Targeting natural inhibitors of bone formation heralds a new direction in the treatment of osteoporosis. Results from an international phase II clinical trial published in the New England Journal of Medicine show that the use of romosozumab – a humanized monoclonal antibody targeting sclerostin – increases bone mineral density (BMD) in individuals with low bone mass. Sclerostin is a glycoprotein produced by osteoblasts that inhibits osteoblast function through the Wnt and bone-forming protein signaling systems, resulting in decreased bone formation. Because sclerostin is confined to the skeletal system, inhibition of this protein may be an ideal direction for targeted therapeutic intervention. Preliminary results from a 28-center randomized controlled phase II clinical study showed significant alterations in BMD at baseline in the lumbar spine. A second focus of the study included the percentage of changes in BMD in terms of anatomical structure and biochemical indicators of bone transformation. The study evaluated five different doses of romosozumab administered subcutaneously and observed over 12 months in 419 postmenopausal women (mean age 67 years) with reduced bone mass or osteoporosis. In addition to comparing romosozumab with placebo, it was also compared with two drugs commonly used to treat osteoporosis, alun phosphate sodium and teriparatide. The investigators found that all doses of romosozumab significantly increased spine and hip BMD. Also, the largest dose (210 mg/month) of romosozumab (11.3%) significantly increased lumbar spine BMD after 12 months of dosing compared to alendronate (4.1%) and teriparatide (7.1%), while over the entire observation time window, the placebo group BMD was reduced by 0.1%. Biochemical markers of bone formation increased during the first 6 months of treatment with romosozumab but then decreased back to baseline levels; levels of bone resorption markers showed a small decrease after 12 months of romosozumab treatment. Injection site reactions were more frequent in the romosozumab group compared to the placebo group. The incidence of serious adverse reactions was 7% in the romosozumab group compared with 14% in the placebo group. Carolyn Becker, a specialist at Brigham and Woman Hospital in Boston, confirmed the study’s new findings and the future potential for targeted osteoporosis treatment. The