Abstract
Mini abstract
This meta-analysis demonstrated that a greater prevalence of delayed union and nonunion and a longer time to fracture healing in the group that did not receive TPTD treatment after AFFs than in the group that received TPTD treatment.
Purpose
To date, there is no hard evidence for medical management after atypical femoral fracture (AFF), even though weak data indicate faster healing with teriparatide (TPTD). Herein, we aimed to investigate the effect of postfracture TPTD treatment on AFF healing using a pairwise meta-analysis focusing on delayed union, nonunion, and fracture healing time.
Methods
A systematic search of the MEDLINE (PUBMED), Embase, and Cochrane Library databases was performed for studies investigating the effect of TPTD after AFF up to October 11, 2022. We compared the incidence of delayed union and nonunion and the time of fracture healing between the TPTD ( +) and TPTD (-) groups.
Results
The 6 studies analyzed a total of 214 AFF patients, including 93 who received TPTD therapy after AFF and 121 who did not. The pooled analysis showed a significantly higher rate of delayed union in the TPTD (-) group than in the TPTD ( +) group (OR, 0.24; 95% CI, 0.11–0.52; P < 0.01; I2 = 0%), and a higher nonunion rate was observed in the TPTD (-) group than in the TPTD ( +) group with low heterogeneity (OR, 0.21; 95% CI, 0.06–0.78; P = 0.02; I2 = 0%). The TPTD (-) group required 1.69 months longer to achieve fracture union than the TPTD ( +) group, with statistical significance (MD = − 1.69, 95% CI: − 2.44 to − 0.95, P < 0.01; I2 = 13%). Subgroup analysis for patients with complete AFF showed that the TPTD (-) group had a higher rate of delayed union with low heterogeneity (OR, 0.22; 95% CI, 0.10–0.51; P < 0.01; I2 = 0%), but there was no significant difference in the nonunion rate between TPTD ( +) and TPTD (-) groups (OR, 0.35; 95% CI, 0.06–2.21; P = 0.25; I2 = 0%). Fracture healing took significantly longer in the TPTD (-) group (MD = − 1.81, 95% CI: − 2.55 to − 1.08; P < 0.01; I2 = 48%). The reoperation rate showed no significant difference between the two groups (OR, 0.29; 95% CI, 0.07–1.20; P = 0.09; I2 = 0%).
Conclusions
The current meta-analysis supported the hypothesis that TPTD treatment following AFF might benefit fracture healing, lowering the rate of delayed union and nonunion and shortening the fracture healing time.
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References
Nguyen HH, van de Laarschot DM, Verkerk A, Milat F, Zillikens MC, Ebeling PR (2018) Genetic Risk Factors for Atypical Femoral Fractures (AFFs): A Systematic Review. JBMR Plus 2:1–11. https://doi.org/10.1002/jbm4.10024
Dell RM, Adams AL, Greene DF, Funahashi TT, Silverman SL, Eisemon EO, Zhou H, Burchette RJ, Ott SM (2012) Incidence of atypical nontraumatic diaphyseal fractures of the femur. J Bone Miner Res 27:2544–2550. https://doi.org/10.1002/jbmr.1719
Lim SJ, Yeo I, Yoon PW, Yoo JJ, Rhyu KH, Han SB, Lee WS, Song JH, Min BW, Park YS (2018) Incidence, risk factors, and fracture healing of atypical femoral fractures: a multicenter case-control study. Osteoporos Int 29:2427–2435. https://doi.org/10.1007/s00198-018-4640-4
Kang JS, Won YY, Kim JO, Min BW, Lee KH, Park KK, Song JH, Kim YT, Kim GH (2014) Atypical femoral fractures after anti-osteoporotic medication: a Korean multicenter study. Int Orthop 38:1247–1253. https://doi.org/10.1007/s00264-013-2259-9
Giusti A, Hamdy NA, Papapoulos SE (2010) Atypical fractures of the femur and bisphosphonate therapy: A systematic review of case/case series studies. Bone 47:169–180. https://doi.org/10.1016/j.bone.2010.05.019
Shane E, Burr D, Abrahamsen B 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 29:1–23. https://doi.org/10.1002/jbmr.1998
Oh YK, Moon NH, Shin WC (2022) Management of Osteoporosis Medication after Osteoporotic Fracture. Hip Pelvis 34:191–202. https://doi.org/10.5371/hp.2022.34.4.191
van de Laarschot DM, McKenna MJ, Abrahamsen B, Langdahl B, Cohen-Solal M, Guanabens N, Eastell R, Ralston SH, Zillikens MC (2020) Medical Management of Patients After Atypical Femur Fractures: a Systematic Review and Recommendations From the European Calcified Tissue Society. J Clin Endocrinol Metab 105:1682–1699. https://doi.org/10.1210/clinem/dgz295
Yeh WL, Su CY, Chang CW, Chen CH, Fu TS, Chen LH, Lin TY (2017) Surgical outcome of atypical subtrochanteric and femoral fracture related to bisphosphonates use in osteoporotic patients with or without teriparatide treatment. BMC Musculoskeletal Disorders 18. https://doi.org/10.1186/s12891-017-1878-5
Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, Shekelle P, Stewart LA, Group P-P (2015) Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 4:1. https://doi.org/10.1186/2046-4053-4-1
Shea BJ, Grimshaw JM, Wells GA, Boers M, Andersson N, Hamel C, Porter AC, Tugwell P, Moher D, Bouter LM (2007) Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews. BMC Med Res Methodol 7:10. https://doi.org/10.1186/1471-2288-7-10
Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6:e1000097. https://doi.org/10.1371/journal.pmed.1000097
Abu-Zidan FM, Abbas AK, Hefny AF (2012) Clinical “case series”: a concept analysis. Afr Health Sci 12:557–562
Miyakoshi N, Aizawa T, Sasaki S, Ando S, Maekawa S, Aonuma H, Tsuchie H, Sasaki H, Kasukawa Y, Shimada Y (2015) Healing of bisphosphonate-associated atypical femoral fractures in patients with osteoporosis: a comparison between treatment with and without teriparatide. J Bone Miner Metab 33:553–559. https://doi.org/10.1007/s00774-014-0617-3
Slim K, Nini E, Forestier D, Kwiatkowski F, Panis Y, Chipponi J (2003) Methodological index for non-randomized studies (minors): development and validation of a new instrument. ANZ J Surg 73:712–716. https://doi.org/10.1046/j.1445-2197.2003.02748.x
Schmidt FL, Oh IS, Hayes TL (2009) Fixed- versus random-effects models in meta-analysis: model properties and an empirical comparison of differences in results. Br J Math Stat Psychol 62:97–128. https://doi.org/10.1348/000711007X255327
Higgins JPT GSe (2011) Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration,
Chiang CY, Zebaze RMD, 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 52:360–365. https://doi.org/10.1016/j.bone.2012.10.006
Lee KJ, Yoo JJ, Oh KJ, Yoo JH, Rhyu KH, Nam KW, Suh DH (2017) Surgical outcome of intramedullary nailing in patients with complete atypical femoral fracture: A multicenter retrospective study. Injury 48:941–945. https://doi.org/10.1016/j.injury.2017.02.036
Shin WC, Moon NH, Jang JH, Seo HU, Suh KT (2019) A retrospective bicenter comparative study of surgical outcomes of atypical femoral fracture: Potential effect of teriparatide on fracture healing and callus formation. Bone 128. https://doi.org/10.1016/j.bone.2019.08.006
Sreenivas S, Manda SR, Vipanchi S (2022) Surgical outcome assessment in femoral fracture patients with or without teriparatide treatment. Eur J Mole Clin Med 9:1445–1450
Takakubo Y, Ohta D, Ishi M et al (2017) The Incidence of Atypical Femoral Fractures in Patients with Rheumatic Disease: Yamagata Prefectural Committee of Atypical Femoral Fractures (YamaCAFe) Study. Tohoku J Exp Med 242:327–334. https://doi.org/10.1620/tjem.242.327
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 36:678–687. https://doi.org/10.1016/j.bone.2005.02.002
Mognetti B, Marino S, Barberis A, Martin AS, Bala Y, Di Carlo F, Boivin G, Barbos MP (2011) Experimental stimulation of bone healing with teriparatide: histomorphometric and microhardness analysis in a mouse model of closed fracture. Calcif Tissue Int 89:163–171. https://doi.org/10.1007/s00223-011-9503-3
Watts NB, Aggers D, McCarthy EF, Savage T, Martinez S, Patterson R, Carrithers E, Miller PD (2017) Responses to Treatment With Teriparatide in Patients With Atypical Femur Fractures Previously Treated With Bisphosphonates. J Bone Miner Res 32:1027–1033. https://doi.org/10.1002/jbmr.3081
Im GI, Lee SH (2015) Effect of Teriparatide on Healing of Atypical Femoral Fractures: A Systemic Review. J Bone Metab 22:183–189. https://doi.org/10.11005/jbm.2015.22.4.183
Yoon BH, Kim KC (2020) Does Teriparatide Improve Fracture Union?: A Systematic Review. J Bone Metab 27:167–174. https://doi.org/10.11005/jbm.2020.27.3.167
Takakubo Y, Miyaji T, Ohta D et al (2021) Differences in subtrochanteric and diaphyseal atypical femoral fractures in a super-aging prefectural area: YamaCAFe Study. J Bone Miner Metab 39:700–711. https://doi.org/10.1007/s00774-021-01215-4
Nguyen HH, Milat F, Ebeling PR (2017) A new contralateral atypical femoral fracture despite sequential therapy with teriparatide and strontium ranelate. Bone Rep 6:34–37. https://doi.org/10.1016/j.bonr.2017.01.002
Nguyen HH, Lakhani A, Shore-Lorenti C, Zebaze R, Vincent AJ, Milat F, Ebeling PR (2020) Asian ethnicity is associated with atypical femur fractures in an Australian population study. Bone 135:115319. https://doi.org/10.1016/j.bone.2020.115319
Funding
This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2020R1F1A1063582).
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Seong-Eun Byun, Kyung-Jae Lee, Won Chul Shin, Nam Hoon Moon, and Chul-Ho Kim declare that they have no conflict of interest.
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Byun, SE., Lee, KJ., Shin, W.C. et al. The effect of teriparatide on fracture healing after atypical femoral fracture: A systematic review and meta-analysis. Osteoporos Int 34, 1323–1334 (2023). https://doi.org/10.1007/s00198-023-06768-w
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DOI: https://doi.org/10.1007/s00198-023-06768-w