Particles generated from wear of
prosthesis joint bearing surfaces induce
inflammation-mediated periprosthetic
bone resorption (
osteolysis). Morbidly obese
leptin-deficient ob/ob mice are resistant to
polyethylene particle-induced bone loss, suggesting that
leptin, a
hormone produced by adipocytes that circulates in concentrations proportional to total body adiposity, increases
osteolysis. To confirm that particles induce less
osteolysis in
leptin-deficient mice after controlling for cold stress (room temperature)-induced bone loss, ob/ob mice on a C57BL/6 (B6) background and colony B6 wildtype (WT) mice housed at thermoneutral temperature were randomized to control or particle treatment groups (N = 5/group).
Polyethylene particles were implanted over calvaria and mice sacrificed 2 weeks later. Compared to particle-treated WT mice, particle-treated ob/ob mice had lower
osteolysis score, less infiltration of immune cells, and less woven bone formation. To determine the role of
leptin in particle-induced
osteolysis, ob/ob mice were randomized into one of 4 groups (n = 6-8/group): (1) control, (2) particles, (3) particles + continuous
leptin (osmotic pump, 6 μg/d), or (4) particles + intermittent
leptin (daily injection, 40 μg/d).
Leptin treatment increased particle-induced
osteolysis in ob/ob mice, providing evidence that the adpiokine may play a role in
inflammation-driven bone loss. Additional research is required to determine whether altering
leptin levels within the physiological range results in corresponding changes in
polyethylene-particle-induced
osteolysis.