NEW YORK (Reuters Health)—Denosumab injection delays of more than four months are associated with an increased risk of fracture compared with on-time injections, especially at the spine, new research indicates.
“When starting denosumab, it’s critical for clinicians to discuss this issue with patients. If patients are uncertain that they can remain on the schedule alternative treatments should be considered,” says Daniel Solomon, MD, MPH, with the Division of Rheumatology, Brigham and Women’s Hospital and Harvard Medical School, Boston, in email to Reuters Health.
The researchers studied the electronic health records of 2,594 adults aged 45 and older initiating denosumab therapy (60 mg every six months) for osteoporosis. Together, these patients contributed a total of 6,144 denosumab injections: 1,856 of these injections were administered on time, within four weeks before or after the recommended date, and 4,288 were delayed—either by four to 16 weeks beyond the recommended date (short delay) or more than 16 weeks before the recommended date (long delay).
Compared with on-time denosumab injections, long-delay (but not short-delay) injections were associated with nearly a 4-fold higher risk for clinical vertebral fracture (hazard ratio: 3.91; 95% confidence interval: 1.62–9.45). The risk for vertebral fracture increased throughout the six months after the recommended injection date. There was not enough evidence to draw conclusions about non-vertebral fracture risk with delayed denosumab injections.
The researchers say their results are in line with an earlier study they did in which bone mineral density (BMD) was used as the endpoint. In that study, patients with on-time denosumab injections had an average BMD increase of 3.9% at the lumbar spine, higher than patients with short delays (2.8%) or long delays (1.6%). The association was similar for total hip BMD.2
Denosumab injection delays are “common,” Dr. Solomon tells Reuters Health, “and likely occur because of patient cancellations, clinic scheduling problems, insurance delays, and combinations of these issues.”
“When I start the drug, I discuss the importance of on-time injections with patients. Our clinic nurse who gives the injections is fully educated on the problem with delays. We make sure insurance approval is in place each year. We hope this research will spur others to work on reducing delays in their own practice,” Dr. Solomon says.
The coauthors of an editorial agree that it is of “utmost importance that clinicians considering denosumab treatment carefully counsel patients before its initiation on the importance of not delaying or abruptly discontinuing injections.”3
Kristine Ensrud, MD, and John Schousboe, MD, PhD, from University of Minnesota note that during the COVID-19 pandemic, some organizations recommend transitioning to an oral bisphosphonate in patients on denosumab who can’t continue on time.
“Patients discontinuing denosumab treatment should transition to an alternative antiresorptive medication. The optimal timing and dosing of antiresorptive therapy after denosumab withdrawal is currently being investigated in randomized trials,” they write.
- Lyu H, Yoshida K, Zhao SS, et al. Delayed denosumab injections and fracture risk among patients with osteoporosis: A population-based cohort study. Ann Intern Med. 2020 Jul 28. Online ahead of print.
- Lyu H, Yoshida K, Zhao SS, et al. Delayed denosumab injections and bone mineral density response: An electronic health record-based study. J Clin Endocrinol Metab. 2020 May 1;105(5):1435–1444.
- Ensrud KE, Schousboe JT. Delayed denosumab injections and fracture risk. Ann Intern Med. 2020 Jul 28. Online ahead of print.