TNFα receptor knockout in mice reduces adverse effects of magnesium deficiency on bone

Abstract

Epidemiologic studies have linked low dietary magnesium (Mg) intake to osteoporosis. Dietary Mg restriction in animal models has demonstrated a decrease in bone mass and an increase in skeletal fragility. The exact mechanism for the decrease in bone mass is not clear but a decrease in osteoblast number and an increase in osteoclast number (Oc.No/B.Pm) suggests an uncoupling of bone formation and bone resorption favoring skeletal loss. Mg depletion results in an increase in inflammatory cytokines, which could explain the increase in bone resorption. We have previously demonstrated an increase in TNFα in bone from Mg deficient rodents. Here we report results of a 3 week study of a low magnesium (LM) diet and normal Mg diet in 35-day-old TNFα receptor knockout mice (TNF-r-KO) versus wild type (WT) control mice. Our results indicated that a LM diet resulted in a greater increase in Oc.No/B.Pm in the WT mice, with a trend toward greater eroded bone perimeter, as compared to TNF-r-KO. These findings suggest that TNFα may play a role in Mg deficiency-induced bone loss.

Keywords::

• magnesium
• osteoporosis
• magnesium deficiency
• TNFα receptor
• knockout mice

Acknowledgements

This research was supported by funds from the Orthopaedic Hospital, Los Angeles, CA, Carolinas Medical Center, Charlotte, NC, and the Regional Bone Center, Helen Hayes Hospital, West Haverstraw, NY.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.