CD28 and osteoporosis: Besides, in an animal model of osteoporosis induced by ovariectomy, when the immunoprotective effect of the neutralizing antibodies anti-RANKL, anti-TNF-α, or anti-IL-17A was compared, IL-17A blockade led to a more potent reduction in the number of CD4+CD28- T lymphocytes as compared with RANKL or TNF-α blockade, which translated into an improvement in skeletal parameters and demonstrated the key role for IL-17A in the CD4+ T-cell senescence [72].