MICE LACKING THE TYPE-I INTERLEUKIN-1 RECEPTOR DO NOT LOSE BONE MASS AFTER OVARIECTOMY

We measured the effects of ovariectomy on the bone mass of mice that l acked type I interleukin-1 receptor (IL-1 R1 -/- mice) in two genetic backgrounds (C57BL/6 x 129/Sv and C57BL/6) to investigate the role of interleukin-1 in the actions of estrogen on bone. At three weeks after surgery, ovariectomized wild-type mice decreased trabecular bone volu me in the proximal humerus by 70% in a C57BL/6 x 129/Sv background and 48% in a C57BL/6 background compared to sham-operated controls. In co ntrast, there was no significant decrease in trabecular bone mass in I L-1 R1 -/- mice after ovariectomy. The estrogen status of all groups w as confirmed by measurement of uterine wet weight. These results demon strate that a functional IL-1 response pathway is required for mice to lose trabecular bone mass after ovariectomy in this model and they im ply that IL-1 is an important mediator of the effects of ovariectomy o n bone mass. Hence, therapeutic interventions that block the effects o f IL-1 on bone may be beneficial for treating diseases of rapid bone l oss such as post-menopausal osteoporosis.