Romosozumab, an anti-Sclerostin biologic, is poised to be the next big thing in Osteoporosis treatment, demonstrated in trials to match if not better Teriparatide as a bone former.
Unfortunately, and for reasons yet unclear, it appears to worsen joint inflammation and damage in animal models of RA.
A possible mechanism is as follows:
Sclerostin is produced by Osteocytes residing deep in bone matter, to dampen bone surface residing Osteoblasts from overproducing new bone unnecessarily. It is thus an anti-growth factor inhibiting through a cell’s Wnt signaling pathway.
Apparently, inflamed synovial cells also produce Sclerostin to limit its own growth and joint destruction (a normal functioning immune system is very into “balance”, like The Force).
So, when you administer an anti-Sclerostin antibody, you not only unleash the Osteoblasts to form new bone, you also take the brakes off the marauding RA pannus (inflammatory Synoviocytes) to destroy the joint.