Drug With New Mode of Action Boosts Lumbar BMD

January 6, 2014

New in the New England Journal: Romosozumab, whose target is sclerostin, increased BMD more than teriperatide and alendronate in a phase 2 trial involving postmenopausal women. Also, a puzzle: A rheumatic cause of abdominal pain.

New articles relevant to rheumatology in the top general-interest journals.

Romosozumab in Postmenopausal Women with Low Bone Mineral DensityNew England Journal of Medicine, January 1, 2014

Sclerostin Inhibition for Osteoporosis - A New ApproachNew England Journal of Medicine, January 1, 2014

Romosozumab significantly improved bone mineral density (BMD) and bone formation, and decreased bone resorption, in a phase 2 trial of 419 postmenopausal women with low vone mineral density (BMD).

The study compared romosozumab at three doses, oral subcutaneous teriparatide, alendronate, or subcutaneous placebo for 12 months.

BMD at the lumbar spine, the primary endpoint, increased 11.3% at the highest dose of romosozumab, 7.1% with teriparatide, 4.1% with alendronate, and decreased by 0.1% with placebo.

The pattern of bone-turnover markers was surprising. There was a brief anabolic stimulation, coupled with chronic suppression of bone resorption.

Romosozumab is a humanized monoclonal antibody against sclerostin, which inhibits Wnt and bone morphogenic protein signaling pathways on osteoblasts. Humans (and mice) with genetic deficiencies of sclerostin have high bone mass, increased bone strength, and resistance to fracture.

Also in NEJM last week:

An Unusual Case of Abdominal PainNew England Journal of Medicine, January 2, 2014

A patient presented with abdominal pain occurring in different distributions over time. A screen for antineutrophil cytoplasmic antibodies and complement were normal. Blood pressure was 188/116 mm Hg. Creatinine was 1.5 mg per deciliter. C-reactive protein was 193 mg per deciliter. A CT scan of the kidneys revealed infarcts in both kidneys suggestive of scarring.

Abdominal angiography revealed microaneurysms in multiple vascular territories, including both kidneys and the hepatic and superior mesenteric arteries, consistent with polyarteritis nodosa. Treatment with intravenous methylprednisolone and oral cyclophosphamide produced a decline in creatinine and complete resolution of the abdominal pain.