Poster Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA

Osteocalcin (OC), a Vitamin K dependent protein known to influence bone metabolism, contains three gamma-carboxyglutamic acid residues responsible for calcium-binding properties. Deficiency of Vitamin K results in higher undercarboxylated-osteocalcin (ucOC). Higher ucOC has been associated with increased hip-fracture risk (1). Vitamin K supplementation studies consistently report improvement in carboxylated-osteocalcin (cOC), however effects on bone parameters have been inconsistent (2-4). We hypothesize that the conflicting evidence is due to biological differences and functions of uncarboxylated, ucOC and cOC.  No previous study has examined the interplay between different OC, bone turnover markers (BTMs) and bone properties. We investigated the interaction of cOC:ucOC and Vitamin K with cortical and trabecular bone structure, hip geometry and BTMs. Fifty patients scheduled to undergo hip replacement surgery for osteoarthritis during 2022-2024 with normal kidney function, not taking warfarin or medications affecting bone metabolism, and mean age of 68 years (48-87) were recruited (HREC15811). Patients underwent DXA scans preoperatively. Femoral biopsies and serum specimens were obtained intraoperatively. Trabecular bone was analyzed by microCT. BTMs, vitamin K1, K2-7 were measured using standardized assays, and cOC and ucOC using ELISA kits (Takara-Biosciences). cOC showed significant positive correlation with trabecular number (p=0.037), bone volume/tissue volume (p=0.027), cortical thickness shaft (p=0.02) and all the BTMs (p<0.05). Most bone parameters were better in patients with higher cOC, cross-sectional moment of inertia and femoral neck width being significantly different (Table 1). No difference in eGFR, total hip or spine BMD was observed. The differences in bone structure seem to be driven by differences in bone remodeling and Vitamin K levels. Interestingly, patients with higher Vitamin K2-7 had significantly lower Hip Axis Length (p=0.003), an independent marker of fracture risk, even after controlling for height and age. This study provides the first evidence that higher cOC status may be associated with improved bone strength.