<p>Soluble Biomarkers of Osteoporosis and Osteoarthritis, from Pathway Mapping to Clinical Trials: An Update</p>

Abstract

Serum biomarkers of osteoarticular diseases have been in the limelight of current clinical research trends. Laboratory validation of defined and candidate biomarkers for both osteoarthritis and osteoporosis is of key importance for future decisional algorithms in the diagnosis, monitoring, and prognosis of these diseases. The current guidelines recommend the use of collagen degradation remnants, eg, CTX-I and CTX-II, in the complementary diagnosis of both osteoporosis and osteoarthritis. Besides the collagen degradation markers, enzymes that regulate bone and articular metabolism are useful in the clinical evaluation of osteoarticular pathologies. Along these, several other recommended and new nominee molecules have been recently studied. Wnts and Wnt-related molecules have a cardinal role in the bone-joint homeostasis, making them a promising target not only for pharmaceutical modulation, but also to be considered as soluble biomarkers. Sclerostin and dickkopf, two inhibitor molecules of the Wnt/β-catenin signaling, might have a dual role in the assessment of the clinical manifestations of the osteoarticular unit. In osteoarthritis, besides fragments of collagen type II many pathway-related molecules have been studied and proposed for biomarker validation. The most serious limitation is that a significant proportion of studies lack statistical power due to the reduced number of cases enrolled. Serum biomarkers of bone and joint turnover markers represent an encouraging possibility for the diagnosis and prognosis of osteoarticular diseases, although further studies and laboratory validations should be carried out as to solely rely on them.

The Effect of Physical Activity on Bone Biomarkers in People With Osteoporosis: A Systematic Review

“…According to more recent literature (4,7,10) the most specific and sensitive biomarkers for osteoporosis management and the most accepted for monitoring drug therapy are CTX-1(bone resorption) and P1NP (bone formation). These two biomarkers were not investigated in any of the three studies analyzed.…”

“…The Cochrane risk-of-bias tool for randomized trials analyses seven bias categories for studies classified as a randomized controlled trial (RCT): (1) random sequence generation and (2) allocation concealment (concerning bias of selection and allocation), (3) selective reporting for reporting bias, (4) blinding of participants and personnel (performance bias due to knowledge of the allocated intervention), (5) blinding of outcome assessment for detection bias, (6) incomplete outcomes data for bias in attrition, and another domain (7) called "other bias" based on the probable bias not covered in the other categories. Each category results in a value of high, low or unclear (when the authors did not provide enough evidence about the bias category) risk of bias.…”

“…They are ideal tools to evaluate the actual metabolic status of the bone, as well as a well-established result of abnormal metabolism (5). Table 1 shows the most reviewed bone biomarkers to assess the different phases of bone metabolism process (4,(6)(7)(8)(9)(10)(11).…”

The Dual Role of Vitamin K2 in “Bone-Vascular Crosstalk”: Opposite Effects on Bone Loss and Vascular Calcification

“…OP is classified into a primary and secondary form with distinct etiological backgrounds. Type 1 (primary) is typical of postmenopausal women in whom the decrease in estrogenic levels is associated with an inflammatory state linked to an increase in osteoclast activity and a consequent imbalance of bone metabolism, whereas type 2 (secondary) occurs in both males and females, but its pathologic mechanism has only partially been clarified [ 4 ].…”

Age-dependent changes in protein incorporation into collagen-rich tissues of mice by in vivo pulsed SILAC labelling

“…Collagen 1a2, the most abundant protein in bone matrix, also showed a statistically significant reduction in late adult mouse bone. Degradation fragments of collagen 1 (CTX-1) are regarded as a key biomarker in the diagnosis and treatment of osteoporosis (53). In addition, we found decreased incorporation in two proteins, 14-3-3 protein epsilon and cd44.…”