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Biomedical subjects

P Aspenberg

Publications and source records attributed to P Aspenberg.

At least 19 recordsLinked to original sources

A capsular incision leads to a fast osteoarthritic response, but also elevated levels of activated osteogenic protein-1 in rabbit knee joint cartilage.

We studied whether a small capsular incision alone, or combined with meniscectomy could induce early osteoarthritic changes in the rabbit knee. Thirty-one rabbits were operated on with a capsular incision in the left knee and meniscectomy in the right knee. Another 12 rabbits were used as controls. The rabbits were killed 3, 6 and 12 weeks after surgery. Osteoarthritic changes in the articular cartilage were evaluated by the modified Mankin score. The subchondral bone was evaluated by scintimetry ((99m)Tc-HDP) and semiquantitative grading of histological changes. Osteogenic protein (OP-1) in its mature and pro-form was examined by immunohistochemistry. Both a capsular incision and meniscectomy induced articular cartilage fibrillation and increased bone metabolic activity during the initial weeks after surgery. Capsular incision led to lesser changes than meniscectomy. Mature OP-1 was elevated, and its pro-form reduced, in meniscectomized knees. A similar pattern was observed in knees with capsular incision. Already 3 weeks after surgery, the articular cartilage and subchondral bone showed typical signs of early osteoarthritis (OA), and a reparative response was suggested by increased intensity of OP-1 staining. As these signs were also found in knees with capsular incision only, it appears that trauma-related factors such as increased bleeding and inflammation are critical for the development of OA.

Animals↗

Rinsing morcellised bone grafts with bisphosphonate solution prevents their resorption. A prospective randomised double-blinded study.

During revision total hip replacement using morcellised compacted bone allograft, 16 patients were randomised to receive a graft which had been rinsed in either an ibandronate solution or in saline. Patients were assessed by dual energy x-ray absorptiometry after operation and at 3, 6, 12 and 24 months. A region of interest between the tip of the femoral stem and the distal plastic plug was chosen to measure the changes in bone density over time. The study was double-blinded. In all the control patients the bone density decreased during the first three months and then remained constant at this lower level. A large proportion of the mass of the bone graft was lost. In contrast, all patients with grafts treated with bisphosphonate showed a slight increase in bone density. The difference between the groups was highly significant at all points in time. We conclude that rinsing the graft in a bisphosphonate solution prevents its resorption and may therefore reduce the risk of mechanical failure. The treatment is simple, inexpensive, and appears virtually free of risk.

Absorptiometry, Photon↗

CDMP-2 injection improves early tendon healing in a rabbit model for surgical repair.

This study examines the hypothesis that cartilage-derived morphogenic protein-2 (CDMP-2) can improve tendon healing after surgical repair. We have previously found improved tendon healing by applying CDMP-2 in models for conservative treatment with mechanically loaded Achilles tendon defects in rats and rabbits. In this study, the patellar tendon was unloaded by patello- tibial cerclage and cut transversely in 40 rabbits. Two hours post-operative, the rabbits received a dose of 20 microg of CDMP-2 or vehicle injected into the hematoma. Specimens were harvested after 14 and 28 days and evaluated by biomechanical testing, radiography and histology. At 14 days, CDMP-2 caused a 65% increase in force at failure, a 50% increase in ultimate stress and a 57% increase in stiffness, as compared with controls. There was no effect on callus size. At 28 days, no differences between the treatment groups could be demonstrated. No bone or cartilage was found in any tendon or regenerated tissue at any time point. Thus, early tendon repair can be stimulated by CDMP-2 in an unloaded model. These results suggest that CDMP-2 might be of interest for clinical use as a complement to surgical treatment of tendon ruptures.

Animals↗

Surface immobilized bisphosphonate improves stainless-steel screw fixation in rats.

An increase in the mechanical fixation in bone of metallic biomaterials is considered advantageous in joint replacement and fracture surgery. Different approaches to improve fixation may be e.g. surface roughening, Ca-mineral coating or surface immobilization of growth factors or drugs. In the present work, bisphosphonate, a class of drugs that inhibit bone resorption, was immobilized onto stainless-steel screws. The screws were first roughened and coated with immobilized and cross-linked fibrinogen. Subsequently, an N-bisphosphonate, pamidronate, was immobilized onto fibrinogen, and another N-bisphosphonate, ibandronate, adsorbed on top of this. The so coated screws were inserted into the tibiae of eight male Sprague-Dawley rats. Another eight rats received screws prepared in the same way, but without the bisphosphonate coating. Pullout strength tests were performed after 2 weeks of implantation. The results showed a 28% (p=0.0009) higher pullout force and 90% increased pullout energy for the bisphosphonate coated screws, and support the idea that surface immobilized bisphosphonates can be used to improve biomaterials fixation in bone.

Adsorption↗

Intermittent parathyroid hormone (1-34) enhances mechanical strength and density of new bone after distraction osteogenesis in rats.

Distraction osteogenesis is used both for leg lengthening and for bone transportation in the treatment of fractures and nonunions. The main problem with this method is that the time until full recovery may be up to a year, partly because of the time needed for the new formed bone to consolidate and become strong enough for weight bearing. We have studied whether intermittent parathyroid hormone (PTH(1-34)) could accelerate the consolidation of new formed bone after distraction osteogenesis in rats. Forty-seven, 3-months-old male Sprague-Dawley rats underwent lengthening of the right femur using an external fixator. After a middiaphyseal osteotomy and a 7-day latency period, the callus was distracted during 10 days, with a distraction rate of 0.25 mm twice a day. The consolidation time was either 20 days or 40 days after distraction was completed. A dose of 60 microg of human PTH(1-34)/kg body weight/injection or vehicle was given every second day beginning 30 days before the rats were killed. Both femura of each rat were subjected to mechanical testing and dual-energy X-ray absorptiometry. Blinded histological examination was done for the distracted femura. In the 20 days consolidation experiment, PTH(1-34) increased ultimate load (56%), stiffness (117%), total regenerate callus volume (58%), callus BMC (24%) and histologic bone density (35%) compared to untreated distraction osteogenesis specimens. In the 40 days consolidation experiment, PTH(1-34) increased ultimate load (54%), stiffness (55%), callus BMC (33%) and histologic bone density (23%) compared to untreated distraction osteogenesis specimens. Total regenerate callus volume was unchanged. The contralateral femur also became stronger, stiffer and denser under PTH(1-34) treatment, but to a lesser degree. PTH(1-34) might become useful to shorten the consolidation time after distraction osteogenesis in humans.

Animals↗

Titanium implants and BMP-7 in bone: an experimental model in the rabbit.

This study evaluates the effect of rhBMP-7/OP-1 on the osseointegration of commercially pure titanium implants in an experimental implant model in rabbits. Threaded titanium implants with two transverse parallel canals were inserted in the femur and tibia of rabbits. The canals were filled with, 10 microg of BMP-7/collagen carrier, pure collagen carrier or were left empty as a control. The stiffness of the implant fixation was evaluated by Resonance Frequency Analysis (RFA) at baseline and four weeks postoperatively. Percentage of bone ingrowth in the canals was measured on microradiographs. Histomorphometry along the threaded part of the implants was performed on 15 microm thin sections. The results from the RFA demonstrated a higher mean value for the BMP-7 treated implants in the tibia than the carrier treated implants but not compared to the control implants. The control implants in the tibia demonstrated more bone ingrowth in the upper canal than to the carrier or the BMP-7 treated implants. Apart from these differences there were no significant effects of BMP. In this study BMP-7 did not contribute to any substantially improved bone anchorage of titanium implants.

Journal Article↗

Norian SRS versus functional treatment in redisplaced distal radial fractures: a randomized study in 20 patients.

We compared the use of Norian SRS, an injectable calcium phosphate bone cement, with functional treatment of redisplaced distal radial fractures in a prospective randomized study of 20 patients. The redisplaced fractures were either rereduced and stabilized by Norian SRS, or the displaced position was accepted and was not rereduced. All wrists were immobilized in a short-arm dorsal splint for 1 week, followed by a removable splint for another 3 weeks. The chosen primary effect variable was grip strength at 7 weeks, and this did not differ between the two treatment groups. The clinical results at 6 months in both groups were similar. We conclude that aggressive treatment of redisplaced fractures of the distal radius may be unnecessary in most women aged 50 years or more.

Aged↗

Arch-shaped versus flat arthrodesis of the ankle joint: strength measurements using synthetic cancellous bone.

The aim of this study was to see if preservation of the arch shape of the ankle at arthrodesis contributes to stability. The ankle joint was simulated by paired blocks of a synthetic material corresponding to rheumatoid cancellous bone with low stiffness and strength. Flat end constructs with and without subchondral bone were compared with arch-shape constructs with and without subchondral bone. The pairs were fixed with two screws simulating an arthrodesis. These constructs were then tested to failure in four-point bending and torque. In four-point bending the subchondral bone increased the strength, regardless of shape. Stiffness was higher in the arch-shaped specimens but was not influenced by the subchondral bone. In torque, both arch-shape and subchondral bone increase the strength. Stiffness was increased by arch-shape but not subchondral bone. The results imply that the arch-shape and subchondral bone should be preserved when performing an ankle arthrodesis, especially in weak rheumatoid bone.

Ankle Joint↗

Parathyroid hormone (1-34) increases attachment of PMMA cement to bone.

The attachment of an implant material to bone is related to the surface of the implanted material and the ability of the bone to form around the implant. Intermittent parathyroid (PTH) administration increases bone formation by stimulating osteoblastic activity. Little is known about the effect of PTH administration on orthopedic implant incorporation. The present study determined how PTH (1-34) administration influenced bone bonding, i.e., the bone-cement interfacial tensile strength, of vacuum-mixed polymethylmethacrylate (PMMA) bone cement (surface roughness; Ra, 4.8 microm). Bone bonding was evaluated by a detachment test. We used unloaded cement surfaces, which could be detached from the bone. Titanium plates were developed such that a cement fill was contained within a plate that was contained within a titanium holder. Thus, a flat cement surface came into contact with traumatized bone only, and the rest of the plate had no contact with tissue. After implantation of the plate in the left tibia, 20 adult male rats were injected daily with human PTH (1-34) at 60 microg/kg per injection (n = 10) or vehicle (n = 10); the animals were killed after 4 weeks. The plates were detached from the bone by a perpendicular force. PTH treatment increased the median pull-away strength (0.21 MPa), compared with that in the vehicle-treated rats, (0.04 MPa) (P = 0.02). The results suggest that PTH treatment may have the potential to enhance the incorporation of cemented orthopedic implants.

Animals↗

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.

Animals↗

Radiostereometric analysis of distal radial fracture displacement during treatment: a randomized study comparing Norian SRS and external fixation in 23 patients.

In a randomized study, we included 23 osteoporotic patients with a distal radial fracture and loss of reduction after 1 week. The facture was re-reduced. In one group, a self-setting hydroxyapatite, Norian SRS, was injected into the fracture and the wrist was immobilized for 2 weeks with a dorsal splint (n 12). In the other group, the fracture was immobilized for 5 weeks with an external fixator (n 11). During the operation, the fracture fragments were marked with tantalum markers, so that loss of reduction during the immobilization and after mobilization could be studied with radiostereometric analysis (RSA). We found some recurrence of compression in the fracture in both groups during immobilization. After mobilization, the motion of the fracture, measured by displacement of the fragments along the longitudinal axis, was less than 2 mm, except in 3 cases treated with Norian SRS. A compression along the longitudinal axis of less than 2 mm is not likely to cause any problem in the long term. From the first to the last investigation, 7/12 patients with Norian SRS and 4/11 with external fixation lost more than 2 mm of the reduction along the longitudinal axis. We conclude that 5 weeks of immobilization is sufficient for healing with external fixation in this age group. This immobilization time might be reduced to 2 weeks for fractures treated with Norian SRS, but additional hardware should be used to ensure stability of the fracture system.

Age Factors↗

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.

Animals↗

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.

Animals↗

Combination of growth factors inhibits bone ingrowth in the bone harvest chamber.

Previous studies using bone harvest chambers have shown that bone morphogenetic protein-2 inhibits bone ingrowth. The authors hypothesized that the combination of bone morphogenetic protein-2 and a potent angiogenic factor, basic fibroblast growth factor, would result in increased bone formation in this model. Five New Zealand White rabbits were surgically implanted with bone harvest chambers in the proximal metaphyseal region of both tibias. The right leg of each rabbit was implanted with a bovine collagen sponge that was impregnated with recombinant human bone morphogenetic protein-2, basic fibroblast growth factor, or a combination of these factors. The left leg chamber was implanted with the collagen sponge with no growth factors as a control. The bone that grew into the chambers was harvested after 2 weeks, and histomorphologic analysis was performed to determine the amount of tissue and bone ingrowth. The tissue chambers were left empty for 2 weeks between test implants, and this tissue also was harvested, analyzed, and compared with the other samples. The results showed decreased bone formation for the bone morphogenetic protein-2, basic fibroblast growth factor, and combination of bone morphogenetic protein-2 and basic fibroblast growth factor treated groups when compared with the control and empty groups. The combination of bone morphogenetic protein-2 and basic fibroblast growth factor showed inhibition of bone formation that was greater than either growth factor individually. The reason for the inhibition of bone formation with the combination of factors is unknown.

Analysis of Variance↗

Early effect of parathyroid hormone (1-34) on implant fixation.

Intermittent systemic administration of parathyroid hormone increases bone formation by stimulating osteoblastic activity. The current study determined how parathyroid hormone (1-34) administration influences the bony fixation of stainless steel screws with time. A screw was implanted in the left tibia and a metal rod was implanted in the right tibia in 30 adult male rats that then were injected three times a week with human parathyroid hormone (1-34) at 60 microg/kg/injection (n = 15) or saline (n = 15). The animals were euthanized after 1, 2, or 4 weeks of treatment. Eight additional rats received only the screw and were euthanized immediately after implantation. No significant effects of parathyroid hormone on body weight change or ash weight of the femurs were seen. The degree of fixation was assessed by measuring pullout strength of the screws. The mean pullout strength immediately after implantation was 12 N. The pullout strength of the group injected with saline was 33 N after 1 week, 23 N after 2 weeks, and 41 N after 4 weeks. The pullout strength of the group injected with parathyroid hormone increased to 43 N after 1 week, 58 N after 2 weeks, and 100 N after 4 weeks. The increase at 2 and 4 weeks was statistically significant. Strength reflects the mechanical properties of the bone within the screw threads. The contralateral tibia with its metal rod was used for blinded histologic assessment. Parathyroid hormone increased the fraction of the metal surface having contract with bone without an intervening soft tissue layer from 45% to 69% after 1 week. The current results suggest that intermittent parathyroid hormone treatment can enhance early implant fixation by enhancing the density of the surrounding bone and by increasing the implant bone contact.

Animals↗

Tendon healing stimulated by injected CDMP-2.

UNLABELLED: Tendon healing stimulated by injected CDMP-2. Med. Sci. Sports Exerc., Vol. 33, No. 5, 2001, pp. 685-687. INTRODUCTION: CDMP-2 is a member of the TFG-beta super-family. It is known to induce bone and cartilage formation but has also been shown under certain conditions to induce a tendon- and ligament-like tissue. The purpose of this study was to find possibilities for improvement of Achilles tendon repair during nonoperative treatment, by local injections of CDMP-2. METHODS: Fifty rats had a 3-mm segment of the Achilles tendon removed. Six hours postoperatively, CDMP-2 was injected locally into the defect at a dose of 0, 2, 10, or 50 microg. Eight days after the operation, the rats were killed and the tensile strength of the repairing tendons was measured with a materials testing machine. RESULTS: After 8 d, the CDMP-2-treated tendons were 39% stronger than the controls (P = 0.0008). CONCLUSION: One single injection CDMP-2 can augment tendon repair. Mechanical stimulation is of great importance for tissue differentiation and tendon repair. The tendons in our model were mechanically loaded during healing and this might explain why CDMP-2 injections induced a strong tendon-like tissue instead of bone or cartilage in this model.

Achilles Tendon↗