Expansion
Osteoblasts build, osteoclasts resorb, coupled through RANK ligand
Expansion
- Osteoblasts form bone and express RANK ligand
- Osteoclasts resorb bone and carry the RANK receptor
- Osteoprotegerin, also from osteoblasts, is a decoy receptor that blocks RANK ligand and so inhibits resorption
The ratio of RANK ligand to osteoprotegerin therefore sets the balance, and it is the final common pathway for most influences on bone.
Increase resorption: parathyroid hormone (when continuously elevated), thyroid hormone, cortisol, cytokines in inflammation, and oestrogen deficiency.
Decrease resorption: oestrogen, calcitonin, and osteoprotegerin.
Drug mechanisms follow directly:
- Bisphosphonates: taken up by osteoclasts and induce their apoptosis
- Denosumab: a monoclonal antibody against RANK ligand, mimicking osteoprotegerin
- Teriparatide: intermittent parathyroid hormone, which paradoxically favours formation over resorption, unlike continuous exposure
- Romosozumab: blocks sclerostin, increasing formation
The contrast between intermittent and continuous parathyroid hormone is the key conceptual point.