Chemical sympathectomy impairs bone resorption in rats: A role for the sympathetic system on bone metabolism

The possibility that the nervous system may control bone metabolism has bee n raised, as neuromediators physiologically conveyed by sympathetic fibers (eg, vasoactive intestinal peptide) influence bone resorption in vitro. In this study, the sympathetic system was inactivated by treating rats with gu anethidine (40 mg/kg/day), a sympathetic neurotoxic, for 21 days, after whi ch a wave of osteoclastic resorption was induced along the mandibular bucca l cortex. The effects of denervation were assessed 4 days later (correspond ing to the peak of resorption in this model). The rats exhibited ptosis soo n after starting guanethidine, proving the success of the sympathectomy, Th is was associated with a significant increase in calcitonin gene-related pe ptide- (+54%, p < 0.02) and substance P-immunoreactive sensory fibers (+29% , p < 0.02), a known effect of sympathectomy, For the quantitation of the b one parameters, the study zone was divided into a juxta-osseous alkaline ph osphatase-positive osteogenic compartment and a nonosteogenic compartment, In the osteogenic compartment, the resorption surface was reduced by 56% (p < 0.001) in the treated animals, together with a fall in the number of ost eoclasts (-25%, p < 0.05) and impaired osteoclast access to the bone surfac e. Tartrate-resistant acid phosphatase-positive (TRAP(+)) mononuclear preos teoclasts were found only in this compartment; they were reduced by 43% (p < 0.05) by the sympathectomy, No change in nonspecific esterase (NSE)(+) os teoclast precursors was found. In the nonosteogenic compartment, vasodilati on was the only effect of sympathectomy (+80%, p < 0.05); in particular, th e number of NSE+ cells was not modified. Our results indicate that: (1) int eractions of NSE+ precursors with osteogenic cells are required for their d ifferentiation into TRAP(+) preosteoclasts; (2) the sympathetic nervous sys tem is not involved in osteoclast precursor recruitment; but (3) has a sign ificant effect on resorption by inhibiting preosteoclast differentiation an d disturbing osteoclast activation. These data suggest that depletion of sy mpathetic mediators may disturb osteogenic cell-mediated osteoclast differe ntiation. (C) 1999 by Elsevier Science Inc. All rights reserved.