Bone turnover markers as surrogates of fracture healing after intramedullary fixation of tibia and femur fractures

Aims: Bone turnover markers (BTMs) follow distinct trends after fractures and limited evidence suggests differential levels in BTMs in patients with delayed healing. The effect of vitamin D, and other factors that influence BTMs and fracture healing, is important to elucidate the use of BTMs as surr...

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Main Authors: Christopher C. Stewart, Nathan N. O’Hara, Sofia Bzovsky, Chelsea S. Bahney, Sheila Sprague, Gerard P. Slobogean, On behalf of Vita-Shock Investigators
Format: Article
Language:English
Published: The British Editorial Society of Bone & Joint Surgery 2022-04-01
Series:Bone & Joint Research
Subjects:
Online Access:https://online.boneandjoint.org.uk/doi/epdf/10.1302/2046-3758.114.BJR-2021-0226.R1
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author Christopher C. Stewart
Nathan N. O’Hara
Sofia Bzovsky
Chelsea S. Bahney
Sheila Sprague
Gerard P. Slobogean
On behalf of Vita-Shock Investigators
author_facet Christopher C. Stewart
Nathan N. O’Hara
Sofia Bzovsky
Chelsea S. Bahney
Sheila Sprague
Gerard P. Slobogean
On behalf of Vita-Shock Investigators
author_sort Christopher C. Stewart
collection DOAJ
description Aims: Bone turnover markers (BTMs) follow distinct trends after fractures and limited evidence suggests differential levels in BTMs in patients with delayed healing. The effect of vitamin D, and other factors that influence BTMs and fracture healing, is important to elucidate the use of BTMs as surrogates of fracture healing. We sought to determine whether BTMs can be used as early markers of delayed fracture healing, and the effect of vitamin D on BTM response after fracture. Methods: A total of 102 participants aged 18 to 50 years (median 28 years (interquartile range 23 to 35)), receiving an intramedullary nail for a tibial or femoral shaft fracture, were enrolled in a randomized controlled trial comparing vitamin D3 supplementation to placebo. Serum C-terminal telopeptide of type I collagen (CTX; bone resorption marker) and N-terminal propeptide of type I procollagen (P1NP; bone formation marker) were measured at baseline, six weeks, and 12 weeks post-injury. Clinical and radiological fracture healing was assessed at three months. Results: CTX and P1NP concentrations peaked at six weeks in all groups. Elevated six-week CTX and P1NP were associated with radiological healing at 12 weeks post-injury (odds ratio (OR) 10.5; 95% confidence interval 2.71 to 53.5, p = 0.002). We found no association between CTX or P1NP and functional healing. Baseline serum 25(OH)D showed a weak inverse relationship with P1NP (p = 0.036) and CTX (p = 0.221) at 12 weeks, but we observed no association between vitamin D supplementation and either BTM. Conclusion: Given the association between six-week BTM concentrations and three-month radiological fracture healing, CTX and P1NP appear to be potential surrogate markers of fracture healing. Cite this article: Bone Joint Res 2022;11(4):239–250.
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spelling doaj.art-d975f7ee3e8547d9bda31156de9602022022-12-22T03:42:27ZengThe British Editorial Society of Bone & Joint SurgeryBone & Joint Research2046-37582022-04-0111423925010.1302/2046-3758.114.BJR-2021-0226.R1Bone turnover markers as surrogates of fracture healing after intramedullary fixation of tibia and femur fracturesChristopher C. Stewart0Nathan N. O’Hara1Sofia Bzovsky2Chelsea S. Bahney3Sheila Sprague4Gerard P. Slobogean5On behalf of Vita-Shock InvestigatorsDepartment of Orthopaedic Surgery, University of California, San Francisco, California, USADepartment of Orthopaedics, University of Maryland School of Medicine, Baltimore, Maryland, USADivision of Orthopaedic Surgery, Department of Surgery, McMaster University, Hamilton, CanadaSteadman Philippon Research Institute, Center for Regenerative & Personalized Medicine, Vail, Colorado, USADivision of Orthopaedic Surgery, Department of Surgery, McMaster University, Hamilton, CanadaDepartment of Orthopaedics, University of Maryland School of Medicine, Baltimore, Maryland, USAAims: Bone turnover markers (BTMs) follow distinct trends after fractures and limited evidence suggests differential levels in BTMs in patients with delayed healing. The effect of vitamin D, and other factors that influence BTMs and fracture healing, is important to elucidate the use of BTMs as surrogates of fracture healing. We sought to determine whether BTMs can be used as early markers of delayed fracture healing, and the effect of vitamin D on BTM response after fracture. Methods: A total of 102 participants aged 18 to 50 years (median 28 years (interquartile range 23 to 35)), receiving an intramedullary nail for a tibial or femoral shaft fracture, were enrolled in a randomized controlled trial comparing vitamin D3 supplementation to placebo. Serum C-terminal telopeptide of type I collagen (CTX; bone resorption marker) and N-terminal propeptide of type I procollagen (P1NP; bone formation marker) were measured at baseline, six weeks, and 12 weeks post-injury. Clinical and radiological fracture healing was assessed at three months. Results: CTX and P1NP concentrations peaked at six weeks in all groups. Elevated six-week CTX and P1NP were associated with radiological healing at 12 weeks post-injury (odds ratio (OR) 10.5; 95% confidence interval 2.71 to 53.5, p = 0.002). We found no association between CTX or P1NP and functional healing. Baseline serum 25(OH)D showed a weak inverse relationship with P1NP (p = 0.036) and CTX (p = 0.221) at 12 weeks, but we observed no association between vitamin D supplementation and either BTM. Conclusion: Given the association between six-week BTM concentrations and three-month radiological fracture healing, CTX and P1NP appear to be potential surrogate markers of fracture healing. Cite this article: Bone Joint Res 2022;11(4):239–250.https://online.boneandjoint.org.uk/doi/epdf/10.1302/2046-3758.114.BJR-2021-0226.R1fracturebone turnover markervitamin dctxp1npfracture healingfemur fracturestibiabone turnover markersserumfemoral shaft fracturestype i collagenrandomized controlled trial
spellingShingle Christopher C. Stewart
Nathan N. O’Hara
Sofia Bzovsky
Chelsea S. Bahney
Sheila Sprague
Gerard P. Slobogean
On behalf of Vita-Shock Investigators
Bone turnover markers as surrogates of fracture healing after intramedullary fixation of tibia and femur fractures
Bone & Joint Research
fracture
bone turnover marker
vitamin d
ctx
p1np
fracture healing
femur fractures
tibia
bone turnover markers
serum
femoral shaft fractures
type i collagen
randomized controlled trial
title Bone turnover markers as surrogates of fracture healing after intramedullary fixation of tibia and femur fractures
title_full Bone turnover markers as surrogates of fracture healing after intramedullary fixation of tibia and femur fractures
title_fullStr Bone turnover markers as surrogates of fracture healing after intramedullary fixation of tibia and femur fractures
title_full_unstemmed Bone turnover markers as surrogates of fracture healing after intramedullary fixation of tibia and femur fractures
title_short Bone turnover markers as surrogates of fracture healing after intramedullary fixation of tibia and femur fractures
title_sort bone turnover markers as surrogates of fracture healing after intramedullary fixation of tibia and femur fractures
topic fracture
bone turnover marker
vitamin d
ctx
p1np
fracture healing
femur fractures
tibia
bone turnover markers
serum
femoral shaft fractures
type i collagen
randomized controlled trial
url https://online.boneandjoint.org.uk/doi/epdf/10.1302/2046-3758.114.BJR-2021-0226.R1
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