Carvas J S B, Pereira R M R, Caparbo V F, Fuller P, Silveira C A, Lima L A P, Bonfa E, Mello S B V
Rheumatology Division, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, 455, 3 masculine andar, Reumatologia, São Paulo, SP, 0124-6903, Brazil.
Osteoporos Int. 2010 Oct;21(10):1723-9. doi: 10.1007/s00198-009-1125-5. Epub 2009 Dec 9.
This study evaluates the effect of zoledronic acid (ZOL) on the osseointegration of titanium implants in rabbits with glucocorticoid (GC)-induced bone loss, and our findings demonstrated that a single dose of ZOL is able to reverse the detrimental effects of GCs on the osseointegration of titanium implants.
The purpose of this study is to evaluate the effect of ZOL on the osseointegration of titanium implants in rabbits with GC-induced bone loss.
Three groups of six NZW rabbits were treated for 18 weeks with saline (SALINE), GC (methylprednisolone, 0.35 mg/kg three times a week), or GC + ZOL (methylprednisolone + single dose of ZOL, 0.1 mg/kg). The animals received a titanium implant in the left tibia after 6 weeks and were killed at the 18th week. Bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry at baseline, eighth week (W8), and 18th week (W18) after treatment to determine the change upon treatment (BMD). Histomorphometric and serum bone alkaline phosphatase analysis (BAP) were also performed.
At W8, GC group had a significant reduction in lumbar spine and tibia BMD compared with SALINE (p = 0.003 and p = 0.000), as also observed for GC + ZOL group (p = 0.014 and p = 0.003) just 2 weeks after ZOL treatment. In contrast, at W18, the GC + ZOL had an evident BMD rescue with similar lumbar spine and tibia BMD compared with SALINE (0.043 +/- 0.006 vs. 0.055 +/- 0.009 g/cm(2), p = 0.457 and 0.027 +/- 0.003 vs. 0.041 +/- 0.011 g/cm(2), p = 0.232) and a significantly higher BMD compared with the GC (p = 0.024 and p = 0.001). Histomorphometry revealed that osseointegration was significantly reduced in GC (tibia cortical thickness and diameter, bone-implant contact, total and peri-implant bone area) whereas GC + ZOL had these parameters similar to SALINE (p > 0.05). Likewise, ZOL reversed the BAP alteration induced by GC.
Our findings demonstrated that a single dose of ZOL is able to reverse the detrimental effects of glucocorticoids on the osseointegration of titanium implants, suggesting that ZOL therapy may improve the outcome of bone implants in patients with glucocorticoid-induced osteoporosis.
本研究评估唑来膦酸(ZOL)对糖皮质激素(GC)诱导的兔骨丢失模型中钛植入物骨整合的影响,我们的研究结果表明,单次剂量的ZOL能够逆转GC对钛植入物骨整合的有害影响。
本研究的目的是评估ZOL对GC诱导的兔骨丢失模型中钛植入物骨整合的影响。
将三组,每组六只新西兰白兔分别用生理盐水(SALINE)、GC(甲基强的松龙,0.35mg/kg,每周三次)或GC + ZOL(甲基强的松龙 + 单次剂量的ZOL,0.1mg/kg)治疗18周。6周后,动物在左胫骨植入钛植入物,并在第18周处死。在治疗后的基线、第8周(W8)和第18周(W18)用双能X线吸收法测量骨密度(BMD),以确定治疗后的变化(BMD)。还进行了组织形态计量学和血清骨碱性磷酸酶分析(BAP)。
在W8时,与SALINE组相比,GC组腰椎和胫骨的BMD显著降低(p = 0.003和p = 0.000),在ZOL治疗仅2周后的GC + ZOL组也观察到类似情况(p = 0.014和p = 0.003)。相比之下,在W18时,GC + ZOL组的BMD明显恢复,腰椎和胫骨的BMD与SALINE组相似(0.043±0.006 vs. 0.055±0.009g/cm²,p = 0.457;0.027±0.003 vs. 0.041±0.011g/cm²,p = 0.232),且与GC组相比BMD显著更高(p = 0.024和p = 0.001)。组织形态计量学显示,GC组的骨整合显著降低(胫骨皮质厚度和直径、骨 - 植入物接触、总骨面积和植入物周围骨面积),而GC + ZOL组的这些参数与SALINE组相似(p>0.05)。同样,ZOL逆转了GC诱导的BAP改变。
我们的研究结果表明,单次剂量的ZOL能够逆转糖皮质激素对钛植入物骨整合的有害影响,这表明ZOL治疗可能改善糖皮质激素诱导的骨质疏松症患者骨植入物的治疗效果。