The study was inspired by the fact that the specialists at the Hospital Del Mar, a general hospital in Spain, noted a low incidence of COVID-19 in osteoporosis patients
Representational image.
In a study recently published in the journal Aging, a group of researchers in Spain indicated that some of the main drugs (denosumab, zoledronate and calcium) used for the treatment of non-inflammatory rheumatic conditions like osteoporosis, fibromyalgia and osteoarthritis, may be effective as prophylaxis for COVID-19.
Osteoporosis is an age-related condition that affects millions of people worldwide. The disease requires long-term treatment, which involves a combination of non-steroidal anti-inflammatory drugs (NSAIDs), opioids and antidepressants.
The exact effect of osteoporosis treatment drugs on COVID-19 incidence and disease severity is unknown. Some anti-rheumatic drugs such as IL-6 antagonists have shown to be effective against COVID-19 and various associations including the American College of Rheumatology and International Osteoporosis foundation have recommended osteoporosis patients to continue taking their medications.
However, data to show the safety of osteoporosis drugs in treating COVID-19 is not available yet.
The recent study
The study was inspired by the fact that the specialists at the Hospital Del Mar, a general hospital in Spain, noted a low incidence of COVID-19 in osteoporosis patients.
The researchers included 2,102 volunteers with a mean age of 66.4 years in the study. Over 80 percent of the participants were women, about 63.7 percent had osteoarthritis, 43.5 percent had osteoporosis and 27.2 percent had fibromyalgia.
About 109 of the participants were confirmed to be COVID-19 positive between March and May 2020. These patients also had more comorbid conditions like diabetes, chronic kidney disease, cardiovascular disease and pulmonary disease as compared to those who did not test positive for COVID-19.
They also had less exposure to drugs like denosumab, intravenous zoledronate, vitamin D and selective estrogen receptor modulators (SERMs) and higher exposure to antidepressants as compared to those who did not get the disease.
Based on the study, the researchers suggested that denosumab, zoledronate, calcium and the antidepressant duloxetine were negatively associated with COVID-19 incidence. Specifically, the drugs were found to reduce the rate of infection by 30-40 percent. On the other hand, most other antidepressants and pain-relieving drugs, especially pregabalin, was positively associated with COVID-19 incidence.
Various mechanisms
As per the study, the drugs that were found to be effective had a different mechanism of action.
Denosumab targets the RANK/RANKL system which is involved in the maintenance of balance in the skeletal system. However, it also affects the immune system and is involved in lymph node development and T cell activation. Inhibition of this system reduces pro-inflammatory cytokines in the body and helps control inflammation, which is one of the major causes of life-threatening COVID-19.
Zoledronate normally prevents bone breakdown, reduces the risk of cardiovascular diseases, improves general health and immune system and reduces pneumonia incidence. The study indicated that zoledronate also reduces the susceptibility of certain immune system cells to SARS-CoV-2, which may explain the reduced incidence of COVID-19 in patients.
Calcium deficiency has been seen to be associated with increased risk of mortality in COVID-19 patients. A possible mechanism, the researchers explained, through which it helps manage COVID-19 is the involvement of calcium in the generation of T cells, a type of immune system cells responsible for fighting viruses.
Similarly, the antidepressant duloxetine helps balance T cells and cytokine production.
For more information, read our article on Pre-existing drugs in trial for COVID-19.
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