Osteoarthritis, a degenerative joint disease, is the most prevalent form of arthritis. Osteoarthritis is partly unpredictable and can remain silent for a long time. However, it can progress rapidly and manifests itself and is caused by cartilage loss, osteophytes and to some extent synovial inflammation, resulting in a reduction of joint space leading to joint function loss. The treatment for joint failure is total joint replacement. Pain is one common denominator of osteoarthritis and often the reason for first patient-doctor interaction.

How many people have Osteoarthritis?
Osteoarthritis is the most common form of arthritis and a major cause of disability and pain worldwide. In 2017 osteoarthritis was estimated 4% of the world’s population or approximately 303 million people (Kloppenburg et al. OAC 2020). Women are more likely to get osteoarthritis than men, but risk factors also include risk factors include older age, obesity and joint trauma among others

How is Osteoarthritis treated?
There are currently no approved disease-modifying drugs (DMOADs) for the treatment of osteoarthritis. Instead, the focus is on managing symptoms. Symptomatic treatment options include physiotherapy and exercise, analgesics such as NSAIDS or steroids, and total joint replacement in severe end-stage cases.

How is Osteoarthritis diagnosed?
The current diagnosis methods for osteoarthritis rely on clinical history, imaging (ultrasound, X-ray, CT and MRI scans), arthroscopy, and laboratory blood tests. Clinically, the diagnosis relies on patient history (e.g., pain and functional limitations) and physical examination (tenderness, swelling, restricted movement, bony enlargements).

The medical need for biomarkers in osteoarthritis is two-fold. First, there is still a need for biomarkers in osteoarthritis to inform diagnosis and prognosis and for monitoring disease activity in clinical practice. Current methods rely on clinical examinations and are largely based on clinical examinations, questionnaires and radiographs. Biomarkers quantifying tissue turnover and rate of joint destruction may contribute to the understanding of the underlying disease activity and prognosis.

Second, and perhaps the greatest unmet need is for biomarkers that can be applied in clinical drug development trials to aid patient selection and improve study design optimization. Clinical trials in the osteoarthritis field have notoriously been hampered by the patient heterogeneity and inclusion of patients with low disease progression rates. Identifying the patients who are more likely to progress, or who are more likely to respond to a given treatment will be paramount.

Osteoarthritis is a heterogeneous disease characterized by slow and gradual deterioration of the joint structure.
The tissues of the joint consist mainly of collagens. The collagens are remodeled as part of the normal homeostasis of the joint – that is, collagens are broken down and rebuilt as part of repair and maintenance mechanisms in the tissue. In osteoarthritis, this balance is disturbed, leading to net degradation of the tissue. Nordic ProteinFingerPrint Technology™ biomarkers can quantify this tissue turnover directly in a serum sample.

Visit our rheumatology biomarker portfolio and choose a panel that fits your clinical research or drug development targets!

Although there have been While the rheumatoid arthritis field possesses several diagnostic and disease activity biomarkers, their capacity for predicting treatment response is limited. There is therefore a huge medical and drug development need for biomarkers that can characterize and quantify structural tissue change and predict disease progression and treatment response. In clinical study setting, the tissue-derived Nordic ProteinFingerPrint Technology™ biomarkers can be measured in serum and used to accurately quantify changes in tissue turnover in the different joint tissues in the individual patient.

Biomarkers and tissue characterization:
Cartilage degradation by type II collagen fragments: C2M, CTX-II
Synovial turnover and chronic inflammation:  C3M, CRPM, MMP3, VICM
Bone erosions and remodeling: CTX-I, alpha-CTX, C1M, ICTP, PRO-C1, osteocalcin
Endothelial and epithelial dysfunction: C4M, PRO-C4, C6M, PRO-C6

Our laboratory services offer customized solutions for your osteoarthritis biomarker needs.

Nordic ProteinFingerPrint Technology™ biomarkers measured in serum are only moderately increased in osteoarthritis patients, and are affected by the heterogeneity of the disease manifestation between patients. Several biomarkers have been correlated to radiographic manifestations such as increased Kellgren-Lawrence grade.

Reference: Bay-Jensen et al. Clin. Biochem. 2011

Cartilage degradation quantified by the biomarker C2M (collagen type II degraded by MMPs) is increased in osteoarthritis patients compared to healthy subjects.

Nordic ProteinFingerPrint Technology™ biomarkers allow pharmacodynamic profiling of novel treatments by measuring protein degradation fragments directly in a serum sample. In a recent study, the aggrecan fragment ARGS was dose-dependently reduced by the anti-ADAMTS-5 nanobody, M6495 (Guehring et al. 2019 Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Ascending Doses of the Anti-ADAMTS-5 Nanobody®, M6495, in Healthy Male Subjects: a Phase I, Placebo-Controlled, First-in-Human Study. ACR 2019)

Reference: Wang et al., OAC 2017.

Phase Ib, anti-IL1-DVD (SC injection), Abbvie
Radiographic knee osteoarthritis patients (KL 1, 2, 3 & VAS pain 40 – 80 mm)

The use of symptom-modifying drugs generally provides little structural benefit to the joint, and hence biomarkers of the extracellular matrix often show minimal modulation in these settings. Exceptions to this include treatments that lead to potential alterations in the use of joints, or which seek to lower pain through inhibition of systemic signaling molecules such as NGF.

In these cases, it is important to ensure that treatment of symptoms does not lead to safety issues in the form of rapid progression of the disease, osteoarthritis is observed as rapid deterioration of the joint structure. The tissue-derived Nordic ProteinFingerPrint Technology™ biomarkers can be measured in serum and used to monitor changes in matrix turnover in the different joint tissues to identify potential detriment.

Karsdal et al., OAC 2019

Phase III, baseline prediction of Rapidly progressive osteoarthritis events after treatment with tanezumab.

The applications presented here are for research use only.

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