Anabolic and antiresorptive actions of locally delivered bisphosphonates for bone repair: A review.

During the last decades, several research groups have used bisphosphonates for local application to counteract secondary bone resorption after bone grafting, to improve implant fixation or to control bone resorption caused by bone morphogenetic proteins (BMPs). We focused on zoledronate (a bisphosphonate) due to its greater antiresorptive potential over other bisphosphonates. Recently, it has become obvious that the carrier is of importance to modulate the concentration and elution profile of the zoledronic acid locally. Incorporating one fifth of the recommended systemic dose of zoledronate with different apatite matrices and types of bone defects has been shown to enhance bone regeneration significantly in vivo. We expect the local delivery of zoledronate to overcome the limitations and side effects associated with systemic usage; however, we need to know more about the bioavailability and the biological effects. The local use of BMP-2 and zoledronate as a combination has a proven additional effect on bone regeneration. This review focuses primarily on the local use of zoledronate alone, or in combination with bone anabolic factors, in various preclinical models mimicking different orthopaedic conditions. Cite this article: I. Qayoom, D. B. Raina, A. Sirka, S. Tarasevicius, M. Tägil, A. Kumar, L. Lidgren. Anabolic and antiresorptive actions of locally delivered bisphosphonates for bone repair: A review. Bone Joint Res 2018;7:548-560. DOI: 10.1302/2046-3758.710.BJR-2018-0015.R2.

Do osteoporotic fractures constitute a greater recalcitrant challenge for skeletal regeneration? Investigating the efficacy of BMP-7 and zoledronate treatment of diaphyseal fractures in an open fracture osteoporotic rat model.

Osteoporotic fractures may pose a challenge for skeletal regeneration. This study investigates if pharmaceutical interventions such as bone morphogenetic protein 7 (BMP-7) alone or in combination with Zoledronate have equivalent efficacy in osteoporotic bone? Our findings suggest they do and that an osteoporotic bone environment may increase sensitivity to BMP-7. INTRODUCTION: Osteoporosis is thought to contribute to delayed or impaired bone healing. Bone morphogenetic protein 7 (BMP-7) alone or synergistically combined with zoledronate (ZA) has proven effective in augmenting the regenerative response in healthy young male rats. Yet their comparative efficacy in an osteoporotic bone environment is unknown. Our study aimed to answer the following questions using the ovariectomized (OVX) rat model of osteoporosis: Do osteoporotic fractures pose a greater challenge for skeletal regeneration? Are interventions with BMP-7-alone or combined with ZA of equivalent efficacy in osteoporotic bone? METHODS: Sham operations (n = 33) or ovariectomies (n = 34) were performed in 12-week-old female Sprague-Dawley rats. Mid-diaphyseal open femoral osteotomies were created at 24 weeks of age and the rats allocated to either (i) untreated, (ii) BMP-7-only or (iii) BMP-7 + ZA treatment groups. At 6 weeks post-osteotomy, fracture healing was evaluated by radiography, µCT and 3-point bending mechanical tests. RESULTS: Cumulatively, radiological, micro-structural and mechanical measures were equivalent in both healthy and osteoporotic environments. A reduced response to BMP-7-alone was observed in healthy rats that may be age/gender- or protocol/fracture-model dependent. Conversely, the BMP-7-only treated OVX group attained 100 % union in addition to significantly increased measures of mineralized bone volume, total callus volume, peak force and absorbed energy relative to untreated OVX fractures. CONCLUSIONS: Our findings refute the hypothesis that osteoporotic fractures constitute a greater recalcitrant challenge for skeletal regeneration. Furthermore, our results suggest that an oestrogen-deficient environment may in fact cause an increased sensitivity to BMP-7.

Muscle as an osteoinductive niche for local bone formation with the use of a biphasic calcium sulphate/hydroxyapatite biomaterial.

OBJECTIVES: We have observed clinical cases where bone is formed in the overlaying muscle covering surgically created bone defects treated with a hydroxyapatite/calcium sulphate biomaterial. Our objective was to investigate the osteoinductive potential of the biomaterial and to determine if growth factors secreted from local bone cells induce osteoblastic differentiation of muscle cells. MATERIALS AND METHODS: We seeded mouse skeletal muscle cells C2C12 on the hydroxyapatite/calcium sulphate biomaterial and the phenotype of the cells was analysed. To mimic surgical conditions with leakage of extra cellular matrix (ECM) proteins and growth factors, we cultured rat bone cells ROS 17/2.8 in a bioreactor and harvested the secreted proteins. The secretome was added to rat muscle cells L6. The phenotype of the muscle cells after treatment with the media was assessed using immunostaining and light microscopy. RESULTS: C2C12 cells differentiated into osteoblast-like cells expressing prominent bone markers after seeding on the biomaterial. The conditioned media of the ROS 17/2.8 contained bone morphogenetic protein-2 (BMP-2 8.4 ng/mg, standard deviation (sd) 0.8) and BMP-7 (50.6 ng/mg, sd 2.2). In vitro, this secretome induced differentiation of skeletal muscle cells L6 towards an osteogenic lineage. CONCLUSION: Extra cellular matrix proteins and growth factors leaking from a bone cavity, along with a ceramic biomaterial, can synergistically enhance the process of ectopic ossification. The overlaying muscle acts as an osteoinductive niche, and provides the required cells for bone formation.Cite this article: D. B. Raina, A. Gupta, M. M. Petersen, W. Hettwer, M. McNally, M. Tägil, M-H. Zheng, A. Kumar, L. Lidgren. Muscle as an osteoinductive niche for local bone formation with the use of a biphasic calcium sulphate/hydroxyapatite biomaterial. Bone Joint Res 2016;5:500-511. DOI: 10.1302/2046-3758.510.BJR-2016-0133.R1.

Ten years' experience with a pyrocarbon prosthesis replacing the proximal interphalangeal joint. A prospective clinical and radiographic follow-up.

We prospectively assessed the subjective, objective, and radiographic results at 1, 2, and 5 years in 65 patients who had pyrocarbon proximal interphalangeal prostheses inserted between 2001 and 2010. Further operations were done on 10 of the 89 joints (four for prosthetic extraction and arthrodesis, two for component changes, and four for soft tissue procedures). At 1 year, the visual analogue scale score for pain at rest had improved to 0 cm from a pre-operative 4 cm, pain at activity from 6 to 1.8 cm, and Disability of the Arm, Shoulder and Hand score from 40 to 25. Range of movement and grip strength were unchanged. At 5 years, 31 joints (21 patients) had a complete radiographic follow-up. Seven proximal and 12 distal components showing zones of osteolysis at 1 year had stabilized and were inert or integrated at 5 years. Three proximal and three distal components had osteolytic zones at 5 years. Forty-seven of 59 patients were pain-free at rest at 1 year, and 19 of 21 at 5 years. No late revisions or loosening occurred.

Hemi-hamate osteochondral transplantation in proximal interphalangeal dorsal fracture dislocations: a minimum 4 year follow-up in eight patients.

Fracture dislocations of the PIP joint are challenging to treat. In hemi-hamate arthroplasty, the palmar lip joint surface is reconstructed using an osteochondral graft from the hamate and the immediate stability permits early movement. In the long term, collapse of non-vascularized osteochondral grafts might lead to degenerative arthritis. We examined the radiographic result after a minimum of 4 years with special reference to the development of osteoarthritis and its relation to clinical symptoms in eight patients, mean age 49 (25-66) years. After a mean of 60 (48-69) months, the arc of motion was 67° (45°-95°) at the PIP joint and grip strength was 91% of the uninjured side. The visual analogue score for pain (0-100) was 10 (0-70) mm. Severe arthritis (grade IV) was found in two and mild arthritis (grade II) in another two patients, but only one of these four cases had troublesome pain. The hemi-hamate technique is an attractive alternative to other treatment options, but some cases develop osteoarthritis in the medium term.

Correlation between range of motion and implant fracture: a 5 year follow-up of 72 joints in 18 patients in a randomized study comparing Swanson and Avanta/Sutter MCP silicone prosthesis.

Eighteen out of 18 rheumatoid patients (at one centre of a two-centre 30 patient study previously reported) with a mean age of 56 years, and 72/72 operated joints were randomized to Avanta/Sutter or Swanson MCP prostheses and followed for 5 years. Both ulnar deviation and extension lag were improved already at 6 weeks and remained improved at 5 years. The Avanta prosthesis had a better range of motion (ROM) than the Swanson. Six of nine patients with Avanta/Sutter implants had at least one implant fracture compared to 1/9 patients with the Swanson implant (P = 0.05) but fracture did not change the outcome subjectively. The ROM at 3 months correlated with the occurrence of an implant fracture at 5 years and a greater early ROM may be related to implant fracture. At 5 years patients remained satisfied and the deformities remained corrected.

Wound healing after hand surgery in patients with systemic sclerosis--a retrospective analysis of 41 operations in 19 patients.

This retrospective study evaluates the results of 41 consecutive hand and forearm operations in 19 patients with systemic sclerosis performed between 1985 and 2000. The mean age of the patients was 50 (14-84) years. Twenty-seven operations were elective and 14 were acute, carried out for skin breakdown and/or skin necrosis. One minor wound healing problem occurred in the elective group. In the acute group, seven of 14 operations healed uneventfully. Four patients had necrosis/infections after surgery, which required further surgery. Two patients had repeated wound infections. Another patient only healed after he stopped smoking. In systemic sclerosis, surgery performed electively does not seem to have increased difficulty with wound healing. Even larger operations, such as wrist arthrodesis or wrist replacement, can be performed safely. In acute cases with spontaneous skin breakdown and/or necrosis and/or critically ischaemic fingers, wound healing is more precarious and several procedures may be necessary to achieve skin healing.

Avanta versus Swanson silicone implants in the MCP joint--a prospective, randomized comparison of 30 patients followed for 2 years.

The results of Swanson and Avanta metacarpophalangeal joint arthroplasties in rheumatoid patients were compared in a prospective, randomized study of 30 patients (120 implants). At 2-year follow-up, grip strength was measured, hand function was assessed with the Sollerman test and the subjective outcome was determined with visual analogue scores. With both implants ulnar deviation and flexion deformities decreased, and there was no difference between the groups. The increase in range of motion was 7 degrees greater with Avanta implants than with Swanson implants. Grip strength and hand function were unaltered but the visual analogue scales showed decreased pain levels and subjective improvements in hand function, grip strength and cosmesis. Twenty-four of 30 patients were satisfied. Fracture of the silicone spacer occurred with 12 Avanta (20%) and eight Swanson implants (13%), with a higher fracture frequency in men.

Swanson versus APL arthroplasty in the treatment of osteoarthritis of the trapeziometacarpal joint: a prospective and randomized study in 26 patients.

Twenty-six patients were operated because of osteo-arthritis of the trapeziometacarpal joint. After excision of the trapezium, they were randomized to receive either a Swanson silicone trapezium implant or a tendon interposition arthroplasty using a strip of the abductor pollicis longus tendon (APL). No infection or clinical silicone synovitis occurred and no major radiographic cyst formation was found. Two endoprostheses dislocated early. All 13 patients in the Swanson group and 11 of the 13 in the APL group were subjectively satisfied at 2-5 year (mean, 43 months) follow-up. All patients were free of pain at rest and at light work, but half of the patients in each group still experienced pain with heavy work. Thumb pinch strength and range of motion were not significantly different in the two groups. The trapezial space decreased both with load and length of follow-up in both groups. Five endoprostheses subluxed during stressed pinch. In conclusion, both methods gave good, but not complete, pain relief and neither produced better results than the other in the short term.

Delayed surgery does not reduce the interface strength between the surface of a bone fracture and a self-curing injectable hydroxyapatite (Norian SRS).

The shear strength of the interface between bone and an injectable calcium phosphate bone substitute that cures to form a carbonated apatite (Norian SRS) was measured and related to the time that elapsed between injury and surgery. Eleven rabbits had a 3 mm drill hole made in the retropatellar aspect of the distal femur. After one week, the rabbits were reoperated on and the hole filled with Norian SRS after it had been cleaned gently with a sponge. During the same procedure a similar hole was burred in the opposite femur and filled with Norian SRS after a few minutes ("immediate injection"). Four other rabbits had only one side operated on with immediate injection of Norian SRS to compare with the opposite untreated side. The rabbits were killed four days after the injection of Norian SRS. The femurs were prepared and sawed perpendicularly to the burr channels to produce discs 3.5 mm thick. A push out test of the Norian SRS plug within the bone disc was done to measure the force at failure. In the immediately injected specimens the failure occurred at a mean of 28 N (range 5-57) compared with 42 N (range 25-65) in the specimens injected after a one week delay. There was no significant difference between delayed and immediate treatment (95% confidence interval -5 to 133). The histological examination showed that 9 of the 12 specimens had Norian SRS still adherent to half or more of the circumference of the hole. This indicates that the failure occurred in the Norian SRS rather than in the bone or at the interface.

The fate of mechanically induced cartilage in an unloaded environment.

According to mechanobiologic theories, persistent intermittent mechanical stimulation is required to maintain differentiated cartilage. In a rat model for bone repair, we studied the fate of mechanically induced cartilage after unloading. In three groups of rats, regenerating mesenchymal tissue was submitted to different loading conditions in bone chambers. Two groups were immediately killed after loading periods of 3 or 6 weeks (the 3-group and the 6-group). The third group was loaded for 3 weeks and then kept unloaded for another 3 weeks (the (3 + 3)-group). Cartilage was found in all loaded groups. Without loading, cartilage does not appear in this model. In the 3-group there was no clear ongoing endochondral ossification, the 6-group showed ossification in 2 out of 5 cartilage containing specimens, and in the (3 + 3)-group all cartilage was undergoing ossification. These results suggest a tendency of the cartilage to be maintained also under unloaded conditions until it is reached by bone that can replace it through endochondral ossification.Additional measurements showed less amount of new bone in the loaded specimens. In most of the loaded specimens in the 3-group, necrotic bone fragments were seen embedded in the fibrous tissue layer close to the loading piston, indicating that bone tissue had been resorbed due to the hydrostatic compressive load. In some specimens, a continuous cartilage layer covered the end of the specimen and seemed to protect the underlying bone from pressure-induced resorption. We suggest that one of the functions of the cartilage forming in the compressive loaded parts of a bone callus is to protect the surrounding bone callus from pressure-induced fluid flow leading to resorption.

Fibrous tissue armoring increases the mechanical strength of an impacted bone graft.

Impacted, morselized bone allografts are used with good clinical results in revision of hip prostheses with loosening and osteolysis. The impacted bone graft appears radiographically to remodel, but histological analyses have shown a heterogeneous picture with a mixture of living and dead bone. Thus, complete remodeling of the graft may be neither a prerequisite nor a cause of the good clinical results. The present study concerns the mechanical effect of the mere armoring of the bone graft by ingrowing fibrous tissue. We compared the compression strength of freshly-impacted grafts to grafts that had been inserted into a bone chamber and thus were penetrated by fibrous tissue growing in between the graft trabeculae. The compressive strength was doubled after 4 weeks of fibrous ingrowth. We conclude that the mechanical properties of an impacted graft are enhanced by armoring with ingrowing fibrous tissue. Strengthening of the parts of the impacted grafts which have not yet remodeled, would be clinically relevant for the outcome of the operation, since these parts are at high stress during the whole remodeling period. Complete osseous remodeling may not be necessary to obtain a good clinical result with a morselized impacted graft.

Load-bearing increases new bone formation in impacted and morselized allografts.

The effects of mechanical loading on the incorporation of morselized impacted grafts were addressed in this study. Twelve skeletally mature rabbits were surgically treated. Six rabbits received a proximal tibial joint replacement with a tibial tray and a load-bearing 25-mm long stem. The tibia was packed with fresh frozen, morselized, cancellous rabbit bone. No cement was used. In six other rabbits only the stem was inserted, without a tibial tray, leaving the stem and the likewise impacted bone graft mechanically unloaded. The rabbits were euthanized after 6 weeks, and the tibias were sectioned and analyzed by histomorphometric examination. In the loaded specimens the graft was resorbed and replaced by new bone (30% of area of interest) to a larger extent than in the unloaded specimens. Mechanical loading of an impacted, morselized graft surrounding a conical uncemented stem, increased the amount of new bone that replaced the graft. The ability of morselized impacted grafts to allow mechanical stimulation of ingrown tissue appears to be a principal cause for the success of this grafting procedure.

The morselized and impacted bone graft. Animal experiments on proteins, impaction and load.

The results of primary hip replacements are good. However, dealing with a loose prosthesis has been problematic, especially when major bone deficiencies are encountered. These problems appear to have been solved by the introduction of the Slooff-Ling method of using morselized and impacted allograft chips. The clinical results are excellent in the hands of the innovators. However, it remains confusing that a thick layer of dead, broken, immunogenic tissue taken from another individual does not resorb and collapse during remodeling. Still harder to understand is the impression, as judged by radiography, that this thick layer seems to incorporate and remodel up to a distance of perhaps 10 mm or more from the host bone, whereas the ingrowth distance into a non-morselized graft is limited to a few mms. To clarify the biological basis of the morselized and impacted grafts better, the present study was stated. Three hypotheses were initially proposed to explain the good clinical results: 1. Morselization releases growth factors present in the graft (osteoinduction). 2. Impaction makes it easier for the ingrowing bone to climb up into the graft (osteoconduction). 3. The compliance or elasticity of the graft allows the load to produce deformations that stimulate bone formation (mechanical load). In the first studies, bone chambers were implanted in rats and the distance of new bone ingrowth into a graft in the chamber was measured. In Paper I, a morselized graft was deproteinized by slow heating under high pressure. Ingrowing bone did not reach so far into the deproteinized graft as into a non-treated one. We concluded that the proteins present in the graft partly determine how far ingrowing new bone will extend into a graft. In Paper II, a cancellous graft was impacted so that the bone volume fraction of the graft rose from 35% in the unimpacted to 65%. The impacted grafts were compared to unimpacted ones and it was shown that impaction reduced the ingrowth of new bone into a graft in the chamber at six weeks. In Paper III, this somewhat unexpected finding was further studied. Syngeneic and allogeneic grafts showed a reduced ingrowth distance at six weeks when impacted, compared to unipacted controls. However, the reduction was not found when the time for ingrowth was extended to 12 weeks, indicating a possible catch-up phenomenon. Moreover, an exogenously applied growth factor, osteogenic protein-1, was found to have increased the ingrowth distance of new bone into impacted grafts at six weeks. In Paper IV, a rabbit knee prosthesis was developed to study the effect of a mechanical load on the remodeling of a morselized and impacted graft. All rabbits had their tibial marrow cavity cleansed of cancellous bone, which was replaced by a morselized and impacted bone graft. Six rabbits received a complete tibial prosthesis with a tibial load-bearing tray and a stem transferring the load to the impacted graft with each step made by the rabbit. Another six rabbits had only the stem, without the tibial tray, inserted into the impacted graft. With this design, the load from walking was not transferred to the graft, since there was no joint surface replacement to transfer the load to the stem and the graft. Thus, the graft was loaded in rabbits receiving a full prosthesis, whereas it was unloaded in the animals receiving only the stem. New bone formation and resorption of the graft were increased in the loaded grafts, and we concluded that a load increases the rate or speed of remodeling. In Paper V, four patients were operated on for vertebral fractures. The fractures were stabilized by plates and the vertebral bodies packed with autogenous morselized graft. After 1.5 years, when the fractures were clinically and radiographically healed, a biopsy was taken. It was found, that even after such a long time, large areas remained unremodeled and sometimes even unrevascularized. In some parts, necrotic graft trabeculae were embedded in fibrous vasc

Bone graft incorporation. Effects of osteogenic protein-1 and impaction.

Impaction of cancellous bone grafts in a bone chamber in rats in a previous study led to decreased ingrowth of new bone after 6 weeks compared with unimpacted grafts. The current study analyzes whether this decrease represented a final loss of ingrowth or just a delay, if the decrease was influenced by immunologic factors, and if it was possible to influence the inhibitory effect by adding a bone morphogenetic protein. Bone chambers with impacted or unimpacted bone grafts were implanted bilaterally in rat tibias. The mean bone ingrowth distance into the graft was measured on histologic sections. Three experiments were done: (1) the bone ingrowth into impacted and unimpacted grafts was studied at 6 and 12 weeks; (2) the immunologic influence was studied by comparing isogeneic grafts with allogeneic grafts; and (3) the authors tried to influence the decrease in bone ingrowth in impacted grafts by adding osteogenic protein-1. Bone ingrowth into the impacted graft was decreased at 6 weeks but not at 12 weeks. No difference was found between isografts and allografts at 6 weeks. With the addition of osteogenic protein-1, the impacted grafts showed dramatically increased bone ingrowth. Impacted bone grafts are incorporated at a slower rate than were structural grafts. The delay can be reversed by adding osteogenic protein-1, making ingrowth faster than in structural bone.

Reduced expression of BMP-3 due to mechanical loading: a link between mechanical stimuli and tissue differentiation.

Mechanical signaling and BMP expression appear to be involved in controlling the differentiation of cartilage in fracture repair, but the connection between mechanics and BMP signaling is not known. In this study of rats, we used a bone chamber to see how BMP gene expression was changed by a mechanical loading regime that induces cartilage formation in this model. We compared the still undifferentiated tissue in loaded and unloaded chambers in the same rat regarding the expression of TGFbeta-1, BMP-2, 3, 4, 5, 6, 7, CDMP-1, 2 and ALK-2 and 3 by using RT-PCR normalized against GAPDH. We found expression of TGFbeta-1, BMP-2 and 4 in all specimens, and BMP 5-7 and CDMPs in none. 1 week after loading started, BMP-3 was strongly expressed in the unloaded control specimens in 7 of 8 animals, but detectable in only I of the contralateral loaded ones. After 2 weeks of loading, the BMP-3 expression pattern was less clear, but with both time groups taken together, there was still less BMP-3 expression on the loaded side in 9 rats, more in 1 and no difference in 5 (p = 0.01). ALK-2 at 1 week was expressed in all specimens expressing BMP-3 and in none of the others. At 2 weeks, ALK-2 was expressed in all specimens. Thus, a loading regime, known to induce cartilage in this model, caused down-regulation of BMP-3 and ALK-2. The results are consistent with the view that BMP-3 inhibits differentiation, as recently described. This role appears to be linked to the ALK-2 receptor. Most importantly, the results indicate a link between mechanical signaling and BMP expression such that mechanically-induced down-regulation of the inhibiting BMP-3 enabled the induction of cartilage.

Cartilage induction by controlled mechanical stimulation in vivo.

To study mechanical control of tissue differentiation, we designed a new version of the previously described bone conduction chamber. The bone conduction chamber consists of a cylindrical titanium chamber for implantation in the rat tibia. It has tissue ingrowth openings at one end, located subcortically, and the other end protrudes into the subcutis. The newly developed load chamber has a mobile piston so that an external compressive load can be transferred to the tissue within the chamber. Sprague-Dawley rats had a regular bone conduction chamber implanted in one tibia and a load chamber implanted in the other. Mesenchymal tissue was allowed to grow into the chamber for 3 weeks before the mechanical loading was started. Thereafter, twice a day, 20 cycles of compressive load were applied with a frequency of 0.17 Hz to the load chamber. This was estimated to produce a compressive hydrostatic stress of 2 MPa. The chambers, harvested after 7 weeks of loading, all contained newly formed bone. The bone ingrowth distance into the chamber was decreased in the loaded specimens compared with the contralateral unloaded controls (p = 0.01). Instead, cartilage was found in the loaded chambers next to the piston. Beneath the cartilage was a dense bone plate under which a marrow cavity had formed. No cartilage was found in the unloaded controls, but the architecture of the bone and marrow cavity was similar to that of the loaded specimens. We conclude that this model allows load to be transmitted onto the ingrowing tissue and that the load parameters used cause this tissue to differentiate into cartilage close to the piston.

Incomplete incorporation of morselized and impacted autologous bone graft: a histological study in 4 intracorporally grafted lumbar fractures.

Morselized and impacted bone allografts are used successfully in hip and knee revisions, but experiments using bone chambers indicate that impaction actually can delay ingrowth of new bone into a graft. To understand the remodeling and incorporation process of morselized and impacted grafts, we studied the incorporation of morselized impacted autografts in lumbar fractures histologically. 4 patients were operated on for Th XII-LI fractures. The fractures were stabilized by VSP plates and transpedicular screws in the vertebrae above and below the fractured one. Autologous bone graft was packed into the fractured vertebral body through one of the pedicles. After 18-20 months, the plates were removed and biopsies were obtained from various locations in the fractured vertebra. All fractures were at this time clinically and radiographically healed. Histologically, in all cases, large areas of the autograft in the vertebral body were unvascularized and partially or entirely necrotic. As with morselized bone in hip revisions, evaluation of graft incorporation requires histological examination. Full osseous incorporation of a graft is not always necessary for a good clinical result.

Impaction of cancellous bone grafts impairs osteoconduction in titanium chambers.

The method of using morselized compacted cancellous allografts for hip arthroplasty revision shows results that seem to differ dramatically from other kinds of allografting. In structural cancellous allografts, bone ingrowth usually is limited to 2 to 3 mm, whereas morselized compacted grafts seem to be remodeled totally in several cases, as judged by radiography. In the current study, impacted cancellous allografts were compared with unimpacted allografts. Seventeen rats had a bone conduction chamber implanted in the tibias bilaterally. On one side the chambers contained an impacted graft (bone volume fraction 65%) and on the contralateral side an unimpacted graft (bone volume fraction 35%). Impaction of the grafts was done preoperatively with a pressure of either 25 or 2500 MPa. Ingrowing bone could enter the cylindrical interior of the chamber only at one end. After 6 weeks the mean distance the ingrown bone had reached into the graft was measured on histologic slides. With both impaction pressures, the bone ingrowth distance was decreased to 30% of the unimpacted controls. It appears that impaction alone does not have a favorable effect on the osteoconductive properties of a bone graft. On the contrary, impaction seems to disfavor osteoconduction. However, in the clinical situation this is not necessarily a disadvantage.

Bone graft proteins influence osteoconduction. A titanium chamber study in rats.

Although it is often emphasized that the matrix of bone grafts contains several growth factors, it is not known if these factors become activated and play a role in bone grafting. We therefore compared ground defatted bone which had or had not been deproteinized by heating with water to 270 degrees C at an autogenic pressure of 55 bar. This is a careful ceramic procedure which leaves the mineral unchanged. Deproteinized and non-deproteinized bone granulae derived from cortical rat bone were placed in titanium bone conduction chambers implanted bilaterally in rat tibiae. Ingrowing bone could enter the cylindrical interior of the chamber only at one end. It then penetrated the material in the chamber, but due to the length of the cylinder, it never reached the other end. The mean distance which the ingrown bone had reached in the material was then measured on histological slides. The bone formation activity was measured by TcMDP scintimetry. With the protein-containing granulae, the mean bone ingrowth distance and the scintimetric activity were increased by 41% and 31%, respectively (p < 0.01). We conclude that there is a limited favourable effect of proteins in a graft. Our grounded material had a large fracture surface area with no osteoid lining. The leakage of growth factors from such areas may explain the extraordinarily good clinical incorporation of morselized compacted allografts.