Osteoporosis: Continuing denosumab (Prolia) treatment for patients
Information from the Royal Osteoporosis Society
How to continue denosumab treatment for osteoporosis during the Covid-19 pandemic
The Royal Osteoporosis Society has produced advice on continuing Prolia treatment in primary care during the coronavirus pandemic. Click here for any updates to the guidance below.
Why is it important to continue denosumab treatment?
• Reducing avoidable admissions due to osteoporosis-related fracture is important
• Denosumab delivered as a 6-monthly SC injection is highly effective in reducing the risk of osteoporosis-related fractures
• However, the offset of denosumab treatment effect is very rapid, resulting in accelerated bone loss and an increased risk of “rebound” fracture
- Offset occurs if treatment is delayed by as little as 4 weeks, ie >7m from previous injection
- BMD decreases to pre-treatment baseline within 12 months
- Rebound has been associated with the rapid occurrence of multiple and debilitating vertebral fractures
• Although denosumab is an antibody-based treatment, it is not thought to increase susceptibility to coronavirus (COVID19) infection or risk of complications
The need to continue denosumab treatment during the current pandemic has been highlighted in Covid-19 guidance to clinicians and patients:
• NICE: https://www.nice.org.uk/guidance/ng167 • ROS: https://theros.org.uk/information-and-support/medication-andtreatment/current-osteoporosis-medications/denosumab
The increased risk of fracture if treatment is delayed needs to be balanced against the risk of Covid-19 exposure
Current circumstances dictate the need for pragmatic decisions to be made but as far as possible, these should be based on the individual patient’s circumstances and wishes.
Which patients are at the greatest risk of rebound fractures?
Factors thought to be associated with greater risk of rebound fractures include:
• Longer duration of denosumab treatment o Treatment for less than 2 years is associated with low risk
• History of prior vertebral fracture
• Lower baseline BMD
- As BMD will decrease back to this level within 12m
• Greater increase in BMD since initiation of treatment
- As this predicts the magnitude of bone loss within 12m and accelerated bone loss is an independent risk for fracture
• Concomitant disease/medication increasing fracture risk e.g. glucocorticoids, aromatase inhibitors
- Effects may be dose-dependent
It is particularly important to continue timely treatment in patients meeting one or more of these criteria
How can the risk of Covid-19 exposure be minimized?
• Patients considered to be at low risk of developing hypocalcaemia postinjection may not require a pre-treatment blood test (see below)
• If pre-treatment blood test is considered necessary, local facilities may be available for “minimal contact” blood tests e.g.:
- Domiciliary phlebotomy
- Drive-through service
• Use of treatment administration pathway designed to minimize risk of viral transmission (see below)
What are the options for treatment administration during the pandemic?
• Domiciliary administration by primary care or homecare clinician
• Administration in primary care facility (GP or local pharmacy)
• Self-administration by patient or a family member/carer supported by their healthcare provider and/or the manufacturer’s support programme (PROLONG)
- Details of PROLONG support programme and online resources on patient self-administration available at: https://www.prolia.co.uk/patient/how-is-prolia-denosumabadministered/how-do-i-self-inject
• Administration in secondary care following stringent infection control measures
Patients at low risk of hypocalcaemia for whom omission of the pretreatment blood test may be considered
To reduce contact with healthcare personnel and premises, the pre-treatment calcium check may be omitted during the pandemic in low risk individuals, e.g. those who:
• Have previously received treatment with denosumab on 2 or more occasions without clinical or biochemical evidence of hypocalcaemia pre- or post-treatment
• Are taking adequate calcium and vitamin D supplemention daily or almost daily o Providing ~1000mg calcium and ~800IU vitamin D per day
• Have adequate and stable renal function - defined as CKD G1-3a
• Have no new comorbidities/medications since previous injection likely to affect renal function or calcium handling
Precautions to reduce risk of hypocalcaemia if pre-treatment blood test is omitted
• Ensure dietary and supplemental calcium equates to at least 1000mg per day
• Ensure patient takes at least 800IU colecalciferol per day o a higher dose may be needed in obese patients
• Administration of an additional bolus of oral vitamin D a week or two prior to injection is advised, e.g. oral colecalciferol 20,000IU
• Where feasible, a blood sample to check calcium and creatinine may be obtained at the time of injection.
Note that patients with CKD 3b or worse should be managed within or in conjunction with secondary care services. These patients are at high risk of hypocalcaemia. They all require pre- and in many cases post-treatment blood monitoring and are unlikely to benefit from higher doses of colecalciferol because of inability to undertake renal hydroxylation of 25(OH)-vitamin D to the active form.
If a delay in denosumab treatment is unavoidable, how can the risk of fracture be minimized?
• Consider use of an alternative anti-resorptive agent to attenuate bone loss (providing no contra-indications), e.g.
- Buffered effervescent alendronic acid (Binosto) for patients unable to tolerate the tablet form of treatment
- Weekly oral risedronate or monthly oral ibandronate may be tolerated by patients intolerant of alendronic acid
- Strontium ranelate
• Encourage the patient to continue taking supplements of calcium and vitamin D
• Consider strategies to reduce falls risk
• Ensure denosumab treatment is rearranged as soon as possible
Key messages for patients
• Denosumab treatment is very good at improving your bone strength and greatly reduces the chances of breaking a bone after a fall
• We know that denosumab (Prolia) treatment wears off very quickly so it is important that you continue to have your treatment on time every 6 months
- If your treatment is delayed, your risk of breaking a bone may increase very quickly
• Unlike some other antibody-based medications used to treat inflammatory disease such as rheumatoid arthritis, denosumab does not suppress the immune system and does not increase the risk of viral infection such as Covid-19
• Many people will be worried about leaving their home to have their treatment during the pandemic
- The clinical team looking after your osteoporosis has put measures in place to ensure you can continue to receive your treatment safely
• Please continue to take your usual supplements of calcium and vitamin D
• Please discuss any concerns about your treatment with your clinical team
- You can also contact the Royal Osteoporosis Society’s nurses via their free telephone helpline 0808 800 0035
Further information about osteoporosis and denosumab treatment during the Covid-19 pandemic are available from the Royal Osteoporosis Society: https://theros.org.uk/information-and-support/medication-andtreatment/current-osteoporosis-medications/denosumab
Source: Royal Osteoporosis Society, denosumab advice sheet [published 16 April]