Endocrine Abstracts

JOINT3279

Lately, various bone quality changes inflicted by diabetes mellitus (DM) have been linked to the elevated fracture risk with both type 1 and type 2 DM. Fracture risk is also elevated in patients with advanced chronic kidney disease (CKD), with DM being a key factor in CKD prevalence and CKD patients having an increased risk to develop DM. To decipher the contribution of bone quality parameters contributing to bone fragility, we assessed if diabetes mellitus has differential effects on bone quality in advanced CKD patients. Therefore, CKD stage 4-5D patients with (n = 11, age 58±15 yrs, 10♂, 1♀) and without DM (n = 22, age 59±12 yrs, 16♂, 6♀) were recruited. Double-label tetracyclines were used prior to trans-iliac bone biopsy. Quantitative bone histomorphometry was performed to determine bone turnover, mineralization, and bone structure. Bone quality was evaluated using quantitative backscattered electron imaging (qBEI) to assess bone mineral density distribution and 2D morphological analysis of the osteocyte lacunae. The osteocyte-lacunae network was visualized and quantified with Ploton silver precipitation on LR white resin sections. Additionally, bone matrix composition was analyzed using vibrational Raman spectroscopy to determine the mineral-to-matrix ratio (MMR) with a 50x objective at a laser wavelength of 785 nm. We determined that, trabecular bone volume/tissue volume (BV/TV) was lower in CKD+DM group (17. 5 (13. 9 – 19. 4) % vs. 21. 6 (18. 7 – 26. 1) %, P = 0. 02), with no differences in bone formation (BFR/BS) and bone resorption (Oc. S/BS) parameters on bone histomorphometry between the groups. Bone mineral density distribution as determined by qBEI, presented locally with lower mineral content and the presence of micropetrosis – mineralization of osteocyte lacunae. Raman spectroscopy identified a higher phosphate/amide III peak in the cortical bone in CKD+DM (1. 42 ± 0. 15 vs 1. 32 ± 0. 11 a. u., P = 0. 04), which indicates altered bone matrix composition. The results of our ongoing study point towards minor differences in bone quality between individuals with CKD with or without DM, whereby biopsies from CKD patients with DM had lower trabecular bone volume and slightly altered matrix composition. If and how these changes contribute to bone fragility will have to be explored in future studies.