Osteoporosis – romosozumab

Published: 13-Feb-2014

Osteoporosis occurs when the rate at which new bone is being made is slower than the rate at which it is lost, with the bones becoming more prone to fracture

Osteoporosis is a common condition, particularly in post-menopausal women. It occurs when the rate at which new bone is being made is slower than the rate at which it is lost, with the bones gradually getting weaker over time. This makes them more prone to fracture; the US National Osteoporosis Foundation claims that half of all women over the age of 50 – and a quarter of all men – will have an osteoporosis-related fracture in their remaining lifetime.

Various drugs are already available to counter osteoporosis. Bisphosphonate drugs such as alendronate, etidronate and risedronate can reduce the risk of fracture, but adverse events such as ulcers in the gastrointestinal tracts often limit their use. The recombinant parathyroid hormone teriparatide and the selective oestrogen receptor modulator raloxifene can also have some benefit. And Amgen’s denosumab inhibits the RANK ligand, which is the primary signal for bone removal.

Another Amgen antibody, romosozumab, is under development as a potential osteoporosis treatment.1 Originally invented by Celltech, it works at a different target, scleorstin. This bone-specific protein is produced by the SOST gene and is expressed in osteocytes, which binds to LRP5/6 receptors, and inhibits the Wnt signalling pathway. The result is a decrease in bone formation by the osteoblasts as it inhibits their maturation and function.

Several clinical trials have been carried out. In one Phase II double blind, randomised, ascending dose, placebo controlled trial, 32 post-menopausal women and 16 healthy men with low bone mass were enrolled.2 Women in the study were given six doses of 1 or 2mg/kg once every two weeks, or three doses of 2 or 3mg/kg once every four weeks, or placebo. Men were given 1mg/kg every two weeks or 3mg/kg every four weeks. Lumbar spine bone mineral density was increased by 4–7%, with no significant safety issues.

In another randomised, parallel group, placebo controlled Phase II trial, 419 post-menopausal aged 55–85 with a low mineral density were given monthly subcutaneous doses of 70, 140 or 210mg of romosuzumab, 140 or 210mg every three months, or open-label 70mg weekly oral alendronate or 20µg daily subcutaneous teriparatide.3 All doses of romosozumab gave significant increases in lumbar spine bone mineral density, including an 11% increase at the highest monthly dose; there was an increase of 4.1% with alendronate, 7.1% with teriparatide, and a 0.1% decrease for those on placebo. Those given the antibody also experienced large bone mineral density increases at the total hip and femoral neck, plus transitory increases in bone-formation markers and sustained decreases in a marker of bone resorption. Adverse event profiles were similar across all groups, apart from mild injection site reactions with the antibody.


1. D. Padhi et al. J. Bone Min. Res. 2011, 26, 19

2. D. Padhi et al. J. Clin. Pharmacol. 2013, epub ahead of print, doi: 10.1002/jcph.239

3. M.R. McClung et al. N. Engl. J. Med. 2014, epub ahead of print, doi: 10.1056/NEJMoa1305224

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