Insertion of metal implants in bone is one of the commonest of all surgical procedures. The success of these operations is dependent on the fixation of the implants, which, in turn, depends on the strength of the bone that holds them. If the quality of the bone holding the implant could be improved locally, surgical procedures would become simpler and rehabilitation would become faster. Bisphosphonates are anti-resorptive drugs that act specifically on osteoclasts, thereby maintaining bone density and strength. Once released from the surface of a coated implant, bisphosphonates reduce osteoclast activity, thereby changing the balance of bone turnover in favor of bone formation, leading to a net gain in local bone density. During the last decades, the effects of bisphosphonate treatment on the stability of implants have been tested in several clinical and animal studies, but not in human jaws. This may be because it has been suggested that there is a link between the use of bisphosphonates (especially those given intravenously) and a condition called osteonecrosis of the jaw (ONJ). The pathophysiology and treatment of ONJ is controversial. The difficulty in treating ONJ has highlighted the importance of prevention.

The overall aim of the present thesis was to evaluate the effect of local and systemic use of bisphosphonates on bone tissue. Could a thin, bisphosphonate-eluting fibrinogen coating improve the fixation of metal implants in the human jaw? Would it be possible to reproduce ONJ and prevent the development of this condition in an animal model?

In two clinical studies, a total number of 96 implants were inserted in 21 patients. In a randomized trial with a paired design, one implant in each pair was coated with a thin fibrinogen layer containing two bisphosphonates (pamidronate and ibandronate). The bisphosphonate-coated implants showed better stability as measured by resonancefrequency analysis. Radiographic intraoral films also showed less bone loss. Three animal models were developed. In a study comparing local and systemic effects of bisphosphonates, zoledronate-coated screws inserted in rats showed better fixation in spite of a drug treatment that is known to induce ONJ-like lesions when given systemically. In another rat model, ONJ-like lesions were reproducibly induced at sites of tooth extraction whereas there were no signs of bone cell death in uninjured sites. Finally, rat experiments showed that the development of ONJ-like lesions after tooth extraction could be prevented by early mucoperiosteal coverage.

In conclusion, a thin, bisphosphonate-eluting fibrinogen coating can improve the fixation of dental implants in human bone. This may lead to new possibilities in orthopaedic surgery and dentistry. The pathophysiology of ONJ is strongly linked to bone exposure in combination with drugs that reduce resorption.

There is evidence for a link between the use of systemic bisphosphonates and osteonecrosis of the jaw (ONJ). This condition has the appearance of chronic osteomyelitis, and antibiotics prevent the development of ONJ in animal models. Clinically, ONJ can sometimes be successfully treated by mucoperiosteal coverage. If ONJ is indeed primarily caused by bacterial infection, immediate coverage of the extraction alveolus might reduce the risk of ONJ development in risk patients. Therefore, we studied whether immediate mucoperiosteal coverage after tooth extraction could prevent ONJ development in a rat model. Thirty rats were randomly allocated to three groups of 10. Group I (controls): extraction, no drug treatment; Group II (non-coverage): extraction, dexamethasone plus alendronate; Group III (coverage): dexamethasone plus alendronate, plus coverage by a mucoperiosteal flap. Rats were examined for macroscopic ONJ-like wounds after 2 weeks. All animals in the non-coverage group developed large ONJ-like changes. The coverage and control groups showed an intact overlying mucosa in all rats. Findings were confirmed with histology. Bisphosphonates and dexamethasone caused ONJ-like lesions after tooth extraction in a rat model. This was prevented by immediate mucoperiosteal coverage. The risk of ONJ in patients using bisphosphonates might be reduced by mucoperiosteal coverage after tooth extraction.

J Oral Pathol Med (2012) 41: 494499 Background: Bisphosphonate-related osteonecrosis of the jaw was first described to start with sterile osteocyte death, similar to osteonecrosis in other parts of the skeleton. The typical chronic osteomyelitis was thought to develop when the dead bone was exposed to the oral cavity. An alternative explanation would be that the chronic osteomyelitis is a result of a bisphosphonate-related inability of infected bony lesions to heal. We tested the hypothesis that primary osteocyte death is not necessary for the development of jaw osteonecrosis. Material and methods: Forty rats were randomly allocated to four groups of 10. All animals underwent unilateral molar extraction and received the following drug treatments: Group I, controls with no drug treatment; Group II, 200 mu g/kg per day alendronate; Groups III and IV, 200 mu g/kg per day alendronate and 1 mg/kg of dexamethasone. All rats were euthanized after 14 days. Presence of osteonecrosis was determined by clinical and histological observations for groups IIII. For group IV, osteocyte viability at the contralateral uninjured site was examined using lactate dehydrogenase histochemistry (LDH). Results: All animals in the alendronate plus dexamethasone groups developed large ONJ-like lesions. Lactate dehydrogenase staining showed viable osteocytes in the contralateral jaw with no tooth extraction. No signs of osteonecosis were seen in the other groups. Conclusion: Bisphosphonates and dexamethasone caused no osteocyte death in uninjured bone, but large ONJ-like lesions after tooth extraction. Osteonecrosis of the jaw appears to arise first after the bone has been exposed. Possibly, bisphosphonates hamper the necessary resorption of bone that has become altered because of infection.

Locally applied bisphosphonates may improve the fixation of metal implants in bone. However, systemic bisphosphonate treatment is associated with a risk of osteonecrosis of the jaw (ONJ). We hypothesized that local delivery of bisphosphonate from the implant surface improves the fixation of dental implants without complications in a setting where systemic treatment induces ONJ. Forty rats were randomly allocated to 4 groups of 10. All groups received a titanium implant inserted in an extraction socket. Group I received the implants only. Group II received dexamethasone (0.5 mg/kg). Group III received dexamethasone as above plus alendronate (200 µg/kg). Group IV received zoledronate-coated implants and dexamethasone as above. The animals were sacrificed 2 weeks after tooth extraction. All 10 animals with systemic alendronate treatment developed large ONJ-like changes, while all with local treatment were completely healed. Implant removal torque was higher for the bisphosphonate-coated implants compared with the other groups (p < 0.03 for each comparison). Micro-computed tomography of the maxilla showed more bone loss in the systemic alendronate group compared with groups receiving local treatment (p = 0.001). Local bisphosphonate treatment appears to improve implant fixation in a setting where systemic treatment caused ONJ.

Many surgical procedures use metal implants in bone. The clinical results depend on the strength of the bone holding these implants. Our objective was to show that a drug released from the implant surface can improve parameters reflecting the quality or amount of this bone. Sixteen patients received paired dental titanium implants in the maxilla, in a randomized, double-blinded fashion. One implant in each pair was coated with a thin fibrinogen layer containing 2 bisphosphonates. The other implant was untreated. Fixation was evaluated by measurement of resonance frequency (implant stability quotient; ISQ) serving as a proxy for stiffness of the implant-bone construct. Increase in ISQ at 6 months of follow-up was the primary variable. None of the patients had any complications. The resonance frequency increased 6.9 ISQ units more for the coated implants (p = 0.0001; Cohens d = 1.3). The average difference in increase in ISQ and the effect size, suggested a clinically relevant improvement. X-ray showed less bone resorption at the margin of the implant both at 2 months (p = 0.012) and at 6 months (p = 0.012). In conclusion, a thin, bisphosphonate-eluting fibrinogen coating might improve the fixation of metal implants in human bone. This might lead to new possibilities for orthopedic surgery in osteoporotic bone and for dental implants.

This study comprising 6 separate papers is concerned with the treatment of patients with acute anterior cruciate ligament (ACL) injury. The aim was to compare primary surgical and non-surgical ACL treatment. Treatment was, therefore, instituted at random in all consecutive patients (n = 293) with ACL injury.

Initially all patients were investigated by arthroscopy and examined under anesthesia.

After 4 years patients treated by ACL repair with combined intraarticular and extraarticular augmentation had a better stability, fewer knee symptoms and a higher level of activity than patients treated by nonaugmented ACL repair or by repair of the associated injuries alone. The patients in the latter group commonly developed instability symptoms and ACL reconstruction was required in 20"7o ofthem. Also they frequently had subsequent meniscal injuries, and an impaired knee function at one-leg-hop tests for distance. Running tests, however, was not correlated to ACL treatment.

Another group of patients with acute ACL injury did not have any primary ligamentous repair. At one year 200Jo of the patients needed reconstructive surgery. Moreover, anteriorposterior laxity at one year was increased compared to the initial measurements. The greatest initial laxity was found in patients with an associated tear of the medial collateral ligament (MCL). The patients with combined ACL and MCL injuries had the worst prognosis.

In patients with combined injuries who had primary repair of grade 2-3 MCL tears the outcome was similar as for patients with isolated ACL lesion.

A simple device for static measurements of anterior-posterior knee displacement was valuable for evaluating the results of ACL treatment. lt can also be used as an aid in the diagnosis of acute knee injury.

Growth Hormone stimulates bone growth and fracture repair. It acts mainly by increasing the systemic levels of IGF-1. Local treatment with IGF-1 appears to stimulate tendon healing. We therefore hypothesized that systemic treatment with Growth Hormone would also stimulate tendon healing. Rat Achilles tendons were transected and left to heal. 4 groups were studied. Intramuscular injections of botulinum toxin A (Botox) were used to reduce loading in 2 groups. The animals were randomized to twice daily injections of Growth Hormone (n=2×10) or saline (n=2×10), and killed after 10 days. Healing was assessed by mechanical testing. Muscle paralysis induced by Botox reduced the strength of the healing tendon by two thirds. Growth Hormone increased femoral and tibial length in the unloaded, and femoral and tibial weight in the loaded group. Body weight and muscle weight were increased in both. In contrast, there was no increase in the strength of the healing tendons, regardless of mechanical loading status. An increase in peak force of the loaded healing tendons by more than 5% could be excluded with 95% confidence. In spite of its stimulatory effects on other tissues, Growth Hormone did not appear to stimulate tendon or tendon repair.

Treatment of tendon injuries often involves immobilization. However, immobilization might not prevent mild involuntary isometric muscle contraction. The effect of weak forces on tendon healing is therefore of clinical interest. Studies of tendon healing with various methods for load reduction in rat Achilles tendon models show a consistent reduction in tendon strength by at least half, compared with voluntary cage activity. Unloading was not complete in any of these models, and the healing tendon was therefore still exposed to mild mechanical stimulation. By reducing the forces acting on the tendon even further, we now studied the effects of this mild stimulation. Rat Achilles tendons were transected and allowed to heal spontaneously under four different loading conditions: 1) normal cage activity; 2) calf muscle paralysis induced by botulinum toxin A (Botox); 3) tail suspension; 4) Botox and tail suspension, combined, to eliminate even mild stimulation. Healing was evaluated by mechanical testing after 8 days. Botox alone and suspension alone both reduced tendon callus size (transverse area), thereby impairing its strength compared with normal cage activity. The combination of Botox and suspension did not further reduce tendon callus size but drastically impaired the material properties of the tendon callus compared with each treatment alone. The peak force was only a fifth of that in the normal cage activity group. The results indicate that also the mild loading that occurs with either Botox or suspension alone stimulates tendon healing. This stimulation appears to affect mainly tissue quality, whereas stronger stimulation also increases callus size.

This annotation describes some early rat studies which conclude that parathyroid hormone (PTH) has more dramatic stimulatory effects on bone repair than on untraumatized bone. It also suggests, based on the effects of PTH on osteoblasts, that it is more likely to accelerate normal fracture healing than to prevent nonunion. The only 2 controlled clinical trials that have been published are critically discussed. Although both are encouraging and appear to show acceleration of normal fracture healing, they have methodological shortcomings that preclude definitive conclusions.

Based on their mode of action and preclinical data, one would expect bisphosphonates to improve the healing of fractures in cancellous bone, and bone morphogenetic proteins (BMPs) to reduce the risk of non-union in severe shaft fractures. Parathyreoid hormone (PTH) can be expected to accelerate fracture healing in general. The clinical data in support of this is meager. Stimulation of cancellous bone healing and strength by bisphosphonates has been inadvertently shown in the context of implant fixation, but not convincingly in fractures per se. The clinical BMP literature is confusing, and the chance of ever demonstrating reduced numbers of non-union are small, due to power issues. Still, acceleration of 'normal' healing may be possible, but largely remains to show. For PTH, the two available clinical trials both show accelerated healing, but none of them is flawless, and there is a need for better studies.

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The primary aim of this study was to evaluate the effect of two different surgical methods on nutritional status and functional capacity during the first postoperative year in patients with displaced femoral neck fractures. A further aim was to evaluate the effect of nutritional support. One hundred patients were randomly assigned to treatment with either primary total hip arthroplasty (THA) or osteosynthesis. Half of the patients in each treatment group received protein- and energy-enriched food in the hospital in addition to individual nutritional advice in order to optimize their intake of protein- and energy-rich food. Nutritional state and functional capacity were examined at baseline, one and three months, and one year after the operation. Pain was examined at three months and one year. The effect of nutritional intervention was equal within both surgical groups. Logistic regression showed that the dependent variable "living at one year" was significantly associated with serum albumin levels at one month. Advanced age, mental impairment and deteriorated nutritional status were predominant in the non-survivors. Overall, the primary THA group performed better compared with the osteosynthesis group concerning weight change over time, locomotion and pain. This study also showed that primary THA could safely be performed in the elderly without an increased postoperative mortality rate.

Shoulder pain is very common, affecting 14-21 % of the population at some time during their lifetime. The aims of this thesis were to improve the understanding of various aspects concerning the pathogenesis and treatment of subacromial pain and rotator cuff tears. Patients and healthy individuals were examined and compared in five studies:

Study I) Seventy patients were retrospectively examined, clinically and with ultrasound, 15 years after arthroscopic subacromial decompression. All patients had an intact rotator cuff at surgery. Ultrasound showed significantly fewer rotator cuff tears compared to the prevalence of asymptomatic tears reported in the literature for the same age group. This indicates that arthroscopic subacromial decompression might protect the rotator cuff.

Study II) Forty-two patients were retrospectively examined, clinically and with ultrasound, 39 months (mean) after an acute rotator cuff repair. All patients had pseudoparalysis after trauma, a full thickness tear and no previous history of shoulder symptoms. A delay in surgical treatment of three months and the number of tendons injured did not affect the outcome. Age affected outcome negatively.

Study III) Plasma samples from 17 patients with cuff tears and 16 plasma samples from healthy age- and gender-matched controls were collected and analysed regarding the levels of matrix metalloproteinases and their inhibitors, TIMP1-4. Elevated levels of TIMP-1 were found in the patients with cuff tears compared to controls. Higher levels of TIMP-1, TIMP-3 and MMP-9 were found in patients with full-thickness tears compared to patients with partial-thickness tears.

Study IV) Ninety-seven patients with longstanding subacromial pain, on the waiting-list for arthroscopic subacromial decompression, were prospectively randomised to specific shoulder exercises or control exercises for three months. Thereafter they were clinically examined and asked if they still wanted surgery. The specific shoulder exercises focusing on eccentric exercise for the rotator cuff and scapula stabilisers were found to be effective in reducing subacromial pain and improving shoulder function, thereby reducing the need for surgery.

Study V) All patients including those operated, in Study IV were re-examined after one year using clinical assessment scores. The option of surgery was continuously available up to the one-year follow-up. Ultrasound and radiological examinations performed at inclusion were analysed in relation to the choice of surgery. The positive effects of the specific exercise programme were maintained after one year and significantly fewer patients in this group chose surgery. Surgery was significantly more often chosen by patients who had a low baseline shoulder score, and/or a full thickness rotator cuff tear.  All patients showed significant improvement in the clinical scores one year after inclusion or one year after surgery.

These results support the concept that subacromial pain has a multifactorial aetiology and that the first line of treatment should be specific shoulder exercises. When conservative treatment fails, an acceptable result can be achieved with arthroscopic subacromial decompression. The rotator cuff status is important to consider when treating and studying these patients.

Background and purpose:Extracellular matrix remodelling is altered in rotator cuff tears,16partly due to altered expression of matrix metalloproteinases (MMPs) and their inhibitors. It is unclear if this altered expression can be traced as changes in plasma protein levels.

The purposes were to measure the plasma level of MMPs and their tissue inhibitors (TIMPs) inpatients with rotator cuff tears and to relate changes in the pattern of MMP and TIMP levels with the extent of the rotator cuff tear.

Methods: Blood samples were collected from 17 patients, median 61 (range 39-77) years, with sonographically verified rotator cuff tears (partial- or full-thickness). These were compared with 16 gender and age matched control persons with sonographically intact rotator cuffs. Plasma levels of MMPs and TIMPs were measured simultaneously using Luminex technology and ELISA.

Results: The plasma level of TIMP-1 was elevated in patients with rotator cuff tears, especially in those with full-thickness tears. The levels of TIMP-1, TIMP-3 and MMP-9 were higher in patients with full-thickness tears compared to those with partial-thickness tears, but only TIMP-1 was different from controls.

Interpretation: The observed elevation of TIMP-1 in plasma might reflect local pathological processes in or around the rotator cuff, or a genetic predisposition in these patients. That levels of TIMP-1 and certain MMP´s was found to differ between partial and full thickness tears may reflect the extent of the lesion or different aetiology and pathomechanisms.

Background: A specific exercise strategy focusing on eccentric exercises, for treating sbacromial pain has in a previous study been found effective at three-month followup.

The aim of the present study was to investigate if the positive short-term results were maintained after one year. A further aim was to examine if baseline clinical score, rotator cuff status and radiological findings influenced the choice of surgery.

Methods: 97 patients on the waiting-list for arthroscopic subacromial decompression were in the first study randomized to a three-month specific exercise strategy or unspecific exercises (controls). Patients were examined with radiology, ultrasound and assessed with clinical scores: primary Constant-Murley score. After three months of exercises the patients were asked if they still wanted surgery and this option was available until the one-year follow-up. All patients were re-assessed with clinical scores one year after inclusion or one year after surgical intervention and the number of patients that had chosen surgery in each group was compared. The baseline Constant-Murley score and the status of subacromial structures were analyzed in relation to patient's choice of surgery.

Results: The positive short-term effect (improved shoulder function and pain) of the specific exercises was maintained after one-year. Compared to the three-month followup all patients had improved significantly (p < 0.0001) in Constant-Murley score. The number of patients that had chosen surgery in the control exercise group (63%) was significantly larger (p < 0.0001) than in the specific exercise group (24%). Patients that had chosen surgery had a significantly lower baseline Constant-Murley score and significantly more often a full-thickness tear. Patients with partial-thickness tears did not differ from those with intact cuff tendons.

Conclusions: The positive short-term outcomes after specific exercises were maintained after one year and reduced the need of surgery significantly more than the unspecific control exercises. Patients with low baseline clinical score and/or a full-thickness tear significantly more often chose surgery.

Level of evidence: I, Randomized controlled trail according to Consort statement.

Background and purpose Few authors have considered the outcome after acute traumatic rotator cuff tears in previously asymptomatic patients. We investigated whether delay of surgery, age at repair, and the number of cuff tendons involved affect the structural and clinical outcome. Patients and methods 42 patients with pseudoparalysis after trauma and no previous history of shoulder symptoms were included. A full-thickness tear in at least 1 of the rotator cuff tendons was diagnosed in all patients. Mean time to surgery was 38 (6-91) days. Follow-up at a mean of 39 (12-108) months after surgery included ultrasound, plain radiographs, Constant-Murley score, DASH score, and western Ontario rotator cuff (WORC) score. Results At follow-up, 4 patients had a full-thickness tear and 9 had a partial-thickness tear in the repaired shoulder. No correlation between the structural or clinical outcome and the time to repair within 3 months was found. The patients with a tendon defect at follow-up had a statistically significantly lower Constant-Murley score and WORC index in the injured shoulder and were significantly older than those with intact tendons. The outcomes were similar irrespective of the number of tendons repaired. Interpretation A delay of 3 months to repair had no effect on outcome. The patients with cuff defects at follow-up were older and they had a worse clinical outcome. Multi-tendon injury did not generate worse outcomes than single-tendon tears at follow-up.

The problems associated with the management of proximal femoral fractures gain more attention as the elderly population continue to increase. It has been estimated that the total number of hip fractures in the world will increase from 1.7 million per year in 1990 to 6.3 million per year in 2050 (Cooper et al 1992). Operative treatment of these fractures is a challenge for the orthopaedic surgeon mainly due to poor bone quality, which increases the risk of fixation failure.

More than 50% of the total number of hip fractures are extracapsular fractures. Mortality, morbidity and costs as a result of trochanteric fracture are higher than those for a cervical fracture. The consequence is increased resource consumption in the national health-care system. The estimated total cost of treatment increase 3-fold in case of a complication. Therefore, a variety of different devices have been designed in order to decrease the ratio of complications. However, in spite of this, the reported ratio of fixation failure continues be high and may reach 25% following treatment of unstable trochanteric fractures. We evaluated a new type of fixation device, the RAB-plate (Rigidity Augmentation Baixauli), for the treatment of unstable trochanteric hip fractures. The RAB-plate is a fixed 120-degree angle blade-plate with a buttress rod.

We performed three clinical trials where 391 unstable trochanteric fractures were stabilised with the RAB-plate or a Sliding Hip Screw (SHS). The results showed a statistically significant lower number of complications in fractures stabilised with the RAB-plate.

The fatigue resistance of the RAB-plate was evaluated in a cyclic loading test model. The RAB-plate had a statistically significant higher fatigue strength than two different designs of the SHS.

Stability of the fixation and modes of failure were radiographically analysed in a series of 218 unstable trochanteric fractures treated with the RAB-plate or the SHS. The RAB-plate provided a more stable fixation especially with regard to maintained postoperative alignment. However, positive predictors for fixation failure e.g.implant position within the femoral head, varus reduction in anteroposterior projection and screw/neck angle deviation in the lateral projection were identical for both devices.

Spontaneous femoral neck fracture after removal of the fixation device in healed unstable trochanteric fractures was investigated in a series of 7 patients. Our results indicate that implant-induced osteoporosis (stress protection) is a possible cause of subsequent fracture.

Our conclusions are that the RAB-plate is a safe implant for fixation of unstable trochanteric hip fractures and results in lower incidence of complications compared to SHS. Therefore, the RAB can be recommended for fixation of unstable trochanteric fractures.

Background: The sliding hip screw has gained considerable acceptance in the treatment of unstable trochanteric fractures. However, the new type of 120 degrees fixed angle blade-plate with a buttress rod (RAB-plate) showed encouraging clinical results. The purpose of this study was to assess stability of fixation and analyze modes of failure in unstable trochanteric hip fractures treated with these devices.

Methods: A retrospective radiographic review of 218 unstable fractures was performed. Linear and angular displacements of the major fragments and implant migration into the femoral head during healing were assessed. Additionally, adequacy of the reduction and the location of the implant within the femoral head as predictors of fixation failure were evaluated.

Results: The postreduction neck-shaft angle was maintained in the majority of the fractures in both groups. However, there was a significantly higher incidence of varus angulation by 10 degrees or more by the completion of healing among fractures treated with the sliding hip screw (p = 0.04). There was no statistically significant difference in vertical migration of the device into the femoral head between the implants used (p = 0.3). There was a significant relationship between failure of the fixation and varus reduction (p = 0.04) as well as screw/neck angle deviation more than 20 degrees in the lateral projection (p = 0.005) or if the implant was in a superior or posterior position (p = 0.02).

Conclusion: The RAB-plate provided a more stable fixation, especially with regard to maintained postoperative alignment. However, positive predictors for fixation failure were identical for both devices. Here, the screw/neck angle deviation has had the strongest significance for prediction of fixation failure.

Between January 199 5 and January 1997 138 unstable trochanteric hip  fractures were prospectively randomized to treatment with a fixed angle blade plate with a buttress rod (RAB-plate, group A, n= 59) or a 135° two-way compression hip screw (Medoff sliding plate, group B, n= 79). The minimum follow-up time was 1-year. 44 (91 %) fractures in group A and 32 (46%) fractures in group B healed without any complication (p<0.0001). The ratio of technical failure was 4% in group A and 10% in group B (p=O.S). The most common complication in group B was significant and symptomatic leg-length shortening which was observed in 26 patients. No such complication was registered in group A.

Two hundred thirty-three patients with an unstable trochanteric hip fracture were randomized prospectively for stabilization with a fixed angle blade plate or a compression hip screw. Twenty patients had the implant removed after the fracture was healed (average, 20.5 months; range, 12-42 months). In seven of these 20 patients, a spontaneous fracture of the femoral neck occurred at an average of 19 days after implant removal. Four of the these seven patients had been treated with the fixed angle blade plate and three with the sliding screw plate. The histologic examination of three specimens was inconclusive. The authors have not observed subcapital fracture among patients whose implants were not removed. The mechanism behind this complication is unknown.

The fatigue resistance of a new type of flxation device for the treatment  of unstable trochanteric fractures of the hip was determined. The new device (RAB-plate= Rigidity Augmentation Baixauli) is designed as a fixed, cannulated, 120 degrees angled blade plate with a buttress rod for support of the proximal, lower surface of the blade. A cyclic loading of four times body weight of a 65 kg person was used. Two types of 135 degrees compression hip screw were tested for comparison. The RAB-plate had a significantly higher fatigue resistance than the compared hip screw plates (p< 0,02 and p< 0,01; respectively).

We prospectively randomized 233 patients with unstable trochanteric hip fractures for treatment with a 120° fixed angle blade-plate having a buttress rod (group A, n 111) or a 135° compression hip screw (group B, n 122). the minimum follow-up time was 1 year. the ratio of technical failure was 9% in group A and 19% in group B (p = 0.06). 79 (87%) fractures in group A and 65 (68%) fractures in group B healed without any complication (p = 0.003). Malunion occurred in 2 cases in group A and in 15 cases in group B (p = 0.002).

Measurements of microvascular blood flow in skeletal muscle by using the laser Doppler flowmetry (LDF) technique were first reported in 1979. The introduction of the single fibre technique in 1987 increased the possibilities of studying muscle perfusion under various physiological conditions without causing major tissue trauma.

On-line processing of the LDF- and rms-EMG-signals made possible interpretation of the relationship between the perfusion and the activity of the muscle. Percutaneous single fibre LDF and bipolar surface electromyography (EMG) of the upper portion of trapezius muscle were performed continuously during a 10-minute long series of alternating periods of static contractions and rest, each of a one-minute duration. Regression analyses showed positive correlation between LDF and rms-EMG, as well as LDF and degree of arm elevation. Microcirculation in the trapezius muscle and the supraspinatus were measured simultaneously by continuous LDF during stepwise increased contractions related to the EMG too. Blood flow increased significantly in both muscles during increased shoulder torque. The blood flow in the trapezius muscle increased significantly at increased rms-EMG. But, no significant increase in muscle blood flow occurred in the supraspinatus muscle which thus seems to be more prone to develop ischemia during strenuous static work.

A PC-based signal processor with a digital signal processing board was developed for evaluation of the different fibre tips' optic characters and laser Doppler algorithm, as well as for presentation of the laser Doppler measurement results. The Doppler signal power spectral density and corresponding flux values were visualized on the computer screen continuously in real-time. The single fibre technique has been further developed with the aim of improving the signal quality by modifying the geometry of the fibre tip and increasing the light wavelength, since the small monitored tissue volume in the muscle tissue by single fibre LDF is its drawback. The modified fibre tips, sphere and "pear" type, probes showed a higher flow sensitivity than did the flat end type. An infrared  laser diode with the wavelength of 750 nm was used in the new optical module. These improvements were interpreted as being related mostly to a larger, strongly irradiated tissue volume in front of the fibre. The results were evaluated theoretically with ray tracing simulations and experimentally with the mechanical and flow models. The modified fibre with the new signal processor for monitoring blood flow has been successfully used in intramuscular measurements.

Mechanical loading stimulates tendon healing via mechanisms that are largely unknown. Genes will be differently regulated in loaded healing tendons, compared to unloaded, just because of the fact that healing processes have been changed. In order to avoid such secondary effects and study the effect of loading per se, we therefore studied the gene expression response shortly after a single loading episode in otherwise unloaded healing tendons.

The Achilles tendon was transected in 30 tail suspended rats. The animals were let down from the suspension to load their tendons on a treadmill for 30 min once, 5 days after tendon transection. Gene expression was studied by Affymetrix microarray before, and 3, 12, 24 and 48 h after loading. The strongest response in gene expression was seen 3 hours after loading, when 150 genes were up- or down-regulated (fold change≥ 2, p≤0.05). 12 hours after loading, only 3 genes were up-regulated, while 38 were down-regulated. Less than 7 genes were regulated after 24 and 48 hours. Genes involved in the inflammatory response were strongly regulated at 3 and 12 hours after loading; this included up-regulation of iNOS, PGE synthase, and IL-1β. Also genes involved in wound healing/coagulation, angiogenesis and production of reactive oxygen species were strongly regulated by loading. Microarray results were confirmed for 14 selected genes in a repeat experiment (N=30 rats) using real-time PCR. It was also confirmed that a single loading episode on day 5 increased the strength of the healing tendon on day 12. The fact that there were hardly any regulated genes 24 h after loading suggests that optimal stimulation of healing requires a mechanical loading stimulus every day.

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Enhancing the quantity and quality of cancellous bone with anabolic pharmacologic agents may lead to more successful outcomes of non-cemented joint replacements. Using a novel rabbit model of cancellous bone loading, we examined two specific questions regarding bone formation at the bone-implant interface: (1) does the administration of intermittent PTH, a potent anabolic agent, and mechanical loading individually and combined enhance the pen-implant cancellous bone volume fraction; and, (2) does surgical trauma enhance the anabolic effect of PTH on pen-implant bone volume fraction. In this model, PTH enhanced pen-implant bone volume fraction by 30% in loaded bone, while mechanical loading alone increased bone volume fraction modestly (+10%). Combined mechanical loading and PTH treatment had no synergistic effect on any cancellous parameters. However, a strong combined effect was found in bone volume fraction with combined surgery and PTH treatment (+34%) compared to intact control limbs. Adaptive changes in the cancellous bone tissue included increased ultimate stress and enhanced remodeling activity. The number of proliferative osteoblasts increased as did their expression of pro-collagen 1 and PTH receptor 1, and the number of TRAP positive osteoclasts also increased. In summary, both loading and intermittent PTH treatment enhanced pen-implant bone volume, and surgery and PTH treatment had a strong combined effect This finding is of clinical importance since enhancing early osseointegration in the post-surgical period has numerous potential benefits.

Reliable measurements of spinal deformities in idiopathic scoliosis are vital, since they are used for assessing the degree of scoliosis, deciding upon treatment and monitoring the progression of the disease. However, commonly used two dimensional methods (e.g. the Cobb angle) do not fully capture the three dimensional deformity at hand in scoliosis, of which axial vertebral rotation (AVR) is considered to be of great importance. There are manual methods for measuring the AVR, but they are often time-consuming and related with a high intra- and inter-observer variability. In this paper, we present a fully automatic method for estimating the AVR in images from computed tomography. The proposed method is evaluated on four scoliotic patients with 17 vertebrae each and compared with manual measurements performed by three observers using the standard method by Aaro-Dahlborn. The comparison shows that the difference in measured AVR between automatic and manual measurements are on the same level as the inter-observer difference. This is further supported by a high intraclass correlation coefficient (0.971-0.979), obtained when comparing the automatic measurements with the manual measurements of each observer. Hence, the provided results and the computational performance, only requiring approximately 10 to 15 s for processing an entire volume, demonstrate the potential clinical value of the proposed method.

Traditionally, the success of treatment after anterior cruciate ligament (ACL) injury has been judged from the recovery of muscle strength and knee range of motion (ROM), but also from the static knee stability after ACL reconstruction. However, since the sensory role of the ACL and surrounding tissues for the functional stability of the knee has been documented, the measurement of proprioceptive function related to knee stability is likely to become important in this evaluation.

The main purpose of this thesis was to critically examine some generally accepted principles in the treatment after ACL injury and in the way the outcome of this treatment is judged. In addition, we introduce a dynamic posturography system in order to functionally assess the peripheral contribution to postural control in patients with a chronic ACL insufficiency and in patients after ACL reconstruction.

The hypothesis tested was that dynamic measurement of anterior-posterior (AlP) laxity would be of greater value than the currently used measurement of static AlP laxity for assessing the result of ACL reconstruction and that these measurements could also be used for selection of rehabilitation exercises. We found that open kinetic chain exercises provoked larger sagittal plane translation than closed kinetic chain exercises and therefore should be avoided in early ACL rehabilitation. The present study furthermore shows that dynamic laxity measurements may be clinically useful to identify ACL injured patients, who are unable to limit the anterior translation of tibia during dynamic exercise.

A prospective randomized comparison in patients after ACL reconstruction did not reveal any differences with respect to ROM, static total AlP laxity and subjective knee score and activity level between patients postoperatively treated with an early ROM training and patients treated with five weeks immobilization in plaster. On the contrary, at the 2-year follow-up, the strength deficit in the hamstring and quadriceps muscles tended to be larger in the early ROM trained than in the plaster group (p<0.05 for hamstrings and p=0.07 for quadriceps), possibly related to the greater need for involvement of the physical therapist in the plaster group.

It was found that still several years after injury, non-operated ACL injured patients had a significantly greater body sway while standing on the injured limb but also on the uninjured limb on a stable surface. Furthermore, the measurements during perturbations in the sagittal plane showed a longer reaction time and a greater sway amplitude in the single-limb stance among patients than among c:ontrols, with no difference between the injured and the uninjured leg. On the other hand, following ACL reconstruction most measurements of postural control were not different in patients than in controls (36 months postoperatively). The normalization of postural control as well as in subjective knee score and activity level occurred in spite of the total sagittal laxity being significantly higher in the ACL reconstructed knee than in the uninjured knee and in the control group. However, the patients still had significantly longer reaction times for the postural responses to perturbations forwards and backwards, with no difference between the patients' ACL reconstructed and healthy leg. The impaired postural control in ACL deficient patients both while standing on the injured limb and on the uninjured limb, as well as the lack of correlation between the measured laxity of the reconstructed knee and any of the variables in perturbations provide evidence that rehabilitation with proprioceptive and agility training is an important part of the treatment to condition the dynamic restraints and thus improve the functional stability in the ACL reconstructed knee.

Shoulder pain and disability are common clinical problems. One major cause is subacromial inflammation and impingement of the supraspinatus tendon. These patients are usually offered conservative treatment or arthroscopic subacromial decompression (ASD). However, in some patients pain and a deficient shoulder function persist in spite of conservative and surgical treatment. This reflects the fact that the pathophysiology of this important disease is not fully understood. The general aim of the present thesis was to generate new lmowledge contributing to the understanding of subacromial inflammation through a combination of clinical and experimental studies.

Ketoprofen is a non-steroid antiinflammatory drug with effects on peripherally as well as centrally generated pain. In a randomized, double-blind, prospective study on impingement patients treated with ASD, postoperative administration of ketoprofen showed short-term, but not long-term positive effects on pain, range of movement and satisfaction.

The status of the rotator cuff was found not to influence the postoperative results after ASD. Patients with an intact, partially ruptured or totally ruptured (<2cm) supraspinatus tendon did equally well, both 3 and 6 years after surgery. The results suggest that the presence of an inflamed bursa is more important for the symptoms than the cuff lesion.

In search for an experimental model we found that the shoulder region of the rat shows macroanatomical similarities to the human shoulder. Analysis of the innervation of the rat shoulder showed that the suprascapular nerve and some branches projecting to the subacromial space contain numerous C- and Ao-fibers. Many of these appeared to be polymodally nociceptive units or postganglionic sympathetic units as revealed by capsaicin and chemical sympathectomy. Such fibers are relevant for inflanunatory states.

In the normal rat substance P- (SP), calcitonin gene-related peptide- (CGRP) immunoreactive putative nociceptive fibers and neuropeptide Y- (NPY) and tyrosine hydroxylase- (TH) immunoreactive putative sympathetic fibers were widely distributed in the subacromial space. After induction of an acute subacromial inflammation with carrageenan, the presence of SP- and/or CGRP-immunoreactive fibers in the supraspinatus tendon was increased, with a maximum at two weeks. The results of labeling with the growth-associated protein GAP-43 indicated a de novo sprouting of nociceptive fibers in the tendon. But, radioimmunoassay measurements showed that the content of SP, CGRP and NPY in the supraspinatus tendon were normal or subnormal.

These results called for examination of subacromial tissue biopsies from  impingement patients. Innnunohistochemical analysis showed an increase of SP- and/or CGRP- immunoreactive nerve fibers and of NPY-immunoreactive nerve fibers in tendon tissue. The presence of corresponding neuropeptides was also elevated, as determined by RIA. The analysis also revealed an increase of SP and/or CGRP-immunoreactive nerve fibers and an elevated concentration of corresponding neuropeptides in bursal tissue.

6 patients with symptomatic nonunion of midsnait clavicular fractures were treated by internal fixation with an intramedullary cancellous screw and autologous cancellous bone grafting.

At follow-up after median 21 (12–72) months, all nonunions had healed. The Constant score was median 98 (57–100) points. 1 patient, with shortening of the clavicle, had poor function.

The purpose of the study was to evaluate the clinical effect of ketoprofen after arthroscopic subacromial decompression (ASD). The design was randomized, prospective, and double-blind, with a placebo control group. Forty-one consecutive patients with subacromial impingement syndrome, were randomized to treatment with ketoprofen 200 mg once daily or placebo for 6 weeks following ASD. For additional analgesia, patients used paracetamol if necessary. Clinical follow-up was performed at 6 weeks and at 2 years postoperatively. At the 6-week follow-up, the patients treated with ketoprofen had a statistically significant increase in UCLA total score (P < .05), range of movement (P < .05), and satisfaction (P < .05), and they had significantly less pain (P < .05). There was no statistical difference between the ketoprofen and placebo groups regarding strength. Patients receiving ketoprofen had significantly less need for additional analgesia (P < .05). At the 2-year follow-up, there were no differences in the scores between the ketoprofen and placebo group.

Inflammation activates nociceptive nerve endings and can elicit local sprouting of axons. We hypothesized that axon sprouting might be one factor behind the emergence of painful inflammatory conditions in the shoulder. Here we examine the distribution of sensory and sympathetic axons in the rat subacromial space under normal conditions and after local induction of inflammation with carrageenan. Furthermore, we measured the neuropeptide content in the supraspinatus tendon. In normal rats protein gene product 9.5- (POP 9.5-), substance P- (SP-), calcitonin gene related peptide- (CGRP-), neuropeptide Y- (NPY-) and tyrosine hydroxylase- (TH-) like immunoreactive (LI) axon profiles occurred in the subacromial space and around the glenohumeral joint. In the supraspinatus tendon axon profiles were limited to the tendon-muscle junction. After carrageenan injection inflammatory cells invaded the tendon and the subacromial bursa with a maximum at 2-3 weeks. Moreover, the tendon and the bursa showed signs of sprouting of PGP-9.5-, SP- and CGRP-LI axons, but not NPY- and TH-LI axons. The tendon was also invaded by blood vessels. The occurrence of axon profiles had a maximum at 2 weeks after injection and then subsided. Also, these axons were GAP-43-LI indicating collateral sprouting of nociceptive nerve fibres. There was no significant increase in the concentration of the neuropeptides SP and CGRP in the supraspinatus tendon. No inflammatory reaction or sprouting of nerve fibres was seen in saline-injected controls. We conclude that an acute inflammation in the subacromial space of the rat shoulder region can elicit a transient local sprouting of sensory axons in the tendon stroma and associated aberrant blood vessels.

Background: The pathophysiology of subacromial inflammation is not fully understood. In the present study we evaluate the presence of sensory and sympathetic nerve fibres and some neuropeptides in biopsies from the supraspinatus tendon and the subacromial bursa of patients with chronic subacromial inflammation as well as of control cases.

Methods: The occurrence of nerve fibres was subjectively assessed by immunohistochemistry. The concentration of substance P (SP), calcitonin generelated peptide (CGRP) and neuropeptide Y (NPY) was measured by radioimmunoassay (RIA).

Results: In tendon biopsies from patients with an intact or partially ruptured tendon protein gene product 9.5-like immunoreactive (LI), SP-LI and CGRP-LI nerve fibres were abnormally abundant. In patients with a total tendon rupture nerve fibre occurrence was normal. All biopsies from the bursa exhibited an abnormally high occurrence of SP- and CGRP-LI nerve fibres. In all biopsies the tendon and the bursa contained more blood vessels than normal. The vessels were surrounded by NPY- and tyrosine hydroxylase-LI nerve fibres in a subjectively normal pattern. RIA analysis revealed that the concentration of all three neuropeptides was abnormally high in tendon biopsies from patients with an intact or partially ruptured tendon. Tendon biopsies from patients with total tendon rupture showed statistically normal levels. Biopsies from the bursa showed abnormally high levels of SP and CGRP but normal levels of NPY in all patients.

Conclusion: We conclude, that the supraspinatus tendon and the subacromial bursa exhibit an increased occurrence of nerve fibres and some neuropeptides in patients with chronic subacromial inflammation.

Clinical relevance: Patients with chronic subacromial inflammation have a disabling pain problem. The increased local occurrence of sensory andsympathetic axons in the inflamed tissues as well as the elevated tissue concentration of certain neuropeptides may represent important factors behind that problem.

In the literature operative management of rotator cuff ruptures in the shoulder varies, from tendon repair to debridement of the cuff lesion combined with subacromial decompression. This study was made to evaluate whether patients with intact rotator cuff differed from patients with rotator cuff ruptures regarding functional outcome after arthroscopic subacromial decompression. We performed a clinical review of 39 patients with subacromial impingement who all underwent arthroscopic subacromial decompression; no other surgery was performed. There were 13 patients with intact cuff, 13 patients with partial-thickness supraspinatus ruptures, and 13 patients with full-thickness supraspinatus ruptures <2 cm. Selection was based solely on the status of the supraspinatus tendon. Patients with other pathologic conditions were excluded. Follow-up was performed after 3 and 6 years. The clinical evaluation was performed with the Constant score and the visual analog pain score. The 3- and 6-year follow-up (100% follow-up rate) revealed no significant difference between the groups regarding the Constant scores and the visual analog scale values. Also, no significant difference was seen among the 3 groups in active range of motion or strength, and the patients had no appreciable pain. We conclude that the functional outcome 6 years after arthroscopic subacromial decompression is not obviously related to the preoperative degree of cuff pathology, even if a total rupture of small size is present.

In a 12-year follow-up study, a low-friction, metal-on-plastic hip prosthetic system (Charnley) was compared with a high-friction, metal-on-metal prosthetic system (McKeeFarrar) in a consecutive series of 169 patients, mean age 67 at the start. Satisfactory results were reported in 92 percent of the patients. One-third of the prostheses showed radiographic signs of loosening. The cumulative aseptic failure rate was 8 percent for the Charnley prosthesis and 15 percent for the MKF prosthesis. The difference was not statistically significant.

The performance of a flexible (Bute!) and a rigid (PCA) cementless femoral component was studied in a prospective, randomized study of 28 matched pairs of patients (mean age 52 years). A high rate of stem loosening was observed for the flexible prosthesis and 4 cases of fatigue breakage occurred within the 3- to 5-year follow-up period. Proximal resorption and distal hypertrophy of the femur were frequently noted on the radiographs for the rigid stem. The scintigraphic activity around stems well fixed to bone became normalized in the calcar region. In contrast, it was about 50 percent increased around the prosthetic tip. For loose prostheses, the bony uptake was more intense and did not show the same time-related decrease. The scintimetric results did not correlate well with the signs of bone remodeling seen on the radiographs. Repeated at different time intervals, bone scintimetry may be informative in the followup of noncemented THA.

In a consecutive series of THAs, the straight ITI-I stem (n=65), made of titanium alloy, was compared at a 5-year review with the Lubinus femoral component (n=77), curved and made of cobalt-chrome alloy. The ITH stem showed a high frequency of surrounding radiolucent lines. Six of the stems were considered loose as compared with none of the Lubinus stems. To date, 5 have been revised and 2 more are in need of revision operations, all in the ITH group. Although the initial costs were somewhat reduced with the use of the cheaper ITH prosthesis, the estimated accumulated costs turned out to be higher in the ITH than in the Lubinus group due to the increased need for revisions.

In a study of THA performed on patients 80 years and older, good pain relief was achieved but at the cost of increased postoperative complications and hospital expenses as compared with patients around 65 years of age at operation. Functional improvement was not as evident as pain alleviation. The procedure did not result in decreased use of welfare services in the elderly group of patients.

An experimental study was performed on 10 rabbits. Hydroxyapatite coated titanium plugs were implanted in both femora of each animal. Five were treated for seven days with an NSAID (diclofenac) and five were used as controls, receiving no treatment. A significantly lower force was required to pull out the implants 3 weeks after surgery in the group treated with diclofenac than in the untreated group. The results indicate that even short-term treatment with NSAIDs might interfere with the process of bony ingrowth and thereby endanger primary fixation of the implant despite the presence of a hydroxyapatite coating.

A new cementless prosthesis was designed in titanium alloy in order to integrate the principles ofpressfit and flexibility. In a special test set-up the endurance properties of the stem were determined. Prototypes of the prosthesis were subjected to load cycles of 4,000 N in one ·test and to a more physiologic load pattern in another test. In both tests the prostheses broke after approximately 600,000 cycles without showing any material defects. It was concluded that considerable difftculty exists in constructing an "isoelastic" stem with reasonable safety limits to fatigue failure when using titanium alloy.

A model to calculate bone resorption driven by fluid flow at the bone-soft tissue interface is developed and used as a basis for computer calculations, which are compared to experiments where bone is subjected to fluid flow in a rat model. Previous models for bone remodelling calculations have been based on the state of stress, strain or energy density of the bone tissue as the stimulus for remodelling. We believe that there is experimental support for an additional pathway where an increase in the amount of the cells directly involved in bone removal, the osteoclasts, is caused by fluid pressure, flow velocity or other parameters related to fluid flow at the bone-soft tissue interface, resulting in bone resorption.

The influence of platelet-rich plasma lysates on fibroblast proliferation was studied in culture. Cells were exposed to platelet lysates that had been preincubated at different pHs (5.0, 7.1, and 7.6). Proliferation was evaluated with the MTT assay and incorporation of [³H]thymidine into macromolecules, while type I collagen production was assayed by Western blotting. Enzyme-linked immunosorbent assays were used to determine platelet-derived growth factor and transforming growth factor-β concentrations. Platelets preincubated in an acidic environment (pH 5.0) induced the highest degree of fibroblast proliferation, and the concentration of platelet-derived growth factor in the different treated lysates was the highest at that particular pH. The concentration of transforming growth factor-β, however, was lower after incubation at pH 5.0 than at either pH 7.1 or 7.6. These findings may be relevant to normal wound healing in vivo and useful in the treatment of wounds and delayed healing processes.

We studied the spontaneous and thrombin-induced activation of platelets and their release of platelet-derived growth factor (PDGF) and transforming growth factor-β (TGF-β) at different pH values. Platelet activation was assayed with anti-bodies against P-selectin and performed in serum-free media. The release of PDGF and TGF-β was determined by ELISA after 15 min and 12 h. There was no activation at pH 5.0, while a time-dependent release of growth factors occurred at neutral and alkaline pH. The results suggest that release of growth factors is not only dependent on platelet activation but also on incubation time and pH. Although the used serum-free experimental situation is different from normal conditions for platelets in vivo, the findings of a late release of growth factors may, nevertheless, be relevant to wound healing.

The pathogenesis of trigger finger has generally been ascribed to primary changes in the pulley. Histological examination of the affected tendons has rarely been done. We studied biopsies from tendons of trigger fingers from 29 patients and compared these to biopsies from six intact tendons. We used a modified Movin score, which describes the tendinosis of the Achilles tendon. Trigger finger tendons had a high score (14.2; SD, 2.2) consistent with tendinosis, while the controls were almost normal (2.5; SD, 1.9). This suggests that the tendon is also affected, and that trigger finger is a form of tendinosis.

Surgery for cervical radiculopathy was evaluated in 27 patients after anterior Cloward procedure (19 patients) or posterior decompression (eight patients). In addition, we examined 10 conservatively treated patients. Each patient was studied prospectively with regards to the effects on microcirculation in the local trapezius muscle during a fatiguing series of stepwise increased contractions. The right and left muscles were simultaneously examined pre-operatively and postoperatively after 9 months using laser-Doppler flowmetry and simultaneous surface electromyography (EMG). Preoperatively, a reduced microcirculation was found in the most painful side compared with the opposite side. This is in accordance with earlier reports on patients with chronic neurogenic neck pain, who also show reduced muscle tension on EMG. Postoperatively, the muscle blood flow became increased, but only in patients operated on via a posterior approach. A tendency at increased EMG-amplitude and reduced mean power frequency of the EMG was noted. These EMG signs of muscle fatigue suggest increased ability to exhaust the trapezius muscle postoperatively. The observed postoperative changes were consistently more frequent in the less painful side. We conclude from these objective measurements showing only a tendency at increased microcirculation and muscle tension postoperatively, that the effect on the trapezius muscle is limited. (C) 2001 European Federation of Chapters of the International Association for the Study of Pain.

Background: The combined use of bone mineral density, fracture history and other risk markers for fracture is advocated for ident