Dietary phosphorus consumption alters T cell populations, cytokine production, and bone volume in mice

Abstract

The intake of dietary phosphate far exceeds recommended levels however the long-term health consequences remain relatively unknown. Here, the chronic physiological response to sustained elevated and reduced dietary phosphate consumption was investigated in mice. Although serum phosphate levels were brought into homeostatic balance, the prolonged intake of a high-phosphate diet dramatically and negatively impacted bone volume, generated a sustained increase in the phosphate responsive circulating factors, FGF23, PTH, osteopontin and osteocalcin, and produced a chronic low grade inflammatory state in the bone marrow, marked by increased numbers of T cells expressing IL-17a, RANKL, and TNFα. In contrast, a low-phosphate diet preserved trabecular bone while increasing cortical bone volume over time and reduced inflammatory T cell populations. Cell-based studies identified a direct response of T cells to elevated extracellular phosphate. Neutralizing antibodies to pro-osteoclastic cytokines RANKL, TNFα, and IL-17a blunted the high-phosphate diet induced bone loss identifying bone resorption as a regulatory mechanism. Collectively, this study illuminates that habitual consumption of a high-phosphate diet in mice induces chronic inflammation in bone even in the absence of elevated serum phosphate. Further, the study supports the concept that a reduced phosphate diet may be a simple, yet effective strategy to reduce inflammation and improve bone health during aging.

Nutrition-Based Support for Osteoporosis in Postmenopausal Women: A Review of Recent Evidence

“…61 Experimental human studies have shown that excessive phosphorus intake in women with low calcium intake is associated with increased serum PTH concentrations and bone resorption. 48 , 49 Therefore, following a healthy diet with limited consumption of ultra-processed foods would favour the maintenance of an appropriate calcium/phosphorus ratio.…”

“…[52][53][54] Additionally, studies have shown a positive correlation between dietary folate intake and BMD. 66 48,49 Limit the consumption of ultra-processed foods Magnesium Enzymatic cofactor in bone matrix synthesis Its deficiency alters PTH secretion, reduces vitamin D levels, and increases bone resorption 50,51 Recommend adequate consumption of nuts and legumes Vitamins B Involvement in homocysteine metabolism Deficiency of B6, B9, and B12 leads to increased blood homocysteine levels, which is a risk factor for osteoporosis [52][53][54] More scientific evidence needed Vitamin C Participation in the formation of osteoblasts, as well as in collagen synthesis 55 Ensure proper intake of fruits and vegetables…”