Tag Archive | Bhandari

Drug to Improve Tibial Shaft Fracture Healing Fizzles

In our ongoing attempt to identify pharmacologic interventions that improve fracture healing, the sclerostin inhibitor romosozumab is a logical candidate, as it has been shown to decrease bone resorption, improve bone healing in animal and human studies, and reduce the prevalence of some fragility fractures in postmenopausal women. In the August 19, 2020 issue of The Journal, Bhandari et al. present the results of a randomized trial comparing romosozumab to placebo in the healing of tibial diaphyseal fractures treated with intramedullary (IM) nails. Tibial shaft fractures are common in adults, but even after IM nail fixation there is a significant rate of healing failure and subpar functional outcomes with this fracture type.

The study by Bhandari et al. was very well designed and conducted with high-quality data collection. In terms of the primary outcome—median time to radiographic healing—there was no significant difference between the placebo group (n=100) and 9 romosozumab groups (n=293 total, testing 3 different dose levels and 3 different frequencies). Additionally, analysis revealed no differences between placebo and romosozumab groups in median time to clinical healing or in changes in physical function from baseline. (See related OrthoBuzz post about a recent randomized trial investigating romosozumab for hip fractures.)

Kudos to Amgen for funding the trial and for allowing the 66-center, international academic consortium that conducted it to publish the results, warts and all. Such negative findings appropriately inform decisions about which compounds to investigate and about study designs for retesting the same compounds. For example, Bhandari et al. encourage further study of romosozumab in tibial-fracture patients at high risk of poor fracture healing, such as those with diabetes or patients undergoing treatment with corticosteroids.

We are likely to see many such “failures” in the search for pharmacological adjuncts to improve fracture healing, but it seems our orthopaedic community has laid out a clear roadmap for studying this important question further.

Marc Swiontkowski, MD
JBJS Editor-in-Chief

COVID-19 Evidence from Dr. Bhandari

We are now experiencing the third human coronavirus epidemic of the 21st century. COVID-19 has rapidly endangered the health and well-being of all people, especially vulnerable populations. The offending pathogen, SARS-CoV-2, is a novel coronavirus hitherto unknown to the medical field.

Some of what is known about the virus and the disease it causes has been compiled into a fast-track JBJS Orthopaedic Forum article by orthopaedic surgeon and researcher Mohit Bhandari, MD, PhD and his colleagues. Whether you are an orthopaedist, health care professional in another specialty, or a patient, you may find the following excerpts from the article useful.

The authors begin with a quote from Microsoft founder and philanthropist Bill Gates, who notes that “we’ve invested a huge amount in nuclear deterrents, but we’ve actually invested very little in a system to stop an epidemic.”

Epidemiology
Evidence suggests that asymptomatic, pre-symptomatic, or mildly symptomatic individuals could be drivers of the community spread of the virus. Early evidence from pre-published studies of 2 cohorts indicate that the virus is spread, on average, 2 to 3 days before symptoms present.

The CDC recently published a report on US patients with COVID-19, using data from February 12, 2020, to March 16, 2020 and found that younger age groups had appreciable risks of both hospitalizations and ICU admissions. This is contrary to data from other countries, where serious cases of COVID-19 occurred predominantly in older people with underlying illnesses.

Infection curves with a steep rise place huge demands on health-care systems and can overwhelm limited health-care resources and force clinicians to make agonizing decisions about which patients receive life-saving treatment and which do not. Hence, all the talk about precautions designed to flatten the curve instead of steepening it.

Vaccine Development
Although there has been impressive and rapid progress toward a vaccine already, a vaccine for widespread use is still likely months or years away, because of the testing, regulatory, and manufacturing hurdles that will need to be cleared.

One possible vaccine-development strategy is a subunit vaccine. Subunit vaccines elicit an immune response against the protein on the surface of a coronavirus to prevent its docking with host receptors. Given the similarities between SARS-CoV (the virus that caused the SARS outbreak in 2002 and 2003) and SARS-CoV-2, focusing on a subunit vaccine may be the most promising short-term approach.

Treatment
No specific treatment is currently recommended for COVID-19. Similar to many other viral illnesses, the current mainstays of treatment include early recognition and isolation, along with symptomatic and oxygen therapy.

A randomized controlled trial of the antiviral lopinavir-ritonavir compared with standard care included 199 adult patients with confirmed COVID-19, pneumonia, and compromised oxygen saturation. There was no significant difference between the 2 groups in terms of time to clinical improvement or mortality, with more adverse events occurring in the intervention group.

Dr. Bhandari and his colleagues also offer 9 pieces of practical guidance for surgeons, one of which echoes the experience of Emory University orthopaedists and the orthopaedic community in Singapore: Create multiple teams of clinicians who are completely isolated from one another.

The authors concede that it is impossible to accurately predict the trajectory of COVID-19. Even with aggressive containment procedures, the outbreak is unlikely to see meaningful resolution for weeks to months. Their final message to the health-care community: Exercise continued vigilance and preparedness for a possible second wave and a high index of suspicion for any new cases of undifferentiated respiratory illness in the weeks to months following a slowdown in new cases.