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J W Chow

Publications and source records attributed to J W Chow.

93 records · Page 6Linked to original sources

3-Amino-1-hydroxypropylidine-1-bisphosphonate (AHPrBP) suppresses not only the induction of new, but also the persistence of existing bone-forming surfaces in rat cancellous bone.

Although bone formation is coupled to resorption in both man and the rat, it is not known whether similar mechanisms are involved in these two species. To investigate this, we have attempted to further characterise the suppression of bone formation by the potent bone resorption inhibitor 3-amino-1-hydroxypropylidine-1-bisphosphonate (AHPrBP) in ovariectomised adult female rats. To see whether AHPrBP affects the activity of preexisting bone forming surfaces, as opposed to preventing the induction of new forming surfaces, three consecutive fluorochrome labels were administered 3, 10, and 17 days prior to sacrifice. The percentage of trabecular surface covered by first and second labels only (arrested surface), second and third labels only (induction surface), and all three labels (persisting surface) were recorded at the secondary spongiosa of the proximal tibial metaphysis. As expected, ovariectomy increased the proportion of induction surfaces, with AHPrBP preventing this increase. However, AHPrBP also reduced the proportion of persisting surfaces, implying inhibition of the activity of preexisting bone-forming surfaces. We conclude that resorption inhibitors such as AHPrBP inhibit bone formation in the rat in a manner which appears inconsistent with the site-specific coupling seen in the adult human skeleton.

Animals↗

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)

Animals↗

A comparison of microanatomic basis for coupling between bone formation and bone resorption in man and the rat.

The trabecular bone of the secondary spongiosa of mature rats shows a coupling of bone formation to resorption. In adult man the coupling of formation and resorption involves a site-specific sequence of events, in which bone resorption is normally followed, at the same site, by bone formation. Whether the coupled processes of bone resorption and formation also occur at the same site in the rat is unknown. To elucidate the spatial relationship between bone formation and resorption in the rat, we compared the percentage of crenated and non-crenated cement lines with the percentage of crenated and non-crenated bone surfaces in the proximal tibia of adult rats aged 16 weeks-two years. A similar comparison was also made using bone from adult human iliac crest. We found that the trabecular bones of 16-week and seven-month-old rats exhibited a low percentage of crenated cement lines. In contrast, the surfaces of rat bone trabeculae showed a similar low proportion of crenated surface to human bone. However, in older (two years) rats, in which bones have ceased to grow in length, the percentage of cement lines that were crenated increased to towards human levels. These results imply that most of the bone formed in the secondary spongiosa of growing rats occurs on non-resorbed surfaces. Thus, although there is substantial evidence that bone formation is coupled to resorption in the rat, such that increased resorption is associated with increased formation, and suppression of resorption suppresses bone formation, bone formation does not necessarily occur on a previously resorbed site.(ABSTRACT TRUNCATED AT 250 WORDS)

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