Stimulation of bone growth

Stimulation of bone growth

Stimulation of Bone Growth S. L. HAAS, M.D.,San Francisco, Calijornia I’rom tbe Surgical Research Laboratory, Stanford Universi[v School of Medicin...

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of Bone


S. L. HAAS, M.D.,San Francisco, Calijornia I’rom tbe Surgical Research Laboratory, Stanford Universi[v School of Medicine, San Francisco, California.

guson’s experiments and obtained no increase in Iength. In other experiments they inserted foreign materia1 into the metaphysis with negative results. They found that Iigation of the femora1 artery or the femoral vein causes no acceIeration of growth. They aIso stripped off the periosteum in varying amounts from the shaft of the tibia and obtained length increase up to I.5 cm. Compere and Adams [8] in 1937 made three Iarge driI1 holes through both cortices of the femur of rabbits through puncture wounds. In so doing they produced minima1 injury to the surrounding soft parts. About a haIf of the cortex was removed by this procedure and disrupted the blood suppIy to the medullary cana1. No increase of growth occurred in the femurs. They aIso put markers in the tibia and femur at known distances apart and then fractured the bone between the markers. They detected that growth stimulation only lasted during the heaIing period of the fractures. Some of these experiments suggested that there was interstitia1 growth. The authors then concIuded that the caIIus did not contribute to the increase in Iength-growth. They also found from a study of patients in whom fuII-thickness, cortica1 grafts were removed, that Iengthgrowth increases onIy during the period of heaIing. Superficial, osteoperiostea1 grafts caused no increase in growth. From these procedures, they concIuded that trauma must be severe in order to stimuIate Iength-growth. Chapchal and ZeIdenrust [9] in 1948 based their experiments on the findings of Snook and GaiIIard. The Iatter submitted cultures of osteobIasts of fow1 embryos to various metals and found that the most toxic metaIs inhibited growth. The most toxic meta produced the greatest reaction in bone with the greatest reparative reaction and hyperemia. By placing different metaIs in the bone, they beIieved the galvanic currents wouId act as a stimuIant to

of bone growth has been the many experimenta investigations in an endeavor to obtain some practica1 method for equalizing discrepancies in the length of the extremities. As early as 186g von Langenbeck [I] inserted ivory pegs into the femur and tibia of dogs. He obtained a minima1 growth increase in some of the experiments. Other workers have tried similar experiments, some of which wiI1 be brieff y reviewed. Meisenback [2]in IgIo injected a number of metals, chemicaIs and staphyIococcus aureus into the region of the epiphysea1 cartiIage plate without inff uencing the activity of the growing pIate. Konigswieser [j] in 1925 obtained some stimuIation of growth after fiIIing the meduIIary cavity with camphor and siIver nitrate. Bohlman [4] in 1929 made driI1 hoIes on either side of the epiphysea1 pIate into which he pIaced various metaIs, oiIs and vaccine paste. In generaI, he obtained a loss of growth. This appears to have been due to the fact that he had produced a direct injury to the pIate by his operation. Pearse and Morton [5] in 1930 resected about 3 cm. of the upper end of the fibuIa subperiosteaIIy. On one side of the fibuIa they ligated the popIitea1 vein and found that there was an earIier and greater amount of caIIus than on the side on which the veins were not Iigated. AIthough these experiments were not for Iengthgrowth studies, they are mentioned because of some subsequent studies in which Iigation of vessels was performed. Ferguson [6J in 1933 driIIed hoIes into the metaphysis through which he curetted the meduIIary cavity. He obtained some temporary increase in Iength-growth of the Iimbs. Wu and MiIner [7] in 1937 repeated Fer-

S TIMULATION subject of


American Journal of Surgery. Volume 98. Jonuar~.


Haas stimuIation with a maximum of 3 cm. Reinsection was performed in some cases to acceIerate the stimuIation after a quiescent period. An interesting observation was the crossing of screws that were originally paraIIe1. No definite expIanation was offered aIthough it appears that there is the possibiIity of greater stimuIation of interstitia1 growth at the Iarge head end. The increase in transverse diameter couId be due to stimuIation of subperiostea1 bone or to interstitia1 proliferation of bone. The increase of Iength-growth of the tibia which took pIace with screws onIy in the Iower femur and the increase of growth of the Iower epiphysis with the screws in the upper tibia are diffIcuIt to expIain. Pease concIuded that no vaIid concIusion couId be drawn from his few cases and further studies wiI1 be necessary to substantiate his results. Herndon and Spencer [12] in 1953 reported their experimenta work performed in 1948 to 1949, in which they pIaced eIectroIytic copper immediateIy proxima1 to the epiphyseal cartiIage pIate. In some experiments they obtained a 0.23 cm. increase and in others a 0.23 cm. Ioss of growth. They concIuded that copper does not appreciabIy influence Iinear growth. They did not report this work before because of the negative findings. Negative resuIts may serve a purpose in demonstrating the uselessness of some procedures or Iead the way to a successfu1 method. It may be of interest to report the experimenta1 work which I performed in 1940 to 1941, and compare the methods and findings on this subject with those of subsequent workers previously mentioned.

growth. They found that copper and zinc produced onIy a IocaI reaction. Iron produced variabIe resuIts and copper caused a Iagging of growth. An absorbabIe materia1 such as ivory, preferably Iarge, thick pins of ivory, produced the best resuIts. Pins which were aIlowed to project out from the cortex into the soft tissues because of the poor oxygen (anode) of the buried pin and the rich oxygen (cathode) of the exposed part produced a gaIvanic current. With Iarge, ivory pins inserted IateraIIy, they obtained a valgus deformity without Iengthening. The bone showed thickening in the stimulated area. With a pin pIaced medially, no deformity occurred, but some lengthening took pIace. Contrary to what was expected, there was no Iengthening when pins were placed mediaIIy and IateraIIy at the same time. They concIuded that this method was not suited for humans because of the uncertainty of stimuIation and the development of deformities. WiIson [IO] in 1952, aIso with the idea of setting up an electrolytic reaction, used screws of different metals pIaced in the region of the epiphyseal cartilage plate. He found that twisted strands of different types of wires were better and that the combination of constantan and copper were the most suitabIe for stimuIation of growth. In one experiment he obtained an 0.5 cm. increase in growth. In one human subject, a 1.0 cm. increase in growth was obtained as compared to the norma of 0.6 cm. He believed that there might be some loss of eIectroIytic force with the eIapse of time and reinsertion might be necessary to obtain more Iength growth. Pease [I I] in 1952 inserted two screws of various materiaIs including VitaIlium, brass and ivory, into the femur and tibia of patients with Ieg Iength discrepancies which resuIted from anterior poIiomyeIitis, disIocation of the hip and congenita1 hypopIasia. He found that ivory was the most suitable materia1. The screws were inserted into driI1 hoIes in the metaphysis of the Iower end of the femur and upper end of the tibia, near the epiphyseal pIate. The screws were placed, one anterior to the other with the dista1 end of each screw just passing through the cortex. The patients were given a teaspoonfu1 of phosphorized cod Iiver oi1 for one month prior to operation, and the resulting arrested growth Iines served as markers for measuring the growth increase on the two sides. He obtained a variabIe growth







The experiments were performed on growing rabbits-under genera1 anesthesia with the usual aseptic technic. The Iower end of the radius was exposed and the foIlowing various types of meta were inserted into the bone: (I) singIe fragments of iron, copper or aIuminum in the metaphysis near the epiphysea1 pIate, (2) singIe pieces of the same materia1 in the epiphysis (Fig. IA), (3) a combination of copper and iron in the metaphysis to deveIop a gaIvanic reaction (Fig. IB and C), (4) copper in the metaphysis and iron in the epiphysis, or vice versa, to deveIop a gaIvanic current across the epiphysea1 pIate (Fig. 2A and B.), (5) aIumi126


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FIG. I. A, single piece of meta in epiphysis. No increase over normaI growth. B and C, two pieces of metal in metaphysis-copper and stee1. One piece remains behind with growth and the other, which is displaced IateraIIy, is carried along with growth.




FIG. 2. A and B, a piece of copper in epiphysis and a piece of iron in metaph-

ysis. The meta in the metaphysis remains behind with growth. There is a slight increase in growth over normaI. C, manganese oxide in metaphysis caused a destruction of epiphysea1 pIate with loss of growth.

num in the metaphysis bIack



and epiphysis, and (6) in the metaphysis.




caused a destructive

manganese oxide which reaction to the epiphysea1


(Fig. zC.) Results.

Comments. The reason for the failure of growth stimuIation may be due to the fact that

In only one experiment was there any increase in growth when copper was pIaced in the epiphysis and iron in the metaphysis.

the impIanted material becomes separated from the plate with growth of the bone. Another

In none of the experiments was there a Ioss in 127

3B 3A FIG. 3. A and B, circuIar wire about the epiphyseal pIate.


factor that may pIay a part is that the cartiIage ceIIs wiI1 respond only to certain types of stimuIation or onIy when they have been attenuated by disease or abnorma1 deveIopment. In order to have a continua1 stimuIus to the epiphysea1 pIate, as growth proceeded, the foIIowing experiments were performed upon dogs: (I) After exposing the Iower end of the femur or radius, a loop of wire was passed circularIy around the epiphysea1 cartiIage pIate. (Figs. 3A and B.) (2) Wire Ioops of different meta were passed IateraIIy and mediaIIy to the epiphysea1 pIate. (Fig. 4A.) (3) Loops of wire of different metaIs were inserted into the media1 and IateraI condyIes of the femur through the intercondyIar notch. (Fig. 4B.) Result. In each case there was a Ioss of length-growth. It was not reahzed at first that the wire Ioops compressed the epiphysea1 cartiIage pIate and prevented Iength-growth. AIthough the resuIts as far as stimuIating growth were negative, these experiments opened a new field for the appbcation of methods for mechanica retardation of growth of bone. PITUITARY




FIG. 4. A, wire loops of different metaIs placed medial and latera to the epiphysea1 pIate. B, wire loop of different metals passed about the medial and IateraI condyIes of the femur through the intercondylar notch. which pituitary growth hormone was impIanted near the epiphyseal pIate was there any stimuIation of length-growth. In 1953 the following additional experiments

were performed: The femora1 vein and artery were exposed in the inguinal region. The vein was then Iigated. Pituitary growth hormones were injected directIy into the femora1 artery. It was aIso decided to inject pituitary growth hormones daily about the epiphyseal plate of the lower end of the femur. In contro1 experiments in which the vein was ligated, no stimulation of growth took place. Wu and MiIner [7] aIso found no acceIeration of length-growth.

Results. No increase of Iength growth took pIace after Iigation and injection of pituitary growth hormone. Comments. Ray, Evans and co-workers [I?] found in thyroidectomized-hypophysectomized rats that the greatest response in Iength-growth took pIace when both the growth hormone and thyroxin were injected at the same time. It wouId be of.interest to try this combination or other hormones for injection in this type of experiment. There has been a considerabIe amount of discussion as to whether compression retards growth of bone and causes atrophy or whether


The hormone was pIaced in small cavities in the end of the radius as foIlows: (I) in the metaphysis near the epiphyseal pIate, (2) in the epiphysis, (3) in both epiphysis and metaphysis, and (4) in the metaphysis and surrounding tissues near the epiphysea1 pIate. Result. In none of these experiments in 128


of Bone Growth .

tension stimuIates bone growth and prohferation, or that both compression and tension prevent bone proIiferation. It is aIso maintained that tension wiI1 cause deposition of bone up to certain Iimits, but beyond the Iimits a bone can take, it wiI1 lead to absorption. Without any definite conviction as to which theory is correct, it seems that with the reduction of the Ioad which the epiphysea1 pIate had to overcome in normaI growth, there might be an increase in Iength growth. Strobino, Colonna and French [14] have shown that the force to be overcome before growth was hindered was about 500 pounds in the tibia of a caIf. The amount would be Iess in a smaI1 animal, but wouId be considerabIe. Gelbke [15] in 1951 reported his interesting experiments in which he fastened one end of a wire into the diaphysis of the femur and the other end into the pateIIa. As growth in Iength took pIace in the femur a tension force was exerted by the puI1 of the pateIIa Jigament on the apophysis of the tubercle of the tibia. He found no change in the bone or the epiphyseal cartiIage. In another anaIogous method, he fastened one end of a wire into the shaft of the humerus and the other into the apophysis of the oIecranon process. Thus, as growth took pIace in the humerus, a tension force was transmitted to the apophysis of the oIecranon. There was no growth increase or changes in the bone. He concIuded that, to a considerabIe extent, tension acted the same as pressure and caused a cessation of proliferation of the cartiIage ceIIs. TRACTION

FIG. 5. Traction of tibia.

wire in epiphysis of femur to diaphysis

passed through the epiphysis of the tibia proxima1 to the epiphyseal plate and brought up across the. knee joint and passed through the shaft of the femur, proximal to that epiphysea1 pIate, and then back to the starting point. (Fig. 7.) In the Iatter experiments the pulling force wouId be exerted by the growing femora1 epiphysea1 pIate on the,epiphysis of the tibia. Result. No growth acceIeration took pIace in any of the experiments. There was no 10~s of growth. Comments. The mechanism of these experiments is difhcult to expIain. If the Ioop acted as a compression force on one epiphyseal cartiIage plate, a considerabIe loss in lengthgrowth shouId have taken pIace. There was no appreciable decrease in Iength and growth kept up with norma size. It is possibIe that there is a balance of forces of growth, expansion and compression. In some of the experiments there was an increase in the curve of the lower enc1 of the femur, evidentIy caused by tension.


We have performed two sets of experiments in an endeavor to use the growing epiphyseaI cartiIage pIate of one bone to make traction on the epiphysis of an adjoining bone. After exposing the Iower part of the femur and the upper portion of the tibia, a wire was passed through the epiphysis of the femur and then brought down into the subcutaneous tissue across the knee joint to beyond the epiphysea1 pIate of the tibia. The wire was next passed across the shaft of the tibia and brought tp into the subcutaneous tissue on the opposite side and anchored to the other end of the wire at the origina starting pIace. (Fig. 5 and Fig. 6A and B.) It was hoped that with the growth of the tibia there wouId be a traction force on the femora1 epiphysis. In the other set of experiments the wire was





In the devised so be appIied epiphysea1 129




next experiments a method was that a direct expansion force could about one epiphyseal pIate. The pIate of the lower end of the femur




FIG. 6. A and B, traction wire in epiphysis of the femur to the diaphysis of the tibia. Showing growth changes and spreading of the wire Ioop.

8A FIG. 7 . Traction of fernlur.

wire in epiphysis of tibia and dial Fhysis


FIG. 8. A, expansion apparatus about the epiphyscar cartilaginous plate anchored to the wires through the bone. B, expansion apparatus about the epiphyseal cartilaginous plate anchored to the threaded boIt.


of Bone

Growth Results of animal experimentation. Am.

was exposed by an incision on both the IateraI and media1 sides of the end of the bone. A wire or threaded rod was passed through the epiphysis dista1 to the pIate. A simiIar wire or rod was passed through the diaphysis proximal to the pIate. An expansion apparatus was then anchored to the ends of the wire or boIts on each side. This apparatus consisted of a cyIinder, containing a wire spring at its base, which was compressed by a plunger inserted into the cyIinder. (Fig. 8A and B.) Thus, there was a constant expansion force exerted by the compressed spring. Result. No acceIeration of Iength-growth was obtained by this method. No loss of growth took pIace in the bone. Comments. The expansion power may not have been suflicient to exert any force in excess of the norma growing force of the epiphysea1 pIate. It is aIso possibIe that there are certain properties of the growth pIate that cannot be inAuenced by externa1 forces.

J. Ortbop. Surg., 8: 28-94, 1910. 3. KONIGSWIESER. ExperimeneIIe und pathoIogische Beinffussing des Epiphgsenwachstums. Verbandl. Dent. Ortb.Ges., 20:-28;. 1925. A. BOHLMAN. H. R. ExDeriments with foreien materiaIs in the region of the epiphysea1 cartilage plate of growing bones to increase their Iongitudina1 growth. J. Bone EYJoint Surg., I I : 365-

Ueber Krankhaftes Langenwachsthum der Rohrenknochen und seiner Verwerthung fur die chirurgische Praxis. Bed.

384, 1929. 5. PEARSE, H. E. and MORTON, J. J. The stimuIation of bone growth by venous stasis. J. Bone fl Joint Surg., 12: 97-I 1 I, 1930. 6. FERGUSON, A. B. SurgicaI stimulation of bone growth by a new procedure. PreIiminary report. j. A. M.-A., IO: ;6, 1933. 7. Wu. Y. K. and MILNER. L. J. A Drocedure for &imuIation of IongitudrnaI growth’ of bone. An experimenta study. J. Bone CY Joint Surg., rg: 99-921, 1937. 8. COMPERE. E. L. and ADAMS. C. 0. Studies of IongituhinaI growth of Iong .bones. I. The inffuence of trauma to the diaphgsis. J. Bone CYJoint Surg., Ig: 922336, 1937. o. , CHAPCHAL. G. and ZELDENRUST. J. Experimental research’ for promoting IongitudinaI growth of the Iower extremities by irritation of the growth region of femur and tibia. Acta Ortbop. Scandinav., 17: 371-396, 1948. IO. WILSON, C. L. Experimenta increase in Ieg Iength. A preIiminary report.. American CoIIege of Surge&, 1951. 3. F&m, pp. 438-443, 1952. I I. PEASE. C. N. LocaI stimuIation of growth of Iong bones. A preIiminary report. J. Bone ti Joint Surg., 34-A: 1-23, 19-52. _ 12. HERNDON. C. H. and SPENCER. G. E. An experime&I ‘attempt to stimulate linear growth of Iong bones in rabbits. J. Bone TV Joint Surg., 35-A: 758-759. 1953. I 3. RAY, R. D. et al. Growth and differentiation of the skeleton in thyroidectomized-hypophysectomized rats treated with thyroxin, growth hormone and the combination. J. Bone u Joint Surg., 36-A: 94-103, 1954. 14. STROBINO,L. J., FRENCH, G. 0. and COLONNA, P. C. The effect of increasing tensions on the growth of epiphysea1 bone. Surg., Gynec. ti Obst., 65:

klin. Wcbtrscbr., 6: 265-270, 1869. 2. MEISENBACK, R. 0. A consideration of the cIinica1 and mechanical stimulation of bone with refercnce to the epiphyseal and diaphysea1 Iines.

694-700, 1952. 15. GELBKE, H. The inffuence of pressure and tension on growing bone in experiments with animals. J. Bone CYJoint Surg., 33-A: 947-934, 195 I.


A series of experimenta methods have been presented in which an endeavor was made to acceIerate the norma growth of bone. Although none of the methods was successfu1, it is hoped that they wiI1 serve as a guide to some efficient way of enhancing Iength growth. It is aIso hoped that this work wiI1 stimuIate additiona investigation regarding the inherent growth properties of the epiphysea1 cartiIaginous pIate. REFERENCES I. VOX LANGENBECK, B.