Muhammad Aslam Channa, Muhammad Ashfaq, Sibghatullah Sanghi, Muhammad Azam Qureshi, Muhammad Zahoor Janjua


Background: Administration of quinolone therapy is controversial during juvenile age as stated by earlier workers. The fluroquinolones are currently not indicated for young children, because of the arthropathy and adverse effect on growing cartilage shown by studies. However the effects of ciprofloxacin on secondary ossification centers has remained undocumented. This study is therefore aimed to determine the risk of Ciprofloxacin administration on neonatal skeletal differentiation by a prospective and comparative animal study model using Wistar albino rats.

Methods: Ciprofloxacin was administered to newly born Wistar albino rat pups at a dose of 20 mg/kg body weight intraperitoneally twice daily from day-1 to day-14 after birth. These animals were killed by deep ether anaesthesia and fixed in 80% alcohol. They were then bulk stained with Alizarin red and Alcian blue. Finally they were cleared in 4% KOH and stored in glycerin. The fore and hind limbs were disarticulated from the axial skeleton and observed under stereomicroscope for evidence of skeletal differentiation in the form of presence of secondary ossification centers in long hones (left humerus and left femur). The time of appearance of these centers were noted and compared statistically with those in control animals. Results: The study revealed that the skeletal differentiation in long bones was delayed by 2.4 + 0.2 days at both proximal and distal ends in humerus and 2.4 + 0.2 days at proximal end and 2.2 + 0.2 days at distal end of femur in experimental animals as compared with controls. Conclusion: The ciprofloxacin administration during post-natally presents a risk to skeletal differentiation and therefore to its growth upto the age of six weeks is albino rate pups.

Key Words: Ciprofloxacin, Bone differentiation, Ossification centers

Full Text:



Patterson-Reid D, Illnois-Park A. Quinolone toxicity– Methods of assessment. Am J Med 1991;91(Suppl 6A):35S-37S.

Patterson-Lance R, Lissack LM, Canter K, Asching CE, Counie C et al. Therapy of lower extremity infections with ciprofloxacin in patients with diabetes mellitus, peripheral vascular disease or both. Am J Med 1989; 86: 801-8.

Katzung BG. Quinolones. In:Basic and Clinical pharmacology. 8th ed. New York:MC Graw Hill 2001:797-801.

Gillman GA, Hardman JG; Limbird LE. The Quinolones. In: Goodman and Gillman’s. The parmacological Basis of Therapeutics. 10th ed. New York: MC Graw Hill; 2001, Vol. II: 179–1183.

Pradhan KM, Arora NK, Jena A, Susheela AK, Bhan MK. Safety of Ciprofloxacin therapy in children, magnetic resonance image, body fluid levels of fluoride and linear growth. Acta paediatr 1995;84:555-60.

Hample B, Hulmann R, Schmidt H. Ciprofloxacin in paediatrics. World-wide clinical experience based on compassionate use. Safety report. Pediatr Infect Dis J 1997;16(1):127-9.

Rough R. Reproductive system. In: The mouse. 2nd ed. Minneapolis: Burgess Pub Co, 1968:269-99.

Chang HH, Schwartz Z, Kaufman MH. Limb and other postcranial skeletal defects induced by amniotic sac puncture in mouse. J Anat 1996;189:37-49.

Greene EC. Anatomy of rat. Philadelphia: American Philosophical Society, 1968; Vol. XXVIII, pp 5-30.

Martindale W. The complete drug reference 33rd ed, Swectman, S.C. (ed) London, Chicago: Pharmaceutical press, 2002: 182-5.

Lori EK, Sulik KK. Experimental foetal alcohol syndrome proposed pathogenic basis for a variety of associated facial and brain anomalies. Am J Gen Med 1992; 44: 168-76.

Patton J, Kaufman H. Timing of ossification of limb bones and growth rates of various long bones of the fore and hind limbs of the prenatal and early postnatal laboratory mouse. J Anat 1995;186:175-85.

Bland M. Introduction of medical statistics. 1st ed. Oxford: Oxford University Press, 1987: 165-187.

Arora NK. Are fluoroquinolones safe in children? Indian J Pediatr 1994;61(6):601-3.

Junqueira LC, Carneiro J, Keeley RO. Endochondral ossification. In: Basic histology. 7th ed. Lond: Appleton & Lange. 1992: 151-156.

Stahlmann R. Children as a special population at risk – quinolones as an example for xenobiotics exhibiting skeletal toxicity. Arch Toxicol 2003; 77(1): 7-11.

Williams PL, Bannister LH, Berry MM, Collins P, Dyson M, Dussek JF et al. Histogenisis of bone. In: Gray’s Anatomy. 38th ed. New York: Churchill Livingstone, 1995, 471-80.

Slonaker JR. The normal activity of the albinorats from birth to natural death, its rate of growth and the duration of life. J Animal Behavior 1912;2:20-42.


  • There are currently no refbacks.

Contact Number: +92-992-382571

email: [jamc] [@] [ayubmed.edu.pk]