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Objectives. Osteonecrosis of the femoral head results from interruption of the vascular supply and eventual death of the cellular portion of bone. Effective methods of monitoring response to treatment are needed. Our aim was to evaluate synovial fluid metabolites, glucose and lactate, as biomarkers in a canine model of osteonecrosis.Methods. Osteonecrosis was cryosurgically induced in the right femoral head while the left hip served as control (n = 31). Animals either underwent no further intervention (n = 10), vascular endothelial growth factor (VEGF) injections (n = 4), placement of a vascularized bone graft (n = 6), a combination of VEGF microinjection and vascularized graft placement (n = 5), or treatment with daily oral alendronate (n = 6). After 12 weeks, synovial fluid from each hip joint was obtained for glucose and lactate concentrations.Results. Joints with surgically induced osteonecrosis demonstrated decreased synovial fluid concentrations of glucose (P < 0.05) and elevated concentrations of lactate (P < 0.05) relative to contralateral control hips. When animals were treated with VEGF, the vascularized graft placement, or vascularized graft and VEGF, there were no differences in the synovial fluid concentrations of these metabolites between cryoablated and control hips. In contrast, alendronate did not normalize the concentration of these synovial fluid metabolites in the cryoablated hips.Conclusions. Osteonecrosis of the femoral head is associated with alterations in synovial fluid glucose and lactate, reflecting anaerobic metabolism. These metabolites may serve as useful tools for monitoring response to revascularization therapies. [ABSTRACT FROM AUTHOR]

To evaluate diurnal variation of biomarkers in subjects with osteoarthritis (OA) of the knee.Twenty subjects with radiographic knee OA were admitted to the General Clinical Research Center of Duke University for an overnight stay to undergo serial blood and urine sampling. Biomarkers measured included serum hyaluronan (HA), cartilage oligomeric matrix protein (COMP), keratan sulfate (KS‐5D4), aggrecan neoepitope (CS846), high‐sensitivity C‐reactive protein (hsCRP), osteocalcin, transforming growth factor β1 (TGFβ1), and type II collagen (CII)–related epitopes (neoepitope from cleavage of CII [C2C], carboxy‐terminus of three‐quarter peptide from cleavage of CI and CII [C1,2C], and type II procollagen carboxy‐propeptide [CPII] in serum, and C‐terminal telopeptides of CII [CTX‐II] and C2C in urine).Levels of serum HA, COMP, KS‐5D4, and TGFβ1 increased significantly from T0 (before arising from bed) to T1 (1 hour after arising). More diurnal variation in HA was observed in patients with higher daily mean HA concentrations. CPII increased significantly from T0 to T2 (4 hours after arising). Urinary concentrations of CTX‐II were also found to vary with morning activity, decreasing significantly from T0 to T2. Urinary C2C concentrations increased significantly from T0 until T3 (early evening). No diurnal variations in CS846, hsCRP, osteocalcin, serum C2C, or C1,2C were observed. Six biomarkers (serum C2C, C1,2C, COMP, KS‐5D4, TGFβ1, and urinary CTX‐II) were associated with radiographic knee OA (expressed as the sum of Kellgren/Lawrence radiographic severity grades), with the strongest correlations observed with measurements obtained at later time points (either T2 or T3).Our study results suggest that serum and urine sampling for HA, COMP, KS‐5D4, TGFβ1, CPII, urinary CTX‐II, and urinary C2C should be standardized in future OA clinical trials. Serum and urine sampling at late midday time points may be the optimal approach for OA studies, although this result should be validated in a larger cohort. [ABSTRACT FROM AUTHOR]

Very few studies have evaluated the association of articular hypermobility and radiographic osteoarthritis (OA) in humans. We assessed hypermobility and its relationship to radiographic hand OA in a family‐based study. A total of 1,043 individuals were enrolled in the multicenter Genetics of Generalized Osteoarthritis study, in which families were required to have 2 siblings with radiographic OA involving ≥3 joints (distributed bilaterally) of the distal interphalangeal (DIP), proximal interphalangeal (PIP), or carpometacarpal (CMC) joint groups, and OA in at least one DIP joint. Radiographic OA was defined as a score of ≥2 on the Kellgren/Lawrence scale in one or more joints within the group. The Beighton criteria for assessment of hypermobility were recorded on a 0–9‐point scale. Hypermobility was defined as a Beighton score of ≥4, a threshold generally used to establish a clinical diagnosis of joint laxity. A threshold of ≥2 was also evaluated to assess lesser degrees of hypermobility. The Beighton score for the present was calculated based on clinical examination, and that for the past was based on recall of childhood hypermobility in the first 2 decades of life. The association of hypermobility and radiographic OA of the PIP, CMC, and metacarpophalangeal joints was evaluated in all participants and in men and women separately. Multiple logistic regression was used to examine the relationship of hypermobility with radiographic OA in each joint group, after adjusting for age and sex. The association of hypermobility and DIP OA was not evaluated, because evidence of DIP OA was required for study inclusion. Using a threshold Beighton score of 4, 3.7% of individuals were classified as hypermobile based on the present examination, and 7.4% were classified as hypermobile based on the past assessment. A significant negative association between present hypermobility and age was observed. In persons with hypermobility, the odds of OA in PIP joints was lower (for present, odds ratio [OR] 0.34, 95% confidence interval [95% CI] 0.16–0.71; for past, OR 0.43, 95% CI 0.24–0.78). Similar results were obtained using a threshold Beighton score of 2. The lower odds of PIP OA with hypermobility were significant after adjusting for sex and age (for present, OR 0.44, 95% CI 0.20–0.94; for past, OR 0.48, 95% CI 0.26–0.87). This study demonstrated a joint‐protective effect of hypermobility for radiographic OA of PIP joints. In contrast to previous studies showing an association of hypermobility and CMC OA, in this cohort there was no evidence for increased odds of OA in any joint group of the hand in association with articular hypermobility. [ABSTRACT FROM AUTHOR]