Use of bone turnover markers in postmenopausal osteoporosis

Eastell, Richard; Szulc, Pawel

doi:10.1016/s2213-8587(17)30184-5

Cited by 596Bone health and osteoporosis researchBone health and treatmentsBone Metabolism and Diseases

Use of bone turnover markers in postmenopausal osteoporosis

Eastell, Richard, Szulc, Pawel·2017·The Lancet Diabetes & Endocrinology

DOI 10.1016/s2213-8587(17)30184-5

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Abstract

Bone turnover comprises two processes: the removal of old bone (resorption) and the laying down of new bone (formation). N-terminal propeptide of type I procollagen (PINP) and C-telopeptide of type I collagen (CTX-I) are markers of bone formation and resorption, respectively, that are recommended for clinical use. Bone turnover markers can be measured on several occasions in one individual with good precision. However, these markers are subject to several sources of variability, including feeding (resorption decreases) and recent fracture (all markers increase for several months). Bone turnover markers are not used for diagnosis of osteoporosis and do not improve prediction of bone loss or fracture within an individual. In untreated women, very high bone turnover marker concentrations suggest secondary causes of high bone turnover (eg, bone metastases or multiple myeloma). In people with osteoporosis, bone turnover markers might be useful to assess the response to anabolic and antiresorptive therapies, to assess compliance to therapy, or to indicate possible secondary osteoporosis. Much remains to be learnt about how bone turnover markers can be used to monitor the effect of stopping bisphosphonate therapy (eg, to identify a threshold above which restarting therapy should be considered). More studies are needed to investigate the use of bone turnover markers for assessment of the bone safety of new medications.

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International consensus guidelines recommend assessment of two bone turnover markers: PINP and CTX.
“International consensus guidelines recommend assessment of two BTMs: procollagen type I N-terminal propeptide (PINP) (produced by osteoblasts during bone formation), and C-terminal cross-linking telopeptide of type I collagen (CTX) (released by osteoclasts during bone resorption) (8, 9).”
From Bone Status in Obese, Non-diabetic, Antipsychotic-Treated Patients, and Effects of the Glucagon-Like Peptide-1 Receptor Agonist Exenatide on Bone Turnover Markers and Bone Mineral Density (2019) · cites this paper as [9]

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Reference intervals for bone turnover markers in Spanish premenopausal women
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Effect of high dietary sodium on bone turnover markers and urinary calcium excretion in Korean postmenopausal women with low bone mass
Park, S. M., Joung, J. Y., Cho, Y. Y., Sohn, S. Y., Hur, K. Y., Kim, J. H., Kim, S. W., Chung, J. H., Lee, M. ‐., & Min, Y. ‐. (2015) · European Journal of Clinical Nutrition · doi:10.1038/ejcn.2014.284 · Cited by 36 · see citing works
L-Phenylalanine concentration in blood of phenylketonuria patients: a modified enzyme colorimetric assay compared with amino acid analysis, tandem mass spectrometry, and HPLC methods
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Biochemical markers of bone turnover and clinical outcomes in men with prostate cancer
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Effects of calcium-fortified ice cream on markers of bone health
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Potential Usefulness of BMD and Bone Turnover Monitoring of Zoledronic Acid Therapy Among Women With Osteoporosis: Secondary Analysis of Randomized Controlled Trial Data
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Greater milk intake is associated with lower bone turnover, higher bone density, and higher bone microarchitecture index in a population of elderly Japanese men with relatively low dietary calcium intake: Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Study
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Comparison in bone turnover markers during early healing of femoral neck fracture and trochanteric fracture in elderly patients
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Association between the Healthy Eating Index and bone turnover markers in US postmenopausal women aged ≥45 y
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The efficacy of calcium supplementation alone in elderly Thai women over a 2-year period: a randomized controlled trial
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Dietary patterns in men and women are simultaneously determinants of altered glucose metabolism and bone metabolism
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Eastell, R., Boonen, S., Cosman, F., Reid, I. R., Palermo, L., Cummings, S. R., & Black, D. M. (2014) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2361 · Cited by 23 · see citing works
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A retrospective analysis of nonresponse to daily teriparatide treatment
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Improvement of cancellous bone microstructure in patients on teriparatide following alendronate pretreatment
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Response of bone turnover markers to raloxifene treatment in postmenopausal women with osteopenia
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Low calcium intake is associated with increased bone resorption in postmenopausal Japanese women: Yokogoshi Study
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Early Changes in Bone Specific Turnover Markers During the Healing Process After Vertebral Fracture
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Reducing glucocorticoid dosage improves serum osteocalcin in patients with rheumatoid arthritis—results from the TOMORROW study
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Change in serum undercarboxylated osteocalcin concentration in bilaterally oophorectomized women
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Adherence to raloxifene therapy: assessment methods and relationship with efficacy
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Comparison of clinical cut-points and treatment targets for urine NTX and plasma βCTX-I in osteoporosis
Chubb, S. A. P., Mandelt, C., & Vasikaran, S. D. (2015) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2015.12.002 · Cited by 9 · see citing works
Associations between Systemic Markers of Bone Turnover or Bone Mineral Density and Anti-Resorptive Agent-Related Osteonecrosis of the Jaw in Patients Treated with Anti-Resorptive Agents.
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DIFFERENTIAL EF ECTS OF TERIPARATIDE ON BONE MINERAL DENSITY AFTER TREATMENT WITH RALOXIFENE OR ALENDRONATE
Ettinger, B. B., Martín, J. S., Crans, G., & Pavo, I. J. (2004) · Cited by 7 · see citing works

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Bone Turnover Markers: Basic Biology to Clinical Applications
Schini, M., Vilaça, T., Gossiel, F., Salam, S., & Eastell, R. (2022) · Endocrine Reviews · doi:10.1210/endrev/bnac031 · Cited by 415 · see citing works
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Osteogenesis and aging: lessons from mesenchymal stem cells
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Guidelines for the management of osteoporosis and fragility fractures
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Lactobacillus rhamnosus GG ameliorates osteoporosis in ovariectomized rats by regulating the Th17/Treg balance and gut microbiota structure
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Long-term and sequential treatment for osteoporosis
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Chitosan and gelatin-based electrospun fibers for bone tissue engineering
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Fragility Fractures: Risk Factors and Management in the Elderly
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Advanced Glycation End Products (AGEs), Receptor for AGEs, Diabetes, and Bone: Review of the Literature
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European Consensus Statement on the diagnosis and management of osteoporosis in chronic kidney disease stages G4–G5D
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Exosome-based bone-targeting drug delivery alleviates impaired osteoblastic bone formation and bone loss in inflammatory bowel diseases
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Osteoporosis and Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD): Back to Basics
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The importance of the circadian system & sleep for bone health
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Biomarkers as therapy monitoring for postmenopausal osteoporosis: a systematic review
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Potential of biomarkers during pharmacological therapy setting for postmenopausal osteoporosis: a systematic review
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Update on the role of bone turnover markers in the diagnosis and management of osteoporosis: a consensus paper from The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), International Osteoporosis Foundation (IOF), and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)
Bhattoa, H. P., Vasikaran, S. D., Trifonidi, I., Kapoula, G., Lombardi, G., Jørgensen, N. R., Pikner, R., Miura, M., Chapurlat, R. D., Hiligsmann, M., et al. (2025) · Osteoporosis International · doi:10.1007/s00198-025-07422-3 · Cited by 130 · see citing works
Bone alkaline phosphatase: An important biomarker in chronic kidney disease – mineral and bone disorder
Nizet, A., Cavalier, E., Stenvinkel, P., Haarhaus, M. L., & Magnusson, P. (2019) · Clinica Chimica Acta · doi:10.1016/j.cca.2019.11.012 · Cited by 119 · see citing works
Algorithm for the Use of Biochemical Markers of Bone Turnover in the Diagnosis, Assessment and Follow-Up of Treatment for Osteoporosis
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Systemic immune‐inflammation index acts as a novel diagnostic biomarker for postmenopausal osteoporosis and could predict the risk of osteoporotic fracture
Fang, H., Zhang, H., Wang, Z., Zhou, Z., Li, Y., & Lü, L. (2019) · Journal of Clinical Laboratory Analysis · doi:10.1002/jcla.23016 · Cited by 113 · see citing works
Iron Deficiency and Iron Deficiency Anemia: Potential Risk Factors in Bone Loss
Yang, J., Li, Q., Feng, Y., & Zeng, Y. H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24086891 · Cited by 125 · see citing works
Bone targeting antioxidative nano-iron oxide for treating postmenopausal osteoporosis
Zheng, L., Zhuang, Z., Li, Y., Shi, T., Fu, K., Yan, W., Zhang, L., Wang, P., Li, L., & Jiang, Q. Y. (2021) · Bioactive Materials · doi:10.1016/j.bioactmat.2021.11.012 · Cited by 109 · see citing works
Effects of water extract from epimedium on neuropeptide signaling in an ovariectomized osteoporosis rat model
Liu, H., Xiong, Y., Wang, H., Yang, L., Wang, C., Liu, X., Wu, Z., Li, X., Ou, L., Zhang, R., et al. (2018) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2018.04.035 · Cited by 101 · see citing works
Molecular Classification of Knee Osteoarthritis
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Ferroptosis - A new target of osteoporosis
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Downregulation of METTL14 improves postmenopausal osteoporosis via IGF2BP1 dependent posttranscriptional silencing of SMAD1
Huang, C., & Wang, Y. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-05362-y · Cited by 82 · see citing works
Age-related collagen turnover of the interstitial matrix and basement membrane: Implications of age- and sex-dependent remodeling of the extracellular matrix
Kehlet, S. N., Willumsen, N., Armbrecht, G., Dietzel, R., Brix, S., Henriksen, K., & Karsdal, M. A. (2018) · PLoS ONE · doi:10.1371/journal.pone.0194458 · Cited by 81 · see citing works
Functional Calcium Binding Peptides from Pacific Cod (Gadus macrocephalus) Bone: Calcium Bioavailability Enhancing Activity and Anti-Osteoporosis Effects in the Ovariectomy-Induced Osteoporosis Rat Model
Zhang, K., Li, B., Chen, Q., Zhang, Z., Zhao, X., & Hou, H. (2018) · Nutrients · doi:10.3390/nu10091325 · Cited by 79 · see citing works
Circulating miR-181c-5p and miR-497-5p Are Potential Biomarkers for Prognosis and Diagnosis of Osteoporosis
Ma, J., Lin, X., Chen, C., Li, S., Zhang, S., Chen, Z., Li, D., Zhao, F., Yang, C., Yin, C., et al. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgz300 · Cited by 80 · see citing works
Global epidemiology and burden of osteoporosis among postmenopausal women: insights from the Global Burden of Disease Study 2021
Liang, H., Chen, S., Shi, M., Xu, J., Zhao, C., Yang, B., Zheng, S., & Tan, J. (2025) · npj Aging · doi:10.1038/s41514-025-00269-2 · Cited by 76 · see citing works
Correlations between bone turnover markers, serum magnesium and bone mass density in postmenopausal osteoporosis
Mederle, O. A., Balaş, M., Ioanoviciu, S. D., Gurban, C., Tudor, A., & Borza, C. (2018) · Clinical Interventions in Aging · doi:10.2147/cia.s170111 · Cited by 75 · see citing works
Clinical immunity in bone and joints
Tanaka, Y. (2018) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-018-0965-5 · Cited by 74 · see citing works
The effect of exercise intensity on bone in postmenopausal women (part 1): A systematic review
Kistler-Fischbacher, M., Weeks, B. K., & Beck, B. R. (2020) · Bone · doi:10.1016/j.bone.2020.115696 · Cited by 76 · see citing works
Soy isoflavones prevent bone resorption and loss, a systematic review and meta-analysis of randomized controlled trials
Akhlaghi, M., Ghaseminasab-Parizi, M., Riasatian, M., & Sadeghi, F. (2019) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2019.1635078 · Cited by 72 · see citing works
The potential mechanism of the microbiota-gut-bone axis in osteoporosis: a review
He, Y., & Chen, Y. (2022) · Osteoporosis International · doi:10.1007/s00198-022-06557-x · Cited by 72 · see citing works
18F-Sodium Fluoride PET as a Diagnostic Modality for Metabolic, Autoimmune, and Osteogenic Bone Disorders: Cellular Mechanisms and Clinical Applications
Park, P. S. U., Raynor, W., Sun, Y. Y., Werner, T. J., Rajapakse, C. S., & Alavi, A. A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126504 · Cited by 72 · see citing works
Risk Factors for New Vertebral Fracture After Percutaneous Vertebroplasty for Osteoporotic Vertebral Compression Fractures
Zhang, Z., Yang, J.-S., Hao, D., Liu, T.-J., & Jing, Q. (2021) · Clinical Interventions in Aging · doi:10.2147/cia.s312623 · Cited by 69 · see citing works
Use of bone turnover markers in the management of osteoporosis
Jain, S., & Camacho, P. M. (2018) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000446 · Cited by 65 · see citing works
Evaluating the Activity of Sodium Butyrate to Prevent Osteoporosis in Rats by Promoting Osteal GSK-3β/Nrf2 Signaling and Mitochondrial Function
Xue Ming, T. A. N. G., Ma, S., Li, Y., Sun, Y., Zhang, K., Zhou, Q., & Yu, R. (2020) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.0c01820 · Cited by 63 · see citing works
A Mini Review on Osteoporosis: From Biology to Pharmacological Management of Bone Loss
Chin, K., Ng, B. N., Rostam, M. K. I., Fadzil, N. F. D. M., Raman, V., Yunus, F. M., Hashim, S. A. S., & Ekeuku, S. O. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11216434 · Cited by 61 · see citing works
Brain to bone: What is the contribution of the brain to skeletal homeostasis?
Idelevich, A., & Baron, R. (2018) · Bone · doi:10.1016/j.bone.2018.05.018 · Cited by 60 · see citing works
Bone-derived factors mediate crosstalk between skeletal and extra-skeletal organs
He, T., Qin, L., Chen, S., Huo, S., Li, J., Zhang, F., Yi, W., Mei, Y., & Xiao, G. (2025) · Bone Research · doi:10.1038/s41413-025-00424-1 · Cited by 58 · see citing works
PSMC6 promotes osteoblast apoptosis through inhibiting PI3K/AKT signaling pathway activation in ovariectomy‐induced osteoporosis mouse model
Zhang, Y., Cao, X., Li, P., Fan, Y., Zhang, L., Li, W., & Liu, Y. (2020) · Journal of Cellular Physiology · doi:10.1002/jcp.29261 · Cited by 58 · see citing works
M1 macrophage‐derived exosomes aggravate bone loss in postmenopausal osteoporosis via a microRNA‐98/DUSP1/JNK axis
Yu, L., Hu, M. C., Cui, X., Bao, D., Luo, Z., Li, D., Li, L., Liu, N., Wu, Y., Luo, X., et al. (2021) · Cell Biology International · doi:10.1002/cbin.11690 · Cited by 53 · see citing works
Soluble Biomarkers of Osteoporosis and Osteoarthritis, from Pathway Mapping to Clinical Trials: An Update
Nagy, E., Nagy-Finna, C., Popoviciu, H., & Kovács, B. (2020) · Clinical Interventions in Aging · doi:10.2147/cia.s242288 · Cited by 42 · see citing works
How zoledronic acid improves osteoporosis by acting on osteoclasts
Wang, B., Zhan, Y., Yan, L. W., & Hao, D. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.961941 · Cited by 52 · see citing works
Association between the metabolome and bone mineral density in a Chinese population
Mei, Z., Dong, X. W., Qian, Y., Hong, D., Xie, Z., Yao, G., Qin, A., Gao, S., Hu, J., Liang, L., et al. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.103111 · Cited by 52 · see citing works
Application of machine learning model to predict osteoporosis based on abdominal computed tomography images of the psoas muscle: a retrospective study
Huang, C., Hu, J.-S., Tan, K., Zhang, W., Xu, T.-H., & Yang, L. (2022) · BMC Geriatrics · doi:10.1186/s12877-022-03502-9 · Cited by 49 · see citing works
Soy Isoflavones and Bone Health: Focus on the RANKL/RANK/OPG Pathway
Hooshiar, S. H., Tobeiha, M., & Jafarnejad, S. (2022) · BioMed Research International · doi:10.1155/2022/8862278 · Cited by 48 · see citing works
Biochemical Markers of Bone Fragility in Patients With Diabetes
Meier, C., Eastell, R., Pierroz, D. D., Lane, N. E., Al‐Daghri, N. M., Suzuki, A., Napoli, N., Mithal, A., Chakhtoura, M., Fuleihan, G. E., et al. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad255 · Cited by 50 · see citing works
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Authors: Eastell, R., & Szulc, P.
Affiliations: University of Sheffield (GB)
Corresponding author: Eastell, Richard
ORCID: Eastell, Richard
Venue: The Lancet Diabetes & Endocrinology
Publisher: Elsevier BV
Published: 2017-11
Volume: 5
Issue: 11
Pages: 908-923
ISSN: 2213-8587 (ISSN-L)
DOI: 10.1016/s2213-8587(17)30184-5
OpenAlex: W2733907025
Cited by: 594
References: 168
Citations by year: 2026: 62 · 2025: 94 · 2024: 89 · 2023: 82 · 2022: 92 · 2021: 75 · 2020: 47 · 2019: 32 · 2018: 18 · 2017: 3
FWCI: 4.97
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: The Lancet Diabetes & Endocrinology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute for Health and Care Research (NF-SI-0513-10073)
Medical Research Council (MR/K006312/1, MR/P020941/1)
Topics: Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Health Sciences › Medicine › Oncology › Bone health and treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Keywords: bone turnover markers, postmenopausal osteoporosis, bone resorption, bone formation, P1NP, C-terminal telopeptide of type I collagen, secondary osteoporosis, fracture risk prediction
MeSH terms: Diphosphonates, Humans, Biomarkers, Bone Density, Osteoporosis, Postmenopausal, Bone Remodeling, Fracture Healing, Bone Density Conservation Agents

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Use of bone turnover markers in postmenopausal osteoporosis

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