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Bone Turnover Markers as a New Predicting Factor for Nonunion After Spinal Fusion Surgery

Inose, Hiroyuki, MD, PhD; Yamada, Tsuyoshi, MD, PhD; Mulati, Mieradili, MD; Hirai, Takashi, MD, PhD; Ushio, Shuta, MD; Yoshii, Toshitaka, MD, PhD; Kato, Tsuyoshi, MD, PhD; Kawabata, Shigenori, MD, PhD; Okawa, Atsushi, MD, PhD

doi: 10.1097/BRS.0000000000001995

Study Design. Retrospective observational study.

Objective. We investigated whether bone turnover markers could be a useful indicator for prediction of nonunion.

Summary of Background Data. Nonunion is a major complication of lumbar spinal fusion surgery. The involvement of bone turnover in the process of bony union in spinal fusion surgery is, however, poorly understood.

Methods. Of the 74 patients analyzed, 13 were diagnosed with nonunion. We evaluated the significance of the following risk factors: age, sex, number of fused segments, serum levels of total alkaline phosphatase, procollagen type 1 amino-terminal propeptide (P1NP), tartrate-resistant acid phosphatase 5b (TRACP-5b), and albumin, and history of diabetes mellitus, cigarette smoking, or alcohol use. We also defined the bone turnover ratio (BTR) as a value that equals serum TRACP-5b concentration divided by serum P1NP concentration to evaluate patients’ individual bone turnover balance and investigated the significance of BTR as a risk factor.

Results. Univariate analysis showed that older age, malnutrition, and lower P1NP are risk factors for nonunion. Stepwise logistic regression analysis revealed that in the presence of lower P1NP, higher TRACP-5b becomes a risk factor. Furthermore, we identified BTR as the most significant risk factor for nonunion. The optimum cut-off value of BTR by receiver-operating characteristic curve was 11.74.

Conclusion. These findings show a relation between bone turnover and nonunion after spinal fusion surgery. The measurement of bone turnover markers could potentially be used to predict nonunion after spinal fusion surgery.

Level of Evidence: 4

Department of Orthopaedic Surgery, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.

Address correspondence and reprint requests to Hiroyuki Inose, MD, PhD, Department of Orthopaedic Surgery, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan; E-mail:

Received 18 July, 2016

Revised 28 September, 2016

Accepted 17 October, 2016

The manuscript submitted does not contain information about medical device(s)/drug(s).

No funds were received in support of this work.

No relevant financial activities outside the submitted work.

Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.