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Fracture-induced changes in biomarkers CTX, PINP, OC, and BAP—a systematic review

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Abstract

To assess the time from fracture until bone turnover markers (BTM), which are biochemical markers reflecting in vivo bone formation and resorptive activity, have returned to a stable level since BTM have been shown to be at least as good as bone mineral density in monitoring the effect of anti-resorptive treatment in osteoporosis. This study searched for articles in PUBMED, CINAHL, Medline, EM-BASE, and Cochrane, and identified 3486 unique articles. These articles were screened based on predefined inclusion and exclusion criteria. Seven articles addressing time to normalization of either CTX, PINP, osteocalcin, or bone-specific alkaline phosphatase after a recent fracture were identified and these were analyzed qualitatively. CTX appeared to return to baseline within 6 months. PINP appeared to return to baseline within 6 months and interestingly dip below baseline after a year. Osteocalcin was elevated throughout the first year after a fracture, with most changes in the first 6 months. Bone-specific alkaline phosphatase (BAP) was increased for up to a year, however with a discrepancy between used assays. Seven studies were identified, showing CTX and PINP to return to baseline within 6 months. OC was elevated for 12 months. BAP was increased for up to a year. However, none of these studies had fasting patients and a long follow-up period with regular measurements. The studies could indicate that the BTM CTX and PINP have returned to baseline within 6 months; however, further studies are needed assessing pre-analytical factors while having a long follow-up. Bone turnover markers appear as good as or better than bone mineral density in monitoring the effect of anti-resorptive medication in osteoporosis. This study tries to identify the time from fracture until BTM are back at baseline. Most studies did not however take pre-analytical variation into consideration. Further research is therefore needed.

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Abbreviations

S:

biomarkers measured in serum

U:

biomarkers measured in urine

BAP:

bone-specific alkaline phosphatase

CTX:

carboxy-terminal telopeptide cross-links

DPD:

deoxypyridinoline

ECTS:

European Calcified Tissue Society

ICTP:

cross-linked carboxy-terminal telopeptide of type I collagen

IOF:

International Osteoporosis Foundation

IFCC:

International Federation of Clinical Chemistry

NTX:

amino-terminal telopeptide cross-links

OC:

osteocalcin

Pyr:

pyridinoline

PICP:

type-1 c-terminal propeptide

PINP:

type-1 n-terminal propeptide

PIIINP:

type-3 n-terminal propeptide

POstn:

periostin

TRAcP:

tartate-resistant acid phosphatase

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Authors and Affiliations

  1. Odense Patient Exploratory Network, University of Southern Denmark, Odense, Denmark

    F.D. Højsager, S.B. Pedersen & N.R. Jørgensen

  2. Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark

    F.D. Højsager, S.B. Pedersen & N.R. Jørgensen

  3. Department of Orthopaedic Surgery, Kolding Hospital, Kolding, Denmark

    M.S. Rand & N. Nissen

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  1. F.D. Højsager
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  2. M.S. Rand
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Correspondence to F.D. Højsager.

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Højsager, F., Rand, M., Pedersen, S. et al. Fracture-induced changes in biomarkers CTX, PINP, OC, and BAP—a systematic review. Osteoporos Int 30, 2381–2389 (2019). https://doi.org/10.1007/s00198-019-05132-1

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