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Mini-Review: Toxic Tendinopathy
11 GEMpath, Inc., Longmont, Colorado, USA.
Abstract:
Toxic tendinopathy is a rare but reproducible complication in humans, given agents of four drug classes: aromatase inhibitors, fluoroquinolone antibiotics, glucocorticoids (long-term regimens), and statins. Toxic tendinopathy in humans has been linked less consistently to treatment with anabolic steroids, antiretroviral agents (mainly protease inhibitors), metalloproteinase inhibitors (MMPI), and isotretinoin. Classic drug-induced tendinopathies appear as "tendinosis" (i.e., progressive tendon degeneration without inflammation), although cases associated with aromatase inhibitors exhibit mainly tenosynovitis. Any tendon may be affected, but fluoroquinolones, glucocorticoids, and statins most frequently affect large load-bearing tendons in the lower limb, especially the calcaneal ("Achilles") tendon-which ruptures in approximately 30 to 40% of cases. The time to symptom onset ranges from days (fluoroquinolones) to weeks, months, or even years. The pathogenesis is incompletely understood, but proposed mechanisms include apoptosis of tenoblasts and tenocytes, deficient tenocyte function (leading to abnormal extracellular matrix maintenance and repair as well as disrupted intercellular signaling), and structural disintegration (via a combination of increased expression of lytic enzymes, lessened cholesterol content in cell membranes, and neoangiogenesis within highly ordered tendon tissue). Nonclinical safety assessment of therapeutic candidates in these drug classes should incorporate tendon routinely as a protocol-specified tissue for pathology evaluation.
Insights
Certain medications, including aromatase inhibitors, fluoroquinolones, glucocorticoids, and statins, can cause toxic tendinopathy, a progressive tendon degeneration. This condition, particularly affecting the Achilles tendon, can lead to rupture and requires careful monitoring during drug safety assessments.
Area of Science:
- Pharmacology
- Orthopedics
- Toxicology
Background:
- Toxic tendinopathy is a rare but documented adverse effect associated with several drug classes.
- Commonly implicated drugs include aromatase inhibitors, fluoroquinolone antibiotics, glucocorticoids, and statins.
- Less consistent links exist with anabolic steroids, antiretroviral agents, metalloproteinase inhibitors, and isotretinoin.
Purpose of the Study:
- To review the clinical presentation and proposed pathogenesis of drug-induced toxic tendinopathy.
- To highlight the specific tendons affected and the risk of rupture.
- To recommend incorporating tendon evaluation in nonclinical drug safety assessments.
Main Methods:
- Review of existing literature on drug-induced tendinopathy.
- Analysis of clinical presentations, including affected tendons and time to onset.
- Discussion of proposed pathogenetic mechanisms.
Main Results:
- Drug-induced tendinopathies typically manifest as tendinosis, except for aromatase inhibitor-associated tenosynovitis.
- Load-bearing tendons, particularly the Achilles tendon, are most frequently affected by fluoroquinolones, glucocorticoids, and statins, with a 30-40% rupture rate.
- Symptom onset varies from days to years depending on the causative agent.
Conclusions:
- Toxic tendinopathy is a significant complication of certain medications, necessitating awareness among clinicians and researchers.
- Understanding the pathogenesis, including cellular and molecular mechanisms, is crucial for risk mitigation.
- Routine tendon pathology evaluation in nonclinical safety assessments for relevant drug classes is recommended to prevent adverse events.
