在对去卵巢食蟹猴进行9个月的治疗中,米诺膦酸通过增加骨密度改善椎骨强度。
Minodronic acid ameliorates vertebral bone strength by increasing bone mineral density in 9-month treatment of ovariectomized cynomolgus monkeys.
作者信息
Tanaka Makoto, Mori Hiroshi, Kawabata Kazuhito, Mashiba Tasuku
机构信息
Research Promotion, Ono Pharmaceutical Co., Ltd., Shimamoto, Osaka 618-8585, Japan.
Discovery Research Laboratories, Ono Pharmaceutical Co., Ltd., Shimamoto, Osaka 618-8585, Japan.
出版信息
Bone. 2016 Jul;88:157-164. doi: 10.1016/j.bone.2016.05.001. Epub 2016 May 4.
The effect of treatment for 9months with minodronic acid, a nitrogen-containing bisphosphonate, on vertebral mechanical strength was examined in ovariectomized (OVX) cynomolgus monkeys. Forty skeletally mature female monkeys were randomized into four OVX groups and one sham group (n=8) based on lumbar bone mineral density (BMD). OVX animals were treated orally with 15 and 150μg/kg QD of minodronic acid or 500μg/kg QD alendronate as a reference drug. Measurements of bone turnover markers and lumbar BMD were conducted at 0, 4 and 8months. Measurements of bone mechanical strength and minodronic acid concentration in vertebral bodies were also performed. OVX resulted in a decrease in lumbar BMD and an increase in bone turnover markers at 4 and 8months, compared to the sham group, and the ultimate load on the lumbar vertebra was decreased in OVX animals. Minodronic acid and alendronate prevented the OVX-induced increase in bone turnover markers and decrease in lumbar BMD. Minodronic acid at 150μg/kg increased the ultimate load on lumbar vertebra compared to untreated OVX animals. Regression analysis revealed that the ultimate load was correlated with lumbar BMD and bone mineral content (BMC), and most strongly with the increase in lumbar BMD and BMC over 8months. In a separate analysis within the sham-OVX controls and minodronic acid and alendronate treatment groups, the ultimate loads were also correlated with BMD and BMC. The load-BMD (BMC) correlation in the minodronic acid group showed a trend for a shift to a higher load from the basal relationship in the sham-OVX controls. These results indicate that treatment with minodronic acid for 9months increases vertebral mechanical strength in OVX monkeys, mainly by increasing BMD and BMC.
在去卵巢(OVX)食蟹猴中研究了含氮双膦酸盐米诺膦酸治疗9个月对椎骨机械强度的影响。40只骨骼成熟的雌性猴子根据腰椎骨密度(BMD)随机分为4个OVX组和1个假手术组(n = 8)。OVX动物口服15和150μg/kg每日一次的米诺膦酸或500μg/kg每日一次的阿仑膦酸钠作为参比药物。在0、4和8个月时测量骨转换标志物和腰椎BMD。还进行了椎骨机械强度和椎体中米诺膦酸浓度的测量。与假手术组相比,OVX导致4个月和8个月时腰椎BMD降低以及骨转换标志物增加,并且OVX动物腰椎椎体的极限负荷降低。米诺膦酸和阿仑膦酸钠可防止OVX诱导的骨转换标志物增加和腰椎BMD降低。与未治疗的OVX动物相比,150μg/kg的米诺膦酸增加了腰椎椎体的极限负荷。回归分析显示,极限负荷与腰椎BMD和骨矿物质含量(BMC)相关,并且与8个月内腰椎BMD和BMC的增加相关性最强。在假手术-OVX对照组以及米诺膦酸和阿仑膦酸钠治疗组的单独分析中,极限负荷也与BMD和BMC相关。米诺膦酸组的负荷-BMD(BMC)相关性显示出从假手术-OVX对照组的基础关系向更高负荷转变的趋势。这些结果表明,米诺膦酸治疗9个月可增加OVX猴子的椎骨机械强度,主要是通过增加BMD和BMC来实现。