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Bone Turnover Markers Do Not Predict Stress Fracture in Elite Combat Recruits

  • Basic Research
  • Published:
Clinical Orthopaedics and Related Research®

Abstract

Background

With bone resorption rates greater than formation, stress fracture pathogenesis plausibly involves bone remodeling imbalance. If this is the case, one would anticipate serum levels of bone turnover markers would be higher in patients with stress fractures than in those without.

Questions/purposes

We therefore asked whether: (1) bone turnover markers differ between soldiers who will or will not have stress fractures during basic training; (2) bone turnover markers change during basic training; and (3) serial bone formation or bone resorption markers differ between subjects with and without stress fractures during basic training?

Methods

We performed serial determinations of serum bone formation (bone alkaline phosphatase [BAP] and procollagen type I amino-terminal propeptide [PINP]), and resorption (tartrate-resistant acid phosphatase [TRAP5b] and cross-linked collagen telopeptide [CTx]) biomarkers, measured at 2- to 4-week intervals (during 18 weeks) in 69 male soldiers in the Israeli Defense Forces during elite basic training. Twenty-two soldiers (32%) were diagnosed with stress fractures. The mean training week at diagnosis was 8.0 ± 2.0 weeks.

Results

We observed no differences in bone turnover markers between soldiers with and without stress fractures. During basic training, the mean values of all subjects for bone turnover markers (BAP, PINP, and CTx) changed in comparison to their mean levels at induction (43.9 versus 37.3 μg/L, 110.4 versus 78.0 μg/L, 1.4 versus 1.1 ng/mL, respectively). We found no changes in bone formation and resorption markers between subjects with and without stress fractures.

Conclusions

These specific bone turnover markers cannot be considered as either diagnostic or predictive tools for stress fracture detection in young male military recruits.

Level of Evidence

Level II prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.

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References

  1. Alvarez L, Ricós C, Peris P, Guañabens N, Monegal A, Pons F, Ballesta AM. Components of biological variation of biochemical markers of bone turnover in Paget’s bone disease. Bone. 2000;26:571–576.

    Article  PubMed  CAS  Google Scholar 

  2. Bennell KL, Malcolm SA, Brukner PD, Green RM, Hopper JL, Wark JD, Ebeling PR. A 12-month prospective study of the relationship between stress fractures and bone turnover in athletes. Calcif Tissue Int. 1998;63:80–85.

    Article  PubMed  CAS  Google Scholar 

  3. Bennell KL, Malcolm SA, Thomas SA, Wark JD, Brukner PD. The incidence and distribution of stress fractures in competitive track and field athletes: a twelve-month prospective study. Am J Sports Med. 1996;24:211–217.

    Article  PubMed  CAS  Google Scholar 

  4. Boden BP, Osbahr DC. High-risk stress fractures: evaluation and treatment. J Am Acad Orthop Surg. 2000;8:344–353.

    PubMed  CAS  Google Scholar 

  5. Bolton JG, Patel S, Lacey JH, White S. A prospective study of changes in bone turnover and bone density associated with regaining weight in women with anorexia nervosa. Osteoporos Int. 2005;16:1955–1962.

    Article  PubMed  Google Scholar 

  6. Chaffins JA. Paget disease of bone. Radiol Technol. 2007;79:27–40; quiz 41–43.

    Google Scholar 

  7. Cummings SR, Nevitt MC, Browner WS, Stone K, Fox KM, Ensrud KE, Cauley J, Black D, Vogt TM. Risk factors for hip fracture in white women: study of Osteoporotic Fractures Research Group. N Engl J Med. 1995;332:767–773.

    Article  PubMed  CAS  Google Scholar 

  8. Etherington J, Keeling J, Bramley R, Swaminathan R, McCurdie I, Spector TD. The effects of 10 weeks military training on heel ultrasound and bone turnover. Calcif Tissue Int. 1999;64:389–393.

    Article  PubMed  CAS  Google Scholar 

  9. Evans RK, Antczak AJ, Lester M, Yanovich R, Israeli E, Moran DS. Effects of a 4-month recruit training program on markers of bone metabolism. Med Sci Sports Exerc. 2008;40(11 suppl):S660–670.

    PubMed  CAS  Google Scholar 

  10. Garnero P, Vassy V, Bertholin A, Riou JP, Delmas PD. Markers of bone turnover in hyperthyroidism and the effects of treatment. J Clin Endocrinol Metab. 1994;78:955–959.

    Article  PubMed  CAS  Google Scholar 

  11. Itskoviz D, Marom T, Ostfeld I. Trends of stress fracture prevalence among Israel Defense Forces basic trainees. Mil Med. 2011;176:56–59.

    PubMed  Google Scholar 

  12. Karlsson KM, Karlsson C, Ahlborg HG, Valdimarsson O, Ljunghall S, Obrant KJ. Bone turnover responses to changed physical activity. Calcif Tissue Int. 2003;72:675–680.

    Article  PubMed  CAS  Google Scholar 

  13. Klein P, Bail HJ, Schell H, Michel R, Amthauer H, Bragulla H, Duda GN. Are bone turnover markers capable of predicting callus consolidation during bone healing? Calcif Tissue Int. 2004;75:40–49.

    Article  PubMed  CAS  Google Scholar 

  14. Looker AC, Bauer DC, Chesnut CH 3rd, Gundberg CM, Hochberg MC, Klee G, Kleerekoper M, Watts NB, Bell NH. Clinical use of biochemical markers of bone remodeling: current status and future directions. Osteoporos Int. 2000;11:467–480.

    Article  PubMed  CAS  Google Scholar 

  15. Luria T, Matsliah Y, Adir Y, Josephy N, Moran DS, Evans RK, Abramovich A, Eliakim A, Nemet D. Effects of a prolonged submersion on bone strength and metabolism in young healthy submariners. Calcif Tissue Int. 2010;86:8–13.

    Article  PubMed  CAS  Google Scholar 

  16. Lutz LJ, Karl JP, Rood JC, Cable SJ, Williams KW, Young AJ, McClung JP. Vitamin D status, dietary intake, and bone turnover in female soldiers during military training: a longitudinal study. J Int Soc Sports Nutr. 2012;9:38.

    Article  PubMed  CAS  Google Scholar 

  17. Milgrom C, Giladi M, Stein M, Kashtan H, Margulies JY, Chisin R, Steinberg R, Aharonson Z. Stress fractures in military recruits: a prospective study showing an unusually high incidence. J Bone Joint Surg Br. 1985;67:732–735.

    PubMed  CAS  Google Scholar 

  18. Moran DS, Evans RK, Hadad E. Imaging of lower extremity stress fracture injuries. Sports Med. 2008;38:345–356.

    Article  PubMed  Google Scholar 

  19. Moran DS, Israeli E, Evans RK, Yanovich R, Constantini N, Shabshin N, Merkel D, Luria O, Erlich T, Laor A, Finestone A. Prediction model for stress fracture in young female recruits during basic training. Med Sci Sports Exerc. 2008;40(11 suppl):S636–644.

    PubMed  Google Scholar 

  20. Nishizawa Y, Nakamura T, Ohta H, Kushida K, Gorai I, Shiraki M, Fukunaga M, Hosoi T, Miki T, Chaki O, Ichimura S, Nakatsuka K, Miura M. Guidelines for the use of biochemical markers of bone turnover in osteoporosis (2004). J Bone Miner Metab. 2005;23:97–104.

    Article  PubMed  Google Scholar 

  21. Scott S, Alazraki N, Manaster B. Failure of bone scanning to detect fractures in a woman on chronic steroid therapy. Skeletal Radiol. 1984;12:204–207.

    Article  PubMed  CAS  Google Scholar 

  22. Seebeck P, Bail HJ, Exner C, Schell H, Michel R, Amthauer H, Bragulla H, Duda GN. Do serological tissue turnover markers represent callus formation during fracture healing? Bone. 2005;37:669–677.

    Article  PubMed  CAS  Google Scholar 

  23. Seibel MJ. Molecular markers of bone turnover: biochemical, technical and analytical aspects. Osteoporos Int. 2000;11(suppl 6):S18–29.

    Article  PubMed  Google Scholar 

  24. Siri WE. The gross composition of the body. Adv Biol Med Phys. 1956;4:239–280.

    PubMed  CAS  Google Scholar 

  25. Stoffel K, Engler H, Kuster M, Riesen W. Changes in biochemical markers after lower limb fractures. Clin Chem. 2007;53:131–134.

    Article  PubMed  CAS  Google Scholar 

  26. Valimaki VV, Alfthan H, Lehmuskallio E, Loyttyniemi E, Sahi T, Suominen H, Valimaki MJ. Risk factors for clinical stress fractures in male military recruits: a prospective cohort study. Bone. 2005;37:267–273.

    Article  PubMed  Google Scholar 

  27. Zeger SL, Liang KY, Albert PS. Models for longitudinal data: a generalized estimating equation approach. Biometrics. 1988;44:1049–1060.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank the subjects for volunteering for this study. We also acknowledge the expert laboratory assistance of Jeffrey Staab MSc, United States Army Research Institute of Environmental Medicine, and the staff of Pennington Research Laboratories in Baton Rouge, LA, USA. We also thank the staff at the Institute of Military Physiology at the Heller Institute for Medical Research for their research support, Arie Laor MD for the statistical analysis, Tomer Erlich MD, the Heller Institute physician, Charles Milgrom MD and Aharon Finestone MD, the orthopaedic surgeons, and the staff at the Central Orthopaedic Clinic of the IDF for facilitating this study. In particular, we thank Leonardo Trejo MD, a nuclear medicine specialist, and Israel Cohen MSc, the bone scan technician.

Author information

Authors and Affiliations

  1. Institute of Military Physiology, IDF Medical Corps, Tel-Hashomer, Israel

    Ran Yanovich PhD & Daniel S. Moran PhD

  2. Heller Institute of Medical Research, Sheba Medical Center, Tel-Hashomer, 52621, Israel

    Ran Yanovich PhD & Daniel S. Moran PhD

  3. US Army Research Institute of Environmental Medicine, Natick, MA, USA

    Rachel K. Evans PhD

  4. Susanne Levy Gertner Oncogenetics Unit, Sheba Medical Center, Tel-Hashomer, Israel

    Eitan Friedman MD, PhD

  5. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Eitan Friedman MD, PhD

  6. Ariel University Center of Samaria, Ariel, Israel

    Daniel S. Moran PhD

Authors
  1. Ran Yanovich PhD
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  2. Rachel K. Evans PhD
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  3. Eitan Friedman MD, PhD
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  4. Daniel S. Moran PhD
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Corresponding author

Correspondence to Daniel S. Moran PhD.

Additional information

The institution of one of the authors (DSM) has received, during the study period, funding of USD 10,000–USD 100,000 from the United States Army.

All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research editors and board members are on file with the publication and can be viewed on request.

Clinical Orthopaedics and Related Research neither advocates nor endorses the use of any treatment, drug, or device. Readers are encouraged to always seek additional information, including FDA-approval status, of any drug or device prior to clinical use.

Each author certifies that his or her institution approved the human protocol for this investigation, all investigations were conducted in conformity with ethical principles for research, and informed consent for participation in the study was obtained.

This work was performed at the Heller Institute of Medical Research, Sheba Medical Center, Tel-Hashomer, Israel.

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Yanovich, R., Evans, R.K., Friedman, E. et al. Bone Turnover Markers Do Not Predict Stress Fracture in Elite Combat Recruits. Clin Orthop Relat Res 471, 1365–1372 (2013). https://doi.org/10.1007/s11999-012-2727-3

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  • DOI: https://doi.org/10.1007/s11999-012-2727-3

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