ANZICS CTG Endorsed Study
Bone Loss Prevention with Zoledronic Acid or Denosumab in Critically Ill Women – A Randomised Controlled Trial
Intensive care patients face health issues that extend beyond their critical illness. A specific area where critical illness may adversely affect the well-being of survivors is increased bone turnover during critical illness, and accelerated bone loss in subsequent years. Critical illness bone loss begins in the first days of critical illness, occurs in both men and women, and is greatest in post-menopausal women. One year after critical illness, 80% of women aged 50-years or greater are classified as osteoporotic or osteopenic, compared to 71% of the approximately 3.7 million Australian women aged 50 year or greater.
Bone antiresorptive therapies are effective at reducing bone loss and decreasing fracture risk in non-critically ill populations. Zoledronic acid and denosumab represent antiresorptive agents with established efficacy in non-critically ill women and are potential target interventions able to be delivered during critical illness. Denosumab is a human monoclonal antibody directed against RANKL, a central stimulator of osteoclast activity, and is effective for prevention of fractures and bone loss in osteoporosis and malignancy. Zoledronic acid is a bisphosphonate class agent that binds to bone and suppresses bone resorption by entering osteoclasts and inhibiting the enzyme farnesyl pyrophosphate synthase, resulting in disruption of osteoclast attachment to bone surface. In addition to skeletal effects, there are possible mortality benefits associated with the use of antiresorptive medications in populations with increased bone loss.
Neil Orford, Priya Nair, Rinaldo Bellomo, Allison Bone, Jackie Center, Carol Hodgson, Mark Kotowicz, Bala Venkatesh, Ed Litton, Paul Young, Claire Reynolds, Tony Trapani
ANZIC -RC, Monash University
Alison Bone email