Use of CTX-I and PINP as bone turnover markers: National Bone Health Alliance recommendations to standardize sample handling and patient preparation to reduce pre-analytical variability

Szulc, Paweł; Naylor, Kim; Hoyle, N. R.; Eastell, Richard; Leary, Eileen

doi:10.1007/s00198-017-4082-4

Cited by 237 publications

(224 citation statements)

References 145 publications

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“…We used a cutoff of 20 ng/ml to determine deficiency and 30 ng/ml to determine insufficiency . Several covariates that have been demonstrated to affect CTX and P1NP were tested as possible confounders in the analysis . Age and sex were obtained from the medical records upon patient enrollment.…”

Section: Methodsmentioning

confidence: 99%

Serum 25(OH)D is associated with an altered bone turnover marker response after a hip fracture

Stewart

O’Hara

Orwig

et al. 2019

Journal Orthopaedic Research

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C‐terminal telopeptide of type I collagen (CTX) and procollagen type 1 N‐terminal propeptide (P1NP) are bone turnover markers (BTMs) that are promising surrogate measures of fracture healing; however, it is unknown if their response is affected by other bone healing metabolites. Since 70% of fracture patients are reported to have insufficient serum vitamin D, we sought to determine if serum 25(OH)D levels are associated with differential changes in CTX and P1NP concentrations after hip fracture. This prospective cohort included hip fracture patients 65 years of age or older admitted to one of eight Baltimore‐area hospitals. Serum samples were collected at baseline, 2‐, 6‐, and 12‐month post‐fracture. A mixed‐effects repeated‐measures analysis was used to determine the longitudinal association between vitamin D deficiency (25(OH)D < 20 ng/ml) and CTX and P1NP. Baseline lab values were obtained for 296 participants (mean age, 80.8 years; 51% male; 55% 25(OH)D < 20 ng/ml). During the acute fracture healing period P1NP concentrations increased by 14% (95%CI: 7–21%, p < 0.01) while CTX levels did not change (p = 0.07). Both CTX and P1NP decreased below baseline at 6 and 12 months. CTX levels were higher in participants with baseline 25(OH)D < 20 ng/ml (p = 0.01). There was no association between 25(OH)D < 20 ng/ml and P1NP levels over the study duration (p = 0.33). Data from this large, longitudinal cohort support claims that CTX and P1NP concentrations change during fracture healing; however, the differential response of CTX among vitamin D deficient patients highlights important questions for its utility as a reliable surrogate marker of fracture healing. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res

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Section: Methodsmentioning

confidence: 99%

Serum 25(OH)D is associated with an altered bone turnover marker response after a hip fracture

Stewart

O’Hara

Orwig

et al. 2019

Journal Orthopaedic Research

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“…For bone formation markers, there is a weaker circadian rhythm and so the sample can be drawn at any time of the day (5). Serum or plasma should be measured the same day or stored in the freezer until measured (5). EDTA plasma should not be used for bone ALP measurement (5).…”

Section: Practical Aspectsmentioning

confidence: 99%

“…Serum or plasma should be measured the same day or stored in the freezer until measured (5). EDTA plasma should not be used for bone ALP measurement (5). Osteocalcin is affected by haemolysis, which can lead to a falsely low result.…”

Section: Practical Aspectsmentioning

confidence: 99%

DIAGNOSIS OF ENDOCRINE DISEASE: Bone turnover markers: are they clinically useful?

Eastell

Pigott

Gossiel

et al. 2018

European Journal of Endocrinology

112

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Bone turnover markers (BTMs) are useful in clinical practice as they are inexpensive, and they have proven useful for treatment monitoring and identification of poor adherence. BTMs cannot be used in individual patients for identifying accelerated bone loss or an increase in fracture risk or in deciding on the optimal therapy. They are useful for monitoring both anti-resorptive and anabolic treatment. Response can be defined as a result that exceeds an absolute target, or by a change greater than the least significant change; if such a response is not present, then poor compliance or secondary osteoporosis are likely causes. A baseline BTM measurement is not always made; in that case, a value of BTM on anti-resorptive treatment that is low or low normal or above the reference interval for anabolic therapy may be taken to indicate a satisfactory response. We provide an approach to using these bone turnover markers in clinical practice by describing algorithms for anti-resorptive and anabolic therapy and describing the changes we observe in the clinical practice setting.

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“…Finally, it should be noted that CTX is more stable in EDTA plasma than in serum. For this reason, the National Bone Health Alliance (NBHA) prefers CTX in EDTA plasma if a lab is not able to process a sample immediately . However, we used serum CTX in our study to best reflect clinical practice in the United States because the majority of US commercial labs use serum for CTX processing.…”

Section: Discussionmentioning

confidence: 99%

Commercial Laboratory Reproducibility of Serum CTX in Clinical Practice

et al. 2019

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In 2011, the International Osteoporosis Foundation and the International Federation of Clinical Chemistry and Laboratory Medicine selected serum collagen type‐I crosslinked C‐peptide (s‐CTX) as the reference standard for bone resorption. This study aimed to determine the within and between laboratory reproducibility for s‐CTX assays. To create standardized pools, serum was collected from 10 premenopausal and 10 postmenopausal women. Premenopausal sera were pooled to approximate a population with normal bone turnover; postmenopausal sera were pooled to approximate a population with high bone turnover; and a third pool was created from an equal proportion of the pre‐ and postmenopausal pools. Multiple identical aliquots from each pool were created and frozen; all were labeled as routine clinical specimens. To evaluate longitudinal laboratory reproducibility, an identical aliquot from each of the three pools was sent to four US commercial laboratories on five dates over a 6‐month period. To evaluate within‐run reproducibility, each lab received five identical aliquots from each pool on the fifth date. Three labs (Mayo, ARUP, and Quest) used the Roche Diagnostics Elecsys assay, and one (Esoterix/LabCorp) used the IDS‐iSYS assay. Reproducibility was assessed using the coefficient of variation (CV) with 95% confidence intervals (CIs). Labs were unaware of the investigation. Across labs, mean s‐CTX values were 423, 533, and 480 pg/mL for the premenopausal, postmenopausal, and mixed pools, respectively, but the means differed between labs (p < 0.001). The premenopausal pool longitudinal CVs ranged from 5.0% to 14.9%; the postmenopausal pool CVs ranged from 3.4% to 19.3%; and the mixed pool CVs ranged from 3.3% to 16.0%. The longitudinal reproducibility for Esoterix/LabCorp was higher (CV 13.9%; 95% CI, 10.1% to 22.2%) than for the other labs. Within‐run CVs were also higher for Esoterix/LabCorp (CV 8.6%; 95% CI, 6.3% to 13.6%) compared with the other labs (CVs 2.1% to 6.2%). In conclusion, the reproducibility of s‐CTX varied across US commercial labs, and was poorer for Esoterix/LabCorp, which used the IDS assay, compared with the other three labs, which used the Roche assay. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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Use of CTX-I and PINP as bone turnover markers: National Bone Health Alliance recommendations to standardize sample handling and patient preparation to reduce pre-analytical variability

Cited by 237 publications

References 145 publications

Serum 25(OH)D is associated with an altered bone turnover marker response after a hip fracture

Serum 25(OH)D is associated with an altered bone turnover marker response after a hip fracture

DIAGNOSIS OF ENDOCRINE DISEASE: Bone turnover markers: are they clinically useful?

Commercial Laboratory Reproducibility of Serum CTX in Clinical Practice

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