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Research Profiles

Denis Nam, MD

Taking Another Look at Osteolysis

Denis Nam, MD Resident Clinician Scientist Training Grant

Research Summary
Research topic: Studying the role that fluid pressure plays in causing osteolysis

Research results: The possibility of controlling the flow of fluid around implants and reducing proximal bone loss through pharmacologic inventions, revisions in implant design, or both

Patient care application of results: Reducing the incidence of bone loss and resulting implant loosening associated with implant failure

Simplified patient care application: Less bone loss, longer-lasting implants and fewer repeat surgeries for patients receiving knee and hip replacements

Taking Another Look at Osteolysis

OREF grant recipient examines the role fluid pressure plays
By Mark Crawford

Osteolysis is one of the persistent barriers to long-term success of total joint arthroplasty. And debris due to implant wear has been fingered as a major culprit.

However, Denis Nam, MD, an adult reconstruction and joint replacement fellow at the Hospital for Special Surgery (HSS) Weill Medical College of Cornell University (Weill Cornell) in New York City, is investigating whether dynamic fluid pressures may actually induce bone resorption and play a significant role in the onset of osteolysis.
In the process of formulating an idea for a research project, Dr. Nam spoke with scientists working under HSS Attending Orthopaedic Surgeon and Weill Cornell Professor of Orthopaedic Surgery, Mathias P. G. Bostrom, MD, including Anna Fahlgren, PhD, who is also a lecturer and Marie Curie Vinmer Fellow at Linköping University, Linköping, Sweden.

“I was drawn to Dr. Fahlgren’s idea that fluid pressure may be causing bone loss around implants,” said Dr. Nam. “We all know debris particles are important, but maybe fluid and hydrostatic pressure, and pressure within the joints and around the implants, contribute to bone loss.”

Dr. Nam is using a 2011 OREF/AAHKS Resident Clinician Scientist Training Grant made possible by Zimmer Holdings Inc. to further explore this hypothesis.

What if…
“The accepted theory is that debris erodes from implant surfaces and triggers a response from the body that engulfs the debris, and also removes bone,” said Dr. Nam. “Our study explores the possibility that fluid pressure can also cause osteolysis. For example, considerable literature in the trauma world has shown that even the slightest instability during surgery can cause fluid fluctuations, which result in superficial bone resorption.”

If hydrostatic pressure and fluid flow velocity in the tissues adjacent to the prosthesis activate an alternative signaling pathway that leads to osteoclast activation, this dynamic may be more critical than the classic pro-inflammatory pathway during specific stages of aseptic loosening.  

“It is quite probable that both factors contribute at different times to loosen implants,” said Dr. Nam. “At one point, pressure fluctuations may be causal; at another, it might be particles. In fact, they’re probably working synergistically to cause bone loss. Wear debris is understood to be a long-term phenomenon, so fluid pressure may also explain why some implants fail before debris accumulates.”

Building on past studies
Dr. Nam will use a well-established rat model that uses a piston to apply fluctuating hydrostatic pressure to the bone by compressing a soft-tissue membrane that forms underneath the piston. Cyclic motion of the piston perpendicular to an isolated bone surface creates fluid pressure and flow around the proximal tibia.

This model has been shown to reliably produce an osteolytic lesion both directly below the piston and in adjacent porous bone connected through preformed cavities, leading to pressure-induced bone resorption.

Prior to activating the piston, the soft tissue membrane is allowed to form within a 1-mm space underneath the piston. By applying force to the piston, load is transmitted to the soft tissue through the skin via a dynamometer. Once loading is initiated, an 8N transcutaneous force is applied under anesthesia for 20 cycles at a frequency of 0.17 Hz, twice a day. This stimulus is based on previous levels that have experimentally created osteolytic lesions.

After five days of loading, specimens will be prepared for both histomorphometry and immunohistochemistry analysis, and microCT (micro-computed tomography) analysis. Osteolysis indicators will be assessed under light microscopy, both at x4 and x40 magnification, using hematoxylin and eosin stains and the presence of fibroblasts, macrophages, polymorphonuclear cells, and round cells will be recorded.  

Promising results
Results so far have confirmed that a direct correlation exists between increased fluid pressure loading and bone loss.

“Hopefully this work will lead to new pharmacologic treatments or implant designs that prevent early loosening,” said Dr. Nam. “Perhaps these results will lead to engineering implants in a way that limits the flow of fluid around the implant.  For example, an optimal design might require other innovations to mitigate fluid flow factors.”

Excellent mentors
Dr. Nam said he’s inspired to take on the challenge of a dual career as a clinician and a scientist by others who work hard and achieve results. “My dad is a pulmonologist who immigrated from Korea and always worked hard. I remember coming home from school and always finding him reading Harrison’s textbook on internal medicine,” he recalled. “I’m extremely lucky to have my dad’s example—and so much support from Dr. Bostom and Dr. Fahlgren and others in the lab to guide me. I honestly couldn’t do this without them.” Understanding the osteolytic mechanism at the established bone-implant interface will stimulate further investigation into identifying innovative pharmacologic solutions, preventive strategies, and new ways to modify prosthetic designs. By decreasing periprosthetic fluid pressure and flow, aseptic loosening in total joint arthroplasty may be reduced and implants may last longer.






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