Magnus Tägil

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.

Outcomes of Proximal Interphalangeal Joint Pyrocarbon Implants

PURPOSE To prospectively register and report the hand function and occupational performance of patients with proximal interphalangeal joint-pyrocarbon arthroplasty, using both objective tests and subjective outcome instruments. METHODS From 2004 to 2008, 53 joints in 43 patients were reconstructed with a proximal interphalangeal joint-pyrocarbon prosthesis. The patients underwent a rehabilitation program allowing early motion with an extension stop to limit hyperextension. Range of motion, grip strength, and pain (Visual Analog Scale [VAS]) were recorded and the subjective outcome was evaluated using Canadian Occupational Performance Measure (COPM) and Disabilities of the Arm, Shoulder, and Hand score. RESULTS Seven patients were reoperated on (2 infections, 2 arthrodesis, 2 tenolysis, and 1 hyperextension). Pain (VAS) at rest improved from 3.1 cm preoperatively to 0.4 cm (p < .001) and pain (VAS) at activity from 6.2 to 2.0 cm (p < .001) at the latest follow-up (mean, 24 months; minimum, 12 months [+/- 2 weeks]). Disabilities of the Arm, Shoulder, and Hand score improved from a median of 39 to 29 (p = .026). The COPM subjective measurement of occupational performance, improved from a median of 4.6 preoperatively to 5.9 (p = .013) at the latest follow-up, and the COPM, measurement of satisfaction improved from a median of 3.8 to 5.9 (p = .002). Range of motion and grip strength were unchanged. CONCLUSIONS All patients reported decreased pain, and although we found no improvement in range of motion and grip strength, one third of patients reported a clinically significant improvement in occupational performance and satisfaction. A total of 13% of the joints required a secondary surgical procedure. TYPE OF STUDY/LEVEL OF EVIDENCE Therapeutic IV.

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

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 (Höstner et al. 2000). Bisphosphonates inactivate osteoclasts and can be used to increase allograft bone density after incorporation (Aspenberg and Åstrand 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.

Nonoperative treatment of Achilles tendon rupture: 196 consecutive patients with a 7% re-rupture rate.

Background The best treatment for acute Achilles tendon rupture is unknown. Patients and methods We assessed the outcome of nonoperative treatment in 196 consecutive individuals with an acute total Achilles tendon rupture who were followed until healing. The mean duration of treatment in cast or orthosis was 8 weeks. After 4 years, a questionnaire was sent to all patients who were still alive (182) to supplement and confirm the retrospective data. The questionnaire was completed by 176/182 patients (97%). Results The re-rupture frequency was 7% (n = 14). 7 patients suffered other complications (7 deep venous thrombosis and 1 pulmonary embolism). At follow-up, 62% of the patients reported full recovery. Interpretation The low re-rupture rate after nonoperative treatment challenges the claim in recent studies that acute rupture of the Achilles tendon should be operated.

Intermittent PTH((1-34)) does not increase union rates in open rat femoral fractures and exhibits attenuated anabolic effects compared to closed fractures.

Intermittent Parathyroid Hormone (PTH)((1-34)) has an established place in osteoporosis treatment, but also shows promising results in models of bone repair. Previous studies have been dominated by closed fracture models, where union is certain. One of the major clinical needs for anabolic therapies is the treatment of open and high energy fractures at risk of non-union. In the present study we therefore compared PTH((1-34)) treatment in models of both open and closed fractures. 108 male Wistar rats were randomly assigned to undergo standardized closed fractures or open osteotomies with periosteal stripping. 27 rats in each group were treated s.c. with PTH((1-34)) at a dose of 50 mug/kg 5 days a week, the other 27 receiving saline. Specimens were harvested at 6 weeks for mechanical testing (n=17) or histological analysis (n=10). In closed fractures, union by any definition was 100% in both PTH((1-34)) and saline groups at 6 weeks. In open fractures, the union rate was significantly lower (p<0.05), regardless of treatment. In open fractures the mechanically defined union rate was 10/16 (63%) in saline and 11/17 (65%) in PTH((1-34)) treated fractures. By histology, the union rate was 3/9 (33%) with saline and 5/10 (50%) with PTH((1-34)). Radiological union was seen in 13/25 (52%) for saline and 15/26 (58%) with PTH((1-34)). Open fractures were associated with decreases in bone mineral content (BMC) and volumetric bone mineral density (vBMD) on quantitative computerized tomography (QCT) analysis compared to closed fractures. PTH((1-34)) treatment in both models led to significant increases in callus BMC and volume as well as trabecular bone volume/total volume (BV/TV), as assessed histologically (p<0.01). In closed fractures, PTH((1-34)) had a robust effect on callus size and strength, with a 60% increase in peak torque (p<0.05). In the open fractures that united and could be tested, PTH((1-34)) treatment also increased peak torque by 49% compared to saline (p<0.05). In conclusion, intermittent PTH((1-34)) produced significant increases in callus size and strength in closed fractures, but failed to increase the rate of union in an open fracture model. In the open fractures that did unite, a muted response to PTH was seen compared to closed fractures. Further research is required to determine if PTH((1-34)) is an appropriate anabolic treatment for open fractures.

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.

Incidence of physician-diagnosed carpal tunnel syndrome in the general population.

tween Insulin Sensitivity and Cardiovascular Risk (RISC) study. Diabetes Care. 2010;33(9):2090-2097. 8. Succurro E, Arturi F, Lugarà M, et al. One-hour postload plasma glucose levels are associated with kidney dysfunction. Clin J Am Soc Nephrol. 2010;5 (11):1922-1927. 9. Strandberg TE, Strandberg A, Rantanen K, Salomaa VV, Pitkälä K, Miettinen TA. Low cholesterol, mortality, and quality of life in old age during a 39-year follow-up. J Am Coll Cardiol. 2004;44(5):1002-1008.

Corroboration of mechanobiological simulations of tissue differentiation in an in vivo bone chamber using a lattice-modeling approach.

It is well established that the mechanical environment modulates tissue differentiation, and a number of mechanoregulatory theories for describing the process have been proposed. In this study, simulations of an in vivo bone chamber experiment were performed that allowed direct comparison with experimental data. A mechanoregulation theory for mesenchymal stem cell differentiation based on a combination of fluid flow and shear strain (computed using finite element analysis) was implemented to predict tissue differentiation inside mechanically controlled bone chambers inserted into rat tibae. To simulate cell activity, a lattice approach with stochastic cell migration, proliferation, and selected differentiation was adopted; because of its stochastic nature, each run of the simulation gave a somewhat different result. Simulations predicted the load‐dependency of the tissue differentiation inside the chamber and a qualitative agreement with histological data; however, the full variability found between specimens in the experiment could not be predicted by the mechanoregulation algorithm. This result raises the question whether tissue differentiation predictions can be linked to genetic variability in animal populations.

Open reduction and internal fixation compared to closed reduction and external fixation in distal radial fractures: A randomized study of 50 patients

Background and purpose In unstable distal radial fractures that are impossible to reduce or to maintain in reduced position, the treatment of choice is operation. The type of operation and the choice of implant, however, is a matter of discussion. Our aim was to investigate whether open reduction and internal fixation would produce a better result than traditional external fixation. Methods 50 patients with an unstable or comminute distal radius fracture were randomized to either closed reduction and bridging external fixation, or open reduction and internal fixation using the TriMed system. The primary outcome parameter was grip strength, but the patients were followed for 1 year with objective clinical assessment, subjective outcome using DASH, and radiographic examination. Results At 1 year postoperatively, grip strength was 90% (SD 16) of the uninjured side in the internal fixation group and 78% (17) in the external fixation group. Pronation/supination was 150° (15) in the internal fixation group and 136° (20) in the external fixation group at 1 year. There were no differences in DASH scores or in radiographic parameters. 5 patients in the external fixation group were reoperated due to malunion, as compared to 1 in the internal fixation group. 7 other cases were classified as radiographic malunion: 5 in the external fixation group and 2 in the internal fixation group. Interpretation Internal fixation gave better grip strength and a better range of motion at 1 year, and tended to have less malunions than external fixation. No difference could be found regarding subjective outcome.