J.W.M. Chow

Stimulation of bone formation by dynamic mechanical loading of rat caudal vertebrae is not suppressed by 3-amino-1-hydroxypropylidene-1-bisphosphonate (AHPrBP).

We have recently developed an experimental system whereby pins inserted into the seventh and ninth caudal vertebrae of rat tails are used to load the eighth caudal vertebrae (C-8) in compression. In this model, a single 5-min period of dynamic loading, sufficient to induce strains within the range to which bones are exposed under physiological circumstances, stimulates lamellar bone formation in the cancellous bone of the vertebrae. The rapidity with which the increase in bone formation was induced raised the possibility that this bone formation might have occurred without prior resorption. To test the role of bone resorption in the response of the bone to mechanical stimulation, we compared the anabolic response to a single period of loading, of rats treated with 3-amino-1-hydroxypropylidene-1-bisphosphonate (AHPrBP) or vehicle. We found that mechanical loading caused a significant increase in dynamic and static indices of bone formation. The same indices were unaffected by AHPrBP, while the bone formation rate in the tibiae was reduced by AHPrBP. These results suggest that the increased bone formation induced by mechanical stimulation in the cancellous bone of rat vertebrae is not dependent on bone resorption.

REDUCTION IN DYNAMIC INDICES OF CANCELLOUS BONE FORMATION IN RAT TAIL VERTEBRAE AFTER CAUDAL NEURECTOMY

We have previously noted that a relatively large load (150 N) is required to induce a strain on the cortex of rat vertebrae similar to that induced on weight-bearing bones by normal mechanical usage. It seems unlikely that the musculature of the tail normally imposes loads of this magnitude, and this suggests that the quantity of bone in caudal vertebrae is maintained at a higher level than would be expected for the mechanical environment to which it is exposed. This high bone mass could represent a genetically determined minimum, or could be maintained through increased sensitivity to mechanical stimuli. To distinguish between these two possibilities, we denervated the tails of 13-week-old rats by neurectomy at L6, and assessed the response of the caudal vertebrae to mechanical disuse. We found that caudal neurectomy caused a reduction in the cancellous bone formation rate in the eighth caudal vertebrae to 12% of that seen in sham-operated animals. The cancellous bone formation rate in the thoracic vertebrae of neurectomized rats, which are not mechanically disused by caudal neurectomy, was not significantly reduced. This suggests that the cancellous bone formation rate in vertebrae is maintained by substantially less intense mechanical environments than those prevailing in weight-bearing bones, raising the possibility that bones may differ in their sensitivity to mechanical strain.

Treatment with Fluoride or Bisphosphonates Prevents Bone Loss Associated with Colitis in the Rat

Abstract. Idiopathic inflammatory bowel disease (IBD) is associated with osteoporosis in over 30% of cases. We have previously shown that 2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced colitis in rats is associated with considerable bone loss. In the current study we tested the ability of sodium fluoride (NaF) or the bisphosphonate pamidronate to prevent the bone loss associated with TNBS-induced colitis in 22-week-old male Wistar rats. As previously found, there was a 43% decrease in cancellous bone volume in rats with TNBS-induced colitis after 4 weeks. This was associated with marked suppression of the bone formation rate to less than 25% of control animals. Treatment with NaF had no effect on the severity of colitis, but the bone volume and bone formation rate were increased to levels indistinguishable from those of control animals. In animals treated with pamidronate, cancellous bone volume was also restored to that of control animals despite persistence of the colitis. In these animals there was marked suppression of bone formation, associated with suppression of bone resorption. This data shows the bone loss associated with colitis may be prevented by treatment with NaF or bisphosphonates without requiring improvement in severity of the colitis.

Estrogen induces bone formation on non-resorptive surfaces in the rat

We have recently found that 17 beta-estradiol (E2) stimulates bone formation in rat cancellous bone, and that this bone formation is suppressed by (3-amino-1-hydroxypropylidene)-1-bisphosphonate (AHPrBP). To analyse the relationship between bone resorption and bone formation in the action of E2, we injected 13-week-old female rats sequentially with three fluorochromes (calcein, tetracycline and xylenol orange) at 7-day intervals. E2 (40 micrograms/kg) or vehicle was injected daily for 15 days, starting 24 hrs after the first fluorochrome. A third group was injected with AHPrBP (0.3 mg/kg) 24 hrs after the first two fluorochromes. The rats were killed 48 hrs after the third fluorochrome. We found that the perimeter of all three fluorochrome labels was increased by E2. The entire perimeter of the first label was non-crenated. Since the first label was given before E2-administration, this suggests that label that would otherwise have been eluted from the bone surface had been fixed in bone by E2-induced bone formation, which might have occurred either through prolongation of pre-existing bone formation, or induction of bone formation on quiescent surfaces. In either case, our results suggest that resorption did not precede formation at the site of bone formation. Since induction of bone formation by E2 is suppressed by inhibition of bone resorption, this suggests that the coupling of E2-induced formation to resorption in the rat does not necessarily require that formation occurs at the same site as bone resorption.(ABSTRACT TRUNCATED AT 250 WORDS)