Sclerostin is a major negative regulator of osteoblastic activity at tissue level. Serum sclerostin levels have been associated with bone mineral density and increased fracture risk. However, the relation between serum levels and expression on tissue levels is unknown. The aim of this study was to investigate this relationship. We used serum samples and bone biopsies from 26 patients that were available from a large randomised clinical trial, investigating with the effect of risedronate in patients with Crohns disease and osteopenia (registered as NTR-163 Dutch Trial Register). Sclerostin expression in bone was detected using immunohistochemistry (mouse-human antibody, R&D systems). In cortical bone, sclerostin positive area was measured as a percentage from the total cortical area (NIS elements, Nikon). In trabecular bone, sclerostin expression is detected as number of positively stained osteocytes. Serum concentrations were determined by an enzyme-linked immunosorbent assay (Mesoscale discovery). We also assessed bone mineral density of the hip and lumbar spine with DEXA. Serum sclerostin was associated with the number of sclerostin positive trabecular osteocytes (R=0.54, P=0.004) but not with sclerostin positive area in cortical bone (R=0.07, P=0.73). Serum sclerostin levels and sclerostin expression in cortical bone as well as in trabecular bone showed positive correlations with bone mineral density of the spine. (R=0.55, P=0.001; R=0.38, P=0.02; R=0.35, P=0.03). With bone mineral density of the hip only the sclerostin positive area in cortical bone showed a correlation of 0.54 (P=0.0004). We demonstrated that sclerostin levels in serum reflect the expression of sclerostin by osteocytes mostly in trabecular bone. Sclerostin expression in bone as well as sclerostin levels in serum are associated to bone mineral density, especially of the lumbar spine.
Disclosure: The study was supported by Amgen.
16 - 20 May 2015
European Society of Endocrinology