Bone-Derived 1,25-dihydroxyvitamin D is a determinant of trabecular bone structure in hip fracture patients — ASN Events
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Bone-Derived 1,25-dihydroxyvitamin D is a determinant of trabecular bone structure in hip fracture patients (#114)

Deepti K Sharma 1 , Thomas Robertson 2 , Catherine JM Stapledon 2 , Gerald J Atkins 2 , Peter M Clifton 1 , Paul H Anderson 1 , Bogdan L Solomon 2 , Howard A Morris 1
  1. University of South Australia, School of PMB, ADELAIDE, SOUTH AUSTRALIA, Australia
  2. Centre for Orthopaedic and Trauma Research,, University of Adelaide, Adelaide, South Australia, Australia

 

Calcium and vitamin D supplementation reduce hip fracture risk although there is little information regarding the mechanism. Rodent models have demonstrated positive effects of serum 25-hydroxyvitamin D (s25D) levels on bone structure, independent of serum PTH and 1α,25-dihydroxyvitamin D (s1,25D) levels. As well, the osteoblastic overexpression or deletion of 25-hydroxyvitamin D-1alpha hydroxylase (CYP27B1) mouse models demonstrated that bone-derived 1,25D plays an anabolic role in bone formation. We now report relationships between trabecular bone structure and calciotropic hormone levels in hip fracture patients. Intertrochanteric trabecular bone biopsies together with serum samples were collected from hip fracture patients undergoing surgery for a hip replacement (70 females, 41 males). Trabecular bone structure was analyzed by microCT (Skyscan 1076). Serum 25D, 1,25D and 1-84PTH were analysed by chemiluminescent immunoassay (Diasorin Liaison) and clinical data were collected from medical records. Mean s25D and 1-84PTH levels were 55 nmol/L and 4 pmol/L respectively, indicating that about half of the patients exhibited a degree of vitamin D depletion and secondary hyperparathyroidism. Serum 25D correlated positively with s1,25D (r=+0.329, p=0.0004) further confirming a depleted vitamin D status. Serum 25D correlated positively with trabecular thickness (r= +0.209, p=0.04) and negatively to the ratio of bone surface to bone volume (BS/BV) (r = -0.214, 0.036). Gender, s25D and bone mRNA levels of CYP27B1 and CYP24 accounted for 13% of the variability in BS/BV which increased to 18% in females, with 25D, CYP27B1 and CYP24 all contributing equally (P=0.006). Together, these variables are the determinants of bone-derived 1,25D. Patients with s25D≥60nmol/L had lower BS/BV compared to patients with s25D<60nmol/l (p=0.04) contributing to increased bone strength with increased s25D. These findings provide the first clinical data for an anabolic effect of bone-derived 1,25D on trabecular bone structure in hip fracture patients.