Category: signaling
Bone remodeling balance: osteoclasts (resorption) + osteoblasts (formation). RANKL (from osteoblasts/osteocytes) → RANK on osteoclast precursors → osteoclast differentiation + activation; OPG (osteoprotegerin) is a soluble decoy that buffers RANKL. PTH increases bone turnover (continuous = catabolic; intermittent pulsatile = anabolic — the basis of teriparatide therapy). Sclerostin (from osteocytes) inhibits Wnt signaling → suppresses osteoblast activity; sclerostin-i (romosozumab) is anabolic. Bisphosphonates (alendronate, risedronate, ibandronate, zoledronate) are pyrophosphate analogs that bind hydroxyapatite + are taken up by resorbing osteoclasts → inhibit farnesyl-PP synthase (N-containing BPs) → apoptosis. Denosumab is an anti-RANKL mAb that blocks osteoclast differentiation. Calcitonin (older, weaker antiresorptive) acts at osteoclast calcitonin-R. Cross-link: calcium_phosphate_pth_axis.