Osteoporosis Drugs Don't Worsen COVID-19 Risk, May Help

Miriam E. Tucker

November 17, 2020

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

New observational data are the first to support recommendations to continue osteoporosis medications during the COVID-19 pandemic, and even suggest that some agents may protect against the virus. 

Findings from the cross-sectional study of 2102 patients with osteoporosis, osteoarthritis, and/or fibromyalgia — so-called noninflammatory rheumatic conditions — during March 1 to May 3, 2020 were recently published in Aging by Josep Blanch-Rubió, MD, scientific clinical director of the Rheumatology Service, Hospital del Mar, Barcelona, Spain, and colleagues.

Patients taking denosumab, zoledronate, and calcium showed trends toward lower incidence of developing symptomatic presumed COVID-19 (PCR tests weren't widely available at the time), as did those taking the antidepressant serotonin/norepinephrine inhibitor duloxetine.

Some analgesics, particularly pregabalin and most other antidepressants, were associated with higher incidences of COVID-19, while oral bisphosphonates, vitamin D, thiazide diuretics, antihypertensive drugs, and chronic nonsteroidal anti-inflammatory drugs had no effect on COVID-19 incidence.

These data are the first to support guidance issued in May 2020 by the American Society for Bone and Mineral Research (ASBMR) and four other professional societies advising continuation of osteoporosis medications during the pandemic. That statement's authors acknowledged that, lacking data, their recommendations were based primarily on expert opinion. 

"There were guidelines without any scientific base...This is the first scientific evidence showing that indeed you should continue your osteoporosis treatment if you have COVID-19. This is the first study to provide scientific support for the guidelines," study coauthor Rafael Maldonado, MD, PhD, of the Laboratory of Neuropharmacology, Universitat Pompeu Fabra, Barcelona, Spain, told Medscape Medical News in an interview.

And while the data don't offer proof of benefit for any drug — all of the 95% confidence intervals crossed 1.0 — they do show trends that deserve further study, Maldonado said.

"What we observed is that there is no harm. Treatments should be continued."

"But, we obtained very interesting results with denosumab, zoledronate, calcium, and duloxetine...There is a clear tendency and the message is we should promote studies to see if these four treatments provide benefit."

Different Mechanisms for Each?  

Asked to comment on the findings, Matthew T. Drake, MD, PhD, told Medscape Medical News, "I would agree that there's no reason any of these medications should be stopped or discontinued since there's no evidence that they make the risk for infection worse."

"But how [some of them may] improve or reduce the infection risk in my mind is somewhat unclear...It's hard to come up with a unifying explanation," because those mentioned as potentially beneficial "are fairly different," he noted.

Drake, who is associate professor of medicine in the department of endocrinology at the Mayo Clinic, Rochester, Minnesota, said he agreed with the study authors that denosumab's targeting of the RANK/RANKL system is a possible anti-COVID-19 mechanism for that drug, as that system is involved in immune response.   

Regarding zoledronate/zoledronic acid, both the Spanish authors and Drake pointed to a landmark study linking the intravenous drug to longer survival in patients with hip fracture.

The study authors note that there could be several mechanisms for an overall survival benefit, but additionally, "zoledronate may make dendritic cells and their precursors less susceptible to SARS-CoV-2 infection, which could explain the beneficial effects here...on COVID-19 incidence."

And, the authors hypothesize, the reason for the lack of benefit with oral bisphosphonates might relate to the higher potency of the intravenous zoledronate. Drake added that its higher bioavailability may also play a role.

As for calcium, the authors suggest that the beneficial effect against COVID-19 could relate to its action in generating two immune cell types — T follicular helper cells and T follicular regulatory cells —  which promote an appropriate immune response against infectious agents, including viruses.

Data Supporting the Guidelines

Of the 2102 patients in the study by Blanch-Rubió and colleagues, 80.5% were women and their mean age was 66.4 years. Overall, 63.7% had osteoarthritis, 43.5% had osteoporosis, and 27.2% had fibromyalgia. Treatments included vitamin D in 62%, calcium in 23.3%, denosumab in 12.6%, and intravenous zoledronate in 8.5%. Over half were taking analgesics and nearly a third antidepressants, with 9.9% taking duloxetine.

During the study period, 5.2%, or 109 individuals, were diagnosed with COVID-19 based on presenting for medical care with hallmark symptoms.

After adjustments for sex, age, diabetes, pulmonary disease, cardiovascular disease, chronic kidney disease, and active cancer or treatment, the relative risks for COVID-19 were 0.58 for denosumab, 0.62 for intravenous zoledronate, and 0.64 for calcium, all nonsignificant trends.

No associations were found between COVID-19 and oral bisphosphonates, vitamin D, or thiazide diuretics.

Increased but nonsignificant relative risks for COVID-19 were seen with analgesics, particularly pregabalin (1.55), gabapentin (1.39), and opioids (1.25).

Among antidepressants, there was a relative risk of 1.54 for selective serotonin reuptake inhibitors, 1.38 for amitriptyline, and 1.22 for all dual-action antidepressants together. In contrast, there was a negative association with the dual-action antidepressant duloxetine, with an adjusted relative risk of 0.68.

"The good news," Drake said, "is that none of it appears bad."

Blanch-Rubió has received grants or consulting fees from Amgen, Laboratorio Stada, Gedeon-Rhicter Ibérica, Lilly España, Pfizer, Gebro Pharma, and UCB Pharma. Maldonado has received research grants or consulting fees from Aelis, Almirall, Boehringer Ingelheim, BrainCo, Esteve, Ferrer, GlaxoSmithKline, Grünenthal, GW Pharmaceuticals, Janus, Lundbeck, Pharmaleads, Phytoplant, Rhodes, Sanofi, Spherium, Union de Pharmacologie Scientifique Appliquée, Upjohn, and Uriach. Drake has reported no relevant financial relationships.

Aging. Published online October 20, 2020. Full text

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