Delaying doses of denosumab after the primary injection dramatically boosts the danger that sufferers with osteoporosis will endure vertebral fractures, a brand new examine confirms. Physicians say they’re particularly involved in regards to the danger dealing with sufferers who’re delaying the remedy throughout the coronavirus pandemic.
The beneficial doses of denosumab are at 6-month intervals. Sufferers who delayed a dose by greater than 16 weeks had been almost 4 occasions extra more likely to endure vertebral fractures, in contrast with those that obtained on-time injections, in keeping with the examine, which was revealed in Annals of Inside Medication.
“As a result of sufferers who used denosumab had been at excessive danger for vertebral fracture, methods to enhance well timed administration of denosumab in routine medical settings are wanted,” wrote the examine authors, led by Houchen Lyu, MD, PhD, of Nationwide Medical Analysis Heart for Orthopedics, Sports activities Medication & Rehabilitation at Common Hospital of Chinese language PLA in Beijing.
Denosumab, a human monoclonal antibody, is used to scale back bone loss in osteoporosis. The producer of Prolia, a model of the drug, recommends or not it’s given each 6 months, however the examine experiences that it is common for injections to be delayed.
Researchers have linked cessation of denosumab to increased danger of fractures, and Dr. Lyu led a examine revealed earlier this 12 months that linked less-frequent doses to much less bone mineral density enchancment. “Nonetheless,” the authors of the brand new examine wrote, “whether or not delaying subsequent injections past the beneficial 6-month interval is related to fractures is unknown.”
For his or her new examine, researchers retrospectively analyzed information from 2,594 sufferers within the U.Okay. 45 years or older (imply age, 76; 94% feminine; 53% with a historical past of main osteoporotic fracture) who started taking denosumab between 2010 and 2019. They used a design that aimed to emulate a medical trial, evaluating three dosing intervals: “on time” (inside Four weeks of the beneficial 6-month interval), “quick delay” (inside 4-16 weeks) and “lengthy delay” (16 weeks to six months).
The examine discovered that the danger of composite fracture over 6 months out of 1,000 was 27.Three for on-time dosing, 32.2 for short-delay dosing, and 42.Four for long-delay dosing. The hazard ratio for long-delay versus on-time was 1.44 (95% confidence interval, 0.96-2.17; P = .093).
Vertebral fractures had been much less possible, however delays boosted the danger considerably: Over 6 months, it grew from 2.2 in 1,000 (on time) to three.6 in 1,000 (quick delay) and 10.1 in 1,000 (lengthy delay). The HR for lengthy delay versus on time was 3.91 (95% CI, 1.62-9.45; P = .005).
“This examine had restricted statistical energy for composite fracture and several other secondary finish factors … apart from vertebral fracture. Thus, proof was inadequate to conclude that fracture danger was elevated at different anatomical websites.”
In an accompanying editorial, two physicians from the College of Minnesota, Minneapolis, famous that the examine is “well timed and related” because the coronavirus pandemic could disrupt dosage schedules greater than standard. Whereas the examine has limitations, the “findings are in step with recognized denosumab pharmacokinetics and prior research of fracture incidence after denosumab remedy discontinuation,” wrote Kristine E. Ensrud, MD, MPH, who can also be of Minneapolis VA Well being Care System, and John T. Schousboe, MD, PhD, who can also be of HealthPartners Institute.
The editorial authors famous that, in mild of the pandemic, “some organizations advocate short-term transition to an oral bisphosphonate in sufferers receiving denosumab remedy for whom continued remedy isn’t possible inside 7 to eight months of their most up-to-date injection.”
In an interview, endocrinologist and osteoporosis specialist Ethel Siris, MD, of Columbia College, New York, mentioned lots of her sufferers aren’t coming in for denosumab injections throughout the pandemic. “It is laborious sufficient to get individuals to indicate up each 6 months to get their shot when issues are going properly,” she mentioned. “We’re speaking older girls who could also be on lots of different medicines. Folks neglect, and it is troublesome for the workplace to always remind a few of them to get their photographs at an infusion heart.”
The dearth of signs is one other problem to getting sufferers to return for doses, she mentioned. “In osteoporosis, the one time one thing hurts is in the event you break it.”
Because the pandemic started, many sufferers have been avoiding medical places of work due to worry of getting the coronavirus.
The brand new analysis is useful as a result of it exhibits that sufferers are “extra more likely to fracture in the event that they delay,” Dr. Siris famous. The endocrinologist added that she has efficiently satisfied some sufferers to offer themselves subcutaneous injections within the stomach at dwelling.
Dr. Siris mentioned she has been in a position to watch sufferers do these injections on video to verify their method. Her sufferers have been impressed by “how straightforward it’s and delighted to have completed it,” she mentioned.
The examine was funded by the Nationwide Institutes of Well being China’s Nationwide Medical Analysis Heart for Orthopedics, Sports activities Medication & Rehabilitation. The examine authors, commentary authors, and Dr. Siris report no related disclosures.
SOURCE: Lyu H et al. Ann Intern Med. 2020 Jul 28. doi: 10.7326/M20-0882.
This text initially appeared on MDedge.com.