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How to monitor patients during a treatment break
When commencing a supervised treatment break, it is reasonable to repeat a DXA BMD scan at least every 2 years. If there is significant BMD loss to an osteoporotic range T-score, or occurrence of new fragility fracture, then reinitiating treatment is strongly recommended.
There are no established thresholds for changes in bone turnover markers such as C-terminal telopeptide of type I collagen( CTX) and procollagen type I N-propeptide( P1NP) in determining when bisphosphonates should be recommenced.
Case study 1
A 75-year-old Caucasian woman has been seeing you in clinic for her osteoporosis management. She initially sustained a minimal trauma distal radius fracture 10 years ago after a fall onto her outstretched hand. This was managed conservatively, and she declined antiresorptive therapy at the time. Five years later, she had a fall while crossing the road and experienced a right-sided hip fracture, managed by hip arthroplasty. You commenced her on 70mg oral alendronate weekly. She has tolerated and adhered to five years of continuous treatment, although she is now considering whether to stop treatment. Recent DXA BMD scan results show: lumbar spine T-score-2.5 SD, left total hip T-score-2.8 SD, left femoral neck T-score-2.7 SD. Is this patient suitable for a treatment break?
This woman has had five years of continuous treatment with an oral bisphosphonate, although she likely remains at high fracture risk given osteoporotic T-scores
Treatment breaks are not permanent and should be supervised. in her left hip and fragility hip fracture. Her overall risk of AFF is lower than her risk of a future fragility fracture.
Women at higher risk of vertebral fractures may benefit from continuing alendronate for up to 10 years compared to stopping after five years. 17 This patient could continue oral bisphosphonates if well-tolerated or consider switching to more potent antiresorptives such as zoledronic acid or denosumab. If commencing denosumab, she should be adequately informed that this needs to be continued indefinitely without stopping or delaying doses, due to the risk of rebound bone loss and spontaneous vertebral fractures.
Patients should have an individualised risk assessment prior to a bisphosphonate treatment break.
Case study 2
A 65-year-old Asian woman has been seeing you in clinic for her osteoporosis management. She sustained an L1 vertebral compression fracture after a fall during badminton six years ago and you subsequently initiated her on annual infusions of 5mg zoledronic acid, with six doses received in total. She experienced a mild flu-like reaction the day after her first dose but has tolerated it well since. Her most recent DXA BMD scan shows lumbar spine( L2-L4) T-score-2.0 SD(+ 12 % from baseline) and femoral neck T-score-1.8 SD(+ 8 % from baseline). She has not sustained further minimal trauma fractures. She has no symptoms suggestive of AFF and has six-monthly dental review with no recent invasive dental procedures. Should she commence a treatment break?
She would now be suitable for a treatment break as her BMD has improved significantly into the osteopenic range. Although she has had a prior vertebral fracture, she has not sustained any new fragility fractures while on treatment.
An extension study has demonstrated that hip BMD was stable during a three-year break after six years of zoledronic acid. 17 This study was inadequately powered to inform whether the rate of new fractures off-treatment was greater in those who had a break after six years of treatment compared to those who were treated for nine years.
Although this patient’ s overall risk of AFF is still lower than the risk of a fragility fracture, she may be at relatively greater risk with her Asian background and continuation of treatment towards 10 years. The risk / benefit ratio tips in favour of a treatment break. She is advised to have ongoing BMD monitoring every two years.
Conclusion
While 3-5 years of bisphosphonate treatment appears to offer some durability in BMD gains and anti-fracture effects, there is no‘ one size fits all’ approach when determining the suitability of a bisphosphonate treatment break.
Consider ongoing treatment for patients at high risk of BMD decline or fragility fracture. The effect of risedronate appears to reverse faster compared to zoledronic acid and alendronate, and thus closer monitoring is recommended for treatment breaks from this agent.
Online resources
• RACGP and Healthy Bones Australia: Osteoporosis management and fracture prevention in postmenopausal women and men over 50 years of age 1 bit. ly / 4aRv2mW
• Managing osteoporosis patients after long-term bisphosphonate treatment: Report of a Task Force of the American Society for Bone and Mineral Research 2 bit. ly / 3WRfPMD
• Bisphosphonate drug holidays: Evidence from clinical trials and real-world studies 3 bit. ly / 3WQIiSZ
Patients should have an individualised risk assessment prior to consideration of a bisphosphonate treatment break and understand the importance of ongoing monitoring to ensure that treatment is appropriately recommenced if their risk of fragility fracture increases again.
References on request from kate. kelso @ adg. com. au
Correction As a result of an editing error in the 16 May Therapy Update‘ A GP guide to tuberculosis’, some of the figures in table 1 were incorrect. We apologise for this error. Here is a link to the correct version: bit. ly / 4jj1dhu