JH, Rosenberg ZS, Peck V, Tejwani NC (2013) Healing delayed but generally reliable after bisphosphonate-associated complete femur fractures treated with IM nails. Clin Orthop Relat Res [Epub ahead of print]Google Scholar
  6. 6.
    Thompson RN, Phillips JR, McCauley SH, Elliott JR, Moran CG (2012) Atypical femoral fractures and bisphosphonate treatment: experience in two large United Kingdom teaching hospitals. J Bone Joint Surg Br 94:385–390CrossRefPubMedGoogle Scholar
  7. 7.
    Sasaki S, Miyakoshi N, Hongo M, Kasukawa Y, Shimada Y (2012) Low-energy diaphyseal femoral fractures associated with bisphosphonate use and severe curved femur: a case series. J Bone Miner Metab 30:561–567CrossRefPubMedGoogle Scholar
  8. 8.
    Weil YA, Rivkin G, Safran O, Liebergall M, Foldes AJ (2011) The outcome of surgically treated femur fractures associated with long-term bisphosphonate use. J Trauma 71:186–190CrossRefPubMedGoogle Scholar
  9. 9.
    Gallacher SJ, Dixon T (2010) Impact of treatments for postmenopausal osteoporosis (bisphosphonates, parathyroid hormone, strontium ranelate, and denosumab) on bone quality: a systematic review. Calcif Tissue Int 87:469–484CrossRefPubMedGoogle Scholar
  10. 10.
    Miyakoshi N (2004) Effects of parathyroid hormone on cancellous bone mass and structure in osteoporosis. Curr Pharm Des 10:2615–2627CrossRefPubMedGoogle Scholar
  11. 11.
    Pietrogrande L, Raimondo E (2013) Teriparatide in the treatment of non-unions: scientific and clinical evidences. Injury 44(Suppl 1):S54–57CrossRefPubMedGoogle Scholar
  12. 12.
    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 25:404–414CrossRefPubMedGoogle Scholar
  13. 13.
    Chiang CY, Zebaze RM, Ghasem-Zadeh A, Iuliano-Burns S, Hardidge A, Seeman E (2013) Teriparatide improves bone quality and healing of atypical femoral fractures associated with bisphosphonate therapy. Bone 52:360–365CrossRefPubMedGoogle Scholar
  14. 14.
    Lee YK, Ha YC, Kang BJ, Chang JS, Koo KH (2013) Predicting need for fixation of atypical femoral fracture. J Clin Endocrinol Metab 98:2742–2745CrossRefPubMedGoogle Scholar
  15. 15.
    Gomberg SJ, Wustrack RL, Napoli N, Arnaud CD, Black DM (2011) Teriparatide, vitamin D, and calcium healed bilateral subtrochanteric stress fractures in a postmenopausal woman with a 13-year history of continuous alendronate therapy. J Clin Endocrinol Metab 96:1627–1632CrossRefPubMedGoogle Scholar
  16. 16.
    Huang HT, Kang L, Huang PJ, Fu YC, Lin SY, Hsieh CH, Chen JC, Cheng YM, Chen CH (2012) Successful teriparatide treatment of atypical fracture after long-term use of alendronate without surgical procedure in a postmenopausal woman: a case report. Menopause 19:1360–1363CrossRefPubMedGoogle Scholar
  17. 17.
    Saleh A, Hegde VV, Potty AG, Schneider R, Cornell CN, Lane JM (2012) Management strategy for symptomatic bisphosphonate-associated incomplete atypical femoral fractures. HSS J 8:103–110PubMedCentralCrossRefPubMedGoogle Scholar
  18. 18.
    Orimo H, Hayashi Y, Fukunaga M, Sone T, Fujiwara S, Shiraki M, Kushida K, Miyamoto S, Soen S, Nishimura J, Oh-Hashi Y, Hosoi T, Gorai I, Tanaka H, Igai T, Kishimoto H (2001) Diagnostic criteria for primary osteoporosis: year 2000 revision. J Bone Miner Metab 19:331–337CrossRefPubMedGoogle Scholar
  19. 19.
    Watanabe Y, Arai Y, Takenaka N, Kobayashi M, Matsushita T (2013) Three key factors affecting treatment results of low-intensity pulsed ultrasound for delayed unions and nonunions: instability, gap size, and atrophic nonunion. J Orthop Sci 18:803–810CrossRefPubMedGoogle Scholar
  20. 20.
    Gavaskar AS, Kumar R (2010) Open interlocking nailing and bone grafting for neglected femoral shaft fractures. J Orthop Surg (Hong Kong) 18:45–49Google Scholar
  21. 21.
    Rizzoli R, Akesson K, Bouxsein M, Kanis JA, Napoli N, Papapoulos S, Reginster JY, Cooper C (2011) Subtrochanteric fractures after long-term treatment with bisphosphonates: a European Society on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, and International Osteoporosis Foundation Working Group Report. Osteoporos Int 22:373–390PubMedCentralCrossRefPubMedGoogle Scholar
  22. 22.
    Lin TL, Wang SJ, Fong YC, Hsu CJ, Hsu HC, Tsai CH (2013) Discontinuation of alendronate and administration of bone-forming agents after surgical nailing may promote union of atypical femoral fractures in patients on long-term alendronate therapy. BMC Res Notes 6:11PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.
    Oh CW, Oh JK, Park KC, Kim JW, Yoon YC (2013) Prophylactic nailing of incomplete atypical femoral fractures. ScientificWorldJournal 2013:450148PubMedCentralCrossRefPubMedGoogle Scholar
  24. 24.
    Papadokostakis G, Papakostidis C, Dimitriou R, Giannoudis PV (2005) The role and efficacy of retrograding nailing for the treatment of diaphyseal and distal femoral fractures: a systematic review of the literature. Injury 36:813–822CrossRefPubMedGoogle Scholar
  25. 25.
    Sahota O, Masud T, San P, Hosking DJ (1999) Vitamin D insufficiency increases bone turnover markers and enhances bone loss at the hip in patients with established vertebral osteoporosis. Clin Endocrinol (Oxf) 51:217–221CrossRefGoogle Scholar
  26. 26.
    Yamamoto T, Tsujimoto M, Hamaya E, Sowa H (2013) Assessing the effect of baseline status of serum bone turnover markers and vitamin D levels on efficacy of teriparatide 20 μg/day administered subcutaneously in Japanese patients with osteoporosis. J Bone Miner Metab 31:199–205CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society for Bone and Mineral Research and Springer Japan 2014

Authors and Affiliations

  • Naohisa Miyakoshi
    • 1
    • 9
  • Toshiaki Aizawa
    • 2
    • 9
  • Satoshi Sasaki
    • 3
    • 9
  • Shigeru Ando
    • 4
    • 9
  • Shigeto Maekawa
    • 5
    • 9
  • Hiroshi Aonuma
    • 6
    • 9
  • Hiroyuki Tsuchie
    • 7
    • 9
  • Hiroshi Sasaki
    • 8
    • 9
  • Yuji Kasukawa
    • 1
    • 9
  • Yoichi Shimada
    • 1
    • 9
  1. 1.Department of Orthopedic SurgeryAkita University School of MedicineAkitaJapan
  2. 2.Department of Orthopedic SurgeryNorthern Akita Municipal HospitalKitaAkitaJapan
  3. 3.Higashinaruse National Health Insurance ClinicHigashinaruseJapan
  4. 4.Department of Orthopedic SurgeryYamamoto-Kumiai General HospitalNoshiroJapan
  5. 5.Department of Orthopedic SurgeryOgachi Central HospitalYuzawaJapan
  6. 6.Department of Orthopedic SurgeryKakunodate General HospitalSenbokuJapan
  7. 7.Department of Orthopedic SurgeryNakadoori General HospitalAkitaJapan
  8. 8.Department of Orthopedic SurgeryAkita-Rosai HospitalOdateJapan
  9. 9.Akita Bone and Osteoporosis Network (A-BONE)AkitaJapan

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