In vitro and in vivo effects of antibiotics on bone cell metabolism and fracture healing

Expert Opinion on Drug Safety

Volumn 11, Issue 1, 2012, Pages 15-32

  Kallala, Rami ^a   Graham, Simon Matthew ^a   Nikkhah, Dariush ^a   Kyrkos, Margaritis ^b   Heliotis, Manolis ^c   Mantalaris, Athanassios ^d   Tsiridis, Eleftherios ^b,d  

^a UNIVERSITY OF LEEDS   (United Kingdom)

^b ARISTOTLE UNIVERSITY MEDICAL SCHOOL   (Greece)

^c NORTHWICK PARK HOSPITAL   (United Kingdom)

^d IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

Antibiotics; Bone; Fracture; Osteoporosis

Indexed keywords

AMINOGLYCOSIDE; CEFUROXIME; CEPHALOSPORIN; COLONY STIMULATING FACTOR 1; FIBROBLAST GROWTH FACTOR 1; FIBROBLAST GROWTH FACTOR 2; GENTAMICIN; GLYCOPEPTIDASE; INTERLEUKIN 1; INTERLEUKIN 6; MACROLIDE; PENICILLIN G; PLATELET DERIVED GROWTH FACTOR; POLY(METHYL METHACRYLATE); QUINOLONE; RIFAMPICIN; SULFONAMIDE; TETRACYCLINE; TOBRAMYCIN; TRANSFORMING GROWTH FACTOR BETA; TRIMETHOPRIM; VANCOMYCIN; VASCULOTROPIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; BONE CELL; BONE METABOLISM; CONTROLLED STUDY; DNA REPLICATION; EXTRACELLULAR MATRIX; FRACTURE HEALING; IN VITRO STUDY; IN VIVO STUDY; NONHUMAN; PROTEIN SYNTHESIS; RAT; REVIEW;

ADMINISTRATION, TOPICAL; ANIMALS; ANTI-BACTERIAL AGENTS; BACTERIA; BONE AND BONES; DOSE-RESPONSE RELATIONSHIP, DRUG; FRACTURE HEALING; HUMANS; MITOCHONDRIA;

EID: 84555190218     PISSN: 14740338     EISSN: 1744764X     Source Type: Journal    
DOI: 10.1517/14740338.2012.643867     Document Type: Review

References (138)

1. Hospital Prescribing Information Project, Second Report. Analysis for Health Authority Prescribing Advisers and Senior Hospital Professionals/ Managers., in National Prescribing Centre1999
2. Curtis C, Marriott J, Langley C. Development of a prescribing indicator for objective quantification of antibiotic usage in secondary care. J Antimicrob Chemother 2004;11(2):529-33 (Pubitemid 39177481)
3. Management of infection-guidance for primary care. various dates 23 June 2011. Available from: http://www.hpa. org.uk/Topics/InfectiousDiseases/ InfectionsAZ/PrimaryCareGuidance/
4. Hedstrom SA, Lidgren L, Torholm C, et al. Antibiotic containing bone cement beads in the treatment of deep muscle and skeletal infections. Acta Orthop Scand 1980;51(6):863-9 (Pubitemid 11146057)
5. Ayaslioglu E, Erkek E, Oba AA, et al. Doxycycline-induced staining of permanent adult dentition. Aust Dent J 2005;50(4):273-5 (Pubitemid 43074682)
6. Nelson R, Parker SR. Doxycycline-induced staining of adult teeth: the first reported case. Arch Dermatol 2006;142(8):1081-2 (Pubitemid 44268503)
7. Lochary ME, Lockhart PB, Williams WT Jr. Doxycycline and staining of permanent teeth. Pediatr Infect Dis J 1998;17(5):429-31 (Pubitemid 28232872)
8. Holtom PD, Pavkovic SA, Bravos PD, et al. Inhibitory effects of the quinolone antibiotics trovafloxacin, ciprofloxacin, and levofloxacin on osteoblastic cells in vitro. J Orthop Res 2000;18(5):721-7
9. Duewelhenke N, Krut O, Eysel P. Influence on mitochondria and cytotoxicity of different antibiotics administered in high concentrations on primary human osteoblasts and cell lines. Antimicrob Agents Chemother 2007;51(1):54-63 (Pubitemid 46047687)
10. Perry AC, Prpa B, Rouse MS, et al. Levofloxacin and trovafloxacin inhibition of experimental fracture-healing. Clin Orthop Relat Res 2003;414:95-100 (Pubitemid 37102140)
11. Huddleston PM, Halling-Sørensen B, Sengeløv G, Ingerslev F. Ciprofloxacin inhibition of experimental fracture healing. J Bone Joint Surg Am 2000;82(2):161-73 (Pubitemid 30097016)
12. Ince A, Schütze N, Karl N, et al. Gentamicin negatively influenced osteogenic function in vitro. Int Orthop 2007;31(2):223-8 (Pubitemid 46731529)
13. Naal FD, Salzmann GM, von Knoch F, et al. The effects of clindamycin on human osteoblasts in vitro. Arch Orthop Trauma Surg 2008;128(3):317-23
14. Salzmann GM, Naal FD, von Knoch F, et al. Effects of cefuroxime on human osteoblasts in vitro. J Biomed Mater Res A 2007;82(2):462-8 (Pubitemid 47051678)
15. Pountos I, Georgouli T, Blokhuis TJ, et al. Pharmacological agents and impairment of fracture healing: what is the evidence? Injury 2008;39(4):384-94
16. Lamparter S, Slight SH, Weber KT. Doxycycline and tissue repair in rats. J Lab Clin Med 2002;139(5):295-302 (Pubitemid 34577481)
17. Mont MA, Mathur SK, Frondoza CG, et al. The effects of ciprofloxacin on human chondrocytes in cell culture. Infection 1996;24(2):151-5 (Pubitemid 26137095)
18. Alkan A, Erdem E, Günhan O, et al. Histomorphometric evaluation of the effect of doxycycline on the healing of bone defects in experimental diabetes mellitus: a pilot study. J Oral Maxillofac Surg 2002;60(8):898-904 (Pubitemid 34832778)
19. Isefuku S, Joyner CJ, Simpson AH. Gentamicin may have an adverse effect on osteogenesis. J Orthop Trauma 2003;17(3):212-16
20. Antoci V Jr, Adams CS, Hickok NJ, et al. Antibiotics for local delivery systems cause skeletal cell toxicity in vitro. Clin Orthop Relat Res 2007;462:200-6 (Pubitemid 47367864)
21. Calderon CB, Sabundayo BP. Antimicrobial Classifications: Drugs for Bugs. In: Schwalbe R, Steele-Moore L, Goodwin AC, editor. Antimicrobial Susceptibility Testing Protocols. CRC Press; Taylor & Frances group; 2007
22. Finberg RW, Moellering RC, Tally FP, et al. The importance of bactericidal drugs: future directions in infectious disease. Clin Infect Dis 2004;39(9):1314-20 (Pubitemid 39458517)
23. Drusano G. Pharmacodynamics of anti infectives: target delineation and target attainment. In: Finch RG, editor. Antibiotic and chemotherapy: anti-infective agents and their use in therapy. Livingstone; Churchill: 2003. p. 48-59
24. Sánchez E, Baro M, Soriano I, et al. In vivo-in vitro study of biodegradable and osteointegrable gentamicin bone implants. Eur J Pharm Biopharm 2001;52(2):151-8 (Pubitemid 32755893)
25. Randelli P, Evola FR, Cabitza P, et al. Prophylactic use of antibiotic-loaded bone cement in primary total knee replacement. Knee Surg Sports Traumatol Arthrosc 2010;18(2):181-6
26. Hoff SF, Fitzgerald RH Jr, Kelly PJ. The depot administration of penicillin G and gentamicin in acrylic bone cement. J Bone Joint Surg Am 1981;63(5):798-804 (Pubitemid 11127665)
27. Pirotta MV, Garland SM. Genital Candida species detected in samples from women in Melbourne, Australia, before and after treatment with antibiotics. J Clin Microbiol 2006;44(9):3213-17 (Pubitemid 44413754)
28. Nikaido H. Multidrug resistance in bacteria. Annu Rev Biochem 2009;78:119-46
29. Korkusuz F, Uchida A, Shinto Y, et al. Experimental implant-related osteomyelitis treated by antibiotic-calcium hydroxyapatite ceramic composites. J Bone Joint Surg Br 1993;75(1):111-14 (Pubitemid 23052429)
30. Wininger DA, Fass RJ. Antibiotic-impregnated cement and beads for orthopedic infections. Antimicrob Agents Chemother 1996;40(12):2675-9 (Pubitemid 26404324)
31. Buchholz HW, Engelbrecht H. Depot effects of various antibiotics mixed with Palacos resins. Chirurg 1970;41(11):511-15
32. Gallo J, Korkusuz F, Uchida A, Shinto Y. In vitro testing of gentamicin-vancomycin loaded bone cement to prevent prosthetic joint infection. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2005;149(1):153-8
33. Garvin KL, Hanssen AD. Infection after total hip arthroplasty. Past, present, and future. J Bone Joint Surg Am 1995;77(10):1576-88
34. Hanssen AD. Prophylactic use of antibiotic bone cement: an emerging standard-in opposition. J Arthroplasty 2004;19(4 Suppl 1):73-7 (Pubitemid 38746721)
35. Hanssen AD, Osmon DR. The use of prophylactic antimicrobial agents during and after hip arthroplasty. Clin Orthop Relat Res 1999;369:124-38
36. Jiranek WA, Hanssen AD, Greenwald AS. Antibiotic-loaded bone cement for infection prophylaxis in total joint replacement. J Bone Joint Surg Am 2006;88(11):2487-500 (Pubitemid 44713839)
37. Joseph TN, Chen AL, Di Cesare PE. Use of antibiotic-impregnated cement in total joint arthroplasty. J Am Acad Orthop Surg 2003;11(1):38-47
38. Trippel SB. Antibiotic-impregnated cement in total joint arthroplasty. J Bone Joint Surg Am 1986;68(8):1297-302 (Pubitemid 17198799)
39. Malchau H, Herberts P, Ahnfelt L. Prognosis of total hip replacement in Sweden. Follow-up of 92,675 operations performed 1978-1990. Acta Orthop Scand 1993;64(5):497-506 (Pubitemid 23329852)
40. Espehaug B, Engesaeter LB, Vollset SE, et al. Antibiotic prophylaxis in total hip arthroplasty. Review of 10,905 primary cemented total hip replacements reported to the Norwegian arthroplasty register, 1987 to 1995. J Bone Joint Surg Br 1997;79(4):590-5 (Pubitemid 127469741)
41. Engesaeter LB, Lie SA, Espehaug B, et al. Antibiotic prophylaxis in total hip arthroplasty: effects of antibiotic prophylaxis systemically and in bone cement on the revision rate of 22,170 primary hip replacements followed 0-14 years in the Norwegian Arthroplasty Register. Acta Orthop Scand 2003;74(6):644-51 (Pubitemid 38067862)
42. Itokazu M, Korkusuz F, Uchida A, Shinto Y. Antibiotic-loaded hydroxyapatite blocks in the treatment of experimental osteomyelitis in rats. J Med Microbiol 1997;46(9):779-83 (Pubitemid 27376780)
43. Garvin KL, Miyano JA, Robinson D, et al. Polylactide/polyglycolide antibiotic implants in the treatment of osteomyelitis. A canine model. J Bone Joint Surg Am 1994;76(10):1500-6 (Pubitemid 24355966)
44. Sasaki S, Ishii Y. Apatite cement containing antibiotics: efficacy in treating experimental osteomyelitis. J Orthop Sci 1999;4(5):361-9 (Pubitemid 29506002)
45. Wahlig H, Dingeldein E, Buchholz HW, et al. Pharmacokinetic study of gentamicin-loaded cement in total hip replacements. Comparative effects of varying dosage. J Bone Joint Surg Br 1984;66(2):175-9 (Pubitemid 14019681)
46. Brien WW, Salvati EA, Klein R, et al. Antibiotic impregnated bone cement in total hip arthroplasty. An in vivo comparison of the elution properties of tobramycin and vancomycin. Clin Orthop Relat Res 1993;296:242-8 (Pubitemid 23332146)
47. Masri BA, Duncan CP, Beauchamp CP. Long-term elution of antibiotics from bone-cement: an in vivo study using the prosthesis of antibiotic-loaded acrylic cement (PROSTALAC) system. J Arthroplasty 1998;13(3):331-8 (Pubitemid 28194004)
48. Neut D, van de Belt H, van Horn JR, et al. Residual gentamicin-release from antibiotic-loaded polymethylmethacrylate beads after 5 years of implantation. Biomaterials 2003;24(10):1829-31 (Pubitemid 36184738)
49. Penner MJ, Duncan CP, Masri BA. The in vitro elution characteristics of antibiotic-loaded CMW and Palacos-R bone cements. J Arthroplasty 1999;14(2):209-14 (Pubitemid 29095966)
50. Penner MJ, Masri BA, Duncan CP. Elution characteristics of vancomycin and tobramycin combined in acrylic bone-cement. J Arthroplasty 1996;11(8):939-44
51. Sterling GJ, Crawford S, Potter JH, et al. The pharmacokinetics of Simplex-tobramycin bone cement. J Bone Joint Surg Br 2003;85(5):646-9 (Pubitemid 36927025)
52. Wahlig H, Buchholz HW. Experimental and clinical studies on the release of gentamicin from bone cement. Chirurg 1972;43(10):441-5
53. Wahlig H, Dingeldein E, Bergmann R, et al. The release of gentamicin from polymethylmethacrylate beads. An experimental and pharmacokinetic study. J Bone Joint Surg Br 1978;60-B(2):270-5 (Pubitemid 8356875)
54. Wahlig H, Dingeldein E. Antibiotics and bone cements. Experimental and clinical long-term observations. Acta Orthop Scand 1980;51(1):49-56 (Pubitemid 10173817)
55. Bunetel L, Segui A, Cormier M, et al. Comparative study of gentamicin release from normal and low viscosity acrylic bone cement. Clin Pharmacokinet 1990;19(4):333-40 (Pubitemid 20283429)
56. Schindeler A, McDonald MM, Bokko P, et al. Bone remodeling during fracture repair: The cellular picture. Semin Cell Dev Biol 2008;19(5):459-66
57. Buckwalter J, ET, Marsh L. Bone and Joint Healing. In: Bucholz RW, editor. Rockwood and Green's Fractures in Adults. Lippincott Williams & Wilkins; Philadelphia: 2006. p. 297-311
58. Einhorn TA. The cell and molecular biology of fracture healing. Clin Orthop Relat Res 1998(355 Suppl):S7-21
59. Bolander ME. Regulation of fracture repair by growth factors. Proc Soc Exp Biol Med 1992;200(2):165-70
60. Ai-Aql ZS, Alagl AS, Graves DT, et al. Molecular mechanisms controlling bone formation during fracture healing and distraction osteogenesis. J Dent Res 2008;87(2):107-18
61. Shapiro F. Bone development and its relation to fracture repair. The role of mesenchymal osteoblasts and surface osteoblasts. Eur Cell Mater 2008;15:53-76 (Pubitemid 351958405)
62. Fan X, Biskobing DM, Fan D, et al. Macrophage colony stimulating factor down-regulates MCSF-receptor expression and entry of progenitors into the osteoclast lineage. J Bone Miner Res 1997;12(9):1387-95 (Pubitemid 27375381)
63. Barnes GL, Kostenuik PJ, Gerstenfeld LC, et al. Growth factor regulation of fracture repair. J Bone Miner Res 1999;14(11):1805-15 (Pubitemid 29521774)
64. Dimitriou R, Tsiridis E, Giannoudis PV. Current concepts of molecular aspects of bone healing. Injury 2005;36(12):1392-404 (Pubitemid 41618169)
65. Deckers MM, van Bezooijen RL, van der Horst G, et al. Bone morphogenetic proteins stimulate angiogenesis through osteoblast-derived vascular endothelial growth factor A. Endocrinology 2002;143(4):1545-53 (Pubitemid 34274386)
66. Eghbali-Fatourechi GZ, Lamsam J, Fraser D, et al. Circulating osteoblast-lineage cells in humans. N Engl J Med 2005;352(19):1959-66 (Pubitemid 40638366)
67. Rumi MN, Deol GS, Singapuri KP, et al. The origin of osteoprogenitor cells responsible for heterotopic ossification following hip surgery: an animal model in the rabbit. J Orthop Res 2005;23(1):34-40 (Pubitemid 40045074)
68. Kalfas IH. Principles of bone healing. Neurosurg Focus 2001;10(4):E1
69. Nakase T, Yoshikawa H. Potential roles of bone morphogenetic proteins (BMPs) in skeletal repair and regeneration. J Bone Miner Metab 2006;24(6):425-33 (Pubitemid 44663413)
70. Teitelbaum SL. Bone resorption by osteoclasts. Science 2000;289(5484):1504-8
71. Schell H, Lienau J, Epari DR, et al. Osteoclastic activity begins early and increases over the course of bone healing. Bone 2006;38(4):547-54
72. Blair JM, Zhou H, Seibel MJ, et al. Mechanisms of disease: roles of OPG, RANKL and RANK in the pathophysiology of skeletal metastasis. Nat Clin Pract Oncol 2006;3(1):41-9 (Pubitemid 43108833)
73. Haleem AA, Rouse MS, Lewallen DG, et al. Gentamicin and vancomycin do not impair experimental fracture healing. Clin Orthop Relat Res 2004;427:22-4 (Pubitemid 39362825)
74. Kim SG, Chung TY, Kim MS, et al. The effect of high local concentrations of antibiotics on demineralized bone induction in rats. J Oral Maxillofac Surg 2004;62(6):708-13 (Pubitemid 38736443)
75. Pedersen JG, Lund B. Effects of gentamicin and monomer on bone. An in vitro study. J Arthroplasty 1988(3 Suppl):S63-8 (Pubitemid 18263002)
76. Lindsey RW, Probe R, Miclau T, et al. The effects of antibiotic- impregnated autogeneic cancellous bone graft on bone healing. Clin Orthop Relat Res 1993;291:303-12 (Pubitemid 23164275)
77. Petri WH III. Osteogenic activity of antibiotic-supplemented bone allografts in the guinea pig. J Oral Maxillofac Surg 1984;42(10):631-6
78. Linseman DA, Hampton LA, Branstetter DG. Quinolone-induced arthropathy in the neonatal mouse. Morphological analysis of articular lesions produced by pipemidic acid and ciprofloxacin. Fundam Appl Toxicol 1995;28(1):59-64
79. Gough A, Johnson R, Campbell E, et al. Quinolone arthropathy in immature rabbits treated with the fluoroquinolone, PD 117596. Exp Toxicol Pathol 1996;48(4):225-32 (Pubitemid 26191270)
80. Bendele AM, Hulman JF, Harvey AK, et al. Passive role of articular chondrocytes in quinolone-induced arthropathy in guinea pigs. Toxicol Pathol 1990;18(2):304-12 (Pubitemid 20294465)
81. Burkhardt JE, Hill MA, Lamar CH, et al. Effects of difloxacin on the metabolism of glycosaminoglycans and collagen in organ cultures of articular cartilage. Fundam Appl Toxicol 1993;20(2):257-63 (Pubitemid 23162738)
82. Kato M, Onodera T. Morphological investigation of cavity formation in articular cartilage induced by ofloxacin in rats. Fundam Appl Toxicol 1988;11(1):110-19
83. Ostrov DA, Magis AT, Wronski TJ, et al. Identification of enoxacin as an inhibitor of osteoclast formation and bone resorption by structure-based virtual screening. J Med Chem 2009;52(16):5144-51
84. Tuncay I, Ozbek H, Koem M, et al. A comparison of effects of fluoroquinolones on fracture healing (an experimental study in rats). Ulus Travma Acil Cerrahi Derg 2005;11(1):17-22 (Pubitemid 40283359)
85. Golub LM, Ramamurthy NS, Kaneko H, et al. Tetracycline administration prevents diabetes-induced osteopenia in the rat: initial observations. Res Commun Chem Pathol Pharmacol 1990;68(1):27-40 (Pubitemid 20135326)
86. Bain S, Ramamurthy NS, Impeduglia T, et al. Tetracycline prevents cancellous bone loss and maintains near-normal rates of bone formation in streptozotocin diabetic rats. Bone 1997;21(2):147-53 (Pubitemid 27395402)
87. Klapisz-Wolikow M, Saffar JL. Minocycline impairment of both osteoid tissue removal and osteoclastic resorption in a synchronized model of remodeling in the rat. J Cell Physiol 1996;167(2):359-68 (Pubitemid 26145870)
88. Zhou X, Zhang P, Zhang C, An B. Tetracyclines inhibit rat osteoclast formation and activity in vitro and affect bone turnover in young rats in vivo. Calcif Tissue Int 2010;86(2):163-71
89. Williams S, Wakisaka A, Zeng QQ, et al. Effect of minocycline on osteoporosis. Adv Dent Res 1998;12(2):71-5
90. Li QN, Hu B, Huang LF, Chen Y. Effects of low doses of hydrochloride tetracycline on bone metabolism and uterus in ovariectomized rats. Acta Pharmacol Sin 2003;24(6):599-604
91. Williams S, Barnes J, Wakisaka A, et al. Treatment of osteoporosis with MMP inhibitors. Ann N Y Acad Sci 1999;878:191-200 (Pubitemid 29353570)
92. Pytlik M, Folwarczna J, Janiec W. Effects of doxycycline on mechanical properties of bones in rats with ovariectomy-induced osteopenia. Calcif Tissue Int 2004;75(3):225-30 (Pubitemid 39331651)
93. Bettany JT, Peet NM, Wolowacz RG, et al. Tetracyclines induce apoptosis in osteoclasts. Bone 2000;27(1):75-80 (Pubitemid 30365080)
94. Grevstad HJ, Boe OE. Effect of doxycycline on surgically induced osteoclast recruitment in the rat. Eur J Oral Sci 1995;103(3):156-9
95. Ong SM, Taylor GJ. Doxycycline inhibits bone resorption by human interface membrane cells from aseptically loose hip replacements. J Bone Joint Surg Br 2003;85(3):456-61 (Pubitemid 36511603)
96. Engesaeter LB, Skar AG. Effects of oxytetracycline on the mechanical properties of bone and skin in young rats. Acta Orthop Scand 1978;49(6):529-34 (Pubitemid 9103828)
97. Yen PK, Shaw JH. Effects of tetracyclines on membranous bone growth and dentin apposition in young rhesus monkeys. J Dent Res 1974;53(4):897-906
98. Simmons DJ, Chang SL, Russell JE, et al. The effect of protracted tetracycline treatment on bone growth and maturation. Clin Orthop Relat Res 1983;180:253-9 (Pubitemid 14233117)
99. Ince A, Schütze N, Hendrich C, et al. In vitro investigation of orthopedic titanium-coated and brushite-coated surfaces using human osteoblasts in the presence of gentamycin. J Arthroplasty 2008;23(5):762-71
100. Chang Y, Goldberg VM, Caplan AI. Toxic effects of gentamicin on marrow-derived human mesenchymal stem cells. Clin Orthop Relat Res 2006;452:242-9 (Pubitemid 44690676)
101. Miclau T, Edin ML, Lester GE, et al. Bone toxicity of locally applied aminoglycosides. J Orthop Trauma 1995;9(5):401-6
102. Edin ML, Miclau T, Lester GE, et al. Effect of cefazolin and vancomycin on osteoblasts in vitro. Clin Orthop Relat Res 1996;333:245-51 (Pubitemid 26428036)
103. Oyama M, Emerton ME, Francis MJO, et al. The effect of cefuroxime, ciprofloxacin, flucloxacillin and vancomycin on human osteoblast-like cells in-vitro. J Bone Jt Surg 1998;80 B(Suppl III):274
104. Miclau T, Edin ML, Lester GE, et al. Effect of ciprofloxacin on the proliferation of osteoblast-like MG-63 human osteosarcoma cells in vitro. J Orthop Res 1998;16(4):509-12 (Pubitemid 28427703)
105. Menschik M, Neumüller J, Steiner CW, et al. Effects of ciprofloxacin and ofloxacin on adult human cartilage in vitro. Antimicrob Agents Chemother 1997;41(11):2562-5 (Pubitemid 27467576)
106. Egerbacher M, Seiberl G, Wolfesberger B, et al. Ciprofloxacin causes cytoskeletal changes and detachment of human and rat chondrocytes in vitro. Arch Toxicol 2000;73(10-11):557-63 (Pubitemid 30062487)
107. Zhang C, Tang TT, Ren WP, et al. Inhibiting wear particles-induced osteolysis with doxycycline. Acta Pharmacol Sin 2007;28(10):1603-10 (Pubitemid 47493289)
108. Kupczik F, Vialle LRG, Nobre LO, et al. Influence of ciprofloxacin on femoral fracture healing in rats. Acta Ortop Bras 2009;17(4):228-31
109. Kawaguchi AT, Reddi AH, Olson SA, et al. Are recombinant human bone morphogenetic protein-7 and tobramycin compatible? An experiment in rats. J Orthop Trauma 2004;18(4):225-32 (Pubitemid 38578787)
110. Ince A, Schütze N, Hendrich C, et al. Effect of polyhexanide and gentamycin on human osteoblasts and endothelial cells. Swiss Med Wkly 2007;137(9-10):139-45 (Pubitemid 46465530)
111. Stahlmann R, Forster C, Shakibaei M, et al. Magnesium deficiency induces joint cartilage lesions in juvenile rats which are identical to quinolone-induced arthropathy. Antimicrob Agents Chemother 1995;39(9):2013-18
112. Isefuku S, Joyner CJ, Simpson AH. Toxic effect of rifampicin on human osteoblast-like cells. J Orthop Res 2001;19(5):950-4 (Pubitemid 32799087)
113. Fife RS, Rougraff BT, Proctor C, et al. Inhibition of proliferation and induction of apoptosis by doxycycline in cultured human osteosarcoma cells. J Lab Clin Med 1997;130(5):530-4 (Pubitemid 27526335)
114. Pina C, Ferraz MP, Coelho MJ. The effects of tigecycline on human osteoblasts in vitro. B-Digital-Universidade Fernando Pessoa. Revista da Faculdade de Ciencias da Saude. Porto 2008;5:146-52
115. Vormann J, Forster C, Zippel U, et al. Effects of magnesium deficiency on magnesium and calcium content in bone and cartilage in developing rats in correlation to chondrotoxicity. Calcif Tissue Int 1997;61(3):230-8 (Pubitemid 27360817)
116. Loeser RF. Integrin-mediated attachment of articular chondrocytes to extracellular matrix proteins. Arthritis Rheum 1993;36(8):1103-10 (Pubitemid 23229287)
117. Loeser RF. Modulation of integrin-mediated attachment of chondrocytes to extracellular matrix proteins by cations, retinoic acid, and transforming growth factor beta. Exp Cell Res 1994;211(1):17-23 (Pubitemid 24167329)
118. Castora FJ, Vissering FF, Simpson MV. The effect of bacterial DNA gyrase inhibitors on DNA synthesis in mammalian mitochondria. Biochim Biophys Acta 1983;740(4):417-27 (Pubitemid 13012494)
119. Lawrence JW, Claire DC, Weissig V, et al. Delayed cytotoxicity and cleavage of mitochondrial DNA in ciprofloxacin-treated mammalian cells. Mol Pharmacol 1996;50(5):1178-88 (Pubitemid 26384856)
120. Lawrence JW, Darkin-Rattray S, Xie F, et al. 4-Quinolones cause a selective loss of mitochondrial DNA from mouse L1210 leukemia cells. J Cell Biochem 1993;51(2):165-74 (Pubitemid 23058573)
121. Williams S, Wakisaka A, Zeng QQ, et al. Minocycline prevents the decrease in bone mineral density and trabecular bone in ovariectomized aged rats. Bone 1996;19(6):637-44 (Pubitemid 27035844)
122. Folwarczna J, Pytlik M, Janiec W. Effects of doxycycline on development of changes in histomorphometric parameters of bones induced by bilateral ovariectomy in rats. Pol J Pharmacol 2003;55(3):433-41 (Pubitemid 36975211)
123. Pacifici R. Cytokines, estrogen, and postmenopausal osteoporosis-the second decade. Endocrinology 1998;139(6):2659-61
124. Vernillo AT, Rifkin BR. Effects of tetracyclines on bone metabolism. Adv Dent Res 1998;12(2):56-62
125. Golub LM, Evans RT, McNamara TF, et al. A non-antimicrobial tetracycline inhibits gingival matrix metalloproteinases and bone loss in Porphyromonas gingivalis-induced periodontitis in rats. Ann N Y Acad Sci 1994;732:96-111
126. Rifkin BR, Vernillo AT, Golub LM, et al. Modulation of bone resorption by tetracyclines. Ann N Y Acad Sci 1994;732:165-80
127. Welling PG, Koch PA, Lau CC, et al. Bioavailability of tetracycline and doxycycline in fasted and nonfasted subjects. Antimicrob Agents Chemother 1977;11(3):462-9 (Pubitemid 8065607)
128. Golub LM, Greenwald RA. Clinical applications of non-antibacterial tetracyclines. Pharmacol Res 2011;64(6):549-50
129. Mingeot-Leclercq MP, Glupczynski Y, Tulkens PM. Aminoglycosides: activity and resistance. Antimicrob Agents Chemother 1999;43(4):727-37 (Pubitemid 29165732)
130. Fourmy D, Recht MI, Blanchard SC, et al. Structure of the A site of Escherichia coli 16S ribosomal RNA complexed with an aminoglycoside antibiotic. Science 1996;274(5291):1367-71 (Pubitemid 26391459)
131. Montenez JP, Van Bambeke F, Piret J, et al. Interactions of macrolide antibiotics (Erythromycin A, roxithromycin, erythromycylamine Dirithromycin, and azithromycin) with phospholipids: computer-aided conformational analysis and studies on acellular and cell culture models. Toxicol Appl Pharmacol 1999;156(2):129-40 (Pubitemid 29196576)
132. Tyteca D, Schanck A, Dufrêne YF, et al. The macrolide antibiotic azithromycin interacts with lipids and affects membrane organization and fluidity: studies on Langmuir-Blodgett monolayers, liposomes and J774 macrophages. J Membr Biol 2003;192(3):203-15 (Pubitemid 37020920)
133. Kroon AM, Van den Bogert C. Antibacterial drugs and their interference with the biogenesis of mitochondria in animal and human cells. Pharm Weekbl Sci 1983;5(3):81-7 (Pubitemid 13031470)
134. Riesbeck K, Bredberg A, Forsgren A. Ciprofloxacin does not inhibit mitochondrial functions but other antibiotics do. Antimicrob Agents Chemother 1990;34(1):167-9 (Pubitemid 20019986)
135. Buss WC, Morgan R, Guttmann J, et al. Rifampicin inhibition of protein synthesis in mammalian cells. Science 1978;200(4340):432-4 (Pubitemid 8328883)
136. Buss WC, Kun E. Effects of rifampicin on RNA and protein synthesis in isolated rat liver mitochondria. Biochem Pharmacol 1978;27(17):2139-45 (Pubitemid 9032784)
137. Keating JF, Blachut PA, O'Brien PJ, et al. Reamed nailing of open tibial fractures: does the antibiotic bead pouch reduce the deep infection rate? J Orthop Trauma 1996;10(5):298-303 (Pubitemid 126432705)
138. Hughes S, Field CA, Kennedy MR, et al. Cephalosporins in bone cement: studies in vitro and in vivo. J Bone Joint Surg Br 1979;61(1):96-100 (Pubitemid 10127713)