In a phase 1 study, single injections of romosozumab (a humanized monoclonal anti-sclerostin antibody, stimulated bone formation, decreased bone resorption, and increased bone mineral density. Now, researchers have evaluated the efficacy and safety of romosozumab in postmenopausal women with low bone mass.
Osteoporosis is characterized by low bone mass and defects in microarchitecture that decrease bone strength and increase risk of fracture. Antiresorptive drugs increase bone mineral density and prevent the progression of structural damage. However, bone structure may not be restored. Sclerostin is an osteocyte-secreted glycoprotein, which has been identified as a pivotal regulator of bone formation.
Studies of the molecular effects of sclerostin support the theory that blocking the action of sclerostin results in positive effects on the bones. People with a genetic deficiency of sclerostin have high bone mass, resistance to fractures, and increased bone strength. Researchers found that in estrogen-deficient rat and monkey models of postmenopausal osteoporosis, treatment with anti-sclerostin antibodies restored bone mass and bone strength.
The phase 2 study, involved over 400 participants from 28 study centers internationally. Researchers found that inhibiting sclerostin with romosozumab induced large increases in bone formation markers, decreased a bone-resorption marker, and increased bone mineral density when the drug was given by subcutaneous injections at one month or three month intervals.