CHAPTER 3
HEALING OF BONE

VASCULAR RESPONSES TO FRACTURE OR OTHER INJURY
For the repair of a long-bone, the three primary components of the afferent vascular system (see Fig. 1-8 in Chapter 1) become enhanced as required locally. In addition, a new and supplementary blood supply develops, derived from the surrounding soft tissues. This has been termed the extraosseous blood supply of healing bone.(35) Since it is transitory and does not have to be conveyed by fascial attachments, it is distinct from the blood supply furnished by the normal periosteal arterioles. Consequently, its classification with the periosteal arterioles as part of a so-called periosteal circulation, as appears in the older literature, is misleading. The extraosseous blood supply of healing bone is a discrete entity.

Development of the extraosseous blood supply starts immediately after the injury. It progresses as required, reaching any bony surface where healing is in progress. Illustrations of its various features will be taken from a series of experiments on displaced and undisplaced fractures treated with and without surgery.

FIG. 3-10 Mature canine tibia 3 weeks after fracture and internal fixation with a loose-fitting medullary rod. (A) Roentgenogram shows good position of all the components of the fracture. Note the small butterfly fragment posteriorly (to right). (B) Microangiogram of the area of fracture, corresponding to the lateral roentgenogram. The tissue slice of the microangiogram was somewhat oblique, containing part of the rod tract (above). Observe that the cortex separated from the rod tract has maintained its complete blood supply derived from medullary arterioles, whereas the cortex abutting the rod tract (upper right) is avascular over its inner two thirds. The outer third of this area of cortex, being posterior where periosteal arterioles enter the tibia, remained vascularized. The posterior detached butterfly fragment is itself avascular, but arterioles of the extraosseous blood supply have surrounded it The mass of periosteal callus anteriorly exhibits the typical vascular pattern of extraosseous arterioles approaching the bone surface perpendicularly. (original magnification x 3) (A, Rhinelander FW: Tibial blood supply in relation to fracture healing. Clin Orthop 105:34-81, 1974; B, Rhinelander FW. Some aspects of the microcirculation of healing bone. Clin Orthop 40:12-16, 1965)

The extraosseous blood supply vascularizes early periosteal callus and any detached fragments of cortex that have lost their normal blood supply from the medulla, a situation illustrated in Figure 3-10, which shows a 3-week tibial fracture treated by open reduction and internal fixation with a Rush rod. Intense vascularization can be observed in the space internal to the butterfly fragment. This vascularization is derived chiefly from the new extraosseous blood supply, in anastomosis with the residual periosteal arterioles that are adjacent.

The extraosseous blood supply persists only until the components of the normal circulation have been restored sufficiently to take over. This is demonstrated in Figures 3-16 and 3-19 from experiments in fracture series covered in other sections of this chapter. Healing has progressed to the stage in which the extraosseous blood supply has disappeared, and the persistent periosteal callus is vascularized by branches of the medullary arteries completely traversing the porotic cortex.

Medullary bridging callus, being wholly within the medulla, is vascularized only by the medullary arterial circulation. It produces the first osseous union that develops at a fracture or osteotomy site.

When stabilization is sufficient, this osseous union can occur directly, without an intermediate stage of fibrocartilage as demonstrated at 2 weeks after compression-plate fixation of an osteotomy. (See Fig. 3-23, B.)

Periosteal bridging callus (also termed external callus) is the only callus revealed significantly by standard radiographic examination. Initially it is vascularized entirely by the extraosseous blood supply, the arterioles of which approach the external cortical surface at right angles. That microvascular picture is the hallmark of periosteal callus (see Fig. 3-18).

FIG. 3-11 Diagrammatic representation of the three types of osseous callus encountered at sites of bone repair. (Rhinelander FW, Wilson JW Blood supply to developing mature and healing bone. In Sumner-Smith G (ed): Bone in Clinical Orthopaedics: A Study of Clinical Osteology, chap 2. Philadelphia, WB Saunders, 1982)

FIG. 3-12 Paired radii of a mature dog 8 weeks after osteotomy and internal fixation, with different degrees of stabilization produced by different types of plates applied to the upper corhcal surface. Photomicrographs of histologic sections show the production of osseous callus with respect to the stabilization achieved. (H&E, x 3.5) (Rhinelander FW Circulation in bone. In Bourne G (ed): Vol 2, The Biochemistry and Physiology of Bone, 2nd ed, chap 1. New York, Academic Press, 1972)

After a fracture has healed and the medullary arterial supply has thoroughly regenerated, branches of the medullary artery traverse the full thickness of cortex to vascularize any periosteal callus that remains. The transientsient extraosseous blood supply has by then disappeared. (See Figs. 3-16 and 3-19.)

Formation of a zone of fibrocartilage opposite the fracture site appears to be a necessity with periosteal bridging callus (in contrast to the situation with medullary bridging callus). This is presumably because any tearing of periosteum, as occurs with the bone injury, leads to production of cartilage.

There is no relationship between the amount of periosteal callus and the size of the hematoma in the healing area. More hematoma than what occupies the space between the bone ends is undesirable and is resorbed as quickly as possible. The amount of periosteal callus reflects strictly the need for ancillary stabilization of the fracture fragments as healing progresses. A large amount of external callus indicates the need for additional support beyond the normal contours of the bone. This represents a delay in osseous healing over what can be obtained by stable fixation, but it is a normal repair process of warm-blooded animals and humans. Absence of all external callus results from accurate reduction and rigid fixation, as obtained with compression plating of a long-bone.

Intercortical uniting callus occupies the space between the opposed ends of cortex at the fracture or osteotomy site. When the space is small, its blood supply comes entirely from the medulla and anastomoses with the extraosseous blood supply at the periosteal surface. (See Fig. 3-15, A.) Since the medullary arterial supply cannot extend beyond the contours of the bone itself, a large intercortical space contains chiefly callus of the periosteal type.

The amount of intercortical uniting callus is of course dependent on the accuracy of reduction of the bone fragments. It may be completely absent, as occurs with compression fixation. (See Fig. 3-23 B.) It may be small and without a stage of cartilage formation, as demonstrated in a 2-week undisplaced fracture treated by immobilization in a plaster cast. (See Fig. 3-15 C.) Or it may be large, blending with periosteal callus containing a zone of cartilage, as occurs when fracture fragments remain displaced without rigid fixation.

The basic vascular situation in this experimental series is preservation of the medullary artery and its largest branches. The significant injury is to the vascular channels within cortex. Osseous tissue on each side of a fracture of diaphyseal cortex is devascularized, but not over a full 1-mm zone as has been taught by histologists in the past. Scattered wide areas of devascularization exist, but as can be observed in Fig. 3-13, there is an active blood vessel in a bone canal 30-um from a one-day fracture. In compact bone, close the the fracture site, there are also microfractures which interrupt the canaliculi, and thereby deprive adjacent osteocytes of nutrients.

Adjacent to osteotomies, in contrast to fractures, the cortex is not stressed before dissolution occurs, and microfractures are consequently less prevalent. There is, therefore, less cortical necrosis of the contacting bone fragments. That is one of the differences in the repair of fractures compared with osteotomies.

FIG. 3-13 Photomicrograph of histologic section from 1-day undisplaced fracture of canine radius shows granules of Micropaque (injection medium) in a bone canal very close to the fracture site. (H&E, x 360) (Rhinelander FW, Baragry RA Microangiography in bone healing: 1. Undisplaced closed fractures. J Bone Joint Surg 44A:1273, 1962)

FIG. 3-14 Photomicrograph of histologic section from 5-day undisplaced fracture of canine radius shows early periosteal new-bone formation and abundant capillaries filled with Micropaque. The largest capillary, cut in cross section, measures 11-um, and the smallest capillaries measure approximately 7-um. (H&E, x 400) (Rhinelander FW, Baragry RA Microangiography in bone healing: I. Undisplaced closed fractures. J Bone Joint Surg 44A 1273, 1962)

In this series of experiments on undisplaced fractures of the radius, in which observations were made at daily intervals, histologic new-bone formation was first seen along the periosteal surface on the third day and along the endosteal surface on the fourth day. By 5 days, capillaries and new-bone were abundant along these surfaces, as demonstrated in Figure 3-14 with capillaries of the extraosseous circulation. The smallest capillaries there were measured at 7-um which is the usual size of an erythrocyte. This observation demonstrates that the smallest functional blood vessels are injected by the author's technique when the path to them is open. Failure of blood vessels to be filled in these experiments is therefore indicative of lack of function at the time of infusion. The nonfilled blood vessels are considered to be components of the then resting portion of the circulation.

The microvascular situation in an area of intercortical uniting callus at 2 weeks is shown in Figure 3-15, A and B. All of the blood supply for this callus is derived from the medulla. Histologically (Fig. 3-15, C), the medullary bridging callus and the intercortical uniting callus are seen to be in continuity. Osseous healing has occurred without an intermediate phase of cartilage formation.

The predominance in fracture repair of the medullary arterial circulation, when available, is also shown in Figure 3-16 in a 5 week undisplaced fracture in which the transitory extraosseous blood supply has been supplanted by hypertrophic medullary vessels traversing the full thickness of the porotic cortex in the area of osseous repair.

Figures 3-17 and 3-18 show the results with two 3-week fractures of the middiaphysis of the forelimb bones. Both fractures were produced by the same force and were treated similarly. Unlike the situation that would obtain with paired osteotomies, the paired fractures were far from identical.

In the microangiogram of Figure 3-17, no blood vessels are observed to be crossing directly between the fracture fragments, although they are plentiful in the surrounding tissues. Histologically, large masses of fibrocartilage correspond to avascular areas at the fracture site, with evidence of osseous union. By contrast, the microangiogram of Figure 3-18 shows regenerative medullary arteries crossing the fracture site. The histologic section reveals that a cortical spike of the right-hand fracture fragment is impaled in the medullary cavity of the left-hand fragment, producing stability. Osseous union by medullary callus is present between this spike and the endosteal surface of the cortex just above it.

FIG. 3-15 Mature canine radius 2 weeks after undisplaced closed diaphyseal fracture. (A), Microangiogram of slightly oblique tissue slice (which does not traverse the medullary capacity to the left of the fracture) shows the great vascular response in all areas. (original magnification x3,5) (B) Enlargement from A, centered over the fracture of the lower cortex, shows the blood vessels in the intercortical uniting callus. Note that they all occupy a l-mm tissue slice. (original magnification x 35) (C) Photomicrograph of histologic section shows the osseous callus extending from the medullary cavity into the cortical fracture gap. (H&E, x 22) (Rhinelander FW, Baragry RA: Microangiography in bone healing: 1. Undisplaced closed fractures. J Bone Joint Surg 44A:1273, 1962)

FIG. 3-16 Mature canine radius 5 weeks after undisplaced fracture: microangiogram shows advanced healing. Medullary arterioles penetrate the full thickness of both cortices to supply the external callus that remains. (original magnification x 7 (Rhinelander FW, Baragry RA Microangiography in bone healing: 1. Undisplaced closed fractures. J Bone Joint Surg 44A: 1273, 1962)

In the center of the microangiogram (Fig. 3-18, A) there is an avascular zone, indicative of necrotic cortex along the fracture line. Such localized areas of necrosis, resulting from loss of the essential medullary blood supply, are characteristic of oblique fractures. Here, the superior stabilization overcame the partial devascularization, and excellent healing developed. This experiment and many others emphasize the precept that the two essential factors in the healing of a well-reduced fracture are blood supply and stabilization. Each may be partially compromised, but both must be present to an adequate degree, or nonunion will result. Stabilization is more important than precise reduction, as long as there is sufficient overall blood supply.

The continuing effect of excellent reduction but inadequate immobilization is demonstrated in a 6-week fracture (see Fig. 38-1) that is used to illustrate the condition of fibrocartilaginous delayed union in Chapter 38.

The continued ascendancy of the medullary circulation is emphasized in a 12-week fracture which also developed a fibrocartilaginous delayed union, as shown in Figure 3-19. The large masses of periosteal callus are supplied entirely by arterioles derived from the medulla. Dominance of the medullary arterial supply, when available, is thus a salient feature in the repair of fracture of the diaphysis of long-bones.

FIG. 3-17 Mature canine radius 3 weeks after displaced fracture and unstable fixation in a plaster cast (A) Microangiogram shows blood vessels on all sides of the fracture site but none traversing it. (original magnification x 3) (B) Photomicrograph of histologic section shows abundant periosteal cartilaginous callus but no union of any type across the fracture. (H&E, x 6) (A, Rhinelander FW: Circulation in bone. In Bourne G (ed): Vol 2, The Biochemistry and Physiology of Bone, 2nd ed, chap 1, New York, Academic Press, 1972. B, Rhinelander FW: Tibial blood supply in relation to fracture healing. Clin Orthop 105: 34-81, 1974)

FIG. 3-18 Mature canine radius 3 weeks after displaced fracture and stable fixation in a plaster cast (A) Microangiogram shows regeneration of large medullary arteries across the fracture site. Observe also the characteristic course of the arterioles of the periosteal callus (below) approaching at right angles to the cortical surface. (original magnification x 4) (B) Photomicrograph of histologic section shows osseous union (arrow) between the endosteal surface of the left-hand fracture fragment and the impaling cortical spike of the right-hand fracture fragment. (H&E, x 9) (Rhinelander FW, Phillips RS, Steel WM, Beer JC: Microangiography in bone healing: 11. Displaced closed fractures. J Bone Joint Surg 50A:643-662, 1968)

The one-week experiment of Figure 3-20, with internal fixation by a standard four-hole plate and screws, demonstrates the great regenerative powers of the medullary arterial supply. Observe in the microangiogram that regenerated medullary arterioles are already traversing the osteotomy site.

FIG.3-19 Mature canine radius 12 weeks after displaced fracture with delayed union: microangiogram shows the complete vascular dominance of the medullary blood supply. (original magnification x 6) (Rhinelander FW, Phillips RS, Steel WM, Beer JC: Microangiography in bone healing. 11. Displaced closed fractures. J Bone Joint Surg 50A:643-662, 1968)

FIG. 3-20 Mature canine radius 1 week after osteotomy and internal fixation with a standard four-hole plate and screws: microangiogram shows the arterioles and capillaries of the medullary supply already reconstituted in the medullary bridging callus, across the osteotomy site. (original magnification x 22 5). (Rhinelander FW: Circulation in bone. In Bourne G (ed): Vol 2, The Biochemistry and Physiology of Bone, 2nd. ed, chap 1. New York, Academic Press, 1972)

FIG. 3-21 Mature canine radius at 3 weeks in the experimental series of Figure 3-20: microangiogram shows one end of the plate loosened and elevated (arrow) as a result of two screws having pulled out. Blood vessels stream through the space provided by a loosened screw. Note the vascularity of cortex beneath the loose portion of the plate and the avascularity beneath the tight portion. (original magnification x 3. 5). (Rhine- lander FW: Some aspects of the microcirculation of healing bone. Clin Orthop 40:12-16, 1965)

The four-hole plate used in that experiment proved inadequate for continued stabilization of radial osteotomies in the ambulatory dog. However, the loss of fixation in a 3-week experiment, as depicted in Figure 3-21, contributes valuable information on the relation of plates to blood supply. Where the plate remained tight against bone, no injected blood vessels are seen in the underlying cortex, a result of the normal centrifugal direction of blood flow. Blockade of the exit of venous blood, by the tight plate, prevented the entry of arterial blood from the medulla. The blood in the cortical vascular channels beneath the plate was consequently stagnant. That is equivalent to devascularization, but it is only temporary.

Under the loose portion of the plate in Figure 3-21, normal vascularization of the cortex is observed. Owing to the centrifugal flow of blood through cortex, the elevation of the plate permitted the escape of the trapped blood from the periosteal surface and the concomitant entry of Micropaque into the cortex from the medulla.

In addition to its inhibiting effect on the normal vascularization of cortex, a tight plate blocks the approach of the new extraosseous blood supply and the production of periosteal callus. However, these negative effects involve only a small area of the bone's circumference because the plate is situated longitudinally on the bone. This is in contrast to the devascularizing effects of a rigid band that encircles a long-bone. The transitory nature of the devascularization of cortex beneath a plate is demonstrated in a 6-week experiment in which, again, two of the screws loosened and two remained tight. More importantly, however, this experiment illustrates fibrous nonunion. (See Chapter 38.)

FIG. 3-22 Mature canine radius 6 weeks after osteotomy and secure internal fixation with a standard six hole plate and screws (A) Microangiogram shows medullary arteries and arterioles passing closely around the screws. (original magnification x 5) (B) Photomicrograph of histologic enlargement at the osteotomy site shows advanced osseous repair with some residuals of fibrocartilage. (H&E, x 3) (Rhinelander FW, Wilson JW: Blood supply to developing mature and healing bone In Sumner-Smith G (ed): Bone in Clinical Orthopaedics: A Study of Clinical Osteology, chap 2. Philadelphia, WB Saunders, 1982)

The effect on long-bone vascularization of screws crossing the medullary cavity is shown in Figure 3-22 from an osteotomy experiment on the radius in which an effective six-hole plate was used. The microangiogram (Fig. 3-22, A) centered longitudinally along the screw tracts, shows that blood vessels passed around the screws in close contact. Those that appear interrupted have curved into the adjacent 1-mm tissue slice. The corresponding histologic section (Fig. 3-22, B) shows the deeper portion of the screw tract nearest the osteotomy. Since this was not compression fixation, the residuals of fibrocartilage are present in all the masses of osseous callus. New-bone has grown fully into the screw threads. There has obviously been no significant impairment of blood supply.

FIG. 3-23 Mature canine radius 2 weeks after transverse osteotomy and compression-plate fixation. (A) Microangiogram shows large medullary arteries crossing the osteotomy site. (original magnification x5) (B) Photomicrograph of corresponding histologic section shows direct osseous union by medullary bridging callus without a cartilage stage. (H&E, x 5) (Rhinelander FW, Wilson JW: Blood supply to developing mature and healing bone. In Sumner-Smith G (ed): Bone in Clinical Orthopaedics: A Study of Clinical Osteology, chap 2. Philadelphia, WB Saunders, 1982)

FIG. 3-24 Mature canine radius 4 weeks after transverse osteotomy and compression-plate fixation. (A) Enlarged microangiogram, centered at the cortical osteotomy, shows injected blood vessels crossing the osteotomy crevice. (original magnification x 40) (B) Histologic photomicrograph, corresponding to A with further enlargement, shows a longitudinal osteon crossing the tight osteotomy cleft and active cutter heads approaching the cleft from both sides. Arrow points to layer of new-bone. (H&E, x 180) (Rhinelander FW: Circulation in bone. In Bourne G (ed) Vol 2, The Biochemistry and Physiology of Bone, 2nd ed, chap 1. New York, Academic Press, 1972)

The chief virtue of compression fixation of cortical one fragments is the increased stabilization that it introduces through friction of the opposed ends of the bone fragments against each other. At the same time, it fosters excellent osseous blood supply, the other essential factor in fracture or osteotomy healing.

In the 2-week experiment (Fig. 3-23), large medullary arteries are observed to have regenerated across the osteotomy gap. Medullary bridging callus, without a cartilaginous component, has produced osseous union. The osteotomized cortical surfaces are in tight contact.

At 4 weeks, primary healing of cortical bone, an important development in compression fixation, was observed, with longitudinal osteons traversing the cortical osteotomy. The microangiogram (Fig. 3-24, A) shows the cortex across from the plate, where the tightest compression had been produced by a special experimental fixation device(29) Since there was no overlying plate to block the normal escape of venous blood and thereby prevent the normal entry of arterial blood from the medulla, vascularization of this area of cortex was excellent. Several injected vessels are seen crossing the osteotomy in the 1-mm tissue slice.

FIG. 3-25 Mature canine radius 8 weeks after transverse osteotomy and compression-plate fixation. (A) Enlarged microangiogram shows cortical arterioles from the medulla crossing the osteotomy crevice to supply the cortex beneath the tight plate, which was above. (original magnification x28) (B) Enlarged histologic photomicrograph shows advanced contact healing. (H&E, x 140) (Rhinelander FW: Circulation in bone. In Bourne G (ed): Vol 2, The Biochemistry and Physiology of Bone, 2nd ed, chap 1. New York, Academic Press, 1972)

The corresponding histologic section (Fig. 3-24, B) reveals a short segment of one bone canal, containing a blood vessel, as it crosses the osteotomy. At higher magnification, the endothelial cells of the blood vessel and the osteoblasts in the wall of the bone canal are easily identified. Just below the canal, a layer of newbone, clearly containing osteocytes, has already bridged the osteotomy. Observe, also, the cutter heads, above and below, which are advancing from both sides to conduct additional osteonic new-bone across the osteotomy. Direct osseous bridging of the osteotomy is thus taking place, without the assistance of interosseous uniting callus.

In Figure 3-25, advanced contact healing is demonstrated directly beneath the plate at 8 weeks. In that area, the cortical blood supply would initially have been impaired by the plate (see section entitled General Effects of Plates and Screws, above); hence, the active vascular regeneration is very significant. Even large vessels, emanating from the medulla, cross the osteotomy as they are clearly carrying blood to the cortex beneath the plate

The rigid stabilization of cortical fractures, which is the chief virtue of compression fixation, is also a drawback in that it defeats Wolff's law. The very rigid plate protects the area of osseous repair from the normal external forces that should be acting on it. The osteoporosis of repair consequently persists. Accomplishment of the final stage of the healing process, remodeling of the bone back to its preinjury status, is delayed.

The normal arterial supply of a mature long-bone is not affected by wire cerclage because the major afferent vessels to all areas of the diaphysis are medullary (see Fig. 1-8 in Chapter 1), and the minor afferent supply, the periosteal arterioles, if they have been interrupted, readily grow around a strand of wire. The efflux of venous blood from the periosteal surface is not blocked because wires are round in cross section and contact bone minimally. The efferent vessels easily circumvent them.

The repair of fractures is also not inhibited by wire loops because the arterioles of the extraosseous vascular system approach the cortical surface at right angles, as was shown in Figures 3-10 and 3-18. They readily engulf wire loops to supply the periosteal bridging callus, as demonstrated in Figure 3-26. The microangiogram shows vascularized callus surrounding the tracts of the wires. In the histologic section, the wire is observed to have been in firm contact with bone, closely surrounded by osseous callus.

Fibrous tissue forms around a wire only when the fixation has loosened. Failure with wire cerclage, like failure with plates and screws, should be attributed to faulty application. The fixation method per se should not be blamed. All wires in a series around a bone should be tightened to the same tension, just as all the screws through a plate should be torqued the same amount in order to distribute the support equally among all the fixation devices. Otherwise the tighter devices will be exposed to unwarranted stress and will tend to loosen, with resultant failure of the entire fixation. To achieve equal tension, a practiced hand on a screw driver is effective for a series of screws, but for soft wire the material twists so easily that a hand cannot judge the tension. A tension gauge on the wire-tightening instrument is therefore necessary.(31) Eventual removal of correctly applied and effective wire loops is not required for vascular reasons.

FIG. 3-26 Mature canine radius 4 weeks after internal fixation of oblique fracture by six circumferential wire loops. (A) Microangiogram shows periosteal callus closely investing the small round tracts of the wires, below. (original magnification x 5.5) (B) Greatly enlarged histologic photomicrograph centered over the tract of the second wire from the left in A shows that there had been no erosion of bone or formation of fibrous tissue. Periosteal callus had closely invested the wire. (H&E, x 40.5) (Rhinelander EW: Circulation in bone. In Bourne G (ed) vol 2, The Biochemistry and Physiology of Bone, 2nd ed, chap E New York, Academic Press, 1972)

Parham bands, because they are flat and wide, do interfere with the blood supply of bone. Like plates, they accomplish this by blocking the exit of venous blood from the periosteal surface. However, they do it circumferentially around the bone. That is more insidious than the longitudinal vascular blockage produced by plates. Callus grows over Parham bands less readily than over wires. Parham bands should be removed as soon as their presence for mechanical reasons is no longer required.

Metal bands with transverse humps, a recently developed fixation device, have not been tested experimentally. They would obviously cause spotty interference with blood supply to the underlying cortex, and they would delay the formation of periosteal callus. Eventual removal would be advisable but would be severely inhibited by the new-bone that would grow into the humps. The spotty pressure that humped bands exert on the surface of a bone is a mechanical disadvantage in fracture fixation. A smooth encircling device, which presses evenly on comminuted fracture fragments, facilitates the reduction and control of such fragments.

Nylon straps, as first used for cerclage fixation of human femoral fractures by the British surgeon Partridge,(39) were compared with wire loops for cerclage in my laboratory(42) in a series of experiments on canine femora. The nylon straps were of two types: plain straps with a smooth inner surface, and straps with so-called bumps along the inner surface. These bumps had been added by Partridge on theoretic grounds to provide space for the approach to cortex of the normal periosteal arterioles (at Ligamentous attachments) and of the new extraosseous arterioles (at areas of fracture repair).

In our experiments on the femora of mature dogs, even the plain straps were found not to interfere with the blood supply of long oblique osteotomies, presumably because of nylon's flexibility. The straps loosened slightly by stretching after application, allowing vessels of the extraosseous blood supply to pass beneath them. This led to slight longitudinal displacement of the bone fragments (whereas the wire-loop fixation permitted no displacement), but the fixation was adequate to effect good healing at all time intervals.

The only serious problem encountered in our experiments with nylon cerclage was the lateral displacement of the bone fragments that occurred after all fixations by straps with bumps. An example of this at 8 weeks is shown in Figure 3-27. The smaller bone fragment, above, is displaced markedly to the left between two bumps. It can be observed that the nylon strap had loosened somewhat from the bone's surface, but this occurred during tissue processing when the strap's lock, below, was disrupted. The position of the bone fragments had obviously been established in the animal while the strap was tight.

FIG. 3-27 Mature femur 8 weeks after long oblique midshaft osteotomy fixed internally by a round medullary rod and circumferential straps of nylon, with "bumps" on the inner surface. Microangiogram, through a nylon strap with its lock, below, shows good blood supply to all areas. Note that the bone fragments are markedly displaced laterally between two of the bumps. (original magnification x 15)

The microangiogram (Fig. 3-27) shows normal blood supply of cortex everywhere and excellent vascularization of the area of healing. The same was observed in all the experiments, at time intervals of 2 to 12 weeks, regardless of the type of internal fixation. Since the straps with bumps caused loss of fixation laterally and provided no vascular advantage over the plain straps, we hope that the commercial supplier of the nylon straps for surgery will return to the plain straps that Partridge originally used with great success on long oblique fractures of the proximal human femur.

As with a series of wire loops, a series of nylon straps should all be applied at the same predetermined tension. That is easier to accomplish with the straps because each incorporates its own fixation deviceÑa spring lock. Tightening is effected by a simple "gun" that pulls up the strap to a set tension. A disadvantage of the nylon strap is the rather large tissue space required by its intrinsic spring lock in comparison with the small space occupied by the twist of a wire loop.

FIG. 3-28 Mature canine radius 3 weeks after transverse osteotomy and fixation with a four-hole plate and screws: histologic section shows the thermal necrosis of the cortex on both sides of the osteotomy. The plate was above. (H&E, x 58.5) (Rhinelander FW Circulation in bone In Bourne G (ed) vol 2, The Biochemistry and Physiology of Bone, 2nd ed, chap 1. New York, Academic Press, 1972)

The cortex of the canine radial diaphyses, on which these tests were done, is less dense and thick than the cortex of human long-bones, which are generally cut by power-driven saws; hence, there is less likelihood of extensive heat generation in the small animal than in humans. However, experiments on canines demonstrated also the undesirable thermal effects of inserting pins and drills into living bone at high speed. Both speed of rotation and rate of feed (force applied) must be considered, suggesting that a force gauge should be incorporated into power-driven instruments used for drilling the cortex of diaphyses. The cortex of metaphyses is thinner and is therefore less susceptible to being overheated by either drill or a saw. A small drill or pin, with less frictional contact at the tip, is less liable to burn bone than a large one. Dullness of any cutting instrument is a potent factor heat production. When a surgeon wishes to avoid all possibility of thermal necrosis, he should use sharp cutting tools driven by hand to ensure slow speed.

FIG. 3-29 Mature canine radius I week after osteotomy and internal fixation with a loose-fitting medullary rod. (A) Roentgenogram shows the areas of the endosteal surface where the rod made contact and where it did not. (B) Microangiogram shows the absence of injected blood vessels in the cortex where the medullary rod was in contact. Where the tract of the rod is separated from cortex, the intervening medullary space is well vascularized and furnishes a normal cortical blood supply. (original magnification x 6) (Rhinelander FW, Wilson JW: Blood supply to developing mature and healing bone. In Sumner-Smith G (ed): Bone in Clinical Orthopaedics A Study of Clinical Osteology, chap 2. Philadelphia, WB Saunders, 1982)

The intramedullary situation at 3 weeks was shown in Figure 3-10, which also demonstrated the normal vascularization of the outer third of the posterior tibial cortex from the periosteal arterioles and the vascularization of bone repair from the extraosseous blood supply.

The rapid regenerative ability of the medullary circulation is especially demonstrated in Figure 3-30, from a 7 week experiment showing an area in which the fixation rod came to rest in the center of the medullary cavity, out of contact with any endosteal surface. In the microangiogram (Fig. 3-30, A), all the cortex is well vascularized by arterioles radiating from regenerative medullary arteries. In the histologic section (Fig. 3-30, B), the porosity of the cortex is the same in all areas circumferentially and is consistent with the stage of the repair. Evidently, therefore, none of this cortex was deprived of blood supply for any significant period.

These observations indicated (1) that the medullary arterial supply is regenerated to all areas of cortex, except where a medullary rod remains in contact with the endosteal surface, (2) that the medullary supply, in areas not permanently blocked by the rod, is regenerated so rapidly that no damage to cortical bone results, and (3) that the periosteal arterioles, where present, continue to supply the outer third, and only the outer third, of the diaphyseal cortex.

FIG. 3-30 Mature canine radius 7 weeks after osteotomy and internal fixation with a loose-fitting medullary rod. (A) Microangiogram of cross section shows the rod centrally placed, with normal blood supply to all areas of the surrounding cortex. (original magnification x 6) (B) Photomicrograph of histologic section corresponding to A The porosity, indicative of enhanced blood supply, is equal in all areas of the cortex. (H&E, x6) (Rhinelander EW Circulation in bone. In Bourne G (ed): Vol 2, The Biochemistry and Physiology of Bone, 2nd ed, chap E New York, Academic Press, 1972)

In both series of experiments, the extensive reaming recommended by Kuntscher was performed so that the two fixation devices could be compared under similar conditions. The vascular effect of reaming alone, without other surgery, is shown at 12 weeks in Figure 3-31. This microangiogram reveals that the regenerative branches of the nutrient artery are limited to the posterior cortex (to the right, above). The anterior cortex, opposite, has not yet been vascularized at this level. Distally, regenerative arterioles, derived from the metaphyseal arteries, have regenerated to all cortical areas. The largest artery, on the right, appears to be interrupted, but it is actually coursing between tissue slices.

Thus, the regenerative effectiveness of the multiple metaphyseal arteries is greater than that of the single nutrient artery. This is true for long-bones in general. A parallel consideration is that the extraosseous arterial supply to the metaphysis be intact. That is sometimes not the case, especially when the metaphysis involved is that of the distal tibia. In the femur, the blood supply of the distal metaphysis after fracture is generally normal.

The varying distribution circumferentially of the normal arterial supply to the femoral diaphysis, occurring in the dog and presumably in humans, is presented diagrammatically in Figure 1-12 of Chapter 1. This concept, of highly significant vascularization differences around the diaphysis, is in agreement with all our studies on long-bones. It is ignored in the older literature.

FIG. 3-31 Mature canine femur 12 weeks after medullary reaming alone: microangiogram of the middle third of the diaphysis shows that the chief regenerative blood supply is derived from the distal metaphyseal arteries (below) along both sides of the medullary canal. Regenerative branches from the nutrient artery (above, to right) are observed along only one side of the medulla. (original magnification x 4) (Rhinelander FW: Tibial blood supply in relation to fracture healing. Clin Orthop 105:34 81, 1974)

Distal to the internal expander, where the inside of the nail was empty, small blood vessels filled the nail completely (Fig. 3-32, B). However, the nail's substance blocked these vessels from entering the surrounding cortex. Thus, the presence of the internal expander within the nail was no detriment to cortical blood supply.

After the nailing, the posterior cortex remained vascularized, supplied by the periosteal arterioles in the linea aspera. Almost the full thickness of the anterior-mediallateral cortex was necrotized by the loss of its medullary supply. Only a few external lamellae remained vascularized. Figure 3-33, from a 6-week experiment, illustrates the situation at the endosteal surface of the lateral cortex, where the medullary nail had been in tight contact. Osteoclasts are removing the necrotic cortex to create space for development of a membrane that will bring in regenerative medullary blood vessels. Eventually, this vascularizing membrane will completely surround the nail. (See Fig. 3-35.)

FIG. 3-32 Mature canine femur 4 weeks after transverse mid- shaft osteotomy, reaming, and internal fixation with the clover- leaf nail containing an internal expander. (A) Microangiogram of cross section proximal to the osteotomy at the level of the internal expander shows regenerative medullary arterioles confined to narrow spaces that were present between the nail and the endosteal cortical surface. (In this, and in the other cross-sectional illustrations of the femur, orientation is with the posterior cortex below.) (original magnification x6) (B) Microangiogram of cross section distal to the osteotomy and the internal expander shows the vascular pattern where the nail was not completely tight in the medulla. (original magnification x 7) (Rhinelander FW, Wilson JW: Blood supply to developing mature and healing bone. In Sumner-Smith G (ed): Bone in Clinical Orthopaedics: A Study of Clinical Osteology, chap 2. Philadelphia, WB Saunders, 1982)

FIG. 3-33 Mature canine femur 6 weeks after transverse mid-shaft osteotomy, reaming, and internal fixation with the clover-leaf nail. Photomicrograph of histologic cross section from the proximal diaphyseal cortex bordering the nail tract, on the left, shows active osteoclasts removing the necrotic cortex, which from lack of osteocytes, is observed to be necrotic throughout Osteoclasia is also enlarging a cavity on the right, above. (H&E, x 180) (Rhinelander FW: Circulation in bone. In Bourne G (ed): Biochemistry and Physiology, Vol 2, The Biochemistry and Physiology of Bone, 2nd ed, chap 1. New York, Academic Press, 1972)

FIG. 3-34 Mature canine femur 8 weeks after transverse mid-shaft osteotomy, reaming, and internal fixation with the cloverleaf nail. (A) Microangiogram of the proximal diaphyseal cortex shows large arteries (arrows 1 and 2) Iying just outside the extemal callus of the anterolateral sector of the femur and the nutrient artery (arrow 3) in its cortical canal. Arrows 4 and 5 point to well-vascularized cavities in the old anterior cortex. (original magnification x 7) (B) Photomicrograph of histologic section from the tissue slice adjoining that of A. The nutrient artery is shown as it was turned back into the cortex by the presence of the medullary nail. Observe also the extraosseous arteries and the cortical cavities, which are designated by arrows in the microangiogram. (H&E, x 7). (A, Rhinelander FW: Circulation in bone. In Bourne G (ed): Vol 2, The Biochemistry and Physiology of Bone, 2nd ed, chap 1. New York, Academic Press, 1972; B, Rhinelander FW: Tibial blood supply in relation to fracture healing. Clin Orthop 105:34-81, 1974)

FIG. 3-35 Mature canine femur 12 weeks after transverse midshaft osteotomy, reaming, and internal fixation with the cloverleaf nail. (A) Microangiogram of the proximal diaphyseal cortex shows a regenerative highly vascular membrane completely surrounding the nail tract at the endosteal surface. The posterior cortex contains short arterial segments derived from the nutrient artery after it was turned back into the cortex. (original magnification x 7) (B) Photomicrograph of histologic section corresponding to A shows the thick endosteal membrane. The intracortical regenerative branches of the nutrient artery, in thin cross section, are difficult to discern at this magnification. (H&E, x 5) (C) Photomicrograph of histologic enlargement from B demonstrates details of the posterior femoral cortex. Observe the arterioles of the endosteal membrane and the intracortical arterial trunks. Greater magnification (not shown) reveals the muscular coat of these arteries in greater detail. (H&E, x 14) (Rhinelander FW: Circulation in bone. In Bourne G (ed): Vol 2, The Biochemistry and Physiology of Bone, 2nd ed, chap 1. New York, Academic Press, 1972)

This result contradicts the conclusion, drawn in another laboratory from experiments with a hydrogen electrode, that blood supply derived from periosteal arterioles supplants the medullary supply of the diaphyseal cortex of the canine femur immediately after reaming.(36,45) If that were so, the cortical necrosis revealed in Figure 3-33 would not have developed. Our experiments showed that there was a delay before a new blood supply was obtained by the necrotic diaphyseal cortex and that the new supply did not traverse existing vascular channels. Its source, from the extraosseous blood supply of healing bone, is shown at 8 weeks in Figure 3-34. Large longitudinal arteries are observed external to the periosteal callus, giving offbranches that progress inwardly through the callus and the necrotic cortex to reach the cavities where osteoclasis is in progress.

Figure 3-34 reveals also the result of blockade of the nutrient artery by the tight-fitting medullary nail. Unable to enter the medullary cavity after being cut by the reamer, the nutrient artery has turned back into cortex. There it will subdivide and progress longitudinally within the substance of cortex itself (as observed at 12 weeks). Because burrowing through cortical bone is a slow process, delayed union of the osteotomy developed in this series of experiments. (See Fig. 3-36.)

FIG. 3-36 Mature canine femur observed longitudinally at the osteotomy site after 6 weeks (the same femur illustrated in proximal cross section in Figure 3-32). (A) Microangiogram shows an avascular zone at the cortical osteotomy site and across the masses of periosteal callus. (original magnification x 7) (B) Photomicrograph of histologic section corresponding to A Observe the fibrous tissue lining the central tract of the nail and traversing both cortical osteotomy sites (above and below the nail tract) which have become irregular from the slight loss of position that has occurred. Arrow indicates area shown in C. (H&E, x 7) (c) Photomicrograph of histologic enlargement from area of arrow in B. Observe the injected blood vessels in the fibrous tissue and the active osteoclasts removing the necrotic cortex. (H&E, x 205) (Rhinelander EW, Wilson JW: Blood supply to developing mature and healing bone. In Sumner-Smith G (ed): Bone in Clinical Orthopaedics: A Study of Clinical Osteology, chap 2. Philadelphia, WB Saunders, l982)

At 12 weeks, a thick and highly vascular endosteal membrane is seen in Figure 3-35 to have surrounded the nail completely, occupying space that did not exist immediately after the nail was inserted. This membrane contains only small vessels engaged in local vascularization.

The chief longitudinal supply, progressing from the nutrient artery to the osteotomy site, is observed in the posterior cortex as short segments of large vessels. When viewed in stereo (as all our microangiograms are made), they point right up at the observer, indicating their longitudinal direction. At high histologic magnification their muscular coats are obvious (Fig. 3-35, B and C), identifying them definitely as arteries, which normally are not directed longitudinally in cortex.

The delay in union at the osteotomy site is best demonstrated in longitudinal sections, which were made for each femur in this series. The situation at 6 Weeks is shown in Figure 3-36-for the same femur, of which the proximal cortex was illustrated in cross section. The microangiogram reveals the characteristic picture of fibrous nonunion (compare Fig. 38-2 in Chapter 38) with mounds of external callus containing irregular vascular and avascular areas. Some displacement of the major bone fragments along the nail, as observed histologically in Figure 3-36, is attributable to the fracture of the necrotic cortex locally. There is no pseudarthrotic cavity. The medullary nail maintained stabilization (except for the slight shortening), so the functional development was delayed unionÑrather than nonunion, as suggested by the histology.

With the continued stabilization of the tight medullary nail, eventual osseous union is to be expected in this situation. Use of a very strong nail is of course required, as was recognized by Kuntscher, who was familiar with the vascular studies my colleagues and I had performed. To achieve persistent strength, Kuntscher used very large nails, which required extensive reaming, and he left these nails in human femora permanently. His clinical results over the years have been excellent. However, our experiments demonstrated that the cross-sectional contour of his nails produces a severe deficiency in vascular supply, with consequent cortical necrosis. Use of these nails should, therefore, be confined to the application for which they were specifically designedÑpassage over a previously inserted guide rod in so-called blind nailing.

For surgery, a special guide was produced, a rod threaded at one end to accept the tip of a Schneider nail. In application, the threaded end of the guide was introduced into the femur at the osteotomy site and was passed upward, to exit through a reamed hole at the trochanteric fossa, where the tip of the nail was screwed into it. The guide rod kept the nail in proper alignment as it was driven distally, with its broaching cutters functioning. The guide was unscrewed and removed when the tip of the nail reached the osteotomy, which was then reduced under direct vision. The nail was finally driven into the distal segment of the femur under Polaroid radiographic control.

FIG. 3-37 Photograph of four-fluted Schneider nails with adapter for driver and nail extenders, as prepared for canine femora. (Rhinelander FW, Nelson CL: Experimental implantation of porous materials into bone Proplast for low modulus fixation of prostheses. Acta Orthop Belg 40:771, 1974)

FIG. 3-38 Mature canine femur 4 weeks after transverse mid-shaft osteotomy, reaming, and fixation with the four-fluted nail. (A) Microangiogram of the proximal diaphyseal cortex shows regenerative branches of the nutrient artery entering the medulla in the space provided by a flute of the nail posteriorly. The space of the anterior flute is not vascularized. (original magnification x 8) (B) Microangiogram of the distal diaphyseal cortex shows blood vessels in the spaces of all four flutes. (original magnification x 8) (Rhinelander FW, Wilson JW: Blood supply to developing mature and healing bone. In Sumner-Smith G (ed): Bone in Clinical Orthopaedics A Study of Clincial Osteology, chap 2. Philadelphia, WB Saunders, 1982)

FIG. 3-39 Mature canine femur 12 weeks after transverse midshaft osteotomy, reaming, and fixation with the four-fluted nail. (A) Microangiogram of the proximal diaphyseal cortex shows vascularization in the channels of all the flutes. (original magnification x8) (B) Photomicrograph of histologic section corresponding to A shows medullary callus in all the flutes and minimal periosteal callus. (H&E, x 8) (Rhinelander FW, Nelson CL: Experimental implantation of porous materials into bone: Proplast for low modulus fixation of prostheses. Acta Orthop Belg 40:771, 1974)

When the Schneider nail was first inserted into the femoral medulla at the trochanteric fossa, care was taken to orient it in such a way that one of its flutes was directed posteriorly, along the linea aspera, where the nutrient artery was known to enter. Space was thus provided for the regenerative nutrient artery to enter the medullary cavity, unlike the situation observed with the cloverleaf nail.

The vascular patterns proximal and distal to the osteotomy at 4 weeks are shown in a pair of microangiograms from one femur. The level of the proximal microangiogram (Fig. 3-38, A) is the site of entry of the nutrient artery into the nail's posterior channel. The medial and lateral channels at this level contain injected blood vessels, while the anterior channel has not yet been vascularized. However, in the distal microangiogram (Fig. 3-38, B) all four channels contain afferent blood vessels. That development follows the regeneration of the medullary arterial supply derived distally from the multiple metaphyseal arteries, since this regeneration is more pervasive than that derived proximally from the single nutrient artery, as was shown in Figure 3-31.

Even in the proximal diaphysis, all four channels around the nail were well vascularized at 12 weeks, as demonstrated in Figure 3-39. Histologically, medullary callus occupies all the channels. Consequently, less periosteal callus was required than with the Kuntscher nails, and healing of the osteotomies was more rapid.

The conclusions, drawn from these two series of vascular studies on canine femora were: (1) For open medullary nailing with a tight-fitting nail, use of nails with large external channels has the advantage of being able to accommodate major blood vessels, and to accommodate medullary bridging callus with consequent reduction in periosteal bridging callus. (2) Use of Kuntscher's cloverleaf nail should be confined to the procedure for which he designed it: blind nailing over a guide rod without exposure of the fracture site.

SECTION FOUR
CONDITIONS INFLUENCING FRACTURE HEALING

RICHARD L CRUESS AND JACQUES DUMONT

Because healing of a fracture in a living organism is accomplished by cells, it can be modified by almost any endogenous or exogenous factor that has an influence on the metabolic function of cells. The literature abounds with reports of factors that can either promote or retard bone healing (Table 3-1).(87) While most of these factors do, in all probability, exert an influence that can be measured in the laboratory, in clinical practice fracture healing appears to proceed with a certain degree of predictability and is modified by relatively few factors.

TABLE 3-1 FACTORS INFLUENCING BONE HEALING

OTHERS
Thyroid hormone, calcitonin, insulin, vitamins A and D in physiologic doses, and anabolic steroids have been reported to enhance the rate of fracture healing in experimental situations (Table 2-1). Diabetes, castration, hypervitaminosis D, hypervitaminosis A, as well as the rachitic state have been shown to retard fracture healing in experimental situations. Rarely in clinical practice do these substances pose a serious problem.

 

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