| 1. |
- Abtahi, Jahan, 1965-, et al.
(författare)
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Impact of a zoledronate coating on early post-surgical implant stability and marginal bone resorption in the maxilla-A split-mouth randomized clinical trial.
- 2019
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Ingår i: Clinical Oral Implants Research. - : John Wiley & Sons. - 0905-7161 .- 1600-0501. ; 30:1, s. 49-58
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The objective of this clinical study was to evaluate the effect of a bisphosphonate coating on a titanium implant on the implant stability quotient (ISQ) and the radiographic marginal bone levels at implants during early healing (2-8 weeks).MATERIALS AND METHODS: In a randomized double-blind trial with internal controls, 16 patients received a dental implant coated with zoledronate and one uncoated implant as a control. The coated and uncoated implants which were visually indistinguishable were bone level titanium implants with a moderately rough surface and a microthreaded neck. ISQ values were obtained at insertion and at 2, 4, 6, and 8 weeks. Radiographs were obtained at insertion and at 8 weeks. The primary outcome was the difference in ISQ values between the coated implants and the control implants at 4 and 6 weeks, corrected for insertion values. The secondary outcome was loss of marginal bone level from insertion to 8 weeks.RESULTS: Implant stability quotient values remained largely constant over the 8 weeks, and there was no significant difference between coated and uncoated implants at any time point. There was 0.12 (SD 0.10) mm marginal bone loss at the control implants and 0.04 (SD 0.08) mm at the coated implants. The difference was 0.17 mm; SD 0.14; p < 0.006). On blind qualitative scoring, 13 of the 15 control implants and two of 15 coated implants showed small marginal bone defects (p = 0.003).CONCLUSIONS: There were no statistically significant differences observed in ISQ values between the coated and uncoated implants during the early healing. There was less marginal bone loss at the coated implants.
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| 2. |
- Abtahi, Jahan, et al.
(författare)
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Randomised trial of bisphosphonate-coated dental implants: Radiographic follow-up after five years of loading
- 2016
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Ingår i: International Journal of Oral and Maxillofacial Surgery. - : CHURCHILL LIVINGSTONE. - 0901-5027 .- 1399-0020. ; 45:12, s. 1564-1569
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Tidskriftsartikel (refereegranskat)abstract
- The results of a randomised trial with bisphosphonate-coated dental implants have been reported previously. Each patient received one coated and one uncoated implant in a double-blind split-mouth design study. After 6 months of osseointegration, resonance frequency analysis indicated better fixation of the coated implants. Reduced marginal bone resorption was also shown. However, it was not known whether the advantage of the bisphosphonate coating would persist over time. The radiographic results at 5 years after implant installation are reported herein. A blinded investigator measured marginal resorption on fresh radiographs obtained for 14 of the 16 patients (two had died) and compared these with the post-implantation images. Non-parametric statistics were used. All implants functioned well. The median marginal bone loss for control implants was found to be 0.70 mm, which is less than usually reported in the literature. The bisphosphonate-coated implants showed even less resorption (median 0.20 mm). The median difference within each pair of implants after 5 years of use was 0.34 mm (95% confidence interval 0.00-0.75 mm; P = 0.04). The present data suggest that bisphosphonate-coated implants enable prolonged preservation of the marginal bone.
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| 3. |
- Amirhosseini, Mehdi, et al.
(författare)
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Mechanical instability and titanium particles induce similar transcriptomic changes in a rat model for periprosthetic osteolysis and aseptic loosening
- 2017
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Ingår i: Bone Reports. - : Elsevier. - 2352-1872. ; 7, s. 17-25
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Tidskriftsartikel (refereegranskat)abstract
- Wear debris particles released from prosthetic bearing surfaces and mechanical instability of implants are two main causes of periprosthetic osteolysis. While particle-induced loosening has been studied extensively, mechanisms through which mechanical factors lead to implant loosening have been less investigated. This study compares the transcriptional profiles associated with osteolysis in a rat model for aseptic loosening, induced by either mechanical instability or titanium particles. Rats were exposed to mechanical instability or titanium particles. After 15 min, 3, 48 or 120 h from start of the stimulation, gene expression changes in periprosthetic bone tissue was determined by microarray analysis. Microarray data were analyzed by PANTHER Gene List Analysis tool and Ingenuity Pathway Analysis (IPA). Both types of osteolytic stimulation led to gene regulation in comparison to unstimulated controls after 3, 48 or 120 h. However, when mechanical instability was compared to titanium particles, no gene showed a statistically significant difference (fold change = ± 1.5 and adjusted p-value = 0.05) at any time point. There was a remarkable similarity in numbers and functional classification of regulated genes. Pathway analysis showed several inflammatory pathways activated by both stimuli, including Acute Phase Response signaling, IL-6 signaling and Oncostatin M signaling. Quantitative PCR confirmed the changes in expression of key genes involved in osteolysis observed by global transcriptomics. Inflammatory mediators including interleukin (IL)-6, IL-1ß, chemokine (C-C motif) ligand (CCL)2, prostaglandin-endoperoxide synthase (Ptgs)2 and leukemia inhibitory factor (LIF) showed strong upregulation, as assessed by both microarray and qPCR. By investigating genome-wide expression changes we show that, despite the different nature of mechanical implant instability and titanium particles, osteolysis seems to be induced through similar biological and signaling pathways in this rat model for aseptic loosening. Pathways associated to the innate inflammatory response appear to be a major driver for osteolysis. Our findings implicate early restriction of inflammation to be critical to prevent or mitigate osteolysis and aseptic loosening of orthopedic implants.
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| 4. |
- Aspenberg, Per, 1949-
(författare)
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Apropå! En arrogant organisation
- 2017
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Ingår i: Läkartidningen. - Stockholm, Sweden : Läkartidningen Förlag AB. - 0023-7205 .- 1652-7518. ; 114
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
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| 5. |
- Aspenberg, Per, 1949-, et al.
(författare)
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Artrosskolan : evidensen måste stärkas
- 2018
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Ingår i: Läkartidningen. - : Läkartidningen Förlag AB. - 0023-7205 .- 1652-7518. ; 115
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 6. |
- Aspenberg, Per
(författare)
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Atypical fractures, a biased perspective
- 2016
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Ingår i: Injury. - : ELSEVIER SCI LTD. - 0020-1383 .- 1879-0267. ; 47:1, s. S28-S30
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Tidskriftsartikel (refereegranskat)abstract
- When stress fractures started to show up in the femurs of elderly ladies, it was soon evident that bisphosphonate use lay behind, and the absolute risk increase due to bisphosphonate use was reasonably well estimated already in 2008. Thereafter followed a period of confusion: the term atypical fracture was introduced, with a definition so vague that the true stress fractures tended to disappear in a cloud of ambiguity. This cast doubt on the association with bisphosphonates. The association was then re-established by large epidemiological studies based on radiographic adjudication. Atypical fractures are largely caused by bisphosphonates. With a correct indication, bisphosphonates prevent many more fractures than they cause, at least during the first years of use. With an incorrect indication they are likely to cause more harm than good. (C) 2016 Elsevier Ltd. All rights reserved.
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| 7. |
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| 8. |
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| 9. |
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| 10. |
- Aspenberg, Per, et al.
(författare)
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Effects of Teriparatide Compared with Risedronate on Recovery After Pertrochanteric Hip Fracture Results of a Randomized, Active-Controlled, Double-Blind Clinical Trial at 26 Weeks
- 2016
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Ingår i: Journal of Bone and Joint Surgery. American volume. - : JOURNAL BONE JOINT SURGERY. - 0021-9355 .- 1535-1386. ; 98:22
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Tidskriftsartikel (refereegranskat)abstract
- Background: Osteoporosis drugs might affect fracture-healing. We therefore studied the effects of teriparatide in comparison with risedronate on recovery after pertrochanteric hip fractures. Methods: The study was a randomized, multicenter, active-controlled, 78-week trial comparing teriparatide (20 mg/day) with risedronate (35 mg/week) initiated within 2 weeks after fixation of a low-trauma pertrochanteric hip fracture (AO/OTA 31-A1 or 31-A2). The main inclusion criteria were a bone mineral density T-score of amp;lt;=-22.0 and 25-OH-vitamin D of amp;gt;= 9.2 ng/mL. During the first 26 weeks, patients received study medication with oral or injectable placebo plus calcium and vitamin D in a double-blinded fashion. Secondary (Timed Up-and-Go [TUG] test, hip pain, Short Form [SF]-36 health status, and safety) and exploratory (radiographic outcomes and ability to walk) 26-week end points are reported. Results: Of the 224 patients who were randomized, 171 (86 teriparatide, 85 risedronate) were included in the analysis. The mean age was 77 +/- 8 years, 77% were female, and 26% had a prior history of low-trauma fracture. The teriparatide group completed the TUG test in a shorter time at 6, 12, 18, and 26 weeks (differences of 25.7, -4.4, -3.1, and -3.1 seconds, respectively; p = 0.021 for the overall difference). They also reported less pain on a visual analog scale immediately after the TUG test at 12 and 18 weeks (adjusted absolute differences of 10.6 and 11.9 mm, respectively; p amp;lt; 0.05). There were no significant between-group differences in the SF-36 score, Charnley hip pain score, ability to walk, or use of walking aids during follow-up. Radiographic healing at 6, 12, and 26 weeks, mechanical failure of the implant (teriparatide, 7; risedronate, 8), loss of reduction (teriparatide, 2; risedronate, 4), and nonunion (0 cases) were not significantly different. Mild hypercalcemia and hyperuricemia were more frequent with teriparatide. Conclusions: Teriparatide was associated with less pain and a shorter time to complete the TUG test between 6 and 26 weeks compared with risedronate. Other fracture-recovery outcomes were similar. The results should be interpreted with caution as these were secondary end points.
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| 11. |
- Aspenberg, Per
(författare)
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Förekomst av trutsjuka och onormal fågeldöd i Gävlebukten sommaren 2017
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Besök har sommaren 2017 skett vid samtliga kända kolonierna i landskapets kustområde. Undersökningen har gjorts på så sätt att antalet par gråtrut som inleder häckning först bedömts genom ett eller flera tidiga besök. Vid ett senare tillfälle längre fram i häckningscykeln har eventuella döda fåglar räknats.Vid besöken på häckningslokalerna 2017 hittades bara en enda död gammal gråtrut med riktigt typiska symptom på den tidigare grasserande trutsjukan. Fågeln hittades döende på östra delen av Eggegrund. Inte heller hittades särskilt många individer av andra skärgårdsfågelarter som uppvisade sjukdomssymptom utan predation. Ännu sommaren 2017 kunde Gävlebukten därmed i stort sett friskförklaras med avseende på förlamningsepidemier. Inte sedan 2006 har trutsjukan grasserat i större omfattning i området.Summering av totalpopulationen i undersökningsområdet visade på ett ökande bestånd av gråtrut. Efter tre år av nedgång från toppnivån på 720 par 2013 kom nu en ökning på 8% jämfört med 2016 upp till 633 par.Ejdern har fortfarande en gynnsam utveckling med ökningar i antal och god förekomst av kullar med ungar. Situationen är därmed mer positiv vid Bottenhavet än i skärgårdarna från Roslagen och längre söderut.
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| 12. |
- Aspenberg, Per
(författare)
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FÖREKOMSTEN AV TRUTSJUKA OCH ONORMAL FÅGELDÖD I GÄVLEBUKTEN SOMMAREN 2019
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Denna PM är utformad enligt samma textmall som tidigare upplagor av den årliga rapporteringen om onormal sjöfågeldöd. En upprepning av texterna från tidigare versioner av rapporteringen kan tyckas onödig, men görs här för att i ett och samma dokument ge tillgång till t.ex. en fyllig bakgrundsbeskrivning utan att behöva söka fram tidigare rapporter. Rapporten fokuserar således i första hand på tillståndet för Gästriklands kusthäckande gråtrutar. Dessa fåglar har i länsstyrelsens regi specialstuderats årligen sedan 2008 med inriktning på populationsutveckling och förekomsten av döda, sjuka eller förlamade fåglar under häckningstid. Besök har sommaren 2019 skett vid samtliga kända kolonierna i landskapets kustområde. Björns båk utanför Norrsundet besöktes bara vid ett tillfälle i juni. Men på övriga öar med gråtrutkolonier har både tidiga och sena landstigningar skett. På dessa platser har datummässigt tidiga inventeringen fokuserat på populationsstorlek medan de sena har fokuserat på uppföljning av sjuka och döda fåglar. Undersökningen har således gjorts på så sätt att antalet par gråtrut som inleder häckning först bedömts genom ett eller flera tidiga besök i månaden maj. Vid ett senare tillfälle, normalt i början eller mitten av juli längre fram i häckningscykeln, har eventuella döda fåglar räknats. Med tillgång till detta material kan dels totalpopulationen kolonihäckande bestämmas och dels även andelen av de adulta fåglarna som drabbats av ”trutdöden”. Totalt sett har ett 50-tal öar, med eller utan trutkolonier, men med ansamlingar av häckande tärnor och/eller skrattmås hunnit besökas sommaren 2019. På samtliga dessa inventerade fågelöar har förekomsten av döda häckfåglar undersökts. Sammanfattningsvis kan sägas att påtagliga tecknen på minkangrepp, i form av t.ex mängder av ihjälbitna ungar, varit ovanligt få sommaren 2019 jämfört med tidigare år. Ändå har tärnkolonierna haft ojämn och på många öar oroväckande låg produktion av flygga ungar. I vissa fall kan predation från gråtrut och korp ha varit en del av förklaringen. Men på många andra öar har tärnorna helt enkelt mer oförklarligt helt misslyckats med häckningarna. Om vi återvänder till gråtrutarna så visade räkningarna 2019 på en ökning av antalet häckande gråtrutar i undersöknings-området från fjolårets svaga siffra på 612 häckande par upp till nu 666 par 2019. Fynden av sannolika fall av offer för trutsjukan var fåtaliga. De nio funna döda adulta gråtrutarna på häckningslokalerna visade tecken på att ha drabbats av den tiaminbristrelaterade sjukdomen, men dödsorsaken bedömdes ändå i vissa fall inte vara helt säker. Bilden blev att trutsjukan fick mindre fäste 2019 än 2018. Det verkar subjektivt sett som trutdöden har ett samband med varmt väder sommartid. Förra året, med fler döda trutar, var ju osedvanligt varm. På Eggegrund återfanns även denna sommar en del döda fiskmåsungar med tydliga tecken på trutsjuka. De hittades i mitten av juli under sommarens varmaste period.. Tiaminbrist hos Gävlebuktens måsfåglar verkar just för närvarande inte vara något särskilt iögonfallande problem. Men sänkta nivåer av B1 är ju konstaterade för många av kustens djurarter, från blåmusslor och fisk till fåglar över hela Norra halvklotet. Hälsotillståndet hos gråtrutarna bör fungera som ett värdefullt instrument för att studera problematiken lokalt.
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| 13. |
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| 14. |
- Aspenberg, Per, et al.
(författare)
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Substantial creep in healing human Achilles tendons : A pilot study
- 2015
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Ingår i: MLTJ Muscles, Ligaments and Tendons Journal. - Rome, Italy : C I C Edizioni Internazionali. - 2240-4554. ; 5:3, s. 151-155
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: healing after rupture of the Achilles tendon can be described in terms of mechanical properties of the new-formed tissue, constituting the tendon callus. In previous human studies, the elastic modulus and the density remained almost constant during 3 months after mobilization started, and then improved up to one year. So far, time-dependent deformation of the healing human tendon has not been reported.Methods: in a series of 16 patients, operated with Achilles tendon suture, we implanted tantalum beads into the tendon and measured the distance between them repeatedly during 3 min of constant loading, using an ordinary image intensifier. The patients unloaded their leg for 30 min before the test. To avoid bias, all images were investigated in a randomized and blinded order.Results: total strain during 3 min of constant loading at 7 weeks post injury amounted to 5%, and at 19 weeks to 3%. About half of the strain, after the loading was applied, occurred during the second and third min. Considerable strain also occurred just before loading, when the patient was told that a load would be applied, but before this was actually done.Conclusion: the measurements were crude, and this study should be seen as a pilot. Still, viscoelastic properties seem to dominate the mechanical behavior the healing Achilles tendon from start of mobilization to 19 weeks, at least when tested after 30 min rest. This deserves further studies with more precise methods.
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| 15. |
- Aspenberg, Per
(författare)
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Örngruppens verksamhet 1978-2017 : Rapport till Länsstyrelsen augusti 2017
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Detta är en ny årsrapport från GLOF:s örngrupp. Här redogörs för det regionala arbetet inom projekt Havsörn i Gävleborgs län fram till och med sommaren 2017.Beräkningen av totalt antal besökande havsörnar (inklusive omärkta) vid de två kontinuerligt drivna vinterutfodringarna landar på 400 individer, betydligt lägre än förra säsongens 656.Under våren-sommaren 2017 undersöktes 62 olika kända havsörnsrevir inom örngruppens traditionella område (Hälsingland-Gästrikland-Nedre Dalälven samt Älvkarleby kommun). Inom kärnområdet kunde häckningsförsök konstateras i 45 av reviren av vilka hela 37 (66%) ledde till lyckade häckningar. I dessa producerade örnarna 59 flygga ungar, varav 45 kunde ringmärkas. Räknat på häckningarna i kärnområdet utföll alltså andelen lyckade till höga 82% (jämfört med fjolårets mycket låga 66% och åren innan dess 87% 2015, 74% 2014, rekorddåliga 54% 2013, 75% 2012, 67% 2011, och 72% 2009). Antalet ungar per lyckad häckning blev för regionen det nära normala 1,6 (mot 1,45 ifjol,1,5 år 2015, 1,7 år 2014, 1,6 år 2013, 1,7 år 2012 och bara 1,3 år 2011).
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| 16. |
- Bernhardsson, Magnus, 1989-, et al.
(författare)
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Abaloparatide versus teriparatide: a head to head comparison of effects on fracture healing in mouse models
- 2018
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Ingår i: Acta Orthopaedica. - : TAYLOR & FRANCIS LTD. - 1745-3674 .- 1745-3682. ; 89:6, s. 674-677
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose - Teriparatide accelerates fracture healing in animals and probably in man. Abaloparatide is a new drug with similar although not identical effects on the teriparatide receptor. Given at 4 times the teriparatide dose in a human osteoporosis trial, abaloparatide increased bone density more than teriparatide, and both reduced fracture risk. We investigated in mice whether abaloparatide stimulates fracture healing, and if it does so with the suggested dose effect relation (4:1). Patients and methods - In a validated mouse model for metaphyseal healing (burr hole with screw pull-out), 96 mice were randomly allocated to 11 groups: control (saline), teriparatide or abaloparatide, where teriparatide and abaloparatide were given at 5 different doses each. In a femoral shaft osteotomy model, 24 mice were randomly allocated to 3 groups: control (saline), teriparatide (15 mu g/kg) or abaloparatide (60 mu g/kg). Each treatment was given daily via subcutaneous injections. Results were evaluated by mechanical testing and microCT. Results - In the metaphyseal model, a dose-dependent increase in screw pull-out force could be seen. In a linear regression analysis (r = 0.78) each increase in ln(dose) by 1 (regardless of drug type) was associated with an increase in pull-out force by 1.50 N (SE 0.18) (p amp;lt; 0.001). Changing drug from teriparatide to abaloparatide increased the force by 1.41 N (SE 0.60; p = 0.02). In the diaphyseal model, the callus density was 23% (SD 10), 38% (SD 10), and 47% (SD 2) for control, for teriparatide and abaloparatide respectively. Both drugs were significantly different from controls (p = 0.001 and p = 0.008), but not from each other. Interpretation - Both drugs improve fracture healing, but in these mouse models, the potency per mu g of abaloparatide seems only 2.5 times that of teriparatide, rather than the 4:1 relation chosen in the clinical abaloparatide-teriparatide comparison trial.
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| 17. |
- Bernhardsson, Magnus, et al.
(författare)
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Anti-RANKL treatment improves screw fixation in cancellous bone in rats
- 2015
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Ingår i: Injury. - : Elsevier. - 0020-1383 .- 1879-0267. ; 46:6, s. 990-995
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Tidskriftsartikel (refereegranskat)abstract
- Bisphosphonates improve implant fixation in randomised clinical trials of knee prostheses, hip prostheses and dental implants. However, a limited amount of bone resorption is required for bisphosphonates to exert an effect. Anti-RANKL treatment does not have this limitation, and we therefore tested whether if they might be more effective for improvement of implant fixation. This is of interest, as anti-RANKL treatment with denosumab is now in common clinical use. Male SD rats received a stain-less steel screw in the right proximal tibia and a drill hole in the left (n = 42). They were randomised to subcutaneous injections of either alendronate (20 mu g/kg/day), alendronate (200 mu g/kg/day), osteoprotegerin with an Fc tag (OPG-Fc; 8 mg/kg, twice weekly), or saline control. After 4 weeks, the fixation of the steel screw was measured by pull-out test. The tibia with the drill hole was evaluated with mu CT. OPG-Fc increased the pull-out force compared to saline controls by 153% (p less than 0.001). There was no significant difference between OPG-Fc and the alendronate groups. OPG-Fc increased the bone density (BV/TV) in the previous drill hole compared to controls 7-fold (p less than 0.001). This increase was higher than with any alendronate dose (p less than 0.001). OPG-Fc increased the bone density of the L5 vertebral body, but there was no significant difference between OPG-Fc and alendronate. Our results suggest that screw fixation in cancellous bone can be dramatically improved by an antiRANKL agent. The effect was comparable to very high bisphosphonate doses. Screw insertion in cancellous bone elicits a metaphyseal fracture healing response, and our findings might be relevant not only for implant fixation, but also for fracture healing in cancellous bone.
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| 18. |
- Bernhardsson, Magnus, 1989-, et al.
(författare)
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Depletion of cytotoxic (CD8+) T cells impairs implant fixation in rat cancellous bone
- 2019
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Ingår i: Journal of Orthopaedic Research. - : John Wiley & Sons. - 0736-0266 .- 1554-527X. ; 37:4, s. 805-811
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Tidskriftsartikel (refereegranskat)abstract
- As cytotoxic (CD8(+)) T cells seem to impair shaft fracture healing, we hypothesized that depletion of CD8(+) cells would instead improve healing of cancellous bone. Additionally, we also tested if CD8-depletion would influence the healing of ruptured Achilles tendons. Rats received a single injection of either anti-CD8 antibodies or saline and put through surgery 24 h later. Three different surgical interventions were performed as follows: (1) a drill hole in the proximal tibia with microCT (BV/TV) to assess bone formation; (2) a screw in the proximal tibia with mechanical evaluation (pull-out force) to assess fracture healing; (3) Achilles tendon transection with mechanical evaluation (force-at-failure) to assess tendon healing. Furthermore, CD8-depletion was confirmed with flow cytometry on peripheral blood. Flow cytometric analysis confirmed depletion of CD8(+) cells (p amp;lt; 0.001). Contrary to our hypothesis, depletion of CD8(+) cells reduced the implant pull-out force by 19% (p amp;lt; 0.05) and stiffness by 34% (p amp;lt; 0.01), although the bone formation in the drill holes was the same as in the controls. Tendon healing was unaffected by CD8-depletion. Our results suggest that CD8(+) cells have an important part in cancellous bone healing.
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| 19. |
- Bernhardsson, Magnus, et al.
(författare)
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Experimental models for cancellous bone healing in the rat Comparison of drill holes and implanted screws
- 2015
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Ingår i: Acta Orthopaedica. - : TAYLOR & FRANCIS LTD. - 1745-3674 .- 1745-3682. ; 86:6, s. 745-750
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose - Cancellous bone appears to heal by mechanisms different from shaft fracture healing. There is a paucity of animal models for fractures in cancellous bone, especially with mechanical evaluation. One proposed model consists of a screw in the proximal tibia of rodents, evaluated by pull-out testing. We evaluated this model in rats by comparing it to the healing of empty drill holes, in order to explain its relevance for fracture healing in cancellous bone. To determine the sensitivity to external influences, we also compared the response to drugs that influence bone healing. Methods - Mechanical fixation of the screws was measured by pull-out test and related to the density of the new bone formed around similar, but radiolucent, PMMA screws. The pull-out force was also related to the bone density in drill holes at various time points, as measured by microCT. Results - The initial bone formation was similar in drill holes and around the screw, and appeared to be reflected by the pull-out force. Both models responded similarly to alendronate or teriparatide (PTH). Later, the models became different as the bone that initially filled the drill hole was resorbed to restore the bone marrow cavity, whereas on the implant surface a thin layer of bone remained, making it change gradually from a trauma-related model to an implant fixation model. Interpretation - The similar initial bone formation in the different models suggests that pull-out testing in the screw model is relevant for assessment of metaphyseal bone healing. The subsequent remodeling would not be of clinical relevance in either model.
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| 20. |
- Bernhardsson, Magnus, et al.
(författare)
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Marrow compartment contribution to cortical defect healing
- 2018
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Ingår i: Acta Orthopaedica. - : TAYLOR & FRANCIS LTD. - 1745-3674 .- 1745-3682. ; 89:1, s. 119-123
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose - Healing of shaft fractures is commonly described as regards external callus. We wanted to clarify the role of the bone marrow compartment in the healing of stable shaft fractures. Patients and methods - A longitudinal furrow was milled along the longitudinal axis of the femoral shaft in mice. The exposed bone marrow under the furrow was scooped out. The mice were then randomized to no further treatment, or to receiving 2 silicone plugs in the medullary canal distal and proximal to the defect. The plugs isolated the remaining marrow from contact with the defect. Results were studied with histology and flow cytometry. Results - Without silicone plugs, the marrow defect was filled with new bone marrow-like tissue by day 5, and new bone was seen already on day 10. The new bone was seen only at the level of the cortical injury, where it seemed to form simultaneously in the entire region of the removed cortex. The new bone seemed not to invade the marrow compartment, and there was a sharp edge between new bone and marrow. The regenerated marrow was similar to uninjured marrow, but contained considerably more cells. In the specimens with plugs, the marrow compartment was either filled with loose scar tissue, or empty, and there was only minimal bone formation, mainly located around the edges of the cortical injury. Interpretation - Marrow regeneration in the defect seemed to be a prerequisite for normal cortical healing. Shaft fracture treatment should perhaps pay more attention to the local bone marrow.
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| 21. |
- Bernhardsson, Magnus, 1989-, et al.
(författare)
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Osteoblast precursors and inflammatory cells arrive simultaneously to sites of a trabecular-bone injury
- 2018
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Ingår i: Acta Orthopaedica. - : TAYLOR & FRANCIS LTD. - 1745-3674 .- 1745-3682. ; 89:4, s. 457-461
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose - Fracture healing in the shaft is usually described as a sequence of events, starting with inflammation, which triggers mesenchymal tissue formation in successive steps. Most clinical fractures engage cancellous bone. We here describe fracture healing in cancellous bone, focusing on the timing of inflammatory and mesenchymal cell type appearance at the site of injury. Material and methods - Rats received a proximal tibial drill hole, A subgroup received clodronate-containing liposomes before or after surgery. The tibiae were analyzed with micro-CT and immunohistochemistry 1 to 7 days after injury. Results - Granulocytes (myeloperoxidase) appeared in moderate numbers within the hole at day 1 and then gradually disappeared. Macrophage expression (CD68) was seen on day 1, increased until day 3, and then decreased. Mesenchymal cells (vimentin) had already accumulated in the periphery of the hole on day 1. Mesenchymal cells dominated in the entire lesion on day 3, now producing extracellular matrix. A modest number of preosteoblasts (RUNX2) were seen on day 1 and peaked on day 4. Osteoid was seen on day 4 in the traumatized region, with a distinct border to the uninjured surrounding marrow. Clodronate liposomes given before the injury reduced the volume of bone formation at day 7, but no reduction in macrophage numbers could be detected. Interpretation - The typical sequence of events in shaft fractures was not seen. Mesenchymal cells appeared simultaneously with granulocyte and macrophage arrival. Clodronate liposomes, known to reduce macrophage numbers, seemed to be associated with the delineation of the volume of tissue to be replaced by bone.
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| 22. |
- Bernhardsson, Magnus, et al.
(författare)
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Shining dead bone-cause for cautious interpretation of [F-18]NaF PET scans
- 2018
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Ingår i: Acta Orthopaedica. - : Taylor & Francis. - 1745-3674 .- 1745-3682. ; 89:1, s. 124-127
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose — [18F]Fluoride ([18F]NaF) PET scan is frequently used for estimation of bone healing rate and extent in cases of bone allografting and fracture healing. Some authors claim that [18F]NaF uptake is a measure of osteoblastic activity, calcium metabolism, or bone turnover. Based on the known affinity of fluoride to hydroxyapatite, we challenged this view.Methods — 10 male rats received crushed, frozen allogeneic cortical bone fragments in a pouch in the abdominal wall on the right side, and hydroxyapatite granules on left side. [18F]NaF was injected intravenously after 7 days. 60 minutes later, the rats were killed and [18F]NaF uptake was visualized in a PET/CT scanner. Specimens were retrieved for micro CT and histology.Results — MicroCT and histology showed no signs of new bone at the implant sites. Still, the implants showed a very high [18F]NaF uptake, on a par with the most actively growing and remodeling sites around the knee joint.Interpretation — [18F]NaF binds with high affinity to dead bone and calcium phosphate materials. Hence, an [18F]NaF PET/CT scan does not allow for sound conclusions about new bone ingrowth into bone allograft, healing activity in long bone shaft fractures with necrotic fragments, or remodeling around calcium phosphate coated prostheses
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| 23. |
- Blomgran, Parmis, et al.
(författare)
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A possible link between loading, inflammation and healing: Immune cell populations during tendon healing in the rat
- 2016
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 6:29824
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Tidskriftsartikel (refereegranskat)abstract
- Loading influences tendon healing, and so does inflammation. We hypothesized that the two are connected. 48 rats underwent Achilles tendon transection. Half of the rats received Botox injections into calf muscles to reduce mechanical loading. Cells from the regenerating tissue were analyzed by flow cytometry. In the loaded group, the regenerating tissue contained 83% leukocytes (CD45(+)) day 1, and 23% day 10. The M1/M2 macrophage ratio (CCR7/CD206) peaked at day 3, while T helper (CD3(+)CD4(+)) and T-reg cells (CD25(+) Foxp3(+)) increased over time. With Botox, markers associated with down-regulation of inflammation were more common day 5 (CD163, CD206, CD25, Foxp3), and M1 or M2 macrophages and T-reg cells were virtually absent day 10, while still present with full loading. The primary variable, CCR7/CD206 ratio day 5, was higher with full loading (p = 0.001) and the T-reg cell fraction was lower (p amp;lt; 0.001). Free cage activity loading is known to increase size and strength of the tendon in this model compared to Botox. Loading now appeared to delay the switch to an M2 type of inflammation with more T-reg cells. It seems a prolonged M1 phase due to loading might make the tendon regenerate bigger.
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| 24. |
- Blomgran, Parmis, 1985-, et al.
(författare)
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Cox-2 inhibition and the composition of inflammatory cell populations during early and mid-time tendon healing
- 2017
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Ingår i: Muscles, ligaments and Tendons journal. - Rome, Italy : CIC Edizioni Internazionali. - 2240-4554. ; 7:2, s. 223-229
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Tidskriftsartikel (refereegranskat)abstract
- Background: During early tendon healing, the cells within the regenerating tissue are, to a large part, inflammatory leukocytes (CD45+). In a rat Achilles tendon healing model, the inflammation resolves between 5 and 10 days. In the same model, Cox inhibitors (NSAIDs) impair healing when given during the first 5 days, but have a positive effect if given later. We tested the hypothesis that a Cox inhibitor would exert these effects by influencing inflammation, and thereby the composition of the inflammatory cell subpopulations.Methods: Achilles tendon transection was performed in 44 animals. Animals were randomized to either parecoxib or saline injections. Healing was evaluated by mechanical testing day 7 after surgery and by flow cytometry day 3 and 10.Results: Cross-sectional area, peak force and stiffness were reduced by parecoxib 31, 33, and 25% respectively (p=0.005, p=0.002, and p=0.005). By flow cytometry, there was a strong effect of time (p<0.001) on virtually all inflammatory cell subpopulations (CD45, CD11b, CD68, CCR7, CD163, CD206, CD3, CD4), but no significant effect of parecoxib at any time point.Conclusion: The results suggest that the negative effects of Cox inhibitors on tendon healing might be exerted mainly via mechanisms not directly related to inflammatory cells.
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| 25. |
- Blomgran, Parmis, 1985-
(författare)
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Inflammation and tendon healing
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Tendons heal through three different overlapping phases; the inflammatory, proliferative and remodeling phase. Many studies have investigated what factors influence healing of tendons. However, little was known about inflammation and the immune cells present during Achilles tendon healing by the time this thesis started. We developed a flow cytometry method for our rat model of tendon healing, which enabled us to study different leukocyte subpopulations during Achilles tendon healing.The general aim of this thesis was to understand more about inflammation and the immune cell populations present during tendon healing and how the immune cell composition changes during normal tendon healing. Moreover, we investigated how different factors that are known to influence tendon healing affected the composition of the immune cell population.First, we described the immune cells during the time course of tendon healing focusing on different subpopulations of macrophages and T cells. Then, we studied how these cells were influenced by reduced mechanical loading. Mechanical loading prolonged the presence of M1 macrophages and delayed the switch to regulatory T cells and M2 macrophages compared to reduced mechanical loading. Next, the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the leukocyte composition revealed that, even though NSAIDs influence the mechanical properties of healing tendon, this effect was not mediated via changes in the leukocyte sub-populations during early and mid-time tendon healing. Further, the effect of corticosteroids during the inflammatory and remodeling phases of tendon healing was an improved healing of tendons and a reduction of CD8a T cells when corticosteroid was administered after the inflammatory phase. Lastly, we investigated if impairment of tendon healing by NSAIDs was related to mechanotransduction or microdamage during mechanical loading and showed that NSAIDs impair tendon healing by reducing the response to microdamage.In conclusion, these studies show that inflammation plays an important role during Achilles tendon healing, and factors that influence healing can also alter the presence or polarization of immune cell populations.
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