ABSTRACT
Objective To observe the effect of raloxifene, a selective estrogen receptor modulator, on osteoporosis in the osteoprotegerin (OPG) gene knock-out female and male mice. Methods Two groups of OPG gene deficient (OPG-/-) female and male mice, 20 mice in each group, were assigned to raloxifene-treated (3 mg The effect of raloxifene was evaluated by comparing the values of bone mineral density (BMD) , bone strength,histomorphometric measurement and osteoclast number between the raloxifene treated group and placebo group.Results As compared with placebo group osteoporotic manifestations were improved in OPG-/- female mice treated with raloxifene orally. BMD was increased both in lumbar vertebrae (P<0.05) and femurs (P<0.01).Bone strength was measured in femurs by three-point bending test and vertebrae by stress test. Results showed that ultimate load, ultimate stress and Young's modulus were increased both at lumbar and femur bone, suggesting decreased risk of fracture. Tartrate-resistant acid phosphatase, a marker enzyme of osteoclasts, was detected, and the number of osteoclasts declined significantly after the treatment of raloxifene. At the same time, results of histomorphometric measurements indicated that bone trabecular volume was increased and bone formation rate decreased from(8.05±4.02)mm3·mm-2·year-1 to (5.48±1.89)mm3·mm-2· year-1(P＜0.05).These findings were found in the group of OPG-/- female mice treated with reloxifene but not in male mice. Conclusions Raloxifene is effective in treating osteoporosis in female OPG-/- mice, indicating that its action is at least in part independent of OPG gene. But it is ineffective in male OPG-/- mice.
ABSTRACT
Objective To observe the bone density, serum osteoprotegerin (OPG) level,relevant parameters of bone metabolism and sex hormones in elderly men with osteoporosis before and after treatment with oral Fosamax for 3 years. Methods The serum OPG level was compared between 72 randomly selected elderly male patients with osteoporosis and age-matched healthy controls. The bone density, serum OPG level, sex hormones, serum calcium and phosphorus,parathyroid hormone (PTH), osteoealein and urine type Ⅰ collegen crosslinked N-telopeptides (NTX),urine calcium and cretinine were tested in all elderly male patients with osteoporosis before and after 3 years of oral Fosamax treatment. The role of OPG in anti-osteoporotic therapy was studied by comparison of the parameters tested during the course of treatment. Results The serum levels of OPG osteoealcin, PTH and urine NTX were obviously higher in elderly men with osteoporosis than in healthy controls [(10.56±2.56) pmol/L vs. (8.91±2.20) pmol/L, (9.544±4.40) g/L vs. (6.774±2.87)rig/L, (70.39±35.58) ng/L vs. (47.11±21.80) ng/L, (72.06±9.78) nmol/L vs. (63.36±14.61)nmol/L, all P<0.05]. After treatment with oral Fosamax , the bone density was significantly increased. However, serum levels of OPG[(8.23±2.96)pmol/L], osteocalcinE(6.18±2.27)μg/L],PTH[(40.46±14.43) ng/L] and urine NTX[(64.83±11.40) nmol/L] were significantly decreased after treatment (all P<0.05). Spearman analysis showed that the improvement of bone density after treatment was closely associated with serum OPG level. Conclusions Serum OPG level in elderly patients with osteoporosis is much higher than that in control group. The improvement in bone density after treatment is associated with the decrease in OPG level. Bone density and relevant parameters of bone metabolism can be improved in elderly male patients with osteoporosis by using oral Fosamax.