A crucial role for thiol antioxidants in estrogen-deficiency bone loss
J. Clin. Invest. Jenny M. Lean, et al. 112:915 doi:10.1172/JCI18859 [Go to this article.]

Figure 2
Ascorbate and NAC prevent bone loss in ovariectomized mice. (a–g) Ascorbate (2 mmol/kg/day) prevents ovariectomy-induced bone loss in mice. (a) Representative images of microscope sections of femora from mice subjected to sham ovariectomy (sham) or ovariectomy (ovx) and treated for 2 weeks with ascorbate (1 nmol/kg twice daily) or vehicle. (b–g) Histomorphometric analysis shows that ascorbate prevented ovariectomy-induced bone loss (b). Indices of bone resorption (c–e) (osteoclast number per millimeter of bone surface; percentage of bone surface covered by osteoclasts; percentage of bone surface that shows scalloped, eroded appearance) were increased by ovariectomy and suppressed by ascorbate. Ascorbate also normalized (f and g) the number of osteoblasts per millimeter of bone surface and the percentage of bone surface covered by osteoblasts to sham levels. Total glutathione in bone marrow fell significantly (P < 0.05) from 32 ± 5 nmol/mg protein in controls to 22 ± 1.2 nmol/mg protein in ovariectomized mice and was increased by ascorbate to 54 ± 12.3 nmol/mg protein. (h–m) NAC (100 mg/kg/day) prevents ovariectomy-induced bone loss in mice. Indices of bone resorption and bone formation show that while ovariectomy caused a reduction in bone volume (h), this was prevented by NAC. NAC also normalized the number of osteoclasts per millimeter of the bone surface (i), the percentage of bone surface that was covered by osteoclasts (j), and the percentage of bone surface that showed a crenated, eroded surface characteristic of osteoclastic activity (k). NAC also reversed the ovariectomy-induced increase in osteoblast numbers (l) and the percentage of surface that was covered by osteoblasts (m). *P < 0.05 versus other groups. Data expressed as mean ± SEM. Oc, osteoclast; ES/BS(%), percentage of bone surface that shows an eroded surface appearance; Ob, osteoblast.