Trabecular Reorganization in Consecutive Iliac Crest Biopsies when Switching from Bisphosphonate to Strontium Ranelate Treatment
Figure 4
Reorganization pattern, µCT mean density and 2D histomorphometry.
A) µCT reconstruction of biopsy 5. Note the coarse structure with surface irregularities and the occurrence of an intratrabecular ‘tunnel’. The area with the dark-colored background demonstrates the 2D section plane as it can be seen on the histology section in panel B. B) Congruent histology section following the µCT slice in panel A. Note the irregular trabecular structure with varying trabecular diameter. The thickened trabecular architecture indicates intratrabecular resorption sites filled with fibrovascular tissue (mineralized bone = light purple; Giemsa, 40x). C) A high magnification of the µCT reconstruction of biopsy 5 indicates the irregular trabecular surface with multiple hook-like, tunneling and sometimes perforating resorption lacunae. Virtual serial sections can show that all intratrabecular ‘tunnels’ are connected at some point and have openings to the trabecular surface. Small humps due to bone formation (mini-modeling) arise from the trabecular surface (→). D) Axial µCT section of biopsy 5: Distribution of local mineral densities (mg HA/cm3) represented by different gray levels. Due to bone formation, a low mineral content is detected in the proximity of new osteons, whereas the interstitial regions show a higher mineral content due to an older tissue age. E) Two (re-)modeling sites with distinct osteoid seems are visible. The osteoid seam on the trabecular surface at the bottom (white arrow) is covered with some cubic-shaped osteoblasts that become flattened to the lower image border. Non-active endosteal appostion is evident on the top of the image (black arrow) without prior resorption (modeling) as flat osteoblasts or lining cells cover osteoid (mineralized bone = green, osteoid = red; Goldner-Masson, 400x). F–I) Osteoid and cellular indices determined by 2D histomorphometry point to a low bone turnover situation at the time of biopsies 1, 2 and 4. Normal bone turnover, leading to an increase in osteoid apposition and thus increasing osteoid surface and volume appeared only after 50 months of BP treatment and after the treatment was switched to strontium ranelate. Osteoid indices did not indicate any signs of hyperosteoidosis considering the reference ranges reported by Lips et al. [73].