Recent Advances in Biomarkers in Osteoarthritis
Recent Advances in Biomarkers in Osteoarthritis
Purpose of review Osteoarthritis is a joint disease characterized by a nonsymptomatic, preradiographical phase that if distinguished would allow earlier osteoarthritis diagnosis. Biochemical biomarkers offer a potential nonradiographical alternative to detect early, nonsymptomatic osteoarthritis.
Recent findings Biomarker development for osteoarthritis diagnosis is still in the forefront of the research repertoire in osteoarthritis. A number of previously identified biomarkers derived from cartilage breakdown or enzymes that cause cartilage degeneration still have prominence and are now better characterized with increasing use in identifying disease severity, progression, and testing treatment options. Combinations of cartilage-derived and bone-derived biomarkers have been used to subgroup osteoarthritis patients that could impact treatment and address the importance of bone turnover in cartilage integrity. Increasingly, inflammation markers have been used to profile osteoarthritis progression attesting to the inflammatory nature of osteoarthritis. The application of proteomic technologies has generated several new, nonconventional biomarkers that could allow better profiling of osteoarthritis.
Summary Biomarker combinations have the ability to subgroup the heterogenous osteoarthritis population to allow a better scrutiny of diagnosis and treatment options. The application of different technological platforms to osteoarthritis would allow a better understanding of its pathology and could provide for appropriate candidates for earlier detection of osteoarthritis.
Accurate diagnosis of early osteoarthritis is a critical unmet need in today's medical scenario, as the number of people suffering from osteoarthritis increases every year. Although a lack of complete understanding of the pathophysiology of osteoarthritis has contributed to this dilemma, it is further compounded by the inability to detect osteoarthritis sufficiently early because of the slow progressive nature of the disease. The concept of noninvasive, in vitro, biochemical biomarkers to specifically detect osteoarthritis, though not novel, has yet to achieve its goal to routinely screen for early osteoarthritis to halt further disease progression. Furthermore, a disease-modifying osteoarthritis drug (DMOAD) to halt osteoarthritis disease progression has not been developed to the point of routine application. Paradoxically, the monitoring of DMOAD efficacy is also dependent on the availability of an effective biomarker that will inform pharmacological trials of its success. Thus, the compounding impediments in this field have stymied an effective early osteoarthritis diagnosis in humans.
Here, we have summarized the advancements in osteoarthritis biomarker development in the past 12 months. Cognizant readers will recognize a number of old players in the field; but there are also some innovative and much needed, novel directions that the osteoarthritis biomarker movement has taken. Readers are also directed to the OA Research Society International (OARSI)–Food and Drug Administration (FDA) initiative that has summarized the application of biomarkers in monitoring pharmacological interventions during osteoarthritis and provides a summary of the classification system for biomarkers. We have not categorized biomarkers based on their tissue origins as there are several excellent reviews that have documented this nor have we classified them as per BIFED(S) classification. We have restricted this review to studies in humans, though some notable biomarker studies in animal models pertaining to efficacy of a matrixmetalloproteinase (MMP)-13 inhibitor through use of collagen and aggrecan neoepitope biomarkers, the use of oral salmon calcitonin (sCT) in reducing cartilage pathology, the monitoring of aggrecan neoepitope biomarkers after monosodium iodoacetate injection, and the clinical value of serum (s) CTX-II levels in late stage osteoarthritis could be of interest to readers.
Abstract and Introduction
Abstract
Purpose of review Osteoarthritis is a joint disease characterized by a nonsymptomatic, preradiographical phase that if distinguished would allow earlier osteoarthritis diagnosis. Biochemical biomarkers offer a potential nonradiographical alternative to detect early, nonsymptomatic osteoarthritis.
Recent findings Biomarker development for osteoarthritis diagnosis is still in the forefront of the research repertoire in osteoarthritis. A number of previously identified biomarkers derived from cartilage breakdown or enzymes that cause cartilage degeneration still have prominence and are now better characterized with increasing use in identifying disease severity, progression, and testing treatment options. Combinations of cartilage-derived and bone-derived biomarkers have been used to subgroup osteoarthritis patients that could impact treatment and address the importance of bone turnover in cartilage integrity. Increasingly, inflammation markers have been used to profile osteoarthritis progression attesting to the inflammatory nature of osteoarthritis. The application of proteomic technologies has generated several new, nonconventional biomarkers that could allow better profiling of osteoarthritis.
Summary Biomarker combinations have the ability to subgroup the heterogenous osteoarthritis population to allow a better scrutiny of diagnosis and treatment options. The application of different technological platforms to osteoarthritis would allow a better understanding of its pathology and could provide for appropriate candidates for earlier detection of osteoarthritis.
Introduction
Accurate diagnosis of early osteoarthritis is a critical unmet need in today's medical scenario, as the number of people suffering from osteoarthritis increases every year. Although a lack of complete understanding of the pathophysiology of osteoarthritis has contributed to this dilemma, it is further compounded by the inability to detect osteoarthritis sufficiently early because of the slow progressive nature of the disease. The concept of noninvasive, in vitro, biochemical biomarkers to specifically detect osteoarthritis, though not novel, has yet to achieve its goal to routinely screen for early osteoarthritis to halt further disease progression. Furthermore, a disease-modifying osteoarthritis drug (DMOAD) to halt osteoarthritis disease progression has not been developed to the point of routine application. Paradoxically, the monitoring of DMOAD efficacy is also dependent on the availability of an effective biomarker that will inform pharmacological trials of its success. Thus, the compounding impediments in this field have stymied an effective early osteoarthritis diagnosis in humans.
Here, we have summarized the advancements in osteoarthritis biomarker development in the past 12 months. Cognizant readers will recognize a number of old players in the field; but there are also some innovative and much needed, novel directions that the osteoarthritis biomarker movement has taken. Readers are also directed to the OA Research Society International (OARSI)–Food and Drug Administration (FDA) initiative that has summarized the application of biomarkers in monitoring pharmacological interventions during osteoarthritis and provides a summary of the classification system for biomarkers. We have not categorized biomarkers based on their tissue origins as there are several excellent reviews that have documented this nor have we classified them as per BIFED(S) classification. We have restricted this review to studies in humans, though some notable biomarker studies in animal models pertaining to efficacy of a matrixmetalloproteinase (MMP)-13 inhibitor through use of collagen and aggrecan neoepitope biomarkers, the use of oral salmon calcitonin (sCT) in reducing cartilage pathology, the monitoring of aggrecan neoepitope biomarkers after monosodium iodoacetate injection, and the clinical value of serum (s) CTX-II levels in late stage osteoarthritis could be of interest to readers.
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