This computed tomography image shows a large osteolytic cyst in a 63-year-old male patient 4 years after undergoing total ankle arthroplasty.
Courtesy of Murray J. Penner, MD, FRCSC


Published 11/1/2014
Jennie McKee

Taking a Closer Look at Osteolysis in TAA Patients

Questions remain regarding potential triggers of bone matrix resorption

“Osteolysis is a frustrating condition: it’s what leads to total ankle arthroplasty (TAA) failure even when the surgeon has done everything right,” said Murray J. Penner, MD, FRCSC, of the University of British Columbia, Vancouver Coastal Health Authority, and Providence Health Care in Vancouver, British Columbia.

According to Dr. Penner, polyethylene wear may be a causative factor for osteolysis in these patients. Given that “early onset of osteolysis in TAA patients points away from polyethylene particles as the primary cause of the osteolysis,” noted Dr. Penner, implant design and insertion may be more important causes.

Dr. Penner explored possible causes of osteolysis in TAA patients during a symposium at the 2014 annual meeting of the American Orthopaedic Foot & Ankle Society.

Trying to head off a “blindside hit”
Even with careful patient selection and expertly performed TAA, noted Dr. Penner, annual follow-up with TAA patients may lead to a “blindside hit,” with radiographic evidence of osteolysis in an asymptomatic patient. Although patients may remain pain-free for years, surgery may eventually be required due to problems such as talar subsidence or talar cysts.

“Osteolysis has been researched extensively in the realm of hip replacement, leading to the now well-accepted etiologic theory that polyethylene wear particles are the primary causative agent of osteolysis around hip implants,” said Dr. Penner. However, contributing factors in the ankle may be different.

In general, he noted, bone resorption is likely a function of osteoclasts recruited to sites of osteolysis and activated by osteoclastogenic molecules, including RANKL, a chemical that stimulates cells whose sole purpose is to destroy bone. “But what stimulates RANKL production in osteoblasts at the site of osteolysis?” he asked. “In total hip arthroplasty, the common stimulant is polyethylene particles. These particles are bioactive in part due to their size and their shape. They are small and they are typically elongated with rough surfaces.”

But applying hip data to other types of total joint arthroplasty (TJA) may be an oversimplification, suggested Dr. Penner.

“If we equate polyethylene wear with osteolysis in every anatomic area where it occurs, we end up focused on some simplified solutions and fail to consider other causes that could be at play,” said Dr. Penner. “Although every TJA results in particle wear, most TJA patients don’t get severe osteolysis. The key is to understand why that is so.”

For example, he noted that polyethylene wear particles in knee implants is significantly different than in hip replacement implants.

“In total knee patients, polyethylene wear occurs through fatigue, which generates larger, rounder particles, compared to those generated in total hip patients,” he said.

“Several studies have shown that wear particles in the knee are typically about 3 times larger than those seen around the hip,” he continued. “As a result, they are significantly less bioactive than particles in the hip. So it’s almost certain that other factors play a larger role in osteolysis around the knee compared to the hip.”

Analyzing osteolysis in TAA patients
One study, noted Dr. Penner, showed that polyethylene particle size in TAA is very similar to that in TKA. “This implies that the relative role of polyethylene particulate in ankle replacement is going to be closer to that found in the knee. In other words, polyethylene wear is likely a contributor, but not necessarily the only factor, for osteolysis.

“Furthermore, hip and knee replacement osteolysis tends to occur fairly late,” he continued. “We don’t see that late osteolysis in TAA as much. He cited the example of a 74-year-old male TAA patient whose radiographs showed “a little shadow poking down from below his talar component,” indicating the beginnings of osteolysis, just 6 months after undergoing TAA.

“At 1 year out, he was not much different,” said Dr. Penner. “But at 2 years, it was clear something bad was going on, and it continued through years 3 and 4. At 5 years, the patient’s ankle had become painful. Clearly, this patient did not have any period in the use of his ankle replacement without evidence of osteolysis. That’s not characteristic of polyethylene wear.”

Dr. Penner and his colleagues have analyzed the pathology of 18 TAA patients who underwent revision surgery for either osteolysis or implant loosening.

“We found little or no polyethylene debris in almost half of these cases,” he said. “The only other similar study had comparable results, with just over half of the cases showing no significant amounts of polyethylene debris at mean revision time of 5 years. No macroscopic polyethylene wear was found on any of the retrieved specimens.”

Looking for other potential causes
This evidence raises the question of what other factors might be at play. In Dr. Penner’s view, potential clues may come from a Finnish study conducted in 2012 that detailed the histochemical and histologic analysis of 10 retrieved total ankle implants.

“The researchers found mostly necrotic tissue, with significant amounts of RANKL present,” said Dr. Penner. “They concluded that osteolysis in early ankle replacement isn’t being driven by implant-derived particles, but is a RANKL-driven reaction to necrotic autologous tissue. The cause of this tissue necrosis is unknown, but might include bone injury, ischemia, stress shielding, high intra-articular fluid pressure, and micromotion, all of which are known potential causes of osteolysis, in the knee setting.”

Considering that a sprained ankle can lead to localized osteolysis, it is not surprising, said Dr. Penner, that osteolysis can result from TAA. Genetic variations in patients may also influence the development and severity of osteolysis after TAA.

“In summary,” he concluded, “osteolysis in TAA patients typically occurs early, without any significant amount of bioactive polyethylene particulate in the area, which suggests that something other than polyethylene debris is stimulating RANKL. These factors seem to be associated with and linked to localized tissue and bone necrosis occurring adjacent to the prosthesis and may be modulated by an individual patient’s genetics.”

Treatment strategies
When cysts are identified and seen to progress in TAA patients with osteolysis, noted Dr. Penner, “bone grafting or revision is likely warranted.”

He outlined the treatment strategy followed for a TAA patient who had a massive tibial cyst. After removing the cyst, Dr. Penner hoped to salvage the TAA with a bone graft.

“Because the implant appeared to be stable, I filled the defect with a mix of morselized femoral head allograft, some of the patient’s own iliac crest bone graft, and some recombinant platelet-derived growth factor.

“At 7 months out,” he continued, “the patient had reasonable graft consolidation. The radiographs looked better, but he continued to have pain, and will soon undergo revision surgery. We just hope that some of the talar bone stock has been restored so that it can support an implant.”

Few studies have been conducted regarding treatment options for TAA patients with osteolysis, noted Dr. Penner. “Pursuit of a greater understanding of osteolysis in these patients is certainly warranted.”

Disclosure information: Dr. Penner—Wright Medical Technology, Inc.; Integra LifeSciences; Arthrex, Inc.; Bioimimetic; CONMED Linvatec; Synthes; Cartiva; Foot & Ankle Specialist; Clinical Orthopaedics and Related Research; Journal of Bone and Joint Surgery; American Orthopaedic Foot & Ankle Society, Canadian Orthopaedic Foot & Ankle Society

Jennie McKee is a senior science writer for AAOS Now. She can be reached at

Bottom Line

  • Most of the existing literature on post-arthroplasty osteolysis focuses on total hip and total knee patients, rather than TAA patients.
  • According to Dr. Penner, implant design and insertion factors are as important or more important than implant wear as causes of osteolysis in TAA patients, given the early onset of osteolysis in TAA patients.
  • Early osteolysis in TAA patients may be a RANKL-driven reaction to necrotic tissue resulting from bone injury, ischemia, stress shielding, high intra-articular fluid pressure, and micromotion.
  • More research focusing on osteolysis in TAA patients is needed to determine all the factors that may trigger it.


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  3. Koivu H, Mackiewicz Z, Takakubo Y et al: RANKL in the osteolysis of AES total ankle replacement implants. Bone 2012; 51(3):546-52.
  4. Shanbhag AS, Bailey HO, Hwang DS et al: Quantitative analysis of ultrahigh molecular weight polyethylene (UHMWPE) wear debris associated with total knee replacements. J Biomed Mater Res 2000; 53(1):100-10.