Bajwa Nikita M, Sanchez Cheryl P, Lindsey Richard C, Watt Heather, Mohan Subburaman
Musculoskeletal Disease Center, VA Loma Linda Healthcare System, 11201 Benton Street, Loma Linda, CA, 92357, USA.
Department of Pediatrics, Loma Linda University, Loma Linda, CA, 92354, USA.
BMC Nephrol. 2018 Feb 2;19(1):24. doi: 10.1186/s12882-018-0822-8.
Changes in mineral metabolism and bone structure develop early in the course of chronic kidney disease and at end-stage are associated with increased risk of fragility fractures. The disruption of phosphorus homeostasis leads to secondary hyperparathyroidism, a common complication of chronic kidney disease. However, the molecular pathways by which high phosphorus influences bone metabolism in the early stages of the disease are not completely understood. We investigated the effects of a high phosphorus diet on bone and mineral metabolism using a 5/6 nephrectomy model of chronic kidney disease.
Four-week old rats were randomly assigned into groups: 1) Control with standard diet, 2) Nephrectomy with standard rodent diet, and 3) Nephrectomy with high phosphorus diet. Rats underwent in vivo imaging at baseline, day 14, and day 28, followed by ex vivo imaging.
Cortical bone density at the femoral mid-diaphysis was reduced in nephrectomy-control and nephrectomy-high phosphorus compared to control rats. In contrast, trabecular bone mass was reduced at both the lumbar vertebrae and the femoral secondary spongiosa in nephrectomy-high phosphorus but not in nephrectomy-control. Reduced trabecular bone volume adjusted for tissue volume was caused by changes in trabecular number and separation at day 35. Histomorphometry revealed increased bone resorption in tibial secondary spongiosa in nephrectomy-control. High phosphorus diet-induced changes in bone microstructure were accompanied by increased serum parathyroid hormone and fibroblast growth factor 23 levels.
Our study demonstrates that changes in mineral metabolism and hormonal dysfunction contribute to trabecular and cortical bone changes in this model of early chronic kidney disease.
矿物质代谢和骨结构的变化在慢性肾脏病病程早期就已出现，而在终末期与脆性骨折风险增加相关。磷稳态的破坏会导致继发性甲状旁腺功能亢进，这是慢性肾脏病的常见并发症。然而，在疾病早期高磷影响骨代谢的分子途径尚未完全明确。我们使用慢性肾脏病的5/6肾切除模型研究了高磷饮食对骨和矿物质代谢的影响。
将4周龄大鼠随机分为几组：1）标准饮食对照组；2）肾切除后给予标准啮齿动物饮食组；3）肾切除后给予高磷饮食组。大鼠在基线、第14天和第28天进行体内成像，随后进行体外成像。
与对照大鼠相比，肾切除-对照组和肾切除-高磷组大鼠股骨干中段皮质骨密度降低。相反，肾切除-高磷组大鼠腰椎和股骨次级松质骨的小梁骨量减少，而肾切除-对照组未出现这种情况。在第35天时，经组织体积校正的小梁骨体积减少是由小梁数量和间距的变化引起的。组织形态计量学显示肾切除-对照组胫骨次级松质骨的骨吸收增加。高磷饮食引起的骨微结构变化伴随着血清甲状旁腺激素和成纤维细胞生长因子23水平的升高。
我们的研究表明，在这个早期慢性肾脏病模型中，矿物质代谢变化和激素功能障碍导致了小梁骨和皮质骨的改变。
