Bone microarchitecture and turnover in the irradiated human mandible.

OBJECTIVES: The aim of this study was to assess the microarchitecture and turnover in irradiated cancellous mandibular bone and the relation with radiation dose, to elucidate the effects of radiotherapy on the mandible. PATIENTS AND METHODS: Mandibular cancellous bone biopsies were taken from irradiated patients and controls. Micro-CT scanning was performed to analyze microstructural bone parameters. Bone turnover was assessed by histomorphometry. Local radiation dose at the biopsy site (Dmax) was estimated from radiotherapy plans. RESULTS: Twenty-seven irradiated patients and 35 controls were included. Osteoid volume (Osteoid Volume/Bone Volume, OV/BV) [0.066/0.168 (median/interquartile range (IQR), OV/BV; %), P < 0.001], osteoid surface (Osteoid Surface/Bone Surface, OS/BS) [0.772/2.17 (median/IQR, OS/BS; %), P < 0.001] and osteoclasts number (Osteoclasts per millimetre bone surface, Ocl/mmBS; mm2) [0.026/0.123 (median/IQR, Ocl/mmBS; mm2), P < 0.001] were decreased; trabecular number (Tb.N) was lower [1.63/0.63 (median/IQR, Tb.N; 1/mm-1), P = 0.012] and trabecular separation (Tb.Sp) [0.626/0.24 (median/IQR, Tb.Sp; µm), P = 0.038] was higher in irradiated mandibular bone. With higher Dmax, trabecular number increases (Spearman's correlation R = 0.470, P = 0.018) and trabecular separation decreases (Spearman's correlation R = -0.526, P = 0.007). Bone mineral density (BMD, milligrams hydroxyappetite per cubic centimetre, mgHA/cm3) [1016/99 (median/IQR, BMD; mgHA/cm3), P = 0.03] and trabecular separation [0.739/0.21 (median/IQR, Tb.Sp; µm), P = 0.005] are higher whereas connectivity density (Conn Dens) [3.94/6.71 (median/IQR, Conn Dens), P = 0.047] and trabecular number [1.48/0.44 (median/IQR, Tb.N; 1/mm-1), P = 0.002] are lower in Dmax ≤50 Gy compared to controls. CONCLUSIONS: Radiotherapy dramatically impairs bone turnover in the mandible. Deterioration in microarchitecture only affects bone irradiated with a Dmax of <50 Gy. The 50 Gy value seems to be a critical threshold to where the effects of the radiation is more detrimental.

The irradiated human mandible: A quantitative study on bone vascularity.

OBJECTIVES: Hypovascularisation is thought to play an important role in the pathogenesis of osteoradionecrosis. The objective of this study was to assess the microvascular system in the irradiated mandibular bone marrow. MATERIALS AND METHODS: Mandibular bone biopsies were taken from 20 irradiated patients and 24 controls. Blood vessels were visualized using CD34 antibody stain to detect endothelial cells. The vascular density (VD) and vascular area fraction (VAF) were measured. Mean vessel lumen area, perimeter and diameter of the vessels were calculated for each vessel. A distinction was made between large and small vessels (cut-off point <400 µm2). RESULTS: Vascular density and vascular area fraction were lower in the irradiated group. The mean vascular perimeter and mean vascular diameter were higher in samples with a local radiation dose of ≥50 Gy, whereas the percentage of small vessels was lower. Larger vessel perimeter is associated with higher radiation dose. A longer interval between biopsy and radiotherapy is associated with a larger mean vessel perimeter and a lower percentage of small vessels. CONCLUSIONS: Radiation dosages higher than 50 Gy mainly affect the smaller vessels. With increased time after irradiation, the share of smaller vessels in the mandibular bone marrow seems to decrease. In search of the exact mechanisms of irradiation damage and osteoradionecrosis of the mandible, the role of the microvascular system in the mandibular bone marrow should be further explored.