Carboxylated and uncarboxylated osteocalcin levels are not linked with insulin resistance in osteoarthritis patients

Purpose: Normal 0 21 false false false FR-CA X-NONE X-NONE An association between knee osteoarthritis (OA) and the metabolic syndrome (MetS) has been proposed and in particular between OA and type 2 diabetes (T2D). Altered glucose metabolism and insulin resistance (IR) are observed in TD2 individuals. In animal studies, a link between glycemia/insulin resistance (IR) and circulating levels of either carboxylated and uncarboxylated osteocalcin (OC) has been observed. Previous studies reported an increased production of osteocalcin by OA osteoblasts. Herein, we evaluated if OA patients present evidence of IR and if this could be linked with circulating OC levels. Methods: Normal 0 21 false false false FR-CA X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:“Tableau Normal”; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:””; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:“Calibri”,“sans-serif”;} Fasting blood samples were taken from 34 OA patients classified according to the American College of Rheumatology criteria and 14 normal individuals. Body mass index (BMI) was determined for each participant. Serum analyses included cholesterol, HDL-cholesterol, triglycerides, fasting glucose, and insulinemia. Insulin resistance was evaluated by the Homeostasis model assessment of insulin resistance (HOMA-IR), with the product of fasting triglycerides x glucose (TyG index), and the TyG with adiposity status (TyG-BMI). Total osteocalcin (OC), carboxylated OC (carbOC) and undercarboxylated OC (unOC) were determined using selective ELISA. Statistical analysis of continuous variables was performed using the Mann-Whitney test whereas multivariate analysis was performed using an ANCOVA adjusted for age and BMI. Results: Normal 0 21 false false false FR-CA X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:“Tableau Normal”; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:””; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:“Calibri”,“sans-serif”;} BMI was more elevated in OA patients than normal individuals (p<0.0002). Cholesterol and LDL levels were slightly lower in OA patients compared to normal (p<0.045 and 0.037 respectively) whereas triglycerides and HDL-cholesterol levels were similar. Glucose and insulin levels were more variable in OA patients and lead to variable HOMA-IR indexes. Total OC was elevated in OA patients (p<0.004) via an increase in carbOC (p<0.016) and unOC (p<0.022) and these differences remained following multivariate analysis (p<0.006, 0.013 and 0.012 respectively). There was no correlation between cholesterol, triglycerides or insulin and BMI. Moreover, we could not detect a correlation with HOMA-IR for OC, carbOC and unOC. The TyG-BMI index was consistently higher in OA patients compared to normal individuals whereas the HOMA-IR index was more variable and could not reach significance. The TyG index showed a positive correlation with insulin levels in OA patients only, while the TyG-BMI showed a positive correlation with HOMA-IR (p<0.005) and insulin levels (p<0.003). Last, OC, carbOC and unOC levels showed no correlation with the TyG or the TyG-BMI index in either normal individuals or OA patients, nor with insulin levels or HOMA-IR. Conclusions: Normal 0 21 false false false FR-CA X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:“Tableau Normal”; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:””; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:“Calibri”,“sans-serif”;} Our data indicate that OC, carbOC and unOC levels are increased in OA patients. Variations in HOMA-IR are significantly different in a subgroup of OA patients, however OC levels remained higher in OA patients with «normal» or «high» HOMA-IR. This suggests that bone alterations observed in OA patients are distinct from their MetS status.