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Bone Biomarkers Related to Osteoarthritis

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Biomarkers in Bone Disease

Abstract

It is evident that the bone plays a vital role in osteoarthritis (OA) disease pathogenesis, progression, and symptomatology. The close interaction of the bone and cartilage in the pathogenesis of OA and the knowledge that OA is a disease of the whole joint provide a strong rationale for investigating bone biomarker changes in OA. The evaluation of bone biomarkers is important for gaining a greater understanding of the role of bone pathology in OA and a means for developing new diagnostic and prognostic tools for therapeutic developments and early OA intervention. Although comparisons among studies are difficult because different assays and assay parameters are used and different assays reflect different outcomes, many bone-related biomarkers have shown great promise as diagnostic, prognostic, and efficacy of intervention biomarkers for OA. These include the traditional bone biomarkers, CTX-I and NTX-I and osteocalcin. The strong association of these traditional bone biomarkers with urinary C-terminal telopeptide of type II collagen (CTX-II) from the articular cartilage confirms the strong association of bone resorption with cartilage degradation. To date, results using bone biomarkers in OA trials provide examples of the modifiability of the whole joint organ by bone-acting agents. Based on recent data, tartrate-resistant acid phosphatase 5b (TRAP5b), periostin, and endothelin-1 (ET-1) show great promise and can be considered new OA-related bone biomarkers. More studies are required in the context of treatment trials to determine which bone biomarkers will be most relevant for drug development and use in the clinic.

M. P. Engbersen and Z. Huang have contributed equally.

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Abbreviations

ALP:

Alkaline phosphatase

BIPEDS:

Burden of disease, Investigative, Prognostic, Efficacy of intervention, Diagnostic or Safety biomarkers

BMD:

Bone mineral density

BML:

Bone marrow lesion

BSP:

Bone sialoprotein

CT:

Computed tomography

CTX and CTX-I:

C-terminal telopeptide of type I collagen

CTX-II:

C-telopeptide of type II collagen

DKK-1:

Dickkopf WNT signaling pathway inhibitor 1

DMOADs:

Disease-modifying OA drugs

Dpd:

Deoxypyridinoline (also called lysyl-pyridinoline or LP)

ECLIA:

Electrochemiluminescence immunoassay

ELISA:

Enzyme-linked immunosorbent assay

ET-1:

Endothelin-1

HYL-Pyr:

Hydroxylysyl-pyridinoline (also called pyridinoline or HP)

ICTP:

Carboxy-terminal telopeptide of type I collagen

IL-6:

Interleukin-6

JSN:

Joint space narrowing

KL-score:

Kellgren and Lawrence grade (of radiographic severity of OA)

KOOS:

Knee injury and osteoarthritis outcome score

MMPs:

Matrix metalloproteinases

MRI:

Magnetic resonance imaging

NTX and NTX-I:

N-terminal telopeptide of type I collagen

OA:

Osteoarthritis

OC:

Osteocalcin (intact protein indicative of bone formation; fragments of OA indicative of bone resorption)

OFELY:

“Os des Femmes de Lyon,” a longitudinal cohort study for assessing osteoporosis and secondary OA

PICP:

Procollagen type I C-terminal propeptide

PINP:

Procollagen type I N-terminal propeptide

PIIANP:

N-propeptide of type IIA procollagen

POSTN:

Periostin

S:

Serum

SF:

Synovial fluid

TRACP5b:

Tartrate-resistant acid phosphatase 5b

WNT:

Wingless-related integration site

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    Authors and Affiliations

    1. Division of Rheumatology, Duke Molecular Physiology Institute, Duke University School of Medicine, Room 51-205, Carmichael Building, 300 N Duke St, 104775, Durham, NC, 27701-2047, USA

      M. P. Engbersen, Z. Huang & V. B. Kraus

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    1. M. P. Engbersen
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    2. Z. Huang
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    3. V. B. Kraus
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    Correspondence to V. B. Kraus .

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    1. Department of Biomedical Sciences, Faculty of Science and Technology, University of Westminster, London, United Kingdom

      Vinood B. Patel

    2. Department of Nutrition and Dietetics, Division of Diabetes and Nutritional Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, United Kingdom

      Victor R. Preedy

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    Engbersen, M.P., Huang, Z., Kraus, V.B. (2017). Bone Biomarkers Related to Osteoarthritis. In: Patel, V., Preedy, V. (eds) Biomarkers in Bone Disease. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7693-7_35

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