Careful selection of osteoporosis therapy is needed in younger patients who may at risk of a rebound rise in fractures after stopping long term treatment with agents such as denosumab, an endocrinologist says.
Patients who stop the anti-RANKL agent denosumab after many years of treatment show accelerated bone loss and a corresponding rise in fracture risk, according to Dr Frances Milat, who is head of Metabolic Bone Services at Monash Health.
Speaking at the Australian Rheumatology Association conference in Melbourne, Dr Milat drew attention to the findings from the FREEDOM study, in which vertebral fracture rates increased from 1.2 to 7.1 per 100 participant‐years among patients who stopped denosumab after taking it long term.
The findings – which also included a risk of multiple vertebral fractures – showed a need for additional osteoporosis medications to attenuate the accelerated bone loss after stopping denosumab, she said.
“Because of the nature of denosumab it just switches off bone resorption – and the thinking is that a one off zoldedronic infusion won’t be enough in terms of bone remodelling,” she told the conference.
Dr Milat said her clinic also used a weekly bisphosphonate to prevent the accelerated bone loss, but this may not be tolerated by some older patients with multiple co-morbidities.
She told the conference her main concern was over the use of denosumab in younger women who may face many years of treatment.
“My fear is using it in patients in whom people haven’t thought about the long term consequences … if patients are very elderly then the risk balance may well be on the side of denosumab but in our younger perimenopausal and early post-menopausal women and younger men we have to think of that [and] and consider options for therapy,” she said.
“What concerns me is when patients are sent to my clinic from their GP and they’re younger than me and already on denosumab. I think we need to be thoughtful in regards to these women. As an endocrinologist I tailor my therapy to the patient’s age. In my younger patients I use hormone replacement therapy if that’s appropriate.”
Dr Milat stressed that the balance of benefit and risk was still greatly in favour of treatment of osteoporosis, but clinicians needed to be aware of the lack of long term data for some drugs.
“I wish I had all the answers… I think we need to have more dialogue between the ARA and the Australia and New Zealand Bone and Mineral Society and the Endocrine Society because I think this is a really important issue going forward,” she said.
Responding to a request for comment, a spokesperson for Amgen, who market denosumab (Prolia) in Australia said: “Osteoporosis is a chronic disease affecting an estimated 1.2 million Australians [ Osteoporosis Australia website], and we advise patients who have questions around osteoporosis and treatment options to contact their doctor. The benefit/risk profile of Prolia is favourable in the approved indications.”