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April 23, 2020

Recommendations for Continuing Bone-Modifying Agents During the COVID-19 Pandemic

By Kathy Sharp, MSN, FNP-BC, CCD, Ballad Health Cancer Care

The COVID-19 pandemic has interrupted the treatment and supportive care of patients with cancer, including those receiving agents for the prevention of cancer treatment–induced bone loss (CTIBL) and treatment of bone metastasis and osteoporosis. In some clinics, CTIBL agents may be deferred in order to limit COVID-19 exposures.

Effect of Treatment Delays

CTIBL agents have been used by providers in oncology, as per ASCO guidelines, for many years (Dhesy-Thind et al., 2017). These treatments include IV bisphosphonates, romosozumab, and denosumab. Bisphosphonate cessation has historically not been associated with a rapid rise in bone turnover, due to the mechanism of action of binding to the bone and long half-life. Treatment delays should not pose a significant risk for loss of bone in patients receiving these agents. There is currently no information on the loss of effectiveness of romosozumab when injections are delayed. The logical, but unproven, conclusion is that delayed injections would result in diminished anabolic effect overall, but would not result in detriment or loss of bone.

However, in the past 3 years, emerging evidence has shown that sudden discontinuance of denosumab has resulted in a rapid rise in bone turnover, with potential increased risk of bone loss and an apparent increase in the risk of multiple vertebral fractures (Cummings et al., 2018 ; Lewiecki, 2020; Tsourdi et al., 2017). The loss of bone can begin to occur as early as 4 weeks after denosumab is due, making it crucial to keep patients on schedule for their injections. Patients who have had more than 2 doses of denosumab and those who have had previous fractures seem to be more vulnerable to increased risk of multiple vertebral fractures (Amgen Inc., 2019; Bone Health ECHO, personal communication, April 7, 2020).

In light of the current COVID-19 situation, providers need to be aware of the increased risk for bone loss and fracture risk in these patients due to cancellation of office visits or interruption of clinic schedules. With this sense of urgency, providers need to have contingency plans in place.

Setting a Plan

For patients on denosumab, the preferred plan is to reschedule the patient’s injection with no more than a 1-month delay. Another approach, which many providers are embracing, is a drive-through or curbside injection. Many providers across the nation are currently employing this strategy (Bone Health ECHO, personal communication, April 7, 2020). This approach is for patients who have previously been on denosumab. In most cases, the requirement for a pre-treatment calcium level is waived if previous calcium levels have been stable.

A variety of methods of check-in and patient identification have been used, and institutional and state guidelines may regulate this service. In this author’s institution, the ambulance entrance has been used as an entrance for patients receiving injections, so entry into the main clinic is eliminated and thus exposure is limited for the nurse administering the medication. This approach has been accepted by patients and has allowed the majority of patients to receive their injections without delays. Diligence is required to ensure that these patients do not “fall through the cracks.” Follow-up appointments should be made and communicated to the patient at the time of phone contact or curbside visit.

Another proposed plan is switching to an oral therapy for the duration of the denosumab delay. This may be an option for patients who are anxious about coming to the clinic. To date, there are no recommendations and no clinical research on how to switch to oral therapies, although this has been suggested as the most reasonable way to mitigate the increase in fracture risk for patients who do not want to come to the clinic.

Electronic prescribing of a weekly or monthly oral bisphosphonate is a reasonable alternative until the patient can return to the clinic to resume injections. Patients need to be educated about the need for an alternative therapy, the correct method for taking an oral bisphosphonate, and the side effects.

The COVID-19 pandemic has created many challenges for all providers. It is hoped that these suggestions can be utilized by oncology providers to prevent rebound bone loss and increased fracture risk in our at-risk population.

References

Amgen Inc. (2019). Evenity (romosozumab) package insert. Retrieved from https://www.pi.amgen.com/~/media/amgen/repositorysites/pi-amgen-com/evenity/evenity_pi.ashx

Cummings, S. R., Ferrari, S., Eastell, R., Gilchrist, N., Jensen, J. B., McClung, M.,…Brown, J. P. (2018). Vertebral fractures after discontinuation of denosumab: A post hoc analysis of the randomized placebo‐controlled FREEDOM trial and its extension. Journal of Bone and Mineral Research, 33(2), 190–198. https://doi.org/10.1002/jbmr.3337

Dhesy-Thind, S., Fletcher, G. G., Blanchette, P. S., Clemons, M. J., Dillmon, M. S., Frank, E. S.,…Van Poznak, C. H. (2017). Use of adjuvant bisphosphonates and other bone-modifying agents in breast cancer: A Cancer Care Ontario and American Society of Clinical Oncology Clinical Practice Guideline. Journal of Clinical Oncology, 35(18), 2062–2081. https://doi.org/10.1200/JCO.2016.70.7257

Lewiecki, E. M. (2020). Denosumab: Mechanisms and therapeutic effects in the treatment of osteoporosis. In B. Leder & M. Wein (Eds.), Osteoporosis: Pathophysiology and Clinical Management (Contemporary Endocrinology) (pp. 309–322). Humana, Cham. https://doi.org/10.1007/978-3-319-69287-6_15

Read more from the APSHO Advance: Special COVID-19 Series