Medicines Healthcare Products Regulatory Agency
Advice for healthcare professionals:
an increased risk of multiple vertebral fractures has been reported in patients within 18 months of stopping or delaying ongoing denosumab 60mg treatment for osteoporosis; cases have been reported in patients in the UK
patients with a previous vertebral fracture may be at highest risk
- evaluate a patients individual factors for benefits and risks before initiating treatment with denosumab, particularly in patients at increased risk of vertebral fractures for example those with previous vertebral fracture
patients should not stop denosumab without specialist review
the optimal duration of denosumab treatment for osteoporosis has not been established; re-evaluate the need for continued treatment periodically based on the expected benefits and potential risks of denosumab on an individual patient basis, particularly after 5 or more years of use
risks of long-term treatment with denosumab include rare cases of osteonecrosis of the jaw and atypical femoral fractures; osteonecrosis of the external auditory canal has also been reported in association with denosumab
NICE rapid guidance (30 April 2020) advises not to postpone ongoing treatment with denosumab during the coronavirus (COVID-19) pandemic
- report suspected adverse drug reactions to denosumab on a Yellow Card
Advice to give to patients:
- there have been reports of increased risk of multiple fractures in the spine after stopping or delaying ongoing treatment with denosumab 60mg (Prolia) treatment
- do not stop denosumab treatment without talking to your doctor to discuss your individual risk factors
- if you miss a prescribed dose of denosumab, the missed injection should be administered as soon as possible. After this, your next injection will be scheduled 6 months from the date of your last injection
- continue to regularly review your treatments for osteoporosis with your doctor
Increased risk of vertebral fractures
Denosumab 60mg (Prolia) is indicated for the treatment of osteoporosis and bone loss, see background section for full indication. The Commission on Human Medicines Pharmacovigilance Expert Advisory Group has considered EU and worldwide safety data, together with data submitted by the manufacturer, suggesting an increased risk of multiple vertebral fractures after stopping denosumab for osteoporosis, alongside national and international clinical guidance advising of the potential risk on treatment cessation.1 2
Given the reports and guidance in the UK (see later section), we make healthcare professionals aware of this risk and advice for patients not to stop denosumab without specialist review.
UK reports of vertebral fractures after stopping denosumab
Between 1 January 2015 and 31 December 2019, approximately 396,000 denosumab 60mg pre-filled syringes were dispensed in the UK, making the estimated UK exposure in this time about 197,000 patient-years.3
Since 2015 and up to and including June 2020, 44 cases of vertebral fracture, including multiple fractures, have been reported in the UK in post-marketing settings in patients after stopping or delaying ongoing treatment with denosumab (Prolia). Where reported, these fractures occurred within 18 months of stopping or delaying denosumab treatment, with some in the first 9 months. These fractures were described as life-changing in some cases.
Patient information and support regarding the use of denosumab in osteoporosis is available from the Royal Osteoporosis Society.
Denosumab 60mg (Prolia) is indicated for treatment of:
Osteoporosis in postmenopausal women and in men at increased risk of fractures. In postmenopausal women Prolia significantly reduces the risk of vertebral, non-vertebral and hip fractures.
Bone loss associated with hormone ablation in men with prostate cancer at increased risk of fractures. In men with prostate cancer receiving hormone ablation, Prolia significantly reduces the risk of vertebral fractures
Treatment of bone loss associated with long-term systemic glucocorticoid therapy in adult patients at increased risk of fracture
Denosumab is also available as a 120mg dose (Xgeva) for the prevention of skeletal related events in adults with advanced malignancies involving bone and for the treatment of adults and skeletally mature adolescents with giant cell tumour of bone that is unresectable or where surgical resection is likely to result in severe morbidity. Although data for risk of multiple vertebral fractures after stopping treatment is insufficient for similar advice to be issued for the 120mg dose at the present time, the risks will be kept under review.
Report suspected adverse drug reactions on a Yellow Card
Please continue to report suspected adverse drug reactions (ADRs) on a Yellow Card. Reporting suspected ADRs, even those known to occur in association with the medicine, adds to knowledge about the frequency and severity of these reactions and can be used to identify patients who are most at risk. Your report helps the safer use of medicines.
Healthcare professionals, patients, and caregivers can report suspected ADRs via the Yellow Card website or via the Yellow Card app. Download the app today via iTunes Yellow Card for iOS devices or via PlayStore Yellow Card for Android devices. You can also view recent alerts from the MHRA and read Drug Safety Updates through the App newsfeed.
Article citation: Drug Safety Update volume 14, issue 1: August 2020: 3.
National Osteoporosis Guideline Group (NOGG) 2017. Clinical guideline for the prevention and treatment of osteoporosis. Updated July 2019.?
Data derived from IQVIA MIDAS, January to December 2019, and analysed by the MHRA, March 2020.?