Rude R K, Gruber H E, Norton H J, Wei L Y, Frausto A, Kilburn J
University of Southern California and the Orthopaedic Hospital, 1975 Zonal Ave., GNH 6602, Los Angeles, CA 90089-9317, USA.
Osteoporos Int. 2006;17(7):1022-32. doi: 10.1007/s00198-006-0104-3. Epub 2006 Apr 7.
The objective of this study was to determine the effect of a moderate reduction of dietary magnesium [50% of nutrient requirement (50% NR)] on bone and mineral metabolism in the rat, and to explore possible mechanisms for the resultant reduced bone mass.
Female rats were 6 weeks of age at the start of study. Serum magnesium (Mg), calcium (Ca), parathyroid hormone (PTH), 1,25(OH)(2)-vitamin D, alkaline phosphatase, osteocalcin, and pyridinoline were measured during the study at 3- and 6-month time points in control (dietary Mg of 100% NR) and Mg-deficient animals (dietary Mg at 50% NR). Femurs and tibias were also collected for mineral content analyses, micro-computerized tomography, histomorphometry, and immunohistochemical localization of substance P, TNFalpha, and IL-1beta at 3 and 6 months.
Although no significant change in serum Mg was observed, Mg deficiency developed, as assessed by the reduction in bone Mg content at the 3- and 6-month time points (0.69+/-0.05 and 0.62+/-0.04% ash, respectively, in the Mg depletion group compared to 0.74+/-0.04 and 0.67+/-0.04% ash, respectively, in the control group; p=0.0009). Hypercalcemia did not develop. Although serum Ca level remained in the normal range, it fell significantly with Mg depletion at 3 and 6 months (10.4+/-0.3 and 9.6+/-0.3 mg/dl, respectively, compared to 10.5+/-0.4 and 10.1+/-0.6 mg/dl, respectively, in the control group; p=0.0076). The fall in serum Ca in the Mg-depleted animals was associated with a fall in serum PTH concentration between 3 and 6 months (603+/-286 and 505+/-302 pg/ml, respectively, although it was still higher than the control). The serum 1,25(OH)(2)-vitamin D level was significantly lower in the Mg depletion group at 6 months (10.6+/-7.1 pg/ml) than in the control (23.5+/- 12.7 pg/ml) (p<0.01 by the t-test). In Mg-deficient animals, no difference was noted in markers of bone turnover. Trabecular bone mineral content gain was less over time in the distal femur with Mg deficiency at 3 and 6 months (0.028+/-0.005 and 0.038+/-0.007 g, respectively, compared to 0.027+/-0.004 and 0.048+/-0.006 g, respectively, in the control group; p<0.005). Histomorphometry at these time points demonstrated decreased trabecular bone volume (15.76+/-1.93 and 14.19+/-1.85%, respectively, compared to 19.24+/-3.10 and 17.30+/-2.59%, respectively, in the control group; p=0.001). Osteoclast number was also significantly increased with Mg depletion (9.07+/-1.21 and 13.84+/-2.06, respectively, compared to 7.02+/-1.89 and 10.47+/-1.33, respectively, in the control group; p=0.0003). Relative to the control, immunohistochemical staining intensity of the neurotransmitter substance P and of the cytokines TNFalpha and IL-1beta was increased in cells of the bone microenvironment in the Mg depletion group, suggesting that inflammatory cytokines may contribute to bone loss.
These data demonstrate that Mg intake of 50% NR in the rat causes a reduced bone mineral content and reduced volume of the distal femur. These changes may be related to altered PTH and 1,25(OH)(2)-vitamin D formation or action as well as to an increase release of substance P and the inflammatory cytokines TNFalpha and IL-1beta.
本研究的目的是确定适度减少饮食中的镁（达到营养需求的50%[50%NR]）对大鼠骨骼和矿物质代谢的影响，并探讨导致骨量减少的可能机制。
研究开始时雌性大鼠为6周龄。在研究期间，于3个月和6个月时间点测量对照组（饮食中镁含量为100%NR）和缺镁动物（饮食中镁含量为50%NR）的血清镁（Mg）、钙（Ca）、甲状旁腺激素（PTH）、1,25(OH)₂-维生素D、碱性磷酸酶、骨钙素和吡啶啉。在3个月和6个月时还收集股骨和胫骨用于矿物质含量分析、微型计算机断层扫描、组织形态计量学以及P物质、TNFα和IL-1β的免疫组织化学定位。
尽管血清镁未观察到显著变化，但缺镁情况出现，这通过3个月和6个月时间点骨镁含量的降低得以评估（缺镁组分别为0.69±0.05%和0.62±0.04%灰分，对照组分别为0.74±0.04%和0.67±0.04%灰分；p = 0.0009）。未出现高钙血症。尽管血清钙水平保持在正常范围内，但在3个月和6个月时随着镁缺乏而显著下降（分别为10.4±0.3和9.6±0.3mg/dl，对照组分别为10.5±0.4和10.1±0.6mg/dl；p = 0.0076）。缺镁动物血清钙的下降与3至6个月期间血清PTH浓度的下降相关（分别为603±286和505±302pg/ml，尽管仍高于对照组）。缺镁组6个月时血清1,25(OH)₂-维生素D水平显著低于对照组（10.6±7.1pg/ml）（t检验，p<0.01）。在缺镁动物中，骨转换标志物未观察到差异。3个月和6个月时，缺镁的远端股骨小梁骨矿物质含量随时间增加较少（分别为0.028±0.005和0.038±0.007g，对照组分别为0.027±0.004和0.048±0.006g；p<0.005）。这些时间点的组织形态计量学显示小梁骨体积减少（分别为15.76±1.93%和14.19±1.85%，对照组分别为19.24±3.10%和17.30±2.59%；p = 0.001）。破骨细胞数量也随着镁缺乏而显著增加（分别为9.07±1.21和13.84±2.06，对照组分别为7.02±1.89和10.47±1.33；p = 0.0003）。相对于对照组，缺镁组骨微环境细胞中神经递质P物质以及细胞因子TNFα和IL-1β的免疫组织化学染色强度增加，表明炎性细胞因子可能导致骨质流失。
这些数据表明，大鼠摄入50%NR的镁会导致骨矿物质含量降低以及远端股骨体积减小。这些变化可能与PTH和1,25(OH)₂-维生素D形成或作用的改变以及P物质和炎性细胞因子TNFα和IL-1β释放增加有关。
