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Fluorescence of Tetracycline Antibiotics in Bone
ROBERT AUSTIN MILCH; DAVID P. RALL; JOHN E. TOBIE
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Surgery Branch; Clinical Pharmacology and Experimental Therapeutics Section, National Cancer Institute; Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Public Health Service, United States Department of Health, Education, and Welfare, Bethesda
1958 by The Journal of Bone and Joint Surgery, Incorporated
J Bone Joint Surg Am, 1958 Jul 01;40(4):897-910
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Abstract

Antibiotics of the tetracycline series (tetracycline, chlortetracycline, and oxytetracycline) were administered to human subjects and laboratory animals under a variety of clinical and experimental conditions. The drugs were administered orally to human subjects in the usually employed clinical schedule (one to two grams per day) and by the oral and all parenteral routes to male and female animals of varying ages in doses from 0.1 to 200 milligrams per kilogram of body weight. In all circumstances, brilliant yellow-gold induced fluorescence was detectable in ultraviolet light (365 millimicra) following administration of each of the drugs.

In the animals the induced fluorescence was apparent in diffusely distributed tissues, with the exception of brain, almost instantaneously following intravenous injection and within thirty minutes of intraperitoneal administration. It persisted for approximately six hours in all tissues and was undetectable grossly in soft tissues twelve to twenty-four hours later. Long and flat bones, however, and the incisor teeth of rodents as well, showed persistence of the fluorophor for prolonged periods of time. Striking fluorescence was observed after doses in the range of fifty to 200 milligrams per kilogram of body weight and unequivocal, minimal fluorescence could be detected with doses in the range of 0.2 milligram per kilogram of body weight.

Localization and intensity of the bone fluorophor, which appears to be chemically unaltered drug, was entirely unaffected by the route of administration, by the dose schedule employed, or by the sex of the individual. Microscopically, localization in bone appeared to be limited to regions of true new-bone proliferation (mineral and matrix phases) in both adult and young animals and in both normal and certain pathological conditions. This localization accounted for the gross pattern observed in young animals and for the characteristic cream-colored type of induced fluorescence typical of adult animals. No differences in localization could be detected between all species observed, including humans, except on the basis of the relative physiological age of the particular bone region examined.

It is suggested that bone fluorescence, following administration of the tetracycline antibiotics, arises from a complex interfacial interaction which presumably involves the four-ringed naphthacenecarboxamide nucleus of the tetracyclines, calcium, and the organic matrix of newly proliferated bone.

The investigative, public health, and therapeutic implications of this precise localization of tetracyclines in bone would seem to be obvious.

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    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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