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Biomedical subjects

Per Aspenberg

Publications and source records attributed to Per Aspenberg.

At least 37 records · Page 2Linked to original sources
PubMed2004

Alendronate prevents collapse in mechanically loaded osteochondral grafts: a bone chamber study in rats.

BACKGROUND: Subchondral bone necrosis is important in osteonecrosis, Mb Kienboeck, intraarticular fractures or osteochondral grafting. As revascularization follows, bone resorption may lead to collapse in load bearing areas during the remodeling. Bisphosphonates are potent osteoclast inhibitors. Our hypothesis was that local bisphosphonate treatment of an osteochondral graft, in a high load environment, would protect the subchondral bone from collapse and maintain the joint architecture during remodeling. To investigate this, we used a rat bone chamber model to subject a necrotic osteochondral graft to a large mechanical load during remodeling. METHOD: Cylindrical osteochondral grafts were taken from the patellar groove of rats, one end of the cylinder being the joint surface. The grafts were frozen, thawed and treated with alendronate. The length of the cylinder was measured and the grafts were placed in the chambers, which were inserted into the proximal tibia of rats. The chambers were left to heal in for two weeks to allow establishment of a vascular supply, and then the transplanted osteochondral plugs were mechanically loaded for 4 weeks, once a day with 10 cycles of 2 MPa pressure at 0.16 Hz. RESULTS: At harvest, the graft length had decreased during remodeling in 5 of the 6 untreated controls, but only in 2 out of 8 alendronate-treated rats (p = 0.05). Histologically, the bone graft in the non-treated controls was resorbed in the remodeled part of the graft, whereas in the alendronate-treated rats a dense trabecular bone was found consisting of both new bone and graft. INTERPRETATION: Local treatment of the graft with bisphosphonate diminishes the risk of collapse during revascularization and bone remodeling in a mechanically loaded osteochondral graft. This could be useful in a variety of situations when bone remodeling occurs after a necrosis close to a joint, either spontaneously after osteonecrosis or a fracture, or after surgical procedures such as mosaic-plasty or other osteochondral grafting.

Alendronate↗
PubMed2003

Synovial fluid depletion: successful arthrodesis without operative cartilage removal.

Operative arthrodesis has been thought to require surgical removal of remaining joint cartilage, but we have found in rabbits that even a joint with intact cartilage can fuse if rigidly fixed. This may enable new percutaneous techniques for arthrodesis. Rigid adaptation of the joint surfaces deprives the cartilage of mechanical stimulation and depletes the cells of synovial fluid transport of oxygen and nutrition. To better understand the requirements for successful arthrodesis, we studied the histological consequences of the complete absence of mechanical stimulation alone or in combination with synovial depletion by placing a metal cap over part of the joint cartilage in rabbits. The cap was either closed or had an opening to permit synovial fluid to reach the cartilage. We also studied if penetration of the bone-cartilage junction by a drill hole would facilitate cartilage resorption. Synovial fluid depletion in combination with a drill hole through the bone-cartilage junction led to disappearance of all cartilage matrix after 7 weeks. Synovial fluid depletion with an intact bone-cartilage junction led to complete disappearance of the cartilage matrix in four of seven rabbits after 7 weeks. With a hole in the cap for synovial fluid, the cartilage matrix was still present to varying degrees after 7 weeks in all the rabbits. In conclusion, percutaneous arthrodesis by rigid adaptation may lead to cartilage disappearance due to synovial depletion rather than due to the absence of mechanical stimulation. A combination with perforation of the bone-cartilage junction appears to lead to reasonably quick removal of the cartilage matrix.

Animals↗
PubMed2003

PMMA particles and pressure--a study of the osteolytic properties of two agents proposed to cause prosthetic loosening.

Amongst the wear debris particles implicated in the particle hypothesis for prosthetic loosening are polymethylmethacrylate (PMMA), and particularly PMMA with barium sulphate contrast agent. Another suggested cause for loosening is hydrostatic pressure. PMMA particles were combined with hydrostatic pressure in a study to investigate whether there could be a synergistic or additive effect between these two factors. Titanium plates were fastened onto tibiae of 59 rats. After osseointegration, PMMA particles with barium sulphate were administered to the bone-implant interface. Further, PMMA particles were introduced into a previously published model for hydrostatic pressure induced osteolysis. There was measurable resorption in response to the PMMA particles but no additive or synergistic effect from introducing particles to the pressure model, and the effect of pressure was far greater than that of particles. These results suggest that, whereas particles can be shown to elicit an osteolytic response, the much less studied osteolytic effects of pressure could be far more important.

Animals↗
PubMed2003

A comparative dose-response study of cartilage-derived morphogenetic protein (CDMP)-1, -2 and -3 for tendon healing in rats.

Cartilage-derived morphogenetic proteins (CDMPs), belonging to the bone morphogenetic protein (BMP) family, are known to be cartilage and bone inducers as well as to induce tendon and ligament-like tissue. In this study we investigated the influence of CDMP-1, -2 or -3 at four different doses (0, 0.4, 2 and 10 microg) on tendon healing in a rat model, as well as differences in osteogenesis between the different CDMPs and doses.In 110 rats, a 3 mm segment of the Achilles tendon was removed via a 2 mm skin incision. CDMP-1, -2 or -3 was injected into the defect 6 h postoperative. The rats were killed 8 days after operation. The tendon regenerates were tested biomechanically. There was a significant dose-related increase in strength and stiffness with all three CDMPs, but no difference between the CDMPs was found. Another 50 rats were used to compare the highest dose of the CDMPs with controls and osteogenic protein 1 (OP-1), as regards cartilage or bone formation after 4 weeks. Cartilage occurred in all groups, including the controls. Some specimens in all groups contained bone, except the controls. No difference between the CDMPs could be demonstrated. The CDMP-1, CDMP-3 and OP-1 groups contained significantly more calcium than controls. Only the CDMP-2 group and the controls contained significantly less calcium than the OP-1 group.In conclusion, the three CDMPs appeared similar as regards improvement of tendon repair and osteogenicity in this setting.

Achilles Tendon↗
PubMed2003

Cartilage injuries in distal radial fractures.

Subchondral hematomas have been found with arthroscopy in one third of patients with dislocated distal radial fractures. The aim of the present, prospective study was to determine whether these hematomas might cause radiographic osteoarthrosis. We studied 41 patients (age 20-57 years, 22 women) with a dislocated distal radial fracture. At the time of fracture, 12 patients had subchondral hematomas in a radiocarpal compartment without a fracture line, as defined by arthroscopy. The 1-year follow-up included clinical and radiographic examinations. At follow-up, radiographic subchondral bone plate changes occurred in unfractured compartments in 8 patients, of whom 7 had had a previous arthroscopically diagnosed subchondral hematoma (p = 0.02) in the same compartment. Of the 8 patients with radiographic changes, 4 had also developed joint space narrowing (osteoarthrosis (OA) grade 1) after 1 year and 6 after 3 years. All but 1 had had a hematoma in the same compartment. More importantly, 3 of the 16 patients with entirely extra-articular fractures had subchondral bone plate changes in a compartment corresponding to a previous subchondral hematoma (p = 0.02). One of these had also developed joint space narrowing. The patients with radiographic changes had a worse outcome, as measured with the Gartland and Werley wrist score (p = 0.06). In conclusion, subchondral hematomas in distal radial fractures can lead to early onset of mild OA and worse outcome after 1 year.

Adult↗
PubMed2003

Meniscectomy leads to an early increase in subchondral bone plate thickness in the rabbit knee.

We evaluated morphological changes in the tibial bone after meniscectomy in a rabbit model. 15 rabbits subjected to a medial meniscectomy in the right knee and a sham-operation in the left. Histomorphometric parameters were evaluated in the subchondral bone plate and the underlying trabecular bone, 13, 25 and 40 weeks after surgery. 5 rabbits were used as unoperated controls. Meniscectomized knees had a thicker subchondral bone plate than sham-operated contralateral ones in 13 of the 15 rabbits (p = 0.01), but the trabecular bone showed no morphological differences. The meniscectomized knees of these rabbits developed mild osteoarthrosis, described elsewhere, which may have been partly due to a change in the mechanical properties of the thickened subchondral bone plate. Our findings suggest that the first bony response after meniscectomy occurs in the subchondral bone plate rather than in the trabecular bone.

Animals↗
PubMed2003

Indomethacin and celecoxib improve tendon healing in rats.

Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the formation of bone. However, they have been shown to increase tensile strength in healing tendons. Most NSAIDs inhibit two isoforms of cyclooxygenases called Cox-1 and Cox-2. Thanks to fewer side-effects, the recently introduced selective cyclooxygenase-2 (Cox-2) inhibitors will probably promote more widespread use of this kind of drug. To clarify the effects on tendon healing of a general Cox-inhibitor (indomethacin) as well as a selective Cox-2 inhibitor (celecoxib), we resected 3 mm of the Achilles tendon in rats and measured the strength of the tendon regenerate. Indomethacin given as daily injections in doses of 1.5, 3.0 and 5.0 mg/kg reduced the thickness (cross-sectional area) of the tendon regenerate at 14 days, as compared to controls, but there was no difference in the failure load or stiffness. In another series of measurements, indomethacin in a dose of 3.0 mg/kg reduced the cross-sectional area at 10, 14 and 18 days after transsection. Failure load was not affected, but tensile stress at failure was increased by indomethacin at 14 and 18 days. Indomethacin (3 mg/kg) was then compared to celecoxib (4.5 mg/kg) and controls 14 days after tendon transsection. No difference between the drugs was seen. Again, the transverse area was smaller in the treated tendons than in the controls. Failure load was unchanged and the tensile stress was higher in the treated tendons than in the controls. Because of the reduction in cross-sectional area without an effect on failure load, the use of Cox-inhibitors may be beneficial in clinical situations where thickening of a healing tendon is a problem--e.g., in the hand or shoulder.

Analysis of Variance↗
PubMed2003

A combination of bisphosphonate and BMP additives in impacted bone allografts.

OP-1 increases bone ingrowth distance of new bone into allografts (Tägil et al. 2000), but the bone density after incorporation may be reduced by an increase in resorption (Höistner et al. 2000). Bisphosphonates inactivate osteoclasts and can be used to increase allograft bone density after incorporation (Aspenberg and Astrand 2002). A combination of locally-applied bisphosphonate and OP-1 in the graft could therefore be expected to increase both new bone ingrowth and density. We tested this by using a rat bone chamber model. OP-1 alone increased the ingrowth distance of bone. Clodronate increased final bone density greatly, but reduced the ingrowth distance of new bone into grafts that were extremely impacted. This reduction was improved by adding OP-1. Regardless of graft density, combinations of OP-1 and clodronate included a high final bone density, but the ingrowth distances were shorter than with OP-1 alone. These data indicate that new bone and tissue ingrowth into a compacted graft depends on resorption and that resorption is a prerequisite for the stimulating effect of OP-1 in this experimental set-up. Although the problems associated with the use of OP-1 in impaction grafting may be solved by adding a bisphosphonate, some of the benefits of OP-1 can be lost.

Animals↗
PubMed2003

No augmentation of morselized and impacted bone graft by OP-1 in a weight-bearing model.

INTRODUCTION: Impacted morselized bone allograft is thought to be remodeled to a great extent. We have previously shown that load-bearing increases the remodeling of impacted morselized bone allografts in a rabbit knee prosthesis model. Bone Morphogenic Proteins (BMPs) also stimulate bone formation and bone allograft remodeling. In this study, our aim was to determine whether it was possible to increase further the remodeling of impacted morselized bone allografts by combining load-bearing with a BMP. EXPERIMENT: A solution of Osteogenic Protein-1 (OP-1, also called BMP-7) was added to freeze-dried bone allograft chips before impaction grafting in our rabbit knee prosthesis model. 23 skeletally mature rabbits received an uncemented tibial knee prosthetic component inserted into a bed of impacted morselized bone allograft. 12 rabbits were given OP-1-treated allograft (50 microg OP-1 per gram allograft), and 11 rabbits vehicle-treated allograft. Each rabbit received mean 0.53 g graft. The rabbits were killed after 3 or 6 weeks and the grafted region was examined by histomorphometric assessment of the volume fraction of newly formed bone and remaining graft. RESULTS AND INTERPRETATION: We found that OP-1 did not increase the bone density (graft plus new bone) to any substantial extent. However, we can not exclude that this might be due to a carrier problem, since the OP-1 was added as a solution directly to the dry graft.

Animals↗
PubMed2003

Rinsing morselized allografts improves bone and tissue ingrowth.

Bone defects in revision hip surgery can be reconstructed with impacted morselized bone grafts. Rinsing these trabecular allografts may enhance graft incorporation by washing out immunogenic factors present in blood, marrow, and fat. However, it has been proposed that impaction of the graft releases biologically active factors, which can provide sufficient activity to stimulate new bone formation. Rinsing before impaction could enhance bone allograft incorporation, but rinsing after impaction could diminish the incorporation process of impacted bone graft. To study the effect of rinsing and impaction of morselized bone grafts on bone ingrowth, a bone chamber study was done in goats. Autografts and allografts were divided into three treatment groups: (A) impacted; (B) rinsed and impacted; and (C) rinsed, impacted, rinsed, and impacted again. Ten goats received three bone chambers in each proximal tibia. The chambers were filled with either allograft or autograft, yielding six different implants per goat. After 6 weeks, histologic analyses were done and bone and tissue ingrowth were measured. New bone and total tissue ingrowth were higher in autografts than in allografts, especially in the nonrinsed group. With rinsing, total tissue ingrowth increased in the allograft group to approach that of autografts. Rinsing after impaction did not additionally alter bone ingrowth. The current findings show that incorporation of allografts can be improved by rinsing the grafts before impaction.

Animals↗
PubMed2003

A rat model for testing pharmacologic treatments of pressure-related bone loss.

Fluid pressure, instability, or particles have been suggested to initiate the process leading to loosening of prosthetic implants. In a rat model where bone resorption is caused by oscillating fluid pressure, the resorptive response seems much stronger than the response that can be induced by particles or instability. Bone resorption is caused by osteoclasts. It has been suggested that the formation of osteoclasts is influenced by tumor necrosis factor-alpha, which can be blocked by etanercept. Osteoclasts can be inactivated with bisphosphonates, which bind to bone and inactivate osteoclasts when the bisphosphonate-containing bone is resorbed. Bone formation can be increased dramatically by intermittent parathyroid hormone treatment, especially at sites with high bone turnover. This might compensate for increased osteoclastic activity. Forty-two rats received a plate implant, by which fluid pressure was applied to a bone surface by compressing a soft tissue membrane. Eight rats were treated with etanercept 0.75 mg/kg/day, six rats were treated with alendronate 205 microg/kg/day, six rats received saline, and six rats were nonpressurized controls. Nine rats received intermittent parathyroid hormone treatment with nine separate controls. The area of bone resorption under the implant was evaluated by histomorphometry. Alendronate-treated rats showed less bone resorption, but etanercept, intermittent parathyroid hormone treatment, or saline did not reduce the fluid pressure-induced bone resorption. This model is a comparatively simple way of testing pharmacologic reduction of local bone resorption in vivo.

Alendronate↗
PubMed2002

Randomized radiostereometric study comparing osteogenic protein-1 (BMP-7) and autograft bone in human noninstrumented posterolateral lumbar fusion: 2002 Volvo Award in clinical studies.

STUDY DESIGN: Randomized efficacy trial comparing two types of noninstrumented posterolateral fusion between L5 and S1 in patients with L5 spondylolysis and vertebral slip less than 50%, as evaluated by radiostereometric analysis. OBJECTIVE: To determine whether osteogenic protein-1 (BMP-7) in the OP-1 Implant yields better stabilizing bony fusion than autograft bone. SUMMARY OF BACKGROUND DATA: Animal studies of osteoinductive proteins in noninstrumented posterolateral fusions have shown high fusion rates. No similar conclusive study on humans has been performed. METHODS: For this study, 20 patients were randomized to fusion with either OP-1 Implant or autograft bone from the iliac crest, 10 in each group. The patients were instructed to keep the trunk straight for 5 months after surgery with the aid of a soft lumbar brace. At surgery 0.8-mm metallic markers were positioned in L5 and the sacrum, enabling radiostereometric follow-up analysis during 1 year. The three-dimensional vertebral movements, as measured by radiostereometric analysis induced by positional change from supine posture to standing and sitting, were calculated with an accuracy of 0.5 to 0.7 mm and 0.5 degrees to 2.0 degrees. Conventional radiography was added. RESULTS: No significant difference was noted between the radiostereometric and radiographic results of fusion with the OP-1 Implant and fusion with autograft bone. There was a significant relation between reduced vertebral movements and better bone formation. No adverse effects of the OP-1 Implant occurred. Persistent minor pain at the iliac crest was noticed in one patient. CONCLUSIONS: There was no significant difference between the two fusion versions. Thus, the OP-1 Implant did not yield better stabilizing bony fusion than autograft bone.

Adult↗
PubMed2002

Systemic alendronate prevents resorption of necrotic bone during revascularization. A bone chamber study in rats.

BACKGROUND: Avascular necrosis of bone (osteonecrosis) can cause structural failure and subsequent deformation, leading to joint dysfunction and pain. Structural failure is the result of resorption of necrotic bone during revascularization, before new bone has formed or consolidated enough for loadbearing. Bone resorption can be reduced by bisphosphonates. If resorption of the necrotic bone could be reduced during the revascularization phase until sufficient new bone has formed, it would appear that structural failure could be avoided. METHODS: To test whether resorption of necrotic bone can be prevented, structural grafts were subjected to new bone ingrowth during systemic bisphosphonate treatment in a rat model. RESULTS: In rats treated with alendronate the necrotic bone was not resorbed, whereas it was almost entirely resorbed in the controls. CONCLUSION: Systemic alendronate treatment prevents resorption of necrotic bone during revascularization. In patients with osteonecrosis, bisphosphonates may therefore prevent collapse of the necrotic bone.

Journal Article↗
PubMed2002

CDMP-2 induces bone or tendon-like tissue depending on mechanical stimulation.

Cartilage derived morphogenetic proteins (CDMPs, also known as growth and differentiation factors, GDFs) are a subgroup of the bone morphogenetic protein (BMP) gene family. As most BMPs, they are known to induce cartilage or bone formation when implanted subcutaneously or intramuscularly on an appropriate carrier. However, similar implantation experiments with CDMPs have also reported the formation of a tendon-like tissue, without any cartilage or bone. A solution to this apparent contradiction might be offered by the mechanical tissue differentiation theory, suggesting that tissue differentiation depends on the mechanical environment. This study analyzes the response to CDMP-2 implants at different sites and under different loading conditions in the rat. Collagen sponges carrying CDMP-2 were implanted subcutaneously, intramuscularly or inside a freshly created defect in the achilles tendon. Large amounts of bone were induced subcutaneously, smaller amounts intramuscularly, and in the tendons, only small amounts of bone or cartilage were seen in few animals. Thus, the amount of bone appeared inversely related to the degree of mechanical stimulus. To confirm this, CDMP was also injected into tendon defects that were either loaded or partially unloaded. All the unloaded tendons showed bone induction after one CDMP-2 injection, whereas only 4 of 10 loaded ones showed any cartilage or bone (p = 0.0005). Single injections of a similar dose of CDMP-2 have previously been shown to augment tendon repair by increasing the size of the tendon callus. This study suggests that the response to CDMP-2 is dependent on the mechanical situation at the site where it is applied.

Achilles Tendon↗
PubMed2002

Bone allografts pretreated with a bisphosphonate are not resorbed.

Bisphosphonates bind to bone surfaces and inactivate osteoclasts when they start to resorb the bone. Therefore, immersion of a bone graft in a bisphosphonate solution before implantation may protect it from resorption. We implanted frozen cancellous bone allografts into bilateral bone chambers for 6 weeks in 10 rats. One graft in each pair had been immersed in an alendronate solution (1 mg/mL) for 10 minutes, and then rinsed in saline. Controls underwent the same treatment with saline only. Results were evaluated with histomorphometry. Control grafts were almost entirely resorbed, but alendronate-treated grafts seemed intact. In the treated specimens, two thirds of the space behind the bone ingrowth frontier consisted of graft or host bone, but in the controls, only one fifth. Local graft treatment with a bisphosphonate before insertion seems to be risk-free, and may prevent mechanical graft failure due to resorption in patients.

Animals↗
PubMed2002

Reduction of instability-induced bone resorption using bisphosphonates: high doses are needed in rats.

Bone resorption associated with prosthetic loosening can be reduced by giving bisphosphonates since they bind to bone surfaces and inactivate osteoclasts when bisphosphonate-containing bone is resorbed. During loosening, an increase in osteoclastic activity can be triggered by mechanical instability, fluid pressure or wear particles. We used a rat model in which a titanium surface can be made to slide over a bone surface and cause instability-induced bone resorption. 111 rats were operated on with a plate implant and treated with alendronate or clodronate injections in different doses or saline controls. After 4 weeks of osseointegration, the plate was moved during 2 weeks and the findings evaluated with histomorphometry. The percentage of persisting bone-metal contact and the soft tissue area at the interface were measured to estimate bone loss. Low or intermediate doses of the bisphosphonates increased the ash weight of untraumatized bone, but did not inhibit resorption at the unstable interface. Only rats treated with the highest doses of alendronate or clodronate had more bone-metal contact than controls. Instability-induced bone resorption therefore seems to be reduced by bisphosphonates, but higher doses are needed to obtain this effect than to reduce bone resorption associated with normal remodeling of untraumatized bone.

Alendronate↗