Genetics, vascularization, nerve and cell abnormalities linked to tendinopathy

More clinical research is needed to find new and better treatments, a top specialist says.

Issue: Issue 4 2006

INNSBRUCK, Austria — Recent research into the pathology behind tendinopathy is giving physicians greater insight into the best treatments for athletes with damaged patellar, Achilles and supraspinatus tendons, lateral epicondylitis and other conditions.

Pathologies involve genetics, blood vessels, nerves and tendon cells, Karim Khan, MD, FACSP, PhD, associate professor of sports medicine at the University of British Columbia, Vancouver, said at the 12th ESSKA Congress, here.

Researchers are focusing on pathologies like apoptosis and treatments like transdermal glyceral trinitrate (GTN) patches, eccentric training and ablation of abnormal tendinous vessels and nerves with the sclerosing agent polidocaonol.

Karim Khan, MD, FACSP, PhD [photo]
Karim Khan

Khan cited recent South African studies linking the the alpha I Type IV collagen (COL5A1) gene with increased prevalence of tendinopathy. Collagen separation and decreased fiber continuity decrease tendon strength. Tendinopathy is “genetically expressed” at mechanical loading sites, Khan said.

Some researchers have studied vascular endothelial growth factor (VEGF), a pathway associated with angiogenesis and tumor growth, Khan said. Australian researcher Jill Cook, PhD; Norwegian specialist Roald Bahr, MD, PhD; and Swedish specialist Hakan Alfredson, MD, have explored the link between abnormal vascularity and tendinosis, he said.

Also, Cook found that 20% to 30% of asymptomatic basketball and volleyball players have early tendinosis in their patellar tendons, Khan said.

Apoptosis/collagen disarray

“How important are the cells themselves in the loading model?” Khan asked. “Do tendon cells actually undergo apoptosis?”

Alfredson argued that collagen disarray plays a larger role than cell abnormality.

Khan showed slides comparing cellular appearance in normal and abnormal tendon. He pointed out that early on in pathogenesis, abnormal tendon tissue already had irregularly shaped tenocytes. Matrix changes occurred infrequently in the early stage of teninopathy, he said.

He noted that apoptosis was common in ruptured tendons. He cited a study in which Australian researcher George Murrell, MD, MBBS, found “excessive” apoptopic cells in tendon degeneration. Canadian researcher Alex Scott found that hypoxia, which stimulates angiogenesis, caused apoptosis, but the process took 48 hours.

Still, researchers need to do more human studies to assess apoptosis, Khan said.

Mechanotransduction

“There are many anti-apoptic products already available, but there are questions as to whether they’re safe.”
— Karim Khan, MD, FACSP, PhD

Khan recommended exercise — particularly eccentric training which likely functions via the process of mechanotransduction — to repair damaged or degenerated tendons. Mechanotransduction is the non-neural biological process whereby a mechanical signal is converted to tissue adaptation. It is well accepted as the mechanism whereby bone responds to loading, or absence of loading. American researchers Arnoczky and Banes have begun to unravel this process in tendon.

“The clinical implication is that when I’m in the office prescribing exercise for patients and I explain what I think happens, I don’t tell them that they’re getting stronger,” Khan said. “I tell patients that they’re trying to turn on the cell apparatus — flick a switch — so that mechanotransduction can take place.”

Other novel treatments include GTN patches, a traditional treatment for angina, which Murrell pioneered for tendon use in the early 2000s with good results, Khan said. The patches appear to be effective by influencing cell function, not through their effect on blood circulation, Khan said.

Recent findings suggest that anti-inflammatory agents play a limited role in treating tendinopathy.

“There are certain pathways that lead to tendinosis that still need research,” Khan said. “We’ve seen a plethora of new treatments. … Specifically for apoptosis, there are many anti-apoptopic products already available, but there are questions as to whether they’re safe.”

For more information:
Khan K. New laboratory insights into the pathogenesis of tendinopathy: clinical implications. Lecture 2. Presented at the 12th ESSKA Congress and 5th World Congress on Sports Trauma. May 24-27, 2006. Innsbruck, Austria.