| 1. |
- Agholme, Fredrik
(författare)
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Wnt signaling and metaphyseal bone healing
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis relates to some new aspects on the regulation of bone healing. In the last few years, Wnt-signaling has been shown to play a central role in bone biology. As well as being involved in bone maintenance and repair, Wnt-signaling has been presented as one of the key pathways through which bone responds to mechanical load. Two secreted extracellular inhibitors of Wnt-signaling, sclerostin and dickkopf-1 are potent negative regulators of bone formation.Using a rat fracture model we investigated how metaphyseal bone healing is influenced by changes in Wnt-signaling.Antibodies were used to suppress levels of sclerostin and dickkopf-1, and thereby increase Wnt-signaling. Primarily, we investigated if those antibody treatments lead to improved bone healing. Also, we investigated if the response was coupled to the loading conditions of the bone.Our findings suggest that suppression of either sclerostin or dickkopf-1 leads to increased bone formation and improved bone healing. Apart from just having an effect on healing, the treatment also improved bone formation in other parts of the skeleton. Depending on the loading conditions, the effects were different. Dickkopf-1 appeared to have a stronger effect on bone volume density in unloaded bone, implying a role mainly in mechano-transduction, while sclerostin had similar effect in both loaded and unloaded bone. To confirm these findings, we studied how the expression of several Wnt-related genes changed due to trauma and unloading in metaphyseal bone. We found that trauma led to upregulation of most of the genes with the largest effect seen in the unloaded bone. In untraumatized bone, there was mainly an effect on the sclerostin gene.In conclusion, antibodies against sclerostin and dickkopf-1 appear to be able to improve metaphyseal bone healing. There appear to be some differences in how the effect of the two antibodies manifests itself, especially if the loading conditions of the bone are altered. These findings suggest a potential for clinical use to shorten fracture healing time.
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| 2. |
- Dahl, Jon, et al.
(författare)
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Less wear with aluminium-oxide heads than cobalt-chrome heads with ultra high molecular weight cemented polyethylene cups : A ten-year follow-up with radiostereometry
- 2012
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Ingår i: International Orthopaedics. - : Springer Science and Business Media LLC. - 0341-2695 .- 1432-5195. ; 36:3, s. 485-490
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Wear is a major contributor to osteolysis and aseptic loosening of total hip replacements (THR). Both alumina (Al2O3) and cobalt-chrome (CoCr) femoral heads are commonly used. We investigated wear comparing alumina heads to cobalt-chrome heads against conventional cemented polyethylene (PE) cups for up to ten years. Methods Linear wear was measured with radiostereometry (RSA). Our material was derived from two prospective randomised trials that investigated fixation of femoral stems, not wear, and was evaluated retrospectively (Level III). Results The mean (95% CI) proximal head penetration was 0.96 mm (0.68-1.23) in the cobalt-chrome group and 0.42 mm (0.30-0.53) in the alumina group at ten years (P=0.001). The mean (95% CI) 3D penetration was 1.07 mm (0.79-1.35) and 0.53 mm (0.38-0.63), respectively, at ten years (P=0.001). Conclusion Alumina heads performed better than cobalt-chrome heads in this study after ten-year follow-up.
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| 3. |
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| 4. |
- Randers, Engelke Marie, et al.
(författare)
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The effect of minimally invasive sacroiliac joint fusion compared to sham operation : a double-blind randomized-controlled trial
- 2024
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Ingår i: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 68
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Tidskriftsartikel (refereegranskat)abstract
- Background: Minimally invasive fusion of the sacroiliac joint as treatment for low back pain may reduce pain and improve function compared to non-operative treatment, although clear evidence is lacking. The aim of this trial was to evaluate the effect of minimally invasive sacroiliac joint fusion compared to sham surgery on sacroiliac joint pain reduction.Methods: In this double-blind randomized sham surgery-controlled trial patients with clinical diagnosis of sacroiliac joint pain confirmed with sacroiliac joint injection were included at two university hospitals in Sweden and Norway. Patients were randomized by the operating surgeon at each site to minimally invasive sacroiliac joint fusion or sham surgery. The primary endpoint was group difference in sacroiliac joint pain on the operated side at six months postoperatively, measured by the Numeric Rating Scale (0-10). Un-blinding and primary analysis were performed when all patients had completed six months follow-up. The trial is closed for new participants and was registered at clinicaltrials.gov: NCT03507049.Findings: Between September 1st, 2018 and October 22nd, 2021, 63 patients were randomized, 32 to the surgical group, 31 to the sham group. Mean age was 45 years (range 26-63) and 59 of 63 (94%) patients were female. The mean reduction in the operated sacroiliac joint from baseline to six months postoperative was 2.6 Numeric Rating Scale points in the surgical group and 1.7 points in the sham group (mean between groups difference -1.0 points; 95% CI, -2.2 to 0.3; p = 0.13).Interpretation: This double-blind randomized controlled trial could not prove that minimally invasive fusion of the sacroiliac joint was superior to sham surgery at six months postoperative.
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| 5. |
- Risberg, May Arna, et al.
(författare)
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Arthroscopic surgical procedures versus sham surgery for patients with femoroacetabular impingement and/or labral tears : Study protocol for a randomized controlled trial (HIPARTI) and a prospective cohort study (HARP)
- 2018
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Ingår i: Journal of Orthopaedic and Sports Physical Therapy. - : Journal of Orthopaedic & Sports Physical Therapy (JOSPT). - 0190-6011 .- 1938-1344. ; 48:4, s. 325-335
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Tidskriftsartikel (refereegranskat)abstract
- STUDY DESIGN: Study protocol for a randomized controlled trial and a prospective cohort. BACKGROUND: The number of arthroscopic surgical procedures for patients with femoroacetabular impingement syndrome (FAIS) has significantly increased worldwide, but high-quality evidence of the effect of such interventions is lacking. OBJECTIVES: The primary objective will be to determine the efficacy of hip arthroscopic procedures compared to sham surgery on patient-reported outcomes for patients with FAIS (HIP ARThroscopy International [HIPARTI] Study). The secondary objective will be to evaluate prognostic factors for long-term outcome after arthroscopic surgical interventions in patients with FAIS (Hip ARthroscopy Prospective [HARP] Study). METHODS: The HIPARTI Study will include 140 patients and the HARP Study will include 100 patients. The international Hip Outcome Tool-33 will be the primary outcome measure at 1 year. Secondary outcome measures will be the Hip disability and Osteoarthritis Outcome Score, Arthritis Self-Efficacy Scale, fear of movement (Tampa Scale of Kinesiophobia), Patient-Specific Functional Scale, global rating of change score, and expectations. Other outcomes will include active hip range of motion, hip muscle strength tests, functional performance tests, as well as radiological assessments using radiographs and magnetic resonance imaging. CONCLUSION: To determine the true effect of surgery, beyond that of placebo, double-blinded placebo-controlled trials including sham surgery are needed. The HIPARTI Study will direct future evidence-based treatment of FAIS. Predictors for long-term development and progression of degenrative changes in the hip are also needed for this young patient group with FAIS; hence, responders and nonresponders to treatment could be determined.
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| 6. |
- Röhrl, Stephan Maximilian, 1966-
(författare)
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Wear and Fixation of the acetabular component : in vivo evaluation of different polyethylenes and modes of fixation in total hip arthroplasty
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Polyethylene wear and micromotion of the implant play an important role in multifactorial etiology of osteolysis leading to aseptic loosening of the acetabular components. Despite excellent results in primary total hip arthoplasty in a 10-15 year perspective there are still unsolved problems. The weakest link is the longevity of the actabular component. Young and active patients have a clearly worse outcome than older patients. Consequences of polyehtylene wear and ways to reduce wear have therefore been in focus during recent years. Radiostereometry (RSA) is the golden standard in measuring in vivo micromotions. In 4 clinical studies including 332 patients we used therefore RSA to record the efficacy of fixation of cemented and uncemented cups. The amount of wear of old and newly designed polyethylenes (PE) was related to cup stability and radiological and clinical measures of outcome. This study showed that cementless cups inserted with pressfit technique do not need additional augmentation. Screws and pegs increase the risk for radiolucencies and osteolystic lesions but are helpful tools in cases where primary stability is jeopardized. In the second decade clinically silent osteolysis is common for the porous coated Harris Galante cup with unsealed screw holes. The locking mechanism of the PE liner in this cup is unsatisfactory and an increase of liner dissociations is expected. EtO sterilized PE displayed high in vivo wear and we do not recommend its continued use but close monitoring of patients with earlier inserted EtO sterilized implants. The substantially reduced wear in cemented highly cross-linked PE cups without any negative in vivo tradeoffs might have a substantial impact on choice of material and operating technique in the near future. However, we still recommend its restrained use in controlled series until longer follow-up data is available. Nevertheless, the short term in vivo results of modern highly cross-linked PE look promising and ight improve the outcome of cemented and uncemented hip arthroplasties by reducing complication and revisions.
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| 7. |
- Skoglund, Björn, 1975-
(författare)
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Following the mevalonate pathway to bone heal alley
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The mevalonate pathway is an important biosynthetic pathway, found in all cells of virtually all known pro- as well as eukaryotic organisms. This thesis is an investigation into the use of two drugs, originally developed for different applications, but both affecting the mevalonate pathway, in to models of fracture repair.Using two different rodent models of fracture repair, a commonly used cholesterol lowering drug (statin) and two drugs used to treat osteoporosis (bisphosphonate) were applied both systemically as well as locally in order to enhance fracture repair.Papers I and II investigate the potential of simvastatin to improve the healing of femoral fractures in mice. Papers III and IV explore the use of two bisphosphonates to improve early fixation of stainless steel screws into rat bone.The statin simvastatin lead to an increased strength of the healing cellus. The application of bisphosphonates increased early screw fixation.It seems clear that both drugs have uses in orthopaedic applications. One interesting avenue of further research would be to combine the two classes of drugs and see if we can get the benefits while at the same time diminishing the drawbacks.
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| 8. |
- Stenström, Mats, et al.
(författare)
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Bone mineral density and bone structure parameters as predictors of bone strength: an analysis using computerized microtomography and gastrectomy-induced osteopenia in the rat
- 2000
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Ingår i: Journal of Biomechanics. - 0021-9290. ; 33:3, s. 289-297
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Tidskriftsartikel (refereegranskat)abstract
- In this study the relationships of bone mineral density (BMD) and bone structure parameters calculated from 2D microtomography images to bone strength were investigated. Femurs from 21 male Sprague Dawley rats were subjected to dual-energy X-ray absorptiometry, computerized microtomography (CμT) and either three-point cantilever bending (femoral shaft) or two-point bending compression (femoral neck). Gastrectomy was performed on 12 animals and 9 were sham operated. From the tomograms bone structure analysis was performed using a software routine based on grey level run-length method. Correlations of BMD and bone structure parameters to mechanical parameters were investigated as were differences between the gastrectomized and the control samples. The reductions of BMD between the groups were 21 and 27% in the femoral neck and shaft, respectively. For the shaft, the correlations of BMD to all mechanical parameters were significant and BMD was a consistent predictor of bone strength for cortical bone. However, in the femoral neck where cancellous bone predominates, BMD was weakly correlated only to deflection. A significant correlation between trabecular thickness and neck bone strength was found. Hence, compared to trabecular thickness, BMD was of limited value in predicting bone strength in the femoral neck.
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| 9. |
- Tiulpin, Aleksei, et al.
(författare)
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Predicting total knee arthroplasty from ultrasonography using machine learning
- 2022
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Ingår i: Osteoarthritis and Cartilage Open. - : Elsevier BV. - 2665-9131. ; 4:4, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the value of ultrasonographic data in predicting total knee replacement (TKR).DESIGN: Data from the Musculoskeletal Pain in Ullensaker study (MUST) was linked to the Norwegian Arthroplasty Register to form a 5-7 year prospective cohort study of 630 persons (69% women, mean (SD) age 64 (8.7) years). We examined the predictive power of ultrasound (US) features, i.e. osteophytes, meniscal extrusion, synovitis in the suprapatellar recess, femoral cartilage thickness, and quality for future knee osteoarthritis (OA) surgery. We investigated 4 main settings for multivariate predictive modeling: 1) clinical predictors (age, sex, body mass index, knee injury, familial OA and workload), 2) radiographic data (assessed by the Kellgren Lawrence grade, KL) with clinical predictors, 3) US features and clinical predictors. Finally, we also considered an ensemble of models 2) and 3) and used it as our fifth model. All models were compared using the Average Precision (AP) and the Area Under Receiver Operating Characteristic Curve (AUC) metrics.RESULTS: Clinical predictors yielded AP of 0.11 (95% confidence interval [CI] 0.05-0.23) and AUC of 0.69 (0.58-0.79). Clinical predictors with KL grade yielded AP of 0.20 (0.12-0.33) and AUC of 0.81 (0.67-0.90). The clinical variables with ultrasound yielded AP of 0.17 (0.08-0.30) and AUC of 0.79 (0.69-0.86).CONCLUSION: Ultrasonographic examination of the knee may provide added value to basic clinical and demographic descriptors when predicting TKR. While it does not achieve the same predictive performance as radiography, it can provide additional value to the radiographic examination.
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| 10. |
- Tsukanaka, Masako, et al.
(författare)
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Identification of femoral head center of bipolar hemiarthroplasy in radiostereometric analysis with elementary geometrical shape models.
- 2016
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Ingår i: Journal of Biomechanics. - : Elsevier BV. - 1873-2380 .- 0021-9290. ; 49:3, s. 469-473
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Tidskriftsartikel (refereegranskat)abstract
- Elementary geometrical shape (EGS) models are useful in radiostereometric analysis (RSA) on hip stems because tantalum markers attached to the stems can be omitted. In order to create an EGS model of a femoral stem, the center of the femoral head has to be identified. The contour of the femoral head is recommended to be used. However, the contour of the femoral head cannot be detected exclusively by computer if it is combined with a bipolar head or a metal cup. We therefore hypothesized that the contour of the outer head of bipolar hemiarthroplasty can be included in the EGS model as well as the femoral head contour. We calculated the time required for the detection of the contour, the precision of analysis and the stem micromotion at 2 years using the two different methods in the same picture set and compared the results. The detection of the bipolar head contour was 10 times faster than that of the femoral head contour. The precision for subsidence was 0.16mm in EGS RSA with the femoral head contour, and 0.15mm with the bipolar head contour (p=0.68). The precisions were comparable and clinically acceptable. There was no significant difference between the results of the 2-year micromotion with the two different methods. We conclude that this new method is applicable to measure stem micromotion of hemi-arthoplasty with EGS RSA and the method facilitates the Radiostereometric analysis.
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