Reprinted from the University Medical Magazine, December, 1889. THE TRANSPLANTATION OF BONE; WITH TWO ILLUSTRATIVE CASES. J. William White, M.D., Professor of Clinical Surgery, University of Pennsylvania; Surgeon to the University, Philadelphia, and German Hospitals. attsitaiiaiwiwiwtiXwiwiMtwiieiwiwttcitsiWitatw. «i»*it«iw<»i»li»iwit«<wi>•>t«iwi••(wi»•<wiwi»imit«(wi»«»«im»»i«•<Ml«• iMl«eiMlmiwlWi»«imiwi< Reprinted from the University Medical Magazine, December, 1889, THE TRANSPLANTATION OF BONE; WITH TWO ILLUSTRATIVE CASES. J. William White, M.D., Professor of Clinical Surgery, University of Pennsylvania; Surgeon to the University, Philadelphia, and German Hospitals. J. H., 55 years of age, was admitted to the University Hospital May 8th, with the fol- lowing history : On February nth, while engaged in oiling a shaft revolving 180 times a minute, he slipped and fell upon it and was carried around several times and then thrown forward into an ash-pit, a distance of 18 feet. All the clothing even to his shoes had been torn from his body. He had a severe scalp wound, grave sprains, and contusions of the lower limbs, a fracture of the lower end of the left humerus, an oblique fracture of the middle of the shaft of the same bone, and an injury of the left elbow joint leaving great thicken- ing with complete obliteration of all the normal features of the joint and finally firm anchylosis. He did well in all respects except as to the fracture of the humeral shaft which failed to unite, leaving a flail-like condition of the upper arm, for the relief of which he was brought to me by his attending physician. OnWednesday, May8th, the ends of the fragments of bonewere exposed by a longitudinal incision, and after having been first freshened by a free use of the saw were closely wired together, after which the parts were united by cat-gut suture, a few strands of the same material being used fordrainage ; an internal angular splint and a shoulder cap were applied and the arm placed in a sling; the dressing was changed on the following day, having become displaced on account of the restlessness of the patient, but was not again disturbed for a month. At the time of operation I called the attention of the class to the withered and atrophied condition of the ends of the bone, and gave an unfavorable prognosis as to the result of the operation. On the removal of the dressing on June 5th, it was found that not the slightest attempt at union had taken place ; the flail-like condition of the arm remaining unaltered. The failure was evidently due to the inability of the bony ends to take on the necessary reparative action. This is a well-known cause of ununited fracture and is not to be wondered at if we regard the existent pathological conditions. WHITE, THE TRANSPLANTATION OF BONE. 2 In attempting to explain any case of this character it will aid us in arriving at a conclusion if we divide the possible causes into constitutional and local. Under the former head, a large number of conditions have been mentioned, many of them upon very insufficient clinical evidence. Some of them, such as syphilis and cancer, I am quite sure from my personal experience should not be included. Others, such as the existence of pregnancy or lactation, are more than doubtful. It is unquestionable that a severe disease, particularly when acute, and attended with marked febrile reac- tion, such as smallpox, rheumatism, or typhoid fever, may lead to a failure to unite. As a rule of very general application, however, it is safe to say that in an ununited fracture we should expect to find some efficient local cause in a great majority of cases. Among such causes the most common are, mal-posi- tion of the parts, the interposition of foreign bodies, such as portions of the capsule in cases of transverse fracture of the patella, or of muscles closely attached to the surface of the bone, as the brachialis anticus in the present instance ; and above all, mobility of the fragments commonly due, either to the intractability of the patient, or the carelessness of the surgeon. In the present case we have a combination of circumstances any one of which would have been sufficient to account for the non-union. The injury was so extensive, and the soft parts so gravely involved, that it was impossible to apply any fixed dressings for a long time after the accident. The damage to the nerves, which was clearly shown by the purplish, shining skin of the whole forearm and hand, without doubt affected the bones likewise, and was competent to retard, or to prevent consolida- tion. The anchylosis of the elbow by communicating directly to the lower fragment the movement of the hand and forearm was also a probable factor in the case. All these conditions being regarded, it is scarcely a matter for surprise, either, in the first place, that union did not occur, or next, that the opera- tion by freshening and wiring was likewise a failure. It was evident that some- thing more had to be supplied to the part before the material for repair could be furnished by the tissues. The views in regard to the methods by which such repair of solutions of continuity of the osseous structures takes place have recently been greatly modi- fied, first by the investigations of Paget, Klein, Cornil, Ollier, Sedillot, and others ; and still later by the observations of Macewen who has shown that while on the one hand the periosteum is not the potent osteogenic factor which many thought it to be, on the other hand, the soft tissues inclosed in the osseous tissue play the chief role in the development and reproduction of bone. I have had the pleas- ure of examining with him the case of regeneration of the humerus which he has recorded, and in which after destruction of the shaft by acute necrosis he built up a new bone by the transplantation of fragments, and it certainly goes far to establish the truth of the above statement. Among the other propositions which he formulates is the following most important one : " Not only do detached portions of bone deprived of their peri- osteum live when reimplanted in their original position, but such portions are capable of living after transplantation. Parts of deeper layers of bone which had no periosteal connection have been transplanted and lived and grown." This statement is supported by both observation and experiment, and rests upon WHITE, THE TRANSPLANTATION OF BONE. 3 the fact that bone is produced by proliferation of osteoblasts, and both its develop- ment and reproduction can take place independently of the medulla and peri- osteum. So far from regarding the periosteum as the structure which can alone secure or reproduce bone, the surgeon who accepts these teachings will not trust it to regenerate bone unless it has adherent portions of sound osseous tissues from which alone, by the process of proliferation, can osseous regeneration take place. These teachings are not altogether new even in this country. As long ago as 1874 a Committee of the Medical Association of South Carolina reported, through the chairman, Dr. W. H. Bailey, after having investigated the subject of osteo- genesis and the reproduction of bone, that while they admitted that the perios- teum plays a very important part in the formation of bone, and perhaps the most important part in its reproduction after destruction by injury or disease, they were unwilling to assign to it exclusive powers in this respect, or even to admit that its presence is essentially necessary to the process. The applications of these observations to practical surgery lies in the direc- tion of supplying the deficiency of sound osseous tissue in ununited fracture, and after excision of bones or joints, and the problem is one which, combined with the effort to produce complete fixation of the fragments in such cases, has long occupied the attention of the profession. Dieffenbach's ivory pegs, the wire sutures of Flaubert, the seton of Valentine Mott, and the steel pins employed in the treatment of ununited fractures, are examples of various attempts in this direction, which have had varying degrees of success. Max Schuller1 has recently considered at some length the question of the artificial encouragement of bone-growth basing his views upon the general laws of normal growth, upon a series of pathological observations, and upon numer- ous experimental researches into the conditions under which the increase or decrease of bone-formation occurred. Tangenbeck, Bergmann, Dittel, Tillmans, Ollier, and others, have recorded the results of their observations upon the regeneration of bones, and Helferich, Haab, and von Bidder have confirmed them experimentally. Experiments show that after irritation of bone in young animals either directly through the scratching of the periosteum, or by the introduction of pegs in the middle of the diaphysis, an elongation of the bone almost constantly followed, while destruction of the inter-articular cartilage was almost as constantly followed by atrophy. Von Tangenbeck advised, after resection of the knee-joint, the introduction of an ivory peg, in order to avert consecutive failure of develop- ment in infantile paralysis, but never practically applied it. In 1887 von Helferich recommended the establishment of an artificial con- gestion in the affected limb by means of an elastic bandage, giving rise to in- creased activity of nutrition of the bones and of the whole limb. He has espe- cially employed this in cases of delayed union after fracture, in the hastening of the separation of the sequestrum in necrosis, and even in sound individuals with extremities of unequal length, and in all these cases with favorable results. 1 Deutsche med. Zeit., 1888, No. 99. 4 WHITE, THE TRANSPLANTATION OF BONE. In cases of infantile paralysis, however, no good effects were obtained. Schuller, in these latter cases, adopted and tried the elastic bandage, combining with it other processes of local treatment, certain dietetic regulations, and, in some cases, different operative procedures. He applied an Esmarch tube in such a manner that it compressed the veins, but left the arterial supply free. At first it was removed in a few hours ; afterward he left it in place day and night, having careful watch kept as to the effect. In addition, he used massage, bathing, diet favoring the assimilation of lime salts, regular exercise, etc. His results were excellent in a variety of cases. Schuller asserts that he was the first to aim at increasing bone-growth, not only by making the bone hypersemic, but also by giving the shortened or withered limb a greater mass of blood, a more active circulation, and a larger supply of nourishment of the quality to favor bone-formation. By examina- tion of the urine he claims to have discovered what form of food, and which of the lime salts are best fitted to this end, having carefully estimated the quanti- ties excreted and retained. The steel pegs which he sometimes employs need only be left for a short time, and may set up but a trifling degree of hypersemia, but if this is followed by his combined treatment he asserts that a continuous production of bone is almost sure to occur. In the above case I carefully considered this method but rejected it on account of my lack of experience with it, and also because the circulation and nutrition of the limb had already been so much interfered with by the original accident, the subsequent cicatricial contraction, the long-continued disease, etc., that I feared the effect of elastic compression. There was, however, still another method of treatment that seemed worthy of trial before resorting to amputation, viz : the grafting of periosteum after the method of Macewen. As it happened no patients requiring operation upon bones were at that time available and I was therefore led to consider the propriety of transplantation from one of the lower animals. The question of periosteal grafting was long ago thoroughly discussed by Ollier,1 who says the difficulties of periosteal grafts between animals of dif- ferent species indicate the still greater obstacles which exist in cases of true bone grafting. The periosteum, the principal active agent in the graft, which when transplanted alone in such cases has always failed, will be under still more unfav- orable conditions, when adherent to tissues which themselves have so little ten- dency to unite with surrounding parts. He has made numerous exchanges of bone between animals of different species and has never succeeded. The trans- planted bone has resisted absorption for a greater or less time when it has not promptly occasioned an abscess, but has always disappeared finally. Ollier refers to the experiments of Barromeo2 and the similar experience of Brown- Sequard3 who having transplanted a portion of the tail of a cat upon the comb of a cock saw the circulation establish itself in the transplanted organ so that on 1 Regeneration des Os, vol. I, p. 427. 2 Hunter's Complete Works, vol. 1. s Journal de Physiologic, i860. WHITE, THE TRANSPLANTATION OF BONE. 5 the eighth day a puncture was followed by a drop of blood. Ollier says that here, however, the bones were not stripped of the soft parts, and the experi- ment belonged to the general subject of animal grafting and not the reproduction of bone. He says also1 that having exchanged flaps of periosteum between animals of different species in more than sixty instances he had but once suc- ceeded in obtaining a little osseous particle, or at least one having the appear- ance of bone. His experiment showed also that the periosteal graft is equally a failure when transplanted either from a superior to an inferior animal, or vice versa. He concluded that nothing in his experience justifies the use in surgery of hetero-periosteal grafts and summarizes as follows the conditions which his experiments led him to consider essential to successful bone grafting: It is necessary that the bone grafts shall be taken from the same subject, or at least from a subject of the same species. The age of the animal is not of capital im- portance, and bony grafts succeed better in young subjects, or in old subjects it is better to transplant a fragment from a young individual. The younger the bony tissue and the richer in soft tissue, periosteum, and marrow, the more suitable it is for grafting. A bony fragment stripped of its periosteum cannot be grafted at all, or only under very exceptional circumstances. The most favorable conditions are met with when the fragment is part of a subcuta- neous bone. The graft should always be small, the less its volume the quicker it will be penetrated by new vessels. He relates2 the experiments of Percy, who endeavored to repair extensive destruction of the tibia of a man by the transplantation of portions of the tibia of an ox. This was twice attempted, and in each case was an entire failure, showing no tendency whatever to contract adhesions to the surrounding parts. In 1888, in a case of complete excision of the knee-joint, I em- ployed a portion of dog's bone for fixation of the femur and tibia. The case was one of extensive tubercular synovial disease, with softening and disappearance of the cartilages, and with caries of the head of the tibia and the condyles of the femur. At the proper stage in the operation one of the metacarpal bones of a medium-sized dog was removed with thorough antiseptic precautions, and brought to me in a warm carbolized towel. The piece of bone measured about three inches in length. A small cavity, just large enough to receive the end of the bone, was excavated in the lower extremity of the femur, and a corresponding one in the upper end of the tibia. The bone was then fitted tightly in place, and held the parts so firmly in position that the whole limb could be supported by the heel without displacement. It was dressed and placed in a bracketed wire splint. The subsequent course of the case was as follows : After a week or ten days, during which there was no elevation of temperature, there was a sudden rise to 102.5 degrees. I found that there was an accumulation of sero-purulent fluid beneath the upper flap ; on evacuation, this was proved to be quite aseptic, but it continued to discharge for several weeks longer, gradually diminishing in quantity, but retaining a gelatinous consistence, possibly due to admixture with synovial secretion. The temperature also remained slightly above nor- 1 Op. cit. p. 414. 2 Op. pit. vol. ii. p. 443. 6 WHITE, THE TRANSPLANTATION OF BONE. mal. The patient's complexion and general appearance, and a slight cough, gave rise to the suspicion of pulmonary tubercle, though no physical signs were then discoverable. The limb remained in good position, the mechanical effect of the bone-peg having been all that could be desired. There was no evi- dence that it was acting as a foreign body or in any way interfering with the process of repair.1 At about this time I went abroad and did not* see the patient again until the following autumn when he returned complaining of a recently formed sinus on the inner aspect of the limb, or the one furthest removed from the point at which I had inserted the bone-peg. Investigation showed that active disease was going on in the portion of bone representing the remains of the internal condyle which was carious and suppurating. It was decided that a second operation would be required. An anterior flap was raised by an incision along the line of the old cica- trix and the tibio-femoral line exposed. The bones were found incompletely united here and there by patches of new bone, but the disease at the inner aspect of the lower end of the femur was so extensive that it was evident that a new resection would be required. The union was therefore broken up by means of a chisel and a stout bistoury, and the bones again separated. I, of course, looked with great interest for evidence of consolidation of the dog-bone with the parts around it. I found it, however, lying precisely as I had placed it months before, firmly fixed in the tibia and femur, having set up neither irrita- tion, inflammation, nor suppuration ; but, on the other hand, having quite failed to excite any osteo-genetic process in its immediate neighborhood. In other words, the wound having remained aseptic the bone lay there just as a steel peg or an ivory peg might have lain with neither more nor less benefit. ' I pro- ceeded to the resection of the diseased part of the inner condyle which involved the sawing off the lower end of the femur for some distance above the previous line of division, corresponding disease at the inner part of the tibia necessita- ting the removal of a section from that bone also. I brought the bones together, inserted a drainage tube, and placed the limb in a bracketed wire splint. Union was slow but finally complete, and the patient has been in my office within a few weeks, having a useful limb. In 1878, Dr. Alexander Patterson, of Glasgow, reported a case of ununited fracture of both bones of the forearm, in the treatment of which a portion of dog's bone was used as a means of procuring union. The ends of the fractured radius were separated about three-quarters of an inch, and in this interval was placed a corresponding section of the humerus of a dog. It was held in place by a wire passed through holes drilled through the ends of the bones and then through other corresponding holes in the fragments of the radius. Its perios- teum had been first reflected for a short distance, and was then brought down over the line of junction of the bones. The ulna was simply wired together, and later was found firmly united ; but at the end of six weeks union was not complete in the radius, and the wound remained open for twelve months. At the end of that time the dog's bone, reduced to about half its size, came away, after which the wound healed completely. 1 The case up to this period was reported in The Lancet, August i8» 1888. WHITE, THE TRANSPLANTATION OF BONE. 7 In January, 1887, Dr. Bernays,1 of St. Louis, reported some experiments in which by the use of bone sawdust of various degrees of fineness he produced bone in different positions, in the soft parts of the extremities, the abdomen, and back of two dogs. These experiments have not been confirmed, and Dr. Bernays records the fact that all his attempts to graft large pieces of bone in animals were failures, the pieces simply becoming surrounded by "periosteal bone-tissue'' and remaining as foreign bodies, which subsequently had to be extracted. Dr. H. M. Sherman,2 of San Francisco, has reported a case in which the entire ungual phalanx of the right thumb was carried away by an injury. The nail was torn away and there was much contusion of the soft parts. The wound was dressed antiseptically and carefully washed out for two weeks. The cavity was then found to be granulating healthily in its whole extent, except its base, which was formed by the articular cartilage of the proximal phalanx, the parts having absolutely no firmness. A healthy Newfoundland puppy was chloroformed and a wedge was cut from the scapula containing bone and cartilage and the line of ossification. A wedge wrapped in a piece of warm muscular tissue was brought to the operator, cut to the shape and size of the last phalanx, implanted in the cavity, and a snug antiseptic dressing applied. The graft lived, the soft parts healed over, and the patient retained a very use- ful thumb, having full extension and flexion to forty-five degrees, and being able to bear nearly as much pressure upon its tip as upon the tip of the sound thumb. Mr. A. F. McGill,3 of Leeds, has just reported a case of ununited fracture of the radius successfully treated by the transplantation of fragments of the femur of a young rabbit. A previous attempt at securing union by fastening and wiring the broken ends had been a failure. The interval between the frag- ments was about three-quarters of an inch. The ends were stripped of the thick tissue, resembling periosteum, which covered them, and the portions of rabbit bone placed between them. Good union was obtained in about six weeks, with restoration of function. It seems fair to say that there is now good reason, both clinical and experi- mental, to hope for the formation of new bone around grafted fragments of a proper size taken from the same individual or from an individual of the same species. The successful cases of Macewen and others, have, as a rule, been those in which bone-chips or bone-dust were employed. The largest frag- ments successfully re-implanted, so far as I know, have been the buttons removed during trephining. There is, therefore, not the least reason to doubt the possibilities of such transplantation, or to question the propriety of attempt- ing it in suitable cases. It cannot be said, however, that transplantation from one species to another has as yet been put on a similar footing. Ollier's unsuc- cessful experiments, those of Bernays and the cases of Patterson and myself, all pointed in the opposite direction, and at the time when I was compelled to 1 Medical Brief, vol. xv. p. 48. 2 Pacific Med. Journal, June, 1889. 3 The Tancet, October 26, 1889. 8 WHITE, THE TRANSPLANTATION OF BONE. decide as to the next operative procedure the cases of Sherman and McGill had not been published, and if they had been would hardly have been sufficient to generalize from. Considering, however, the thoroughness of my first operation, and the entire failure to develop any callus whatever, I concluded that the case in question was one which warranted the belief that the difficulty lay in the inability of the atro- phied bone to take on any effective reparative action and that another attempt in the same direction was justifiable. I accordingly freshened the ends of the bone carefully by scraping, brought them nearly in apposition, but placed between them, and in the space between them and the soft parts, a number of fragments of a dog's femur taken out under antiseptic precautions and minced into pieces as large as peas. About one-and-a-half teaspoonfuls of these fragments were put in position ; the wound was closed by deep cat- gut suture, a few strands of cat-gut being laid in for drainage ; an antiseptic dressing was applied, and over it a plaster bandage extending from the fin- gers to the shoulder. The patient remained in the hospital for a week, during which the highest temperature was ninety-nine degrees. He then went to his home in Norristown, and no symptoms of any sort devel- oping, the dressing was not removed until the middle of July. It was then taken off in my absence by Dr. Edward Martin, who, finding no attempt at union and no evidence of the formation of callus, very properly re-applied a plaster dressing. In September I removed this bandage, but found the arm in about the same condition as before the first operation, the bulk of the bone at the region of fracture having diminished rather than increased. As the extremity was entirely useless, and was a drag and burden to the patient, I amputated below the shoulder, obtaining union by first intention. The report of Dr. John Shober, who kindly examined the specimens for me, is as follows :- Seat of fracture in middle of shaft shows the upper and lower fragments united by dense, fibrous, connective tissue ; one-half inch separation between ends of fragments, which appear atrophied and tend to point, also dense bands of fibrous tissue uniting the muscles above and below the seat of fracture with the upper and lower fragments. The shaft of the humerus both above and below the fracture is atrophied, the periosteum is loosely adherent and decidedly thickened. This is most marked in the lower fragment. Upon stripping off the periosteum the subjacent bone is found to be softened and porous. The walls of the shaft are thinner than normal and the lumen of the medullary cavity is enlarged. The medullary substance is broken down, soft, tenacious, and yellowish, and shows under the microscope much granular fat, free fat, many leucocytes, and rod-bacilli. Arising from the internal aspect of the shaft of the lowerfragment, about one-and-a-half inches below its upper extremity is a new formation of bone one-eighth inch in diameter and two- and-one-quarter inches long, which extends upward, parallel with the shaft of the humerus, one-eighth inch distant from it beyond the seat of fracture, and has a fibrous attachment with the upper fragment. The radius and ulna are decidedly atrophied in their continuity with thickened walls, encroaching on the lumen of the medullary cavities. The substance of these bones is very dense and hard, presenting the macroscopic appearance of osteo- sclerosis. WHITE, THE TRANSPLANTATION OF BONE. 9 The new formation of bone described is evidently the remains of the implanted dog bone, all the rest having disappeared by absorption, as there was no suppurative or other discharge to carry it away. Its connection with the lower fragment by bony material, and its growth in the direction of the axis of the limb appear to be evidence of a formative effort which under more favorable circumstances might have given the case a successful termination. The attempts which I have made in these two instances are of enough importance to be thus recorded ; as they supply additional evidence in one case, at least, of the innocuousness of the experiment, and in the other of the possibility of vital union taking place between the bone of a lower animal and human bone.