Why does the use of quinolones increase the risk of tendinopathies?
I have read the claim in different places, but I didn't read the reason.
Quinolones are associated with an increased risk of tendinitis and tendon rupture in all age groups. This side effect is most common in but not limited to the Achilles tendon. Fluoroquinolone-associated tendinopathy symptoms have occurred as early as 2 hours after the initial fluoroquinolone exposure and as late as 6 months after the medication was discontinued. The most severe form of tendonopathy associated with fluoroquinolone administration is tendon rupture, which in the great majority of cases involves the Achilles tendon. Younger people typically experience good recovery, but permanent disability is possible, and is more likely in older patients. The overall frequency of fluoroquinolone-associated Achilles tendon rupture in patients treated with ciprofloxacin or levofloxacin has been estimated at 17 per 100,000 treatments (three times the rate in people without fluoroquinolone exposure). Risk is substantially elevated in the elderly and in those with recent exposure to topical or systemic corticosteroid therapy. Simultaneous use of corticosteroids is present in almost one-third of quinolone-associated tendon rupture. Other risk factors include patients with kidney, heart and lung transplants, strenuous physical activity during or immediately after treatment, renal failure or previous tendon disorders like rheumatoid arthritis. Some experts have advised avoidance of fluoroquinolones in athletes.
The use of fluoroquinolone may predispose individuals to tendinopathies.
(1) gives some ideas but is inconclusive, and was published six years ago, so I wonder whether the understanding on that matter has improved since then:
The exact pathophysiology of FQ-induced tendinopathy remains elusive; however, some concepts have been suggested. FQs are synthetic antibiotics that act by inhibiting bacterial DNA gyrase (topoisomerase II).27 DNA gyrase is directly involved in DNA replication and cell division.10 Theoretically, FQs should not exert a negative effect on human cell lines because the affected bacterial enzymes have little homology with mammalian DNA gyrase.10 However, it is possible that FQs have a direct cytotoxic effect on enzymes found in mammalian musculoskeletal tissue.10 Because animal studies have shown that FQs may damage juvenile weight-bearing joints, most FQs are contraindicated in children and during pregnancy and lactation.39–40 FQs have chelating properties against several metal ions (e.g., calcium, magnesium, aluminum), and have been known to cause direct toxicity to type 1 collagen synthesis and promote collagen degradation.33,35 Experiments on immature laboratory animals (dogs, rabbits, and rats) have shown that FQs cause cartilage damage by inducing necrosis of chondrocytes (36 hours after treatment), disruption of the extracellular matrix, and formation of vesicles and fissures at the articular surface.41 In-vitro studies in cultured tendon cells have confirmed the clinical observation that FQs can increase the risk of tendon rupture.42 Under normal circumstances, the rate of matrix turn-over and tendon fibroblast is low.10 Other precipitating factors, such as age and corticosteroid use, do not allow the tendon to repair adequately, resulting in irreversible matrix alteration.43 It has been theorized that FQs disproportionately affect human tendons that have a limited capacity for repair, such as in older patients or structural compromise (i.e., pre-existing tendinopathy or trauma).10
- (1) Kim, Grace K., and James Q. Del Rosso. "The risk of fluoroquinolone-induced tendinopathy and tendon rupture: what does the clinician need to know." J Clin Aesthet Dermatol 3, no. 4 (2010): 49-54. https://scholar.google.com/scholar?cluster=3037507805225920093&hl=en&as_sdt=0,22 ; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2921747/