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We tested the hypothesis that mechanical loading of human bone increases expression of the transcription factor RUNX2 and bone matrix proteins osteopontin (OPN), bone sialoprotein (BSP), dentin matrix protein-1 (DMP1), and matrix extracellular phosphoglycoprotein (MEPE). We examined this in tissue sections of atrophic mandibular bone taken from edentulous patients who had undergone distraction osteogenesis. In undistracted bone, weak to moderate staining for OPN and BSP was found in osteoblasts and bone matrix of immature woven bone. RUNX2 was also detectable in osteoblasts and in cells of the periosteum. In woven bone, but not in lamellar bone, a small number of osteocytes stained for all proteins tested. After distraction, staining intensity had increased in the existing old bone and staining was seen in more bone cells than before distraction. We also found a high expression of DMP1 and MEPE in many osteocytes embedded in woven bone and in some osteocytes of lamellar bone not seen before distraction. New bone trabeculae were forming in the fibrous tissue of the distraction gap containing all stages of intramembranous bone formation. Moderate to strong staining was seen for all five proteins tested in osteocytes located in woven bone of these trabeculae and for RUNX2, OPN, and BSP in osteoblasts lining the trabecular surfaces. We conclude that loading of atrophic human jawbone by distraction activates matrix synthesis of bone cells in and around existing bone. Increased staining of DMP1 and MEPE in osteocytes after loading is in line with the concept that these proteins may be involved in signaling the effector cells to adapt the bone structure to its mechanical demands.

We examined the effect of distraction rate on blood vessel growth in intramembraneous ossification after vertical distraction osteogenesis in the human mandible. Six edentulous patients (aged 60+/-9 years) with a severely atrophic mandible underwent bone augmentation with distraction osteogenesis. Two distraction rates (0.5 and 1 mm/day) were compared and for each group three patients were analyzed. Vascular histomorphometry was carried out in two different areas in the distraction gap: (1) in the first and (2) in the second 1 mm area from the osteotomy line, representing the oldest and younger new-bone area, respectively. Correlation analysis was performed between blood vessel parameters and the amount of new bone formed during distraction. Histological analysis demonstrated the presence of blood vessels throughout the soft connective tissue in the distraction gap. The volume density of blood vessels between the two investigated areas was significantly lower in the 1 mm/day groups, suggesting a delay in angiogenesis in this group of patients. A positive correlation between blood vessel volume and bone volume density was found in the younger new-bone area but not in the oldest new-bone area. This correlation was due to a higher number of blood vessels rather than to a larger size of the blood vessels. Our data suggest that the lower blood vessel density found in the patients with 1 mm/day distraction rate may be related to disruption of angiogenesis in the soft connective tissue of the gap or to a less optimal mechanical stimulation of cells involved in angiogenesis. This probably results in the slower rate of osteogenesis seen at the 1 mm/day distraction rate compared with the 0.5 mm/day distraction rate. The data support the concept that a positive relationship exists between the density of blood vessels and the formation of bone. For distraction of the human mandible in elderly patients, a distraction rate of 0.5 mm/day seems beneficial.

Vertical distraction osteogenesis has received considerable interest as a way to augment bone prior to implant placement. However, very little is known regarding the appropriate distraction protocols in the human mandible. In this study, we evaluate the effect of the distraction rate and the duration of neutrofixation on bone formation and closure of the gap in the human mandible. Vertical distraction was performed in the atrophic mandible of 16 edentulous patients, aged 62+/-6 years. The bone was distracted for approximately 10 mm at a rate of either 0.5 or 1 mm/day. Bone biopsies were taken after 7-20 weeks of neutrofixation. Histological analysis demonstrated newly formed bone in the distraction gap in all biopsies. The bone was predominantly of the woven type. After 10 weeks of neutrofixation, the gap was bridged by new bone in two out of three intact samples in the 0.5 mm/day group, but not in two intact samples of the 1 mm/day group. Histomorphometry revealed longer bone trabeculae (P=0.02) and a somewhat increased bone volume in the area where new bone formation started (P=0.07) in the group of patients having the 0.5 mm/day of distraction rate than in the 1 mm/day group. We conclude that in elderly patients, a distraction rate of 0.5 mm/day results in faster osteogenesis in the distraction gap than a rate of 1 mm/day. A minimum of 10 weeks of neutrofixation seems to be needed to close a 10 mm gap after cessation of distraction.