Treatment Adherence Still Difficult in Osteoporosis



Persistence and adherence to parenteral osteoporosis therapies are suboptimal and worsen with time, a study finds.

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Persistence and adherence to parenteral treatments for osteoporosis varies between therapies, but, overall, rates are suboptimal and decrease over time, the first systematic review and meta-analysis using real-world data to look at the issue has found.

The results published in Osteoporosis International show that, as is the case for oral therapies such as bisphosphonates, persistence is higher with therapies requiring reduced dosing frequency.

Most data on compliance with parenteral medications for osteoporosis have come from clinical trials, and less is known about compliance in a real-world setting, so researchers set out to address this. They identified 40 English language observational studies published up to September 2018 that examined patient adherence and/or persistence to parenteral osteoporosis treatments. Studies which included self-reported data were excluded.

Teriparatide sc was assessed in 29 studies and denosumab sc in 19, and the intravenous treatments zoledronic acid and ibandronate were each looked at in 10 studies.

Dr. Carrie Ye, assistant clinical professor in the department of medicine, division of rheumatology at the University of Alberta in Canada, said that the most important message from the study “is that adherence and particularly persistence is poor even with parenteral therapies for osteoporosis and thus it is important to review osteoporosis medications regularly with patients”.

“In terms of the main differences between the different parenteral drugs, persistence out to 2 years was better with the less frequently dosed options (zoledronic acid and denosumab) compared with the more frequently dosed options (teriparatide and ibandronate),” she said. A similar relationship has been seen with oral therapies, such as bisphosphonates, where adherence and persistence has been found to be greater for those requiring weekly or monthly administration compared to daily dosing.[i],[ii]

The most surprising finding was that less than half of patients were still taking their parenteral osteoporosis medications at two years, she added. “That applies even to zoledronic acid, which is only dosed once a year.”

Persistence rates with denosumab at one year (second dose) and two years (fourth dose) were 61–100% (median 81%) and 36–99% (median 45.5%) respectively. Persistence rates for zoledronic acid were 34–73% (median 42%) at the second dose and 20–54% (median 35.8%) at the third dose.

Persistence rates with teriparatide were 10–87% (median 55%) at one year and 10–69% (median 29.5%) at two years, and adherence rates were 21–89% (median 53%) at one year and 37–68% (median 40%) at two years. Persistence rates for ibandronate at one year were 31–58% (median 47.5%) and 13–35% (median 25%) at 2 years, and adherence rates were 21–72% (median 47.3%) and 15–58% (median 36.5%) respectively.

While persistence may be greater with a treatment requiring less frequent administration, there are obviously a whole host of other factors to consider when choosing the right osteoporosis drug for an individual patient, Dr. Ye said, but that all rheumatologists should be asking patients about and counselling on adherence and reviewing expired prescriptions.

“I make a point of explaining how important adherence and persistence are with osteoporosis medications the first time that I prescribe them to a patient.I also make it clear that although the prescription expires in 1 year, I intend for the treatment to be long term and that they should get renewals from myself or their family doctor,” she said.

“I also find that explaining to a patient why it is so important to take and continue their medication regularly helps to get buy in.”

Dr. Ye also makes a point of discussing the increased risk of vertebral fractures with denosumab cessation with any patients for whom prescribes it, to “emphasize the importance of not stopping or delaying these injections”.

She supports this with practical tips. For example, telling patients on denosumab to put a repeating reminder in their phone, because it can be hard to remember to do something every 6 months.

“I've advised my patients who have a hard time remembering to do their daily teriparatide injection, to ‘couple’ their injection with something else that they already do routinely, such as brushing their teeth, or making their morning coffee,” she adds. “Simply placing the medication on top of their coffee maker can be an easy daily reminder to do their injection.”


Koller G, Goetz V, Vandermeer B, et al. Persistence and adherence to parenteral osteoporosis therapies: a systematic review [published online ahead of print, 2020 Jul 1]. Osteoporos Int. 2020;10.1007/s00198-020-05507-9. doi:10.1007/s00198-020-05507-9

[i]Fatoye F, Smith P, Gebrye T, Yeowell G (2019) Real-world persistence and adherence with oral bisphosphonates for osteoporosis: a systematic review. BMJ Open 9:1–18.

[ii]Cramer JA, Gold DT, Silverman SL, Lewiecki EM (2007) A systematic review of persistence and compliance withbisphosphonates for osteoporosis. Osteoporos Int 18:1023–1031.

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