Bone turnover markers as determinants of bone density and fracture in men with distal forearm fractures: the pathogenesis examined in the Mr F study

Abstract

Summary

The pathogenesis for low-trauma wrist fractures in men is not fully understood. This study found that these men had evidence of significantly higher bone turnover compared with control subjects. Bone turnover markers were negative predictors of bone mineral density and were a predictor of fracture.

Introduction

Men with distal forearm fractures have reduced bone density, an increased risk of osteoporosis and of further fractures. The aim of this study was to investigate whether or not men with distal forearm fractures had evidence of altered bone turnover activity.

Methods

Fifty eight men with low-trauma distal forearm fracture and 58 age-matched healthy control subjects were recruited. All subjects underwent a DXA scan of the forearm, both hips, and lumbar spine, biochemical investigations, and health questionnaires. Measurements of beta crosslaps (βCTX), procollagen type I N-terminal propeptide (PINP), sclerostin, Dickkopf-1 (Dkk1), and fibroblast growth factor 23 (FGF 23) were made.

Results

Men with fracture had significantly higher PINP than controls at 39.2 ng/ml (SD 19.5) versus 33.4 ng/ml (SD13.1) (p<0.001). They also had significantly higher βCTX at 0.45 ng/ml (SD 0.21) versus 0.37 ng/ml (SD 0.17) (p= 0.037). Fracture subjects had significantly lower aBMD and PINP was a negative predictor of aBMD at the total hip and βCTX a negative predictor of forearm aBMD. Sclerostin was a positive predictor of aBMD at the lumbar spine and hip sites. Sex hormone binding globulin (SHBG) at 37nmol/L (SD 15.0) was lower in fracture cohort compared to 47.9 nmol/L (SD 19.2) (p=0.001) in control. Multiple regression revealed that the best model for prediction of fracture included SHBG, P1NP, and ultra-distal forearm aBMD. The likelihood of distal forearm fracture was decreased by 5.1% for each nmol/L increase in SHBH and by 1.4% for every mg/cm2 increase in ultra-distal forearm aBMD, but increased by 6.1 % for every ng/ml increase in P1NP. Men in the highest quartile of PINP had a significantly greater likelihood of distal forearm fracture than those in the lowest quartile.

Conclusion

The fracture group had significantly higher PINP and βCTX compared with the control group, and these markers were negative predictors of aBMD at the total hip and forearm sites, respectively. Sclerostin was a positive predictor of the variance of spinal and hip aBMD. Likelihood of forearm fracture was best predicted by a combination of SHBG, PINP, and ultra-distal forearm aBMD. Findings of such cross-sectional data should be treated with caution, as longitudinal studies would be required to confirm or refute them.

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Acknowledgements

The authors would like to thank all patients and volunteers who took part in the study. They are grateful to Mrs. Gill Wheater for undertaking the laboratory tests and Mrs. Jackie Bates for performing the DXA scans.

Funding

This study was funded by a grant from the National Osteoporosis Society (Grant number: 75/190).

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Correspondence to S.P. Tuck.

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Statement of Human Rights

The study has been approved by the National Research Ethics Committee North East, UK (REC reference 10/H0908/15) and has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Conflicts of interest

Birgit Hanusch, Stephen Tuck and Harish Datta have received grants from the National Osteoporosis Society. Birgit Hanusch, Stephen Tuck, Harish Datta, and Julie Walker are also supported by an innovative award from the National Osteoporosis Society (Grant number CS/250). Stephen Tuck has received speaker fees from Ely Lilly, Servier, Internist, and Amgen. Richard McNally and Michael Prediger declare that they have no conflicts of interest.

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Hanusch, B., Prediger, M., Tuck, S. et al. Bone turnover markers as determinants of bone density and fracture in men with distal forearm fractures: the pathogenesis examined in the Mr F study. Osteoporos Int (2021). https://doi.org/10.1007/s00198-021-06001-6

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Keywords

  • Bone turnover markers
  • Forearm fracture
  • Male
  • Osteoporosis