Interactive effects of PTH and mechanical stress on nitric oxide and PGE2 production by primary mouse osteoblastic cells.

Parathyroid hormone (PTH) and mechanical stress both stimulate bone formation but have opposite effects on bone resorption. PTH increased loading-induced bone formation in a rat model, suggesting that there is an interaction of these stimuli, possibly at the cellular level. To investigate whether PTH can modulate mechanotransduction by bone cells, we examined the effect of 10-9 M human PTH-(1-34) on fluid flow-induced prostaglandin E2 (PGE2) and nitric oxide (NO) production by primary mouse osteoblastic cells in vitro. Mechanical stress applied by means of a pulsating fluid flow (PFF; 0.6 +/- 0.3 Pa at 5 Hz) stimulated both NO and PGE2 production twofold. In the absence of stress, PTH also caused a twofold increase in PGE2 production, but NO release was not affected and remained low. Simultaneous application of PFF and PTH nullified the stimulating effect of PFF on NO production, whereas PGE2 production was again stimulated only twofold. Treatment with PTH alone reduced NO synthase (NOS) enzyme activity to undetectable levels. We speculate that PTH prevents stress-induced NO production via the inhibition of NOS, which will also inhibit the NO-mediated upregulation of PGE2 by stress, leaving only the NO-independent PGE2 upregulation by PTH. These results suggest that mechanical loading and PTH interact at the level of mechanotransduction.

Fate of monocortical bone blocks grafted in the human maxilla: a histological and histomorphometric study.

Local bone defects in the anterior maxilla are commonly grafted with monocortical blocks of autologous bone in order to restore the defect site prior to the placement of dental implants. Increasing evidence suggests that osteocytes are involved in the control of bone remodelling and thus may be important for optimalisation of bone structure around implants, and thus for implant osseointegration. However, it is not well known whether osteocytes will survive when bone blocks are grafted into defects. We grafted 19 patients with monocortical bone blocks derived from the symphysis, to the defect site in the maxillary alveolar process. The bone grafts were left to heal for times varying from 2.5 to 7 months. During implant installation, bone biopsies were removed using a trephine burr, and processed for hard tissue histology. Bone histology and histomorphometry were then carried out in order to gain insight into the density, viability and remodelling of the graft. Clinically, all the bone grafts were successful, with no implant failures, and little resorption was seen. Histologically, bone volume expressed as percentage of tissue volume at the implant site varied from 27% to 57% with an overall average of 41%. Bone fields with empty osteocyte lacunae were observed and measured. The amount of this so-called nonvital bone (NVB) varied between 1% and 34% of the total tissue volume. The amount of NVB decreased significantly with the time of healing. The data suggest that the majority of the osteocytes of the monocortical bone do not survive grafting. The results indicate that the NVB is progressively remodelled into new vital bone 7 months after grafting.