Mastaglia Silvina R, Pellegrini Gretel G, Mandalunis Patricia M, Gonzales Chaves Macarena M, Friedman Silvia M, Zeni Susana N
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Sección Osteopatías Médicas del Hospital de Clínicas J. de San Martín, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Bone. 2006 Oct;39(4):837-44. doi: 10.1016/j.bone.2006.04.015. Epub 2006 Jun 12.
The present study was carried out to obtain an experimental model of vitamin D (vit D) insufficiency and established osteopenia (experiment 1) to then investigate whether vit D status, i.e. normal or insufficient, interferes with bone mass recovery resulting from bisphosphonate therapy (experiment 2). Rats (n = 40) underwent OVX (n = 32) or a sham operation (n = 8). The first 15 days post-surgery, all groups were kept under fluorescent tube lighting and fed a diet containing 200 IU% vit D (+D). They were then assigned during an additional 45 days to receive either +D or a diet lacking vit D (-D) and kept under 12 h light/dark cycles using fluorescent or red lighting. Serum 25HOD was significantly lower in -D rats (P < 0.0001). The type of lighting did not induce differences in 25OHD, calcium (sCa), phosphorus (sP), bone alkaline phosphatase (b-AL), CTX, bone density or histology. No osteoid was observed in undecalcified bone sections. Experiment 2 (105 days): rats were fed either +D or -D according to experiment 1 and were treated with either placebo or 16 mug olpadronate (OPD)/100 g rat/week during the last 45 days. Whereas 25HOD was significantly lower (P < 0.0001) in -D/OPD than in +D/OPD rats, no significant differences in sCa, sP, b-AL or CTX were observed. OPD prevented the loss of lumbar spine (LS) and proximal tibia (PT) BMD and the decrease in bone volume (BV/TV) (P < 0.05) and in the number of trabeculae observed in untreated rats. However, +D/OPD animals presented significantly higher values of LS BMD, PT BMD and BV/TV than -D/OPD rats (P < 0.05). No osteoid was observed in undecalcified sections of bone. In summary, this is the first experimental study to provide evidence that differences in vit D status may affect the anticatabolic response to bisphosphonate treatment. However, the molecular mechanism through which vit D insufficiency reduces the effect of the aminobisphosphonate remains to be defined.
本研究旨在获得维生素D（vit D）不足和建立骨质减少的实验模型（实验1），进而研究vit D状态，即正常或不足，是否会干扰双膦酸盐治疗引起的骨量恢复（实验2）。大鼠（n = 40）接受卵巢切除术（n = 32）或假手术（n = 8）。术后的前15天，所有组均饲养在荧光灯管照明下，并喂食含200 IU% vit D的饮食（+D）。然后在接下来的45天里，它们被分配接受+D饮食或缺乏vit D的饮食（-D），并在荧光或红色照明下保持12小时光照/黑暗循环。-D组大鼠的血清25HOD显著降低（P < 0.0001）。光照类型未引起25OHD、钙（sCa）、磷（sP）、骨碱性磷酸酶（b-AL）、CTX、骨密度或组织学的差异。在未脱钙骨切片中未观察到类骨质。实验2（105天）：根据实验1，大鼠喂食+D或-D饮食，并在最后45天用安慰剂或16 μg奥帕膦酸盐（OPD）/100 g大鼠/周进行治疗。虽然-D/OPD组的25HOD显著低于+D/OPD组大鼠（P < 0.0001），但在sCa、sP、b-AL或CTX方面未观察到显著差异。OPD可防止未治疗大鼠腰椎（LS）和胫骨近端（PT）骨密度的降低以及骨体积（BV/TV）的减少（P < 0.05）和小梁数量的减少。然而，+D/OPD组动物的LS骨密度、PT骨密度和BV/TV值显著高于-D/OPD组大鼠（P < 0.05）。在未脱钙骨切片中未观察到类骨质。总之，这是第一项提供证据表明vit D状态差异可能影响双膦酸盐治疗的抗分解代谢反应的实验研究。然而，vit D不足降低氨基双膦酸盐作用的分子机制仍有待确定。
