Ciprofloxacin Induced Chondrotoxicity and Tendinopathy PDF
Ciprofloxacin Induced Chondrotoxicity and Tendinopathy PDF
ISSN: 1557-4962
©2012 Science Publication
doi:10.3844/ajptsp.2012.94.100 Published Online 7 (3) 2012 (http://www.thescipub.com/ajpt.toc)
remarkably few reactions (Hooper and Wolfson, 1985; (Channa et al., 2008). The above reports could be
Ball, 1986). These reactions include gastrointestinal consistent with the study of Stahlmann et al. (2000)
tract, central nervous system and hematological system who reported that 200 mg kg−1 of Ciprofloxacin
(Petri, 2001; Lode et al., 1998). administered to immature Beagles induced cleft
Despite its safe profile there are reported cases of formation and erosion of joint cartilage. Male wistar
Ciprofloxacin induced chrondrotoxicity, Tendinopathy rats exposed to 50mg kg−1 of Ciprofloxacin for 21
and tendon rupture in animals and humans (Khaliq days inhibit fracture healing with decreased cartilage
and Zhanel 2003; Channa et al., 2008). It was reported cellullarity and fibrous proliferation and matrix
that Ciprofloxacin decreased thickness of the articular degeneration (Huddleston et al., 2000).
cartilage of the femoral condyle, inhibit proliferation Furthermore, 30 and 90 mg kg−1 oral doses of
of cultivated chondrocytes and secretion of soluble Ciprofloxacin was found to induce a characteristic
proteoglycans in a concentration and time dependant arthropathy (blister and erosions) in Juvenile beagle with
manner (Li et al., 2004). Ciprofloxacin induced persisted lesions after five (5) months treatment free period
damage of the articular and epiphysical growth plate (Keutz et al., 2004). Ciprofloxacin in a 2 weeks study
cartilage of knee joint, tendinopathy and tendon induced cartilage blisters when 100 and 200 mg kg−1 were
rupture (Halawa, 2010; Kim, 2010).
administered to Juvenile dogs. In another study, cartilage
The pathogenesis of Ciprofloxacin induced
chrondrotoxicity, tendinopathy and tendon rupture is a alterations in Knee joints were seen after 30-100 mg kg−1 of
multifactoral event (Halawa, 2010). Previous Ciprofloxacin was administered for 3 weeks (Schuter,
studies attributed cartilage damage in growing animals 1987). Several cartilage lesions marked by matrix swelling
to oxidative stress, lipid peroxidation and DNA and loss of chondrocytes were observed when 400, 800 and
oxidative damage of the chondrocytes and collagen 1200 mg kg−1 of Ciprofloxacin was administered to 4
(Simonin et al., 1999; Li et al., 2004). week-old rats for 7 days consecutively. The thickness of
Other authors’ referred to Ciprofloxacin induced the femoral condyle was significantly decreased compare
tendinopathy to their inhibitory effects on DNA, collagen to the control. Proliferation of chondrocytes and
and proteoglycan synthesis (Maslanka et al., 2004). As secretion of soluble proteoglycans were also inhibited
of July 2008, the United State Food and Drug (Li et al., 2004; Pfister et al., 2007).
Administration mandated that Ciprofloxacin product Other authors found that single high oral doses and
should have a black-box warning indicating an increased
multiple low doses of Ciprofloxacin were chondrotoxic
risk in adverse events including tendon rupture (Kim,
2010). This study reviews reported Ciprofloxacin in Juvenile rats. Ciprofloxacin induced scars and
induced Chrondrotoxicity, Tendinopathy and tendon erosions of the joint surface as well as chondrocytes
rupture in humans and animals due to rising trend. clusters with non Cellular areas of the articular matrix
(Foster et al., 1997; Stahlmann, 2003). The study of Li et al.
1.1. Animal Studies (2004) is in support of the above report. He reported that
Experiments with animals have reported cases of Ciprofloxacin inhibited chondrocytes proliferation in a dose
Ciprofloxacin induced chrondrotoxicity, tendinopathy and dependant and time dependant manner. 10-80 mg L−1 of
tendon rupture (Li et al.,1990; Stahlmann, 2003; Tsai et al., Ciprofloxacin decreased secretion of soluble proteoglycans
2008). It was observed that Ciprofloxacin at a dose level after incubation with chondrocytes for 5 days.
of 20 mg kg−1 day administered to rats for 15 days induced Subcutaneous injection of 600 mg kg−1 of
articular damage, cavity Formation wide clefts and Ciprofloxacin administered to 34-day old wistar rats
decrease in both articular and epiphyseal growth plate induced cartilage lesion in 11 of 12 (92%) rats
(Halawa, 2010). This report is in resonance with the report (Stahlmann et al., 1999; Pfister et al., 2007). Ultra
of Channa et al. (2008) who administered 20 mg kg−1 of structural changes were observed in Achilles tenocytes
Ciprofloxacin to wistar albino pulps. He observed of Ciprofloxacin treated Spraque Dawley rats (Stahlmann,
decrease in the width of epiphyseal growth plate cartilage, 2002; Bae et al., 2006). These reports are at variance with
humerus and femur as compared to the control. the study of Kashida and Kato (1997), who observed that
In another study where Ciprofloxacin was 200mg and 900 m kg−1 of Ciprofloxacin administered to
administered to newly born rat-litters intraperitonealy. rats did not induce Achilles tendon toxicity.
Ciprofloxacin induced growth plate retardation by Some researchers observed that Ciprofloxacin
inhibiting mitosis in the proliferative zone. Ciprofloxacin induced cartilage damage in experimental animals when
also affected the mean length of humora and femora administered during certain developmental stages via
leading to reduction in Limb length of rat pulps changes of cytoskeleton morphology (Water et al., 1998;
Egerbacher et al., 2000). Ciprofloxacin at a dose level of rupture were found in 2, 122 Ciprofloxacin treated patients
50 mg kg−1 administered to rats for 3 weeks revealed (Shinohara et al., 1997). In France Pierfitte et al. (2000)
significant deterioration of Biochemical parameters, reviewed 421 cases of Fluoroquinolones associated
hyaline degeneration and fibre disarrangement in the tendinopathy. They reported that only 5% of
tendon of rats (Olcay et al., 2011). Fluoroquinolones associated tendinopathy was attributed
Findings showed that Ciprofloxacin exerts a to Ciprofloxacin.
negative impact on migration and proliferation as well as In a critical literature review of fluoroquinolones
the collagen metabolism of tenocytes (Mehra et al., associated tendinopathy in humans. It was observed that
2004; Tsai et al., 2011). Pauzaud et al. (2004) reported Ciprofloxacin is one of the agents associated with
that Ciprofloxacin showed moderate Cytotoxicity after tendinopathy (Khaliq and Zhanel, 2003; Mirovsky et al.,
28 hours and more severe significant toxicity after 72 1995; Brava et al., 1996; Carrasco et al., 1997). In a case
hours on tendon cells. This agrees with the study which study, 98 cases of fluoroquinolones induced tendon
observed that Ciprofloxacin inhibits tendon cell injury were reported. It was observed that the second most
proliferation and cause cell cycle arrest in rats (Tsai et al., commonly implicated fluoroquinolone associated with
2008). It was reported that cell proliferation in horse and tendon injury was Ciprofloxacin (25.5% of all cases) with
dog chondrocytes decreased in Ciprofloxacin cultivated total daily doses ranging from 500-200 mg for a mean
groups (Egerbacher et al., 2001).
duration of 24±29.3 days (Khaliq and Zhanel, 2003).
Incubation of Achilles tendon, Achilles paratenon
In an observed cohort study of fluoroquinolones and
and shoulder capsule fibroblast with Ciprofloxacin
other antibiotics induced tendon disorder. It was reported
hydrochloride (5-50 pg mL−1) significantly decreased that Ciprofloxacin is also associated with tendon disorder
cell proliferation, collagen synthesis and proteoglycan but with effects lesser than that of Ofloxacin (Wilton et al.,
synthesis in fibroblast cell line (Williams et al., 2000). 1996). In 1795 case report forms for children receiving
Degenerative changes in tenocytes due to swelling and Ciprofloxacin which were collected up to the end of
dilatation of cell organelles, densified nuclei and 1994 by Bayer cooperation Germany (Chysky et al.,
clumped chromatin cell detachment from extracellular 1991; Hampel et al., 1997) shows that Ciprofloxacin is
matrix, decrease in fibril diameter and increase distance safe for children, adolescents and do not have negative
between collagenous fibrils were induced by Ciprofloxacin effects on the linear growth children. This is at variance
in immature wistar rats (Shakibaei et al., 2000). with what was observed in animal studies (Kato, 2008).
1.2. Human Studies The confirmation of the safety of Ciprofloxacin
especially in relation to the skeletal system in large
There is increasing trend of Ciprofloxacin induced scale clinical studies has led to it being approved for
tendinopathy and tendon rapture in human (McEwan and use in pediatric patients with cystic fibrosis (Kato,
Davey, 1988; Movin et al., 1997; Short et al., 2006). 2008). This report could be at variance with the report
There is a reported case of Ciprofloxacin associated of Adefurin et al. (2011). Who stated that a total of
Achilles tendon diseases. Microscopic evaluation revealed
16184 pediatric patients who were exposed to
irregular collagen fibre arrangement, hypercellularity and
Ciprofloxacin and 1065 reported cases of
increase interfibrillar glycosaminoglycan (West and Gow,
1998; Pantalone et al., 2011). Ciprofloxacin induced musculoskeletal adverse effects were observed.
Achilles tendon rupture characterized by degenerative Furthermore, monolayers of human tenocytes were
changes in left Achilles tendon, cystic changes with focal incubated with Ciprofloxacin. Ciprofloxacin significantly
necrosis (Hugo-Persson, 1996; Jagose et al., 1996; decreased type 1 collagen, beta (1)-integrin receptors,
Petersen and Lapress, 1998). cytoskeletal and signaling proteins. It increased matrix
Khazad and Schwenk (2005) reported a case of non metalloproteinases as well as the apoptosis marker activated
traumatic rupture of Achilles tendon in a patient who caspase 3 effects are intensified at higher concentrations and
received oral Ciprofloxacin 500 mg twice orally for longer incubation periods (Corps et al., 2005; Sendzik et al.,
urinary tract infection. This agrees with the report of
2005; 2010).
other authors (Lee and Collins, 1992; Poon and
Sundaram, 1997; Caspirian et al., 2000). 1.3. Pathogenesis
In a case study, 32 patents (76%) had tendinitis and
10 patents (24%) had tendon rupture. 13 (31%) were The pathogenesis of fluoroquinolones (Ciprofloxacin)
attributed to Ciprofloxacin (Linden et al., 2001). This is at induced chrondrotoxicity, tendinopathy and tendon
variance with a study where no cases of Achilles tendon rupture has not been fully established (Khaliq and Zhanel
Egerbacher, M., B. Wolfesberger and C. Gabler, 2001. In Hugo-Persson, M., 1996. Rupture of the Achilles tendon
vitro evidence for effects of magnesium after ciproxine therapy. Lakartidningen, 93: 1520-
supplementation on quinolone-treated horse and dog 1520. PMID: 8667750
chondrocytes. Vet. Pathol., 38: 143-148. PMID: Jagose, J.T., D.R. McGregor, G.R. Nind and R.R. Bailey,
11280370 1996. Achilles tendon rupture due to ciprofloxacin.
Egerbacher, M., G. Seiberl, B. Wolfebergen and I. Walter, N. Z. Med. J., 109: 471-472. PMID: 9006634
2000. Ciprofloxacin causes cytoskeletal changes and Kashida, Y. and M. Kato, 1997. Characterization of
detachment of human and rat chondrocytes in vitro. fluoroquinolone-induced Achilles tendon toxicity in
Arch. Toxicol., 73: 557-563. PMID: 10663387 rats: Comparison of toxicities of 10
Foster, C., R. Schwabe, E. Lozo, U. Zippel and fluoroquinolones and effects of anti-inflammatory
J. Vormann et al., 1997. Quinolone-induced compounds. Antimicrob. Agents Chemother., 14:
arthropathy: Exposure of magnesium-deficient aged 2389-2393. PMID: 9371338
rats or immature rats, mineral concentrations in Kato, M., 2008. Chondrotoxicity of quinolone
target tissues and pharmacokinetics. Arch. Toxicol., antimicrobial agents. J. Toxicol. Pathol., 21: 123-
72: 26-32. PMID: 9458187 131. DOI: 10.1293/tox.21.123
Halawa, A.M., 2010. Effect of ciprofloxacin on the Kelly, M., M. Dodds, J.S. Huntley and C.M. Robinson,
articular cartilage and epiphyseal growthplate 2004. Bilateral concurrent rupture of the Achilles
cartilage in the growing albino rats and the possible tendon in the absence of risk factors. Hosp. Med.,
protective roleof vitamin E (α-Tocopherol): A 65: 310-311. PMID: 15176151
histological and morphometric study. Egypt. J. Keutz, E.V., C. Ruhl, W.F. Drommer and
Histol., 33: 569-582. M. Rosenbrunch, 2004. Effects of ciprofloxacin on
Hall, M.M., J.T. Finnoff and J. Smith, 2011. joint cartilage in immature dogs immediately after
Musculoskeletal complications of fluoroquinolones: dosing and after a 5-month treatment-free period.
Guidelines and precautions for usage in the athletic Arch. Toxicol., 78: 418-424.
population. PM. R., 3: 132-142. PMID: 21333952 Khaliq, Y. and G.G. Zhanel, 2003. Fluoroquinolone-
associated tendinopathy: A critical review of the
Hampel, B., R. Hullmann and R. Schmidt, 1997.
literature. Clin. Infect. Dis., 36: 1404-1410. PMID:
Ciprofloxacin in Pediatrics. Ciprofloxacin in
12766835
pediatrics: Worldwide clinical experience based on
Khazad, A. and A.J. Schwenk, 2005. Irrational Roots of
compassionate use--safety report. Pediatr. Infect. Integers. College Math. J.
Dis., 16: 127-129. PMID: 9002122 Kim, G.K., 2010. The risk of fluoroquinolone-induced
Hayem, G., O. Domarle, M. Lay, M. Thuong-Guyot and tendinopathy and tendon rupture: What does the
J.J. Pocidalo et al., 1996. Lack of correlation clinician need to know? J. Clin. Aesthetic.
between hydrogen peroxide production and nitric Dermatol., 3: 49-54. PMID: 20725547
oxide production by cultured rabbit articular Kotnis, R.A., J.C. Halstead and P.J. Hormbrey, 1999.
chondrocytes treated with fluoroquinolone Atraumatic bilateral Achilles tendon rupture: An
antimicrobial agents. Toxicol. Vitro, 10: 551-555. association of systemic steroid treatment. J. Accid.
PMID: 20650236 Emerg. Med., 16: 378-379.
Hickory, W., R. Nanda and F.A. Gatalanolo, 1979. Fetal Lee, T.W. and J.F. Collins, 1992. Ciprofloxacin
skeletal malformations associated with moderate associated bilateral Achilles tendon rupture. Aust. N
zinc deficiency during pregnancy. J. Nutr., 109: 883- Z. J. Med., 22: 500-500.
891. PMID: 438902 Li, P., N.N. Cheng, B.V. Chen and Y.M. Weng, 2004. In
Hooper, D.C. and J.S. Wolfson, 1985. The vivo and in vitro chondrotoxicity of ciprofloxacin in
fluoroquinolones: Pharmacology, clinical uses and juvenile rats. Arch. Pharmacol. Sin., 25: 1262-1266.
toxicities in humans. Antimicrob. Agents PMID: 15456526
Chemother., 28: 716-721. PMID: 2936302 Li, P., N.N. Cheng, B.Y. Chen and Y.M. Wang, 1990. In
Hooper, D.C., 2000. Quinolones. In: Marvell Douglas vivo and in vitro chondrotoxicity of ciprofloxacin in
and Bennetts Principles and Practice of Infections juvenile rats. Acta Pharmacol. Sin., 25: 1262-1266.
Disease 5th, Mandell, G.L., J.E. Benntt and R. Dolin PMID: 15456526
(Eds.)., Churchhill Livingstone. New York, pp: 403-423. Li, Q., S. Peng, Z. Sheng and Y. Wang, 2010. Ofloxacin
Huddleston, P.M., J.M. Steckelberg, A.D. Hassen, induces oxidative damage to joint chondrocytes of
M.S. Rose and M.E. Bolanda et al., 2000. Juvenile rabbits: Excessive production of reactive
Ciprofloxacin inhibition of experimental fracture oxygen species. Lipid peroxidation and DNA
healing. J. Bone Joint Surge. Am., 82: 161-173. damage. Eur. J. Pharmacol., 626: 146-153. PMID:
PMID: 10682725 19818344
Lica, K. and X. Zhao, 1997. DNA gyrase, topoisomerase Papich, M., 1998. Antibacterial drug therapy. Focus on
IV and the 4-quinolones. Microbial. Mol. Rev., 61: new drugs. Vet. Clin. Pharm. Therapy, 28: 215-231.
377-392. PMID: 9293187 PMID: 9556846
Linden, P.K., R.C. Moellering, C.A. Wood, S.J. Rehm Pauzaud, F., K. Bernard-Beaubois, M. Therenin,
and J. Flaherty, 2001. Treatment of vancomycin- J.M. Warnet and G. Hoyem et al., 2004. In vitro
resistant enterococcus faecium infections with discrimination of fluoroquinolones toxicity on
quinupristin/dalfopristin. Clin. Infect. Dis., 33: tendon cells: Involvement of oxidative stress. J.
1816-1823. Pharmacol. Exp. Ther., 308: 394-402. PMID:
Lode, H., K. Bomer and P. Koeppe, 1998. 14569066
Pharmacodynamics of fluoroquinolones. Clin. Petersen, W. and H. Lapress, 1998. Insidious rupture of
Infect. Dis, 27: 33-39. PMID: 9675446
the Achilles tendon after ciprofloxacin-induced
Lozo, J., M. Vukasinovic, I. Strahinic and A. Topisirovic,
tendopathy. A case report. Unfallchirurgie, 101:
2004. Characterization and antimicrobial activity of
bacteriocin 217 produced by natural isolate 731-734. PMID: 9816984
Lactobacillus paracasei subsp. paracasei BGBUK2- Petri, W.A., 2001. Sulfonamides, Trimethroprim-
16. J. Food Protect., 67: 2727-2734. Sulforne Thoxazole, Quinolones And Agents of
Maslanka, T., J.J. Jaroszewski and M. Chrostowska, Urinary Tract Infections. In: Goodman Gilman’s the
2004. Pathogenesis of quinolone-induced Pharmacological Buns of Therapeutics, Brunron
arthropathy: A review of hypotheses. Pol. J. Vet. L.L., (Ed.)., The MC Graw Hill Companies Inc.,
Sci., 7: 323-331. PMID: 15633793 New York, pp: 1463-1476.
McEwan, S.R. and P.G. Davey, 1988. Ciprofloxacin and Pfister, K., D. Mazur, J. Vormann and R. Stahlman,
tenosynovitis. Lancet, 2: 900-900. PMID: 2902333 2007. Diminished ciprofloxacin-induced
Mehra, A., R. Case and R.C. Croucher, 2004. Bilateral chrondrotoxicity by supplementation with
simultaneous spontaneous rupture of the Achilles magnesium and vitamin E in immature rats.
tendon. Hosp. Med., 65: 308-309. Chemother, 51: 022-1027.
Mirovsky, Y., I. Pollack and A. Arlazoroff, 1995. Pierfitte, C., R.J. Royer, N. Moore and B. Begaud, 2000.
Ciprofloxacin-associated bilateral acute achilles The link between sunshine and phototoxicity of
tendinitis. Harefuah, 129: 470-472. PMID: 8846955 sparfloxacin. Br. J. Clin. Pharmacol., 49: 609-612.
Mitscher, L.A. and Z. Mao, 2003. Structure activity DOI: 10.1046/j.1365-2125.2000.00212.x
relationships of Quinolones. In: Fluoroquinolone Poon, C.C. and N.A. Sundaram, 1997. Spontaneous
Antibiotics, Ronald, A.R. and D.E. Low (Eds.)., bilateral achilles tendon rupture associated with
Springer, Basel, Boston Berlin, ISBN-10: ciprofloxacin. Med. J. Aust., 166: 665-665.
3764365919, pp: 11-48. Prasad, A.S., 1991. Discovery of human zinc deficiency
Movin, T., A. Gad, P. Guntner, Z. Foldhazy and C. Rolf, and studies in an experimental human model. Am. J.
1997. Pathology of the Achilles tendon in Clin. Nutr., 53: 403-412.
association with ciprofloxacin treatment. Foot Ankle Schuter, G., 1987. Ciprofloxacin review of potential
Int., 18: 297-299. PMID: 9167931 toxicological effects. Am. J. Med., 82: 91-93.
Olcay, E., O. Beytemur, F. Kaleagasioghi, T. Gulmez Sendzik, J., M. Shakabaei, M. Schater-Korting, H. Lode
and Z. Mutlu, 2011. Oral toxicity of perfloxacin, and R. Stahlmann, 2010. Synergistic effects of
norfloxacin, ofloxacin and ciprofloxacin: dexamethasone and quinolones on human-derived
Comparison of biochemical and histopathological tendon cells. Int. J. Antimicrob. Agents, 35: 366-
effects on Achilles tendon in rats. J. Toxicol. Sci., 374. PMID: 20034766
36: 339-345. Sendzik, J., M. Shakibaei, M. Schafer-Korting and
Orava, S., M. Hume and J. Leppilahti, 1996. Bilateral R. Stahlmann, 2005. Fluoroquinolones cause
Achilles tendon rupture: A report on two cases. changes in extracellular matrix, signalling proteins,
Scand. J. Med. Sci. Spot., 6: 309-312. PMID: metalloproteinases and caspase-3 in cultured human
8960654 tendon cells. Toxicology, 272: 24-36. PMID:
Pantalone, A., M. Abafe, C. Diovidio, A. Carnevale and 15890441
V. Salini, 2011. Diagnostic failure of ciprofloxacin- Shakibaei, M., K. Pfister, R. Schwabe, J. Vorman and
induced spontaneous bilateral Achilles tendon R. Stahlmann, 2000. Ultrastructure of achilles
rupture: Case-report and medical-legal tendons of rats treated with ofloxacin and fed a normal
considerations. Int. J. Immonopathol. Pharmacol., or magnesium-deficient diet. Antimicrob. Chemother.,
24: 519-522. PMID: 21658328 44: 261-266. DOI: 10.1128/AAC.44.2.261-266.2000
Shinohara, Y.T., S.A. Tasker, M.R. Wallace, K.E. Couch Thuong-Guyot, M., O. Domarle, J.J. Pocidalo and
and P.E. Oison, 1997. What is the risk of Achilles G. Hayem, 1994. Effects of fluoroquinolones on
tendon rupture with ciprofloxacin? J. Rheumat., 24: cultured articular chondrocytes flow cytometric
238-239. PMID: 9002057 analysis of free radical production. J. Pharmacol.
Short, P., N. Wilson and I. Erskin, 2006. Tendinitis: The Exp. Ther., 271: 1544-1549. PMID: 7996468
Achilles heel of quinolones. Emerg. Med. J., 23: 63- Tsai, A.G., D.F. Williamson and H.A. Glick, 2011.
63. PMID: 17130584 Direct medical cost of overweight and obesity in the
Simonin, M.A., P. Gegout, M.A. Pottie, P. Gillet and USA: A quantitative systematic review. Obes Rev.,
P. Netter et al., 1999. Proteoglycan and collagen 12: 50-61. DOI: 10.1111/j.1467-789X.2009.00708.x
biochemical variations during fluoroquinolone- Tsai, J., J.T. Lee, W. Wang, J. Zhang and H. Cho, 2008.
induced chondrotoxicity in mice. Antimicrob. Discovery of a selective inhibitor of oncogenic B-
Agents. Chemother., 43: 2915-2921. PMID: Raf kinase with potent antimelanoma activity.
10582882 PANS, 105: 3041-3046. DOI:
Stahlmann, R., 2000. Clinical toxicological aspects of 10.1073/pnas.0711741105
fluoroquinolones. Toxicol. Lett., 127: 269-277. DOI: Water, I., M. Egerbacher, B. Wolfesberger and G. Seiberl,
10.1016/S0378-4274(01)00509-4 1998. Confocal laser scanning microscopy of
Stahlmann, R., 2003. Children as a special population at chondrocytes in vitro: Cytoskeletal changes after
risk--quinolones as an example for xenobiotics quinolone treatment. Scanning, 20: 511-575. PMID:
9857527
exhibiting skeletal toxicity. Arch. Toxicol., 77: 7-11.
West, M.B. and P. Gow, 1998. Ciprofloxacin, bilateral
PMID: 12491034
Achilles tendonitis and unilateral tendon rupture--a
Stahlmann, R., C. Forster, M. Shakibaei, J. Vormann and
case report. NZ. Med. J., 111: 18-19. PMID:
T. Gunther et al., 1995. Magnesium deficiency
9484431
induces joint cartilage lesions in juvenile rats which Williams, R.J., E. Altia, T.L. Wickiewicz and J.A. Hamafin,
are identical to quinolone-induced arthropathy.
2000. The effect of ciprofloxacin on tendon,
Antimicrob. Agents Chemother., 39: 2013-2018.
paratenon and capsular fibroblast metabolism. Am.
DOI: 10.1128/AAC.39.9.2013 J. Sports Med., 28: 364-369. PMID: 10843129
Stahlmann, R., R. Schwabe, K. Pfister, E. Lozo and Wilton, L.V., G.L. Pearce and R.D. Mann, 1996. A
M. Shakkibaei et al., 1999. Supplementation with comparison of ciprofloxacin, norfloxacin, ofloxacin,
magnesium and tocopherol diminishes quinolone- azithromycin and cefixime examined by
induced chondrotoxicity in immature rats. Drugs, observational cohort studies. Br. J. Clin. Pharmacol.,
58: 393-394. 41: 277-284. DOI: 10.1046/j.1365-
Stahlmann, R., S. Kuhner, M. Shakibaei, R. Schwabe 2125.1996.03013.x
and J. Flores et al., 2000. Chondrotoxicity of
ciprofloxacin in immature Beagle dogs:
Immunohistochemistry, electron microscopy and
drug plasma concentrations. Arch. Toxicol., 73: 564-572.
Sub, B. and B. Lorber, 1995. Quinolones. Med. Clin.
NA., 79: 869-894.