Fig. 4 ∣. The effects of antiresorptive versus senolytic therapies on bone metabolism.

a ∣ Senescent cells accumulate in the bone microenvironment with ageing, where they increase bone resorption by osteoclasts and reduce bone formation by osteoblasts. Antiresorptive drugs inhibit or eliminate osteoclasts and decrease bone resorption. Owing to coupling between osteoclasts and osteoblasts in the bone remodelling cycle, bone formation is also reduced. b ∣ Senolytic therapy reduces the burden of senescent cells, which leads to a reduction in bone resorption with either increased (cortical bone) or maintained (trabecular bone) bone formation, resulting in a beneficial ‘uncoupling’ between bone resorption and bone formation. Dashed lines indicate a reduction in the adverse effects of senescent cells on osteoclasts, osteoblasts, and the coupling between osteoclasts and osteoblasts. Reprinted from REF.⁷⁵, Springer Nature Limited.