Abstract
MR McClung, A Grauer, Boonen S, et al.
N Engl J Med 2014; 370: 412–420
Romosozumab is a humanised monoclonal antibody to sclerostin, an osteocyte-derived glycoprotein that inhibits osteoblast proliferation and function, and thus decreases bone formation.
This article presents the results of an industry-sponsored phase 2, multicentre, randomised, placebo-controlled trial that compared increasing doses of subcutaneous romosozumab with two comparator drugs – oral alendronate (70 mg weekly) and subcutaneous teriparatide (20 µg daily), as well as placebo in healthy postmenopausal women with osteopenia. The primary endpoint was change in bone mineral density (BMD) at the lumbar spine at 12 months. Secondary endpoints included changes in BMD at other sites, and markers of bone turnover (serum P1NP, osteocalcin and BALP (formation), and β-CTX (resorption)).
All dose levels of romosozumab were associated with striking increases in BMD at all sites except the distal radius (no change). Indeed, at the highest dose of 210 mg per month, BMD at the spine increased by 11.3% compared to 4.1% with alendronate and 7.1% with teriparatide. Changes in bone markers differ from existing osteoporosis therapies. Formation markers rose rapidly after the initial dose, but then declined to baseline or below, whereas β-CTX dropped initially and remained below baseline at 12 months in those receiving monthly doses of the drug.
Limitations include small study groups, short trial duration and a non-diseased study population. A phase 3 clinical trial is currently underway in postmenopausal osteoporotic women which will hopefully address whether BMD increases translate into reduced fracture rates.