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  • 51.
    Larsson, Sune
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Fazzalari, Nicola L.
    Anti-osteoporosis therapy and fracture healing2014In: Archives of Orthopaedic and Trauma Surgery, ISSN 0936-8051, E-ISSN 1434-3916, Vol. 134, no 2, p. 291-297Article in journal (Refereed)
    Abstract [en]

    A number of medications are approved for treatment of osteoporosis. As mode of action usually is anti-catabolic/anti-resorptive or anabolic, it is of interest to know whether these drugs affect not only normal bone remodeling, but also fracture healing. The purpose of this paper is to give a short overview of the potential effect of various anti-osteoporotic medication on fracture healing. A narrative literature review was performed to describe the current knowledge. Anti-catabolic/anti-resorptive drugs: for bisphosphonates, the most common class of drugs in this group, experimental studies have shown a larger and stronger callus and delayed remodeling but no evidence of delayed healing. A human monoclonal antibody to RANKL is another anti-catabolic drug, with the only report to date showing enhanced healing in an animal model. Strontium ranelate is a drug where both anti-catabolic and a weak anabolic effect have been proposed, with experimental data ranging from no effect to significant increase in both callus volume and strength. Anabolic drugs: PTH has demonstrated accelerated healing of various experimental fractures and of distal radius and pelvic fractures in humans. While the exact mechanism is not fully understood, PTH results in increased recruitment and differentiation of chondrocytes and enhancement of endochondral ossification. A monoclonal antibody to block sclerostin is another potential anabolic pathway, where animal data have shown increase in bone mass and strength. The potential effect on fracture healing is yet to be studied. There are still large gaps in the understanding of the potential effect of anti-osteoporotic drugs on fracture healing, although based on present knowledge a recent or present fracture should not be considered as a contraindication to such treatment.

  • 52.
    Larsson, Sune
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hannink, Gerjon
    Injectable bone-graft substitutes: Current products, their characteristics and indications, and new developments2011In: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 42, no Suppl. 2, p. S30-S34Article in journal (Refereed)
    Abstract [en]

    More than a decade has passed since the first injectable bone substitutes were introduced for use in orthopaedic trauma, and over recent years the number of commercial products has increased dramatically. Despite the fact that these bone substitutes have been on the market for many years, knowledge amongst potential users on how and when they might be useful is still fairly limited. Most injectable bone substitutes belong to one of two major groups: by far the largest group contains products based on various calcium phosphate (CP) mixtures, whilst the smaller group consists of calcium sulphate (CS) compounds. Following mixing, the CP or CS paste can be injected into - for instance - a fracture space for augmentation as an alternative to bone graft, or around a screw for augmentation if the bone is weak. Within minutes an in situ process makes the substitute hard; the mechanical strength in compression resembles that of cancellous bone, whereas the strength in bending and shear is lower. Over time, CP products undergo remodelling through a cell-mediated process that seems to mimic the normal bone remodelling, whilst CS products are dissolved through a faster process that is not cell-mediated. For CP, a number of clinical studies have shown that it can be useful for augmentation of metaphyseal fractures when a space is present. Randomised studies have verified that CP works especially well in tibial plateau fractures when compared with conventional bone grafting. So far the number of clinical studies on CS products is very low.

    Development at present seems to be heading towards premixed or directly mixed products as well as new compounds that contain fibres or other components to enhance bending and shear strength. Products that are based on combinations of CP and CS are also being developed to combine the fast-dissolving CS with the stronger and more slowly remodelling CP. Injectable bone substitutes, and especially CS, have also been targeted as potentially good carriers for antibiotics and growth factors.

  • 53.
    Larsson, Sune
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Procter, Philip
    Optimising implant anchorage (augmentation) during fixation of osteoporotic fractures: Is there a role for bone-graft substitutes?2011In: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 42, no Suppl. 2, p. S72-S76Article in journal (Refereed)
    Abstract [en]

    When stabilising a fracture the contact between the screw and the surrounding bone is crucial for mechanical strength. Through development of screws with new thread designs, as well as optimisation of other properties, improved screw purchase has been gained. Other alternatives to improve screw fixation in osteoporotic bone, as well as normal bone if needed, includes the use of various coatings on the screw that will induce a bonding between the implant surface and the bone implant, as well as application of drugs such as bisphosphonates locally in the screw hole to induce improved screw anchorage through their anticatabolic effect on the bone tissue. As failure of internal fixation of fractures in osteoporotic bone typically occurs through breakage of the bone that surrounds the implant, rather than the implant itself, an alternative strategy in osteoporotic bone can include augmentation of the bone around the screw. This is useful when screws alone are being used for fixation, as it will increase pull-out resistance, but also when conventional plates and screws are used. In angularly stable plate-screw systems, screw back-out is not a problem if the locking mechanism between the screws and the plate works. However, augmentation that will strengthen the bone around the screws can also be useful in conjunction with angle-stable plate-screw systems, as the augmentation will provide valuable support when subjected to loading that might cause cut-out. For many years conventional bone cement, polymethylmethacrylate (PMMA), has been used for augmentation, but due to side effects - including great difficulties if removal becomes necessary - the use of PMMA has never gained wide acceptance. With the introduction of bone substitutes, such as calcium phosphate cement, it has been shown that augmentation around screws can be achieved without the drawbacks seen with PMMA. When dealing with fixation of fractures in osteoporotic bone where screw stability might be inadequate, it therefore seems an attractive option to include bone substitutes for augmentation around screws as part of the armamentarium. Clinical studies now are needed to determine the indications in which bone augmentation with bone-graft substitutes (BGSs) would merit clinical usage.

  • 54.
    Larsson, Sune
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Stadelmann, V. A.
    Arnoldi, J.
    Behrens, M.
    Hess, B.
    Procter, P.
    Murphy, M.
    Pioletti, D. P.
    Injectable calcium phosphate cement for augmentation around cancellous bone screws: In vivo biomechanical studies2012In: Journal of Biomechanics, ISSN 0021-9290, E-ISSN 1873-2380, Vol. 45, no 7, p. 1156-1160Article in journal (Refereed)
    Abstract [en]

    In lower cancellous apparent bone density, it can be difficult to achieve adequate screw fixation and hence stable fracture fixation. Different strategies have been proposed, one of them is through augmentation using calcium phosphate cement in the region at or close to the screw thread itself. To support the hypothesis of an improved screw fixation technique by augmentation of the bone surrounding the implanted screw, in vivo biomechanical and densitometric studies are performed on rabbit specimen where normal and simulated weak bone quality are considered. In particular, the evolution of screw stability till 12 weeks following the implantation is quantified. A statistical significance in the pull out force for augmented versus non-augmented screws was found for the shorter time periods tested of <= 5 days whilst the pull out force was found to increase with time for both augmented and non-augmented screws during the 12 week course of the study. The results of the study demonstrate that the use of an injectable calcium phosphate cement which sets in vivo can significantly improve screw pull out strength at and after implantation for normal and simulated weak bone quality.

  • 55.
    Lejonklou, Margareta H.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Christiansen, S.
    Tech Univ Denmark, Div Diet Dis Prevent & Toxicol, Morkhoj Bygade 19, DK-2860 Soborg, Denmark..
    Örberg, Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Shen, Ling
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Boberg, J.
    Tech Univ Denmark, Div Diet Dis Prevent & Toxicol, Morkhoj Bygade 19, DK-2860 Soborg, Denmark..
    Hass, U.
    Tech Univ Denmark, Div Diet Dis Prevent & Toxicol, Morkhoj Bygade 19, DK-2860 Soborg, Denmark..
    Lind, P. Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Low-dose developmental exposure to bisphenol A alters the femoral bone geometry in wistar rats2016In: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 164, p. 339-346Article in journal (Refereed)
    Abstract [en]

    Background: Bisphenol A (BPA) is a chemical produced in large volumes for use in manufacturing of consumer products and industrial applications, and an endocrine disruptor known to affect several hormonal systems. Bone produces hormones and is additionally a sensitive hormone target tissue, and is thus potentially sensitive to low doses of endocrine disruptors such as BPA, especially during development. Methods: 110 pregnant Wistar rats were gavaged with 0; 25 mu g; 250 mu g; 5000 mu g or 50,000 mu g BPA/kg bodyweight (bw)/day from gestational day 7 until weaning at postnatal day 22. The three-month-old offspring were sacrificed and right femurs collected for length measurements, geometrical measurements by peripheral quantitative computed tomography (pQCT), as well as for analyses of biomechanical properties using the three-point-bending method. Results: The femur was elongated in female offspring of dams exposed to 25 or 5000 mu g BPA/kg bw/day (1.8% and 2.1%, respectively), and increased cortical thickness (4.7%) was observed in male offspring of dams exposed to 25 mu g BPA/kg bw/day, compared to controls (p < 0.005). The biomechanical properties of the bone were not significantly altered. Conclusions: In utero and lactational exposure to the lowest BPA dose used in this study altered femoral geometry in both male and female offspring. This was observed at 25 mu g BPA/kg bw/day, a dose lower than the Human Equivalent Dose (HED) applied by EFSA to set a temporary TDI (609 mu g BPA/kg bw/day), and far lower than the No-Observed-Adverse-Effect-Level (NOAEL) (5000 mu g BPA/kg bw/day) on which the US FDA TDI is based.

  • 56.
    Lejonklou, Margareta Halin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Karimullina, Elina
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lind, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Jacobson Rasmusson, Annica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Rönn, Monika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Blumberg, Bruce
    Lind, P. Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Does developmental exposure to bisphenol A induce bone and adipose tissue disturbances?2014In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 229, p. S243-S243Article in journal (Other academic)
  • 57.
    Lejonklou, Margareta Halin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Lind, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Rasmusson, Annica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Lind, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Developmental low-dose exposure to bisphenol A results in gender-specific and non-monotonic effects on Fischer F344 rat bone2015In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 238, no 2, p. S255-S255Article in journal (Other academic)
  • 58.
    Lind, Monica
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Öberg, Denise
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Kyle, Carol E.
    Örberg, Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Rhind, Stewart M.
    Pregnant ewes exposed to multiple endocrine disrupting pollutants through sewage sludge-fertilized pasture show an anti-estrogenic effect in their trabecular bone2010In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 408, no 11, p. 2340-2346Article in journal (Refereed)
    Abstract [en]

    Pregnant ewes were maintained on pastures fertilized, twice yearly, with either sewage sludge (2.25tonnes dry matter/ha; Treated; T) or inorganic fertilizer containing equivalent amounts of nitrogen (Control; C), to determine effects on maternal and fetal bone structures, density and mechanical properties of exposure to environmental concentrations of multiple endocrine disrupting compounds (EDCs) and heavy metal pollutants. The ewes were maintained on the respective pastures from the age of about 8months until they were 4-6years of age and they were slaughtered at 110d gestation. Metaphyseal parts of adult ewe femurs exhibited a significantly reduced mean, total cross sectional area (CSA, -4%; p<0.05), lower trabecular bone mineral content (BMC, mg/mm; -18%; p<0.05), trabecular bone mineral density (BMD, mg/cm(3), -8.0%; p<0.05) and trabecular CSA, mm(2), -11.1%; p<0.05) in T compared with C animals. Femurs of T ewes were stronger than those of C ewes but this may reflect greater body weights. At the mid-diaphyseal part of the fetal bones, there was a reduction in endosteal circumference (-6.7%, p<0.05) and marrow cavity area (-13.8%, p<0.05) in the female T fetuses compared with female C fetuses. In the male fetuses the mid-diaphyseal part total bone mineral content was higher (+3.0%, p<0.05) in T than in C animals. No treatment difference in biomechanical bending was detected in the fetuses. It is concluded that ewes grazing pasture fertilized with sewage sludge exhibited an anti-estrogenic effect on their trabecular bone in the form of reduced mineral content and density, despite increased body weight. It is suggested that human exposure to low levels of multiple EDCs may have implications for bone structure and human health.

  • 59.
    Lind, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Lejonklou, Margareta Halin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Dunder, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Kushnir, Mark M.
    ARUP Inst Clin & Expt Pathol, Salt Lake City, UT USA;Univ Utah, Dept Pathol, Salt Lake City, UT USA.
    Öhman-Mägi, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Lind, P. Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Developmental low-dose exposure to bisphenol A induces chronic inflammation, bone marrow fibrosis and reduces bone stiffness in female rat offspring only2019In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 177, article id 108584Article in journal (Refereed)
    Abstract [en]

    Background: Developmental exposure to low doses of the endocrine disruptor bisphenol A (BPA) is known to alter bone tissue in young rodents, although how bone tissue is affected in aged animals is not well known. We have recently shown that low-dose developmental exposure to BPA increases procollagen type I N-terminal propeptide (P1NP) levels, a peptide formed during type 1 collagen synthesis, in plasma of 5-week-old female rat offspring while male offspring showed reduced bone size.

    Objective: To analyze offspring bone phenotype at 52 weeks of age and clarify whether the BPA-induced increase in P1NP levels at 5 weeks is an early sign of bone marrow fibrosis development.

    Methods: As in our 5-week study, pregnant Fischer 344 rats were exposed to BPA via drinking water corresponding to 0.5 mu g/kg BW/day (BPA0.5), which is in the range of human daily exposure, or 50 mu g/kg BW/day (BPA50) from gestational day 3.5 until postnatal day 22. Controls were given only vehicle. The offspring were sacrificed at 52 weeks of age. Bone effects were analyzed using peripheral quantitative and micro-computed tomography (microCT), 3-point bending test, plasma markers and histological examination.

    Results: Compared to a smaller bone size at 5 weeks, at the age of 52 weeks, femur size in male offspring had been normalized in developmentally BPA-exposed rats. The 52-week-old female offspring showed, like the 5-week-old siblings, higher plasma P1NP levels compared to controls but no general increasing bone growth or strength. However, 2 out of 14 BPA-exposed female offspring bones developed extremely thick cortices later in life, discovered by systematic in vivo microCT scanning during the study. This was not observed in male offspring or in female controls. Biomechanical testing revealed that both doses of developmental BPA exposure reduced femur stiffness only in female offspring. In addition, histological analysis showed an increased number of fibrotic lesions only in the bone man ow of female rat offspring developmentally exposed to BPA. In line with this, plasma markers of inflammation, Tnf (in BPA0.5) and Timpl (in BPA50) were increased exclusively in female offspring.

    Conclusions: Developmental BPA exposure at an environmentally relevant concentration resulted in female specific effects on bone as well as on plasma biomarkers of collagen synthesis and inflammation. Even a dose approximately eight times lower than the current temporary EFSA human tolerable daily intake of 4 mu g/kg BW/day, appeared to induce bone stiffness reduction, bone man ow fibrosis and chronic inflammation in female rat offspring later in life.

  • 60.
    Lind, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Lejonklou, Margareta Halin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Dunder, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Rasmusson, Annica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Lind, P. Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Low-dose developmental exposure to bisphenol A induces sex-specific effects in bone of Fischer 344 rat offspring2017In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 159, p. 61-68, article id S0013-9351(17)30727-2Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Bisphenol A (BPA) is a component of polycarbonate plastics to which humans are regularly exposed at low levels, and an endocrine disruptor with effects on several hormonal systems. Bone is a sensitive hormone target tissue, and we have recently shown that in utero and lactational exposure to 25µg BPA/kg BW/day alters femoral geometry in rat offspring.

    OBJECTIVE: To investigate bone effects in rat offspring after developmental exposure to a BPA dose in the range of human daily exposure (0.1-1.5µg/kg BW/day) as well as a dose to corroborate previous findings.

    METHODS: Pregnant Fischer 344 rats were exposed to BPA via drinking water corresponding to 0.5µg/kg BW/day: [0.5], (n=21) or 50µg/kg BW/day: [50], (n = 16) from gestational day 3.5 until postnatal day 22, while controls were given only vehicle (n = 25). The offspring was sacrificed at 5 weeks of age. Bone effects were analyzed using peripheral quantitative computed tomography (pQCT), the 3-point bending test, plasma markers of bone turnover, and gene expression in cortical bone and bone marrow.

    RESULTS: Compared to controls, male offspring developmentally exposed to BPA had shorter femurs. pQCT analysis revealed effects in the [0.5] group, but not in the [50] group; BPA reduced both trabecular area (-3.9%, p < 0.01) and total cross sectional area (-4.1%, p < 0.01) of femurs in the [0.5] group, whereas no effects were seen on bone density. Conversely, bone length and size were not affected in female offspring. However, the procollagen type I N-terminal propeptide (P1NP), a peptide formed during type 1 collagen synthesis, was increased in plasma (42%: p < 0.01) in female offspring exposed to [0.5] of BPA, although collagen gene expression was not increased in bone. The biomechanical properties of the bones were not altered in either sex. Bone marrow mRNA expression was only affected in male offspring.

    CONCLUSIONS: Developmental low-dose exposure to BPA resulted in sex-specific bone effects in rat offspring. A dose approximately eight times lower than the current temporary EFSA human tolerable daily intake of 4µg/kg BW/day, reduced bone length and size in male rat offspring. Long-term studies are needed to clarify whether the increased plasma levels of P1NP in female offspring reflect development of fibrosis.

  • 61.
    Lind, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Lind, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Jacobson, Annica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Hu, Lijuan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Sundqvist, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Risteli, Juha
    Yebra-Rodriguez, Africa
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Rodriguez-Navarro, Alejandro
    Andersson, Göran
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    High dietary intake of retinol leads to bone marrow hypoxia and diaphyseal endosteal mineralization in rats2011In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 48, no 3, p. 496-506Article in journal (Refereed)
    Abstract [en]

    Vitamin A (retinol) is the only molecule known to induce spontaneous fractures in laboratory animals and we have identified retinol as a risk factor for fracture in humans. Since subsequent observational studies in humans and old animal data both show that high retinol intake appears to only have small effects on bone mineral density (BMD) we undertook a mechanistic study of how excess retinol reduces bone diameter while leaving BMD essentially unaffected. We fed growing rats high doses of retinol for only 1week. Bone analysis involved antibody-based methods, histology, pQCT, biomechanics and bone compartment-specific PCR together with Fourier Transform Infrared Spectroscopy of bone mineral. Excess dietary retinol induced weakening of bones with little apparent effect on BMD. Periosteal osteoclasts increased but unexpectedly endosteal osteoclasts disappeared and there was a reduction of osteoclastic serum markers. There was also a lack of capillary erythrocytes, endothelial cells and serum retinol transport protein in the endosteal/marrow compartment. A further indication of reduced endosteal/marrow blood flow was the increased expression of hypoxia-associated genes. Also, in contrast to the inhibitory effects in vitro, the marrow of retinol-treated rats showed increased expression of osteogenic genes. Finally, we show that hypervitaminotic bones have a higher degree of mineralization, which is in line with biomechanical data of preserved stiffness in spite of thinner bones. Together these novel findings suggest that a rapid primary effect of excess retinol on bone tissue is the impairment of endosteal/marrow blood flow leading to hypoxia and pathological endosteal mineralization.

  • 62.
    Lindahl, Katarina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Astrom, Eva
    Karolinska Univ Hosp, Pediat Neurol, Astrid Lindgren Childrens Hosp, Stockholm, Sweden;Karolinska Inst, Dept Woman & Child Hlth, Stockholm, Sweden.
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Symoens, Sofie
    Univ Hosp Ghent, Dept Med Genet, Ghent, Belgium.
    Coucke, Paul
    Univ Hosp Ghent, Dept Med Genet, Ghent, Belgium.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Paschalis, Eleftherios
    Ludwig Boltzmann Inst Osteol, Hanusch Hosp WGKK, Vienna, Austria;Hanusch Hosp, Med Dept 1, AUVA Trauma Ctr Meidling, Vienna, Austria.
    Roschger, Paul
    Ludwig Boltzmann Inst Osteol, Hanusch Hosp WGKK, Vienna, Austria;Hanusch Hosp, Med Dept 1, AUVA Trauma Ctr Meidling, Vienna, Austria.
    Gamsjaeger, Sonja
    Ludwig Boltzmann Inst Osteol, Hanusch Hosp WGKK, Vienna, Austria;Hanusch Hosp, Med Dept 1, AUVA Trauma Ctr Meidling, Vienna, Austria.
    Klaushofer, Klaus
    Ludwig Boltzmann Inst Osteol, Hanusch Hosp WGKK, Vienna, Austria;Hanusch Hosp, Med Dept 1, AUVA Trauma Ctr Meidling, Vienna, Austria.
    Fratzl-Zelman, Nadja
    Ludwig Boltzmann Inst Osteol, Hanusch Hosp WGKK, Vienna, Austria;Hanusch Hosp, Med Dept 1, AUVA Trauma Ctr Meidling, Vienna, Austria.
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Homozygosity for CREB3L1 premature stop codon in first case of recessive osteogenesis imperfecta associated with OASIS-deficiency to survive infancy2018In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 114, p. 268-277Article in journal (Refereed)
    Abstract [en]

    Background: Mutations of the endoplasmic reticulum (ER) stress transducer OASIS (encoded by CREB3L1), cause severe recessive osteogenesis imperfecta (OI) not compatible with surviving the neonatal period, as has been shown in two unrelated families through a whole gene deletion vs. a qualitative alteration of OASIS Heterozygous carriers in the described families have exhibited a mild phenotype. OASIS is a transcription factor highly expressed in osteoblasts, and OASIS(-/-) mice exhibit severe osteopenia and spontaneous fractures. Here, we expand the clinical spectrum by a detailed phenotypic characterization of the first case of OASIS-associated OI surviving the neonatal period, with heterozygous family members being unaffected.

    Methods: All OI-associated genes were sequenced. Primary human osteoblast-like cell (hOB) and fibroblast (FB) cultures were obtained for qPCR, and steady-state collagen biochemistry. FB, hOB and skin biopsies were ultrastructurally analyzed. Bone was analyzed by |mu CT, histomorphometry, quantitative backscattered electron imaging (qBEI), and Raman microspectroscopy.

    Results: The proband, a boy with severe OI, had blue sclera and tooth agenesis A homozygous CREB3L1 stop codon mutation was detected by sequencing, while several family members were heterozygotes Markedly low levels of CREB3L1 mRNA were confirmed by qPCR in hOBs (16%) and FB (21%), however, collagen I levels were only reduced in hOBs (5-10%) Electron microscopy of hOBs showed pronounced alterations, with numerous myelin figures and diminished RER vs. normal ultrastructure of FB. Bone histomorphometry and qBEI were similar to collagen I OI, with low trabecular thickness and mineral apposition rate, and increased bone matrix mineralization. Raman microspectroscopy revealed low level of glycosaminoglycans. Clinical response to lifelong bisphosphonate treatment was as expected in severe OI with steadily increasing bone mineral density, but despite this the boy suffered repeated childhood fractures.

    Conclusions: Deficiency of OASIS can cause severe OI compatible with surviving the neonatal period A marked decrease of collagen type I transcription was noted in bone tissue, but not in skin, and ultrastructure of hOBs was pathological. Results also suggested OASIS involvement in glycosaminoglycan secretion in bone.

  • 63. Lundberg, Rebecca
    et al.
    Jenssen, Björn Munro
    Leiva-Presa, Angels
    Rönn, Monika
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Hernhag, Carolina
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Wejheden, Carolina
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Örberg, Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Lind, Monica
    Institute of Environmental Medicine, Karolinska Institutet.
    Effects of short-term exposure to the DDT metabolite p,p'-DDE on bone tissue in male common frog (Rana temporaria)2007In: Journal of Toxicology and Environmental Health, ISSN 1528-7394, E-ISSN 1087-2620, Vol. 70, no 7, p. 614-619Article in journal (Refereed)
    Abstract [en]

    Experimental studies as well as studies in free-ranging animals have shown that endocrine-disrupting chemicals (EDCs) impair bone tissue composition and strength. The aim of the present study was to expand our studies on bone tissue in a new group of animals by investigating whether bone tissue in frogs is an additional potential target of EDCs. Adult male European common frogs (Rana temporaria) were divided into 5 groups (n = 20) and injected (sc, single injection) with p,p'-DDE, a total dose of 0.01, 0.1, 1, or 10 mg of p,p'-DDE/kg body weight, respectively. A control group was treated with the vehicle (corn oil). Two weeks after injection the frogs were euthanized and samples taken. The diaphysis of the excised left femur was scanned using peripheral quantitative computed tomography (pQCT) and cortical variables, such as cortical bone mineral density (BMD), cortical cross-sectional area (CSA), and periosteal circumference, were determined. In addition, biomechanical three-point bending of the bones was conducted, with the load being applied to the same point as where the pQCT measurement was performed. The results from the pQCT measurements show that bone tissue in male frogs exposed to p,p'-DDE is negatively affected. A significant decrease in cortical BMD at the diaphysis was observed in frogs exposed to 1 mg p,p'-DDE. However, the biomechanical testing of the bones showed no significant differences between exposed and control group. Although this is the only study performed to date examining the possible relationships between EDCs and negative effects on frog bones, it supports both previous experimental findings in rodents and findings in free-ranging animals.

  • 64. Lundberg, Rebecca
    et al.
    Lyche, Jan L.
    Ropstad, Erik
    Aleksandersen, Mona
    Rönn, Monika
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Skaare, Janneche U.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Örberg, Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Lind, Monica
    Institute of Environmental Medicine, Karolinska Institutet.
    Perinatal exposure to PCB 153, but not PCB 126, alters bone tissue composition in female goat offspring2006In: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 228, no 1, p. 33-40Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate if environmentally relevant doses of the putative estrogenic non dioxin-like PCB 153 and the dioxin-like PCB 126 caused changes in bone tissue in female goat offspring following perinatal exposure. Goat dams were orally dosed with PCB 153 in corn oil (98 microg/kg body wt/day) or PCB 126 (49 ng/kg body wt/day) from day 60 of gestation until delivery. The offspring were exposed to PCB in utero and through mother's milk. The suckling period lasted for 6 weeks. Offspring metacarpal bones were analysed using peripheral quantitative computed tomography (pQCT) after euthanisation at 9 months of age. The diaphyseal bone was analysed at a distance of 18% and 50% of the total bone length, and the metaphyseal bone at a distance of 9%. Also, biomechanical three-point bending of the bones was conducted, with the load being applied to the mid-diaphyseal pQCT measure point (50%). PCB 153 exposure significantly decreased the total cross-sectional area (125 mm(2)+/-4) versus non-exposed (142 mm(2)+/-5), decreased the marrow cavity (38 mm(2)+/-4) versus non-exposed (50 mm(2)+/-3) and decreased the moment of resistance (318 mm(3)+/-10) versus non-exposed (371 mm(3)+/-20) at the diaphyseal 18% measure point. At the metaphyseal measure point, the trabecular bone mineral density (121 mg/cm(3)+/-5) was increased versus non-exposed (111 mg/cm(3)+/-3). PCB 126 exposure did not produce any observable changes in bone tissue. The biomechanical testing of the bones did not show any significant changes in bone strength after PCB 153 or PCB 126 exposure. In conclusion, perinatal exposure to PCB 153, but not PCB 126, resulted in altered bone composition in female goat offspring.

  • 65. Madanat, R.
    et al.
    Moritz, N.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Aro, H. T.
    RSA applications in monitoring of fracture healing in clinical trials2006In: Scandinavian Journal of Surgery, ISSN 1457-4969, E-ISSN 1799-7267, Vol. 95, no 2, p. 119-127Article in journal (Refereed)
    Abstract [en]

    Radio stereometric analysis (RSA) was originally developed as a method for performing highly accurate three-dimensional measurements in vivo over time from sequential radiographs. Since its introduction over twenty years ago, the RSA method has proven itself as a powerful tool with numerous orthopaedic applications. RSA has been used extensively in studies of prosthetic fixation and has been shown to be the method of choice for these studies. RSA has, however, also been successfully applied to a limited number of studies examining fracture healing, namely in fractures of the radius, ankle, tibial plateau, trochanter and femoral neck, as well as studies of bone healing following spinal fusion and tibial osteotomies. RSA follow-up of a fracture will provide definitive demonstration of the exact time of union, i.e. the achievement of fracture stability. This information can be invaluable in randomized clinical trials of fracture treatment. Phantom model studies have proven useful for effective preoperative planning and interpretation of RSA results. The RSA method is a highly accurate, precise and safe objective method for studying fracture healing in clinical trials. The RSA method may serve as a scientific tool to accurately evaluate the significance of supporting novel biomaterials for the early stability and the rate of healing in fractures.

  • 66.
    Marsell, Richard
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sisask, Gregor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Nilsson, Yvonne
    Sundgren-Andersson, Anna K
    Andersson, Ulf
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Nilsson, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jonsson, Kenneth B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    GSK-3 inhibition by an orally active small molecule increases bone mass in rats2012In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 50, no 3, p. 619-627Article in journal (Refereed)
    Abstract [en]

    Glycogen synthase kinase 3β (GSK-3β) actions are central in the canonical Wnt pathway, important in many biological processes and a potential drug target for treating several diseases. It is appreciated that a balanced Wnt canonical signaling is crucial for the maintenance of normal bone mass. In this study we investigated the effects of a potent orally active GSK-3 inhibitor, AZD2858, on bone mass in rats. Treatment (1μM) of human osteoblast cells with AZD2858 in vitro increased β-catenin levels after a short period of time. In rats, oral AZD2858 treatment caused a dose-dependent increase in trabecular bone mass compared to control after a two-week treatment with a maximum effect at a dose of 20mg/kg once daily (total BMC: 172% of control; p<0.001). A small but significant effect was also seen at cortical sites (total BMC: 111% of control; p<0.001). Biomechanical testing demonstrated an increase in both vertebral compression strength at a dose of 20mg/kg once daily (Load at failure: 370% of control, p<0.001) and diaphyseal strength of femora subjected to a three point bending test (Load at failure: 115% of control; p<0.01). Furthermore, histomorphometry showed a dramatic increase in bone formation indices, and serum markers of both bone formation (Osteocalcin, 146% of control; p<0.001) and resorption (CTX, 189% of control; p<0.001) were elevated. Our conclusion is that a GSK-3 inhibitor drug may prove effective as an anabolic strategy in the treatment of diseases characterized by low bone mass, since AZD2858 has extensive bone building effects at predominantly trabecular sites.

  • 67.
    Mattsson, P
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Larsson, S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Unstable trochanteric fractures augmented with calcium phosphate cement. A prospective randomized study using radiostereometry to measure fracture stability.2004In: Scand J Surg, ISSN 1457-4969, Vol. 93, no 3, p. 223-8Article in journal (Refereed)
  • 68.
    Mattsson, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Alberts, Akke
    Sohlman, Marjut
    Dahlberg, Gösta
    Hyldahl, Hans-Christian
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Resorbable cement for augmentation of internally fixed unstable trochanteric fractures: A prospective randomised multicenter study2005In: Journal of Bone and Joint Surgery, ISSN 0301-620X, E-ISSN 2044-5377, Vol. 87, no 9, p. 1203-1209Article in journal (Refereed)
    Abstract [en]

    We undertook a multicentre, prospective study of a series of 112 unstable trochanteric fractures in order to evaluate if internal fixation with a sliding screw device combined with augmentation using a calcium phosphate degradable cement (Norian SRS) could improve the clinical, functional and radiological outcome when compared with fractures treated with a sliding screw device alone. Pain, activities of daily living, health status (SF-36), the strength of the hip abductor muscles and radiological outcome were analysed. Six weeks after surgery, the patients in the augmented group had significantly lower global and functional pain scores (p < 0.003), less pain after walking 50 feet (p < 0.01), and a better return to the activities of daily living (p < 0.05). At follow-up at six weeks and six months, those in the augmented group showed a significant improvement compared with the control group in the SF-36 score. No other significant differences were found between the groups. We conclude that augmentation with calcium phosphate cement in unstable trochanteric fractures provides a modest reduction in pain and a slight improvement in the quality of life during the course of healing when compared with conventional fixation with a sliding screw device alone.

  • 69.
    Mattsson, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Calcium phosphate cement for augmentation did not improve results after internal fixation of displaced femoral neck fractures: a randomized study of 118 patients2006In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 77, no 2, p. 251-256Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We wanted to evaluate whether augmentation with calcium phosphate cement can improve clinical and functional outcome following internal fixation of displaced femoral neck fractures. PATIENTS: 118 patients aged 60-98 years (95 women) were included. All patients were physically active and ambulatory before the fracture. Patients were randomized to treatment with closed reduction and fixation with two cannulated screws alone (controls: 60 patients) or screws combined with injection of calcium phosphate for augmentation around the screw threads and at the fracture site (augmented: 58 patients). All patients were allowed free weight bearing. Clinical and radiographic examinations were done by a physiotherapist directly after surgery, at 1 and 6 weeks, and at 6, 12 and 24 months. RESULTS: 24 patients, 14 augmented and 10 controls, died during the follow-up. There was 1 deep infection (augmented). Another 34 patients were reoperated with a total arthroplasty (20 in the augmented group and 14 controls) due to loss of reduction, nonunion or avascular necrosis (p = 0.1). There was no difference in pain or muscle strength between groups. Some activities of daily living (ADLs) were slightly better in the augmented patients during the first weeks, while there were no differences between groups later on. INTERPRETATION: Due to a trend towards more reoperations in the augmented group, and only a temporary clinical improvement during the early rehabilitation, augmentation as we used it cannot be recommended.

  • 70.
    Mei, Xueshuang
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery. Peking Univ, Shenzhen Hosp, Dept Otolaryngol, Beijing, Peoples R China.
    Atturo, Francesca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Wadin, Karin
    Uppsala Univ Hosp, Dept Diagnost Radiol, Uppsala, Sweden.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Agrawal, Sumit
    Western Univ, Dept Otolaryngol Head & Neck Surg, London, ON, Canada.
    Ladak, Hanif M.
    Western Univ, Dept Otolaryngol Head & Neck Surg, London, ON, Canada;Western Univ, Dept Med Biophys, London, ON, Canada;Western Univ, Dept Elect & Comp Engn, London, ON, Canada.
    Li, Hao
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Human inner ear blood supply revisited: the Uppsala collection of temporal bone - an international resource of education and collaboration2018In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 3, p. 131-142Article in journal (Refereed)
    Abstract [en]

    Background: The Uppsala collection of human temporal bones and molds is a unique resource for education and international research collaboration. Micro-computerized tomography (micro-CT) and synchrotron imaging are used to investigate the complex anatomy of the inner ear. Impaired microcirculation is etiologically linked to various inner ear disorders, and recent developments in inner ear surgery promote examination of the vascular system. Here, for the first time, we present three-dimensional (3D) data from investigations of the major vascular pathways and corresponding bone channels.

    Methods: We used the archival Uppsala collection of temporal bones and molds consisting of 324 inner ear casts and 113 macerated temporal bones. Micro-CT was used to investigate vascular bone channels, and 26 fresh human temporal bones underwent synchrotron radiation phase contrast imaging (SR-PCI). Data were processed by volume-rendering software to create 3D reconstructions allowing orthogonal sectioning, cropping, and soft tissue analyses.

    Results: Micro-CT with 3D rendering was superior in reproducing the anatomy of the vascular bone channels, while SR-PCI replicated soft tissues. Arterial bone channels were traced from scala vestibuli (SV) arterioles to the fundus, cochlea, and vestibular apparatus. Drainage routes along the aqueducts were examined.

    Conclusion: Human inner ear vessels are difficult to study due to the adjoining hard bone. Micro-CT and SR-PCI with 3D reconstructions revealed large portions of the micro-vascular system in un-decalcified specimens. The results increase our understanding of the organization of the vascular system in humans and how altered microcirculation may relate to inner ear disorders. The findings may also have surgical implications.

  • 71.
    Michaëlsson, Karl
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Olofsson, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Jensevik, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Leisure physical activity and the risk of fracture in men2007In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 4, no 6, p. 1094-1100Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Data from previous studies are inconsistent, and it is therefore uncertain whether, to what extent, and at what level leisure physical activity influences the risk of osteoporotic fractures in men. METHODS AND FINDINGS: A cohort of 2,205 men, 49-51 y of age, was enrolled in a longitudinal, population-based study. Leisure physical activity and other lifestyle habits were established at baseline and at ages 60, 70, 77, and 82 y. During 35 y of follow-up, 482 men had at least one fracture. Cox's proportional hazards regression was used to determine hazard ratios (HRs) of fracture associated with time-dependent physical activity habits and covariates. Men with a sedentary lifestyle (HR 2.56, 95% confidence interval 1.55-4.24) or men who walked or bicycled only for pleasure (HR 1.61, 95% confidence interval 1.10-2.36) had an increased adjusted risk of hip fracture compared with men who participated in regular sports activities for at least 3 h/wk. At the end of follow-up, 8.4% of the men with a high physical activity, 13.3% of the men with a medium physical activity, and 20.5% of the men with a low physical activity had suffered a hip fracture. According to the estimation of population-attributable risk, one third of all hip fractures could be prevented by participation in regular sports activities. High activity also conferred a reduced overall fracture risk. CONCLUSIONS: Our data indicate that regular sports activities can reduce the risk of fractures in older men.

  • 72.
    Nowak, J
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Holgersson, Margareta
    Larsson, S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Can we predict long-term sequelae after fractures of the clavicle based on initial findings? A prospective study with nine to ten years of follow-up.2004In: J Shoulder Elbow Surg, ISSN 1058-2746, Vol. 13, no 5, p. 479-86Article in journal (Refereed)
  • 73.
    Nowak, Jan
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Holgersson, Margareta
    Larsson, Sune
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Sequelae from clavicular fractures are common: a prospective study of 222 patients.2005In: Acta Orthop, ISSN 1745-3674, Vol. 76, no 4, p. 496-502Article in journal (Refereed)
  • 74.
    Nysjö, Johan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Christersson, Albert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sintorn, Ida-Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Nyström, Ingela
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Malmberg, Filip
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Precise 3D Angle Measurements in CT Wrist Images2013In: Image Analysis and Processing – ICIAP 2013: Part II, Springer Berlin/Heidelberg, 2013, p. 479-488Conference paper (Refereed)
    Abstract [en]

    The clinically established method to assess the displacement of a distal radius fracture is to manually measure two reference angles,the dorsal angle and the radial angle, in consecutive 2D X-ray images of the wrist. This approach has the disadvantage of being sensitive to operator errors since the measurements are performed on 2D projections of a 3D structure. In this paper, we present a semi-automatic system for measuring relative changes in the dorsal angle in 3D computed tomography (CT) images of fractured wrists. We evaluate the proposed 3D measurement method on 28 post-operative CT images of fractured wrists and compare it with the radiographic 2D measurement method used in clinical practice. The results show that our proposed 3D measurement method has a high intra- and inter-operator precision and is more precise and robust than the conventional 2D measurement method.

  • 75. Olofsson, Christina
    et al.
    Ahl, Torbjörn
    Johansson, Torsten
    Larsson, Sune
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Nellgård, Per
    Ponzer, Sari
    Fagrell, Bengt
    Przybelski, Robert
    Keipert, Peter
    Winslow, Nancy
    Winslow, Robert M
    A multicenter clinical study of the safety and activity of maleimide-polyethylene2006In: Anesthesiology, ISSN 0003-3022, Vol. 105, no 6, p. 1153-63Article in journal (Refereed)
  • 76.
    Paidikondala, Maruthibabu
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Wang, Shujiang
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Yan, Hongji
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Podiyan, Oommen
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hilborn, Jöns
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Varghese, Oommen P.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Rational Design of Biomaterials for Growth Factor Delivery: Impact of Hydrogel Crosslinking Chemistry on the In Vitroand In VivoBioactivity of Recombinant Human Bone Morphogenetic Protein-2Manuscript (preprint) (Other academic)
  • 77. Procter, P.
    et al.
    Bennani, P.
    Brown, C. J.
    Arnoldi, J.
    Pioletti, D. P.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Variability of the pullout strength of cancellous bone screws with cement augmentation2015In: Clinical Biomechanics, ISSN 0268-0033, E-ISSN 1879-1271, Vol. 30, no 5, p. 500-506Article in journal (Refereed)
    Abstract [en]

    Background: Orthopaedic surgeons often face clinical situations where improved screw holding power in cancellous bone is needed. Injectable calcium phosphate cements are one option to enhance fixation. Methods: Paired screw pullout tests were undertaken in which human cadaver bone was augmented with calcium phosphate cement. A finite element model was used to investigate sensitivity to screw positional placement. Findings: Statistical analysis of the data concluded that the pullout strength was generally increased by cement augmentation in the in vitro human cadaver tests. However, when comparing the individual paired samples there were surprising results with lower strength than anticipated after augmentation, in apparent contradiction to the generally expected conclusion. Investigation using the finite element model showed that these strength reductions could be accounted for by small screw positional changes. A change of 0.5 mm might result in predicted pullout force changes of up to 28%. Interpretation: Small changes in screw position might lead to significant changes in pullout strength sufficient to explain the lower than expected individual pullout values in augmented cancellous bone. Consequently whilst the addition of cement at a position of low strength would increase the pullout strength at that point it might not reach the pullout strength of the un-augmented paired test site. However, the overall effect of cement augmentation produces a significant improvement at whatever point in the bone the screw is placed. The use of polymeric bone-substitute materials for tests may not reveal the natural variation encountered in tests using real bone structures.

  • 78.
    Procter, Philip
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Pujari-Palmer, Michael
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences. Uppsala University.
    Hulsart Billström, Gry
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Insley, Gerard
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    A new ex-vivo murine model for evaluation of adhesiveness of a novel biomimetic bone glue2018Conference paper (Refereed)
  • 79.
    Procter, Philip
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Pujari-Palmer, Michael
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences. Uppsala University.
    Hulsart Billström, Gry
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Insley, Gerard
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Designing A Commercial Biomaterial For A Specific Unmet Clinical Need –: An Adhesive Odyssey2018Conference paper (Refereed)
    Abstract [en]

    There are clinical situations in fracture repair, e.g. osteochondral fragments, where current implant hardware is insufficient. The proposition of an adhesive enabling fixation and healing has been considered but no successful candidate has emerged thus far. The many preclinical and few clinical attempts include fibrin glue, mussel adhesive and even “Kryptonite” (US bone void filler). The most promising recent attempts are based on phosphorylating amino acids, part of a common cellular adhesion mechanism linking mussels, caddis fly larvae, and mammals. Rapid high bond strength development in the wetted fatty environment of fractured bone, that is sustained during biological healing, is challenging to prove both safety and efficacy. Additionally, there are no “predicate” preclinical animal and human models which led the authors to develop novel evaluations for an adhesive candidate “OsStictm” based on calcium salts and amino acids. Adhesive formulations were evaluated in both soft (6/12 weeks) and hard tissue (3,7,10,14 & 42 days) safety studies in murine models. The feasibility of a novel adhesiveness test, initially proven in murine cadaver femoral bone, is being assessed in-vivo (3,7,10,14 & 42 days) in bilateral implantations with a standard tissue glue as the control. In parallel an ex-vivo human bone model using freshly harvested human donor bone is under development to underwrite the eventual clinical application of such an adhesive. This is part of a risk mitigation project bridging between laboratory biomaterial characterisation and a commercial biomaterial development where safety and effectiveness have to meet today´s new medical device requirements.

  • 80.
    Rahme, H
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Mattsson, P
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Larsson, S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Stability of cemented all-polyethylene keeled glenoid components. A radiostereometric study with a two-year follow-up.2004In: J Bone Joint Surg Br, ISSN 0301-620X, Vol. 86, no 6, p. 856-60Article in journal (Refereed)
  • 81.
    Rahme, Hans
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Mattsson, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Stable fixation of the ulnar component in the Kudo elbow prosthesis: A radiostereometric (RSA) study of 13 prostheses with 2-year follow-up2005In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 76, no 1, p. 104-108Article in journal (Refereed)
    Abstract [en]

    Background Concern has been expressed about the large number of radiolucent lines around the ulnar component of the Kudo elbow prosthesis in medium-term follow-up. Patients and methods We studied the metal-backed cemented ulnar component in 13 Kudo elbow prostheses (type 5) using radiostereometric analysis (RSA). All patients had rheumatoid arthritis. There were 2 men and 9 women with a mean age of 55 years. 2 were operated bilaterally. The metal-backed ulnar component was marked with three 0.8 mm tantalum spheres and the proximal ulna with 5 spheres of 0.8 or 1.0 mm diameter. The initial RSA examination was performed during the first week after the operation. Further examinations were done at 4, 12 and 24 months. Conventional radiographs were taken during the first week postoperatively, and at 12 and 24 months. Results Translations (medial/lateral, antero/posterior and proximal/distal) were less than 0.5 mm in all but 1 patient who had a maximal translation of 3.4 mm distally. The mean rotations around all three axes were less than 0.4 degrees. The patient who had a translation of 3.4 mm also had varus angulation exceeding 4 degrees. This patient also had progressive circumferential radiolucent lines on conventional radiographs. The Mayo elbow score increased from 40 (25-65) before surgery to 92 (45-100) at 2 years. Interpretation The fixation of the metal-backed ulnar component of the Kudo elbow prosthesis at 2 years is good.

  • 82.
    Rahme, Hans
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Mattsson, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Wikblad, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Cement and press-fit humeral stem fixation provides similar results in rheumatoid patients2006In: Clinical Orthopaedics and Related Research, ISSN 0009-921X, E-ISSN 1528-1132, no 448, p. 28-32Article in journal (Refereed)
    Abstract [en]

    It is unclear whether humeral stems should be fixed with or without cement. We question whether press-fit fixation would provide similar results to cemented stem fixation. We prospectively randomized 26 shoulders in 24 patients with rheumatoid arthritis (20 women, 4 men) to have either a cemented or press-fit stem. In the press-fit group, stems were matched to the medullary canal, while lavage, pressurizing and distal plugging were used in the cemented group. We followed patients with conventional radiographs and radiostereometric analysis (RSA) at 5 to 7 days, 4 months, 1 year, and 2 years after surgery. One patient died from unrelated causes before the 1-year followup, while the remaining patients were followed according to the protocol. All but two patients were very satisfied or satisfied at 2 years. No stem was radiographically loose. There was no difference in micromotion between groups. The average rotation for all axes was less than 0.25° for both groups and the average translation was less than 0.32 mm for all three axes including subsidence, which was less than 0.1 mm for the uncemented stems. We concluded at 2 years these stems provided similar fixation in rheumatoid shoulders.

  • 83.
    Sandén, B
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Olerud, C
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    Petren-Mallmin, M
    Johansson, C
    Larsson, S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
    The significance of radiolucent zones surrounding pedicle screws. Definition of screw loosening in spinal instrumentation.2004In: J Bone Joint Surg Br, ISSN 0301-620X, Vol. 86, no 3, p. 457-61Article in journal (Refereed)
  • 84.
    Sandén, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Olerud, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Johansson, Carina
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Improved bone-screw interface with hydroxyapatite coating: an in vivo study of loaded pedicle screws in sheep2001In: Spine, ISSN 0362-2436, E-ISSN 1528-1159, Vol. 26, no 24, p. 2673-8Article in journal (Refereed)
    Abstract [en]

    STUDY DESIGN: An in vivo sheep model with loaded pedicle screws was used, wherein each animal served as its own control. OBJECTIVES: To examine the effects of hydroxyapatite (HA) coating on the bone-to-implant interface in loaded spinal instrumentations. SUMMARY OF BACKGROUND DATA: Spinal instrumentation improves the healing rate in spinal fusion, but screw loosening constitutes a problem. HA coating of other implants has resulted in favorable effects on the bone-to-implant interface. METHODS: Nine sheep were operated on with destabilizing laminectomies at two levels: L2-L3 and L4-L5. Each level was stabilized separately with a four-screw instrumentation. Uncoated screws (stainless steel) or the same type of screws coated with plasma-sprayed HA were used in either the upper or the lower instrumentation in a randomized fashion. The animals were killed at 6 or 12 weeks after surgery. The specimens were embedded in resin, ground to approximately 10 microm, and stained with toluidine blue. Histomorphometric evaluation was carried out in a Leitz Aristoplan (Wetzlar, Germany) light microscope equipped with a Leitz Microvid unit. RESULTS: The average percentage of bone-to-implant contact after 6 weeks was 69 +/- 10 for the HA-coated screws and 18 +/- 11 for the uncoated screws (P < 0.03), and after 12 weeks 64 +/- 31 (HA-coated) and 9 +/- 13 (uncoated, P < 0.02). The average bone volume in the area close to the screw was significantly higher for the HA-coated screws at both 6 and 12 weeks. CONCLUSIONS: HA coating improved the bone-to-implant interface significantly, indicating that HA coating can become useful for improving the purchase of pedicle screws.

  • 85.
    Sandén, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Olerud, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Johansson, Carina
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Improved extraction torque of hydroxyapatite-coated pedicle screws2000In: European spine journal, ISSN 0940-6719, E-ISSN 1432-0932, Vol. 9, no 6, p. 534-7Article in journal (Refereed)
    Abstract [en]

    Loosening of the screws is a problem in instrumentation with pedicle screws. Coating with hydroxyapatite improves the holding characteristics for metal implants, but the possible effects on the anchorage of pedicle screws have not been described. In this study, seven patients were operated on with spinal instrumentation using four stainless steel pedicle screws. Hydroxyapatite-coated screws were used in either the upper or the lower of the instrumented levels. The insertion torque was measured. In four cases the screws were removed after 10-22 months and the extraction torque was measured. The mean insertion torque was found to be significantly greater in the hydroxyapatite-coated screws (107 Ncm) than in the standard screws (76 Ncm). In three cases, the extraction torque for the hydroxyapatite-coated screws exceeded the range for the torque wrench (600 Ncm), while the conventional screws were loose (< 5 Ncm). In one case, the extraction torque was 475 and 550 Ncm for the coated screws, and 5 and 25 Ncm for the conventional screws. The difference in extraction torque was significant. Hydroxyapatite coating was shown to have improved the purchase of pedicle screws very effectively. By using fully coated screws, as in the present study, extraction was extremely difficult compared to extraction of conventional stainless steel screws, which were regularly loose. By reducing the area of the screws that is coated, it may be possible to achieve an enhanced purchase while extraction will be easier when compared to fully coated screws.

  • 86.
    Sandén, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Olerud, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hydroxyapatite coating enhances fixation of loaded pedicle screws: a mechanical in vivo study in sheep2001In: European spine journal, ISSN 0940-6719, E-ISSN 1432-0932, Vol. 10, no 4, p. 334-9Article in journal (Refereed)
    Abstract [en]

    Loosening of the pedicle screws with subsequent non-union or loss of correction is a frequent problem in spinal instrumentation. In a clinical pilot study, coating of pedicle screws with plasma-sprayed hydroxyapatite (HA) resulted in a significant increase of removal torque. An experimental study was performed to investigate the effects of HA coating on the pull-out resistance. Thirteen sheep were operated on with destabilising laminectomies at two levels, L2-L3 and L4-L5. Two instrumentations with four pedicle screws in each were used for stabilisation. Uncoated screws (stainless steel) or the same type of screws coated with plasma-sprayed HA were used in either the upper or the lower instrumentation in a randomised fashion. Four sheep were examined immediately after the application of the screws, three sheep at 6 weeks and four sheep at 12 weeks. Two sheep were euthanised early due to complications. The pull-out resistance was recorded in two HA-coated and two standard screws in each animal. The maximum pull-out resistance was higher for the HA-coated screws at 0 weeks (P< 0.02) and at 12 weeks (P<0.01) when compared to the uncoated screws, while there was no significant difference between the groups at 6 weeks. We believe that the higher pull-out resistance for HA-coated screws at 0 weeks was mainly caused by differences in surface roughness, while the difference at 12 weeks was due to a favourable bone reaction around the HA-coated screws. At 12 weeks, the average stiffness was significantly higher for the HA-coated screws, while there was no significant differences in stiffness between the two screw types at 0 and 6 weeks. Energy to failure was significantly higher for coated screws when compared to the uncoated screws at all three time points. HA coating improves fixation of loaded pedicle screws, with increased pull-out resistance and reduced risk of loosening.

  • 87.
    Sandén, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Olerud, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Robinson, Yohan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Insertion torque is not a good predictor of pedicle screw loosening after spinal instrumentation: a prospective study in 8 patients.2010In: Patient safety in surgery, ISSN 1754-9493, Vol. 4, no 1, p. 14-Article in journal (Refereed)
    Abstract [en]

    In this unique human in-vivo study, the insertion torque could not be used to predict the purchase of lumbar pedicle screws one year after implantation. It could be demonstrated that in vivo insertion torque alone is of minor value to estimate pullout strength, and should be combined with or replaced by more accurate measures.

  • 88.
    Sandén, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Olerud, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Petrén-Mallmin, M.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hydroxyapatite coating improves fixation of pedicle screws: A clinical study2002In: Journal of Bone and Joint Surgery, ISSN 0301-620X, E-ISSN 2044-5377, Vol. 84, no 3, p. 387-91Article in journal (Refereed)
    Abstract [en]

    We investigated the effects of hydroxyapatite (HA) coating on the purchase of pedicle screws. A total of 23 consecutive patients undergoing lumbar fusion was randomly assigned to one of three treatment groups. The first received uncoated stainless-steel screws, the second screws which were partly coated with HA, and the third screws which were fully coated. The insertion torque was recorded. After 11 to 16 months, 21 screws had been extracted. The extraction torque was recorded. Radiographs were taken to assess fusion and to detect loosening of the screws. At removal, the extraction torques exceeded the upper limit of the torque wrench (600 Ncm) for many HA-coated screws. The calculated mean extraction torque was 29 +/- 36 Ncm for the uncoated group, 447 +/- 114 Ncm for the partly-coated group and 574 +/- 52 Ncm for the fully-coated group. There were significant differences between all three groups (p < 0.001). There were more radiolucent zones surrounding the uncoated screws than the HA-coated screws (p < 0.001). HA coating of pedicle screws resulted in improved fixation with reduced risk of loosening of the screws.

  • 89.
    Schart-Moren, Nadine
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Li, Hao
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Anatomical Characteristics of Facial Nerve and Cochlea Interaction2017In: Audiology & neuro-otology, ISSN 1420-3030, E-ISSN 1421-9700, Vol. 22, no 1, p. 41-49Article in journal (Refereed)
    Abstract [en]

    Objective: The aim was to study the relationship between the labyrinthine portion (LP) of the facial canal and the cochlea in human inner ear molds and temporal bones using micro-CT and 3D rendering. A reduced cochlea-facial distance may spread electric currents from the cochlear implant to the LP and cause facial nerve stimulation. Influencing factors may be the topographic anatomy and otic capsule properties.

    Methods: An archival collection of human temporal bones underwent micro-CT and 3D reconstruction. In addition, cochlea-facial distance was assessed in silicone and polyester resin molds, and the association between the LP and upper basal turn of the cochlea was analyzed.

    Results: Local thinning of the otic capsule and local anatomy may explain the development of cochlea-facial dehiscence, which was found in 1.4%. A reduced cochlea-facial distance was noted in 1 bone with a superior semicircular canal dehiscence but not in bones with superior semicircular canal "blue line." The otic capsule often impinged upon the LP and caused narrowing.

    Conclusion: Micro-CT with 3D rendering offers new possibilities to study the topographic anatomy of the human temporal bone. The varied shape of the cross-section of the LP could often be explained by an "intruding" cochlea.

  • 90.
    Schart-Moren, Nadine
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Li, Hao
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Three-Dimensional Analysis of the Fundus of the Human Internal Acoustic Canal2018In: Ear and Hearing, ISSN 0196-0202, E-ISSN 1538-4667, Vol. 39, no 3, p. 563-572Article in journal (Refereed)
    Abstract [en]

    Objectives: Documentation of the nerve components in the internal acoustic canal is essential before cochlea implantation surgery. Interpretations may be challenged by wide anatomical variations of the VIIIth nerve and their ramifications. Malformations may further defy proper nerve identification. Design: Using microcomputed tomography, we analyzed the fundus bone channels in an archival collection of 113 macerated human temporal bones and 325 plastic inner molds. Data were subsequently processed by volume-rendering software using a bony tissue algorithm. Three-dimensional reconstructions were made, and through orthogonal sections, the topographic anatomy was established. Results: The technique provided additional information regarding the anatomy of the nerve foramina/channels of the human fundus region, including variations and destinations. Channel anastomosis were found beyond the level of the fundus. A foramen of the transverse crest was identified. Conclusions: Three-dimensional reconstructions and cropping outlined the bone canals and demonstrated the highly variable VIIIth nerve anatomy at the fundus of the human inner acoustic canal. Myriad channel interconnections suggested an intricate system of neural interactive pathways in humans. Particularly striking was the variable anatomy of the saccule nerve channels. The results may assist in the preoperative interpretation of the VIIIth nerve anatomy.

  • 91.
    Silfverswärd, Carl-Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Ohlsson, Claes
    Frost, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Nilsson, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Reduced Cortical Bone Mass in Mice with Inactivation of Interleukin-4 and Interleukin-132007In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 25, no 6, p. 725-731Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to study the in vivo role of IL-4 and IL-13 on bone metabolism. The skeletal phenotypes of male and female IL-13-/- (n = 7+7), IL-4-/-IL-13-/- (n = 7+7), and WT (n = 7+7) mice were compared. Analysis was made at 6 weeks of age (juvenile) by pQCT, and at 20 weeks of age (adult) by pQCT, biomechanical testing, and by S-IGF-1 and S-Osteocalcin measurements. The skeletal phenotype was affected only in adult male IL-4-/-IL-13-/- mice. These animals displayed a reduction in cortical bone mineral content (BMC) of both the tibia and the femur, as measured by mid-diaphyseal pQCT scans, compared with WT mice (tibia -8.2%; femur -8.5%; p < 0.01). This reduction in cortical BMC was due to a decreased cross-sectional area as a result of a reduced cortical thickness. The mechanical strength of the cortical bone, tested by three-point-bending at the mid-diaphyseal region of the femurs, demonstrated a significant reduction of displacement at failure (-11.4%), maximal load at failure (-10.6%), and total energy until failure (-29.4%). S-IGF-1 and S-Osteocalcin levels as well as trabecular bone mineral density (tvBMD) were unaffected in adult male IL-4-/-IL-13-/- mice. IL-4-/-IL-13-/- male mice show adult onset reduction of cortical bone mass and strength, indicating that the two anti-inflammatory Th2 cytokines IL-4 and IL-13 are involved in the regulation of bone remodeling.

  • 92.
    Silfverswärd, Carl-Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sisask, Gregor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ohlsson, Claes
    Frost, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Nilsson, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Bone Formation in Interleukin-4 and Interleukin-13 depleted Mice2008In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 79, no 3, p. 410-420Article in journal (Refereed)
    Abstract [en]

    Background and purpose Cytokines play an important role in the complex process of bone formation. We have previously found an altered skeletal phenotype with reduction of cortical bone mass in mice depleted of the 2 cytokines interleukin-4 (IL-4) and interleukin-13 (IL 13). The present study was performed to investigate a potential role of IL-4 and IL-13 in fracture healing and bone induction by demineralized xenogenic bone matrix (DXBM). Methods Callus formation in IL-4(-/-)IL-13(-/-) (IL-4/13 knockout) and wild-type (WT) male mice was compared using a standardized fracture model. The capacity of IL-4(-/-)IL-13(-/-) and WT male and female mice to form heterotopic bone was compared using intramuscular implants of DXBM. Bone formation and mechanical properties were evaluated by pQCT, ash weight, 3-point bending, radiology, and immunohistology. Results In the fracture investigation substantial amounts of new bone formation by 5 weeks were found, but no differences in radiographical healing, callus volume, BMD, BMC, or mechanical properties were detected between IL-4(-/-)IL-13(-/-) and WT mice. In the DXBM investigation radiographic analysis confirmed mineralization of implants in both groups, but no difference in the amount of mineral deposition (net bone formation) between IL-4(-/-)IL-13(-/-) and WT mice was found. Immunohistology showed inhibition of autonomic nerves in the capsule of the IL-4(-/-)IL-13(-/-) group along with a lack of vascularization within the implants. Interpretation Depletion of IL-4 and IL-13 does not cause any major alteration in fracture healing or heterotopic bone formation in mice. The pattern of autonomous nerve expression and expression of markers of neovascularization is, however, altered to some extent by the absence of IL-4 and IL-13.

  • 93.
    Sisask, Gregor
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Marsell, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sundgren-Andersson, Anna
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Nilsson, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Metabolic Bone Diseases.
    Jonsson, Kenneth B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Rats treated with AZD2858, a GSK3 inhibitor, heal fractures rapidly without endochondral bone formation2013In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 54, no 1, p. 126-132Article in journal (Refereed)
    Abstract [en]

    Fracture healing is a complex interplay between endochondral and intramembranous bone formation processes. The canonical Wnt/β-catenin pathway enhances new bone formation and may play a role in fracture healing. Glycogen synthase kinase 3β (GSK3β) is a key regulator of β-catenin degradation. In this study, we investigate the effects of AZD2858, an orally bioactive GSK3 inhibitor, on fracture healing. Femoral fractures were produced in rats after the insertion of a femoral nail. The rats were treated with oral administration of AZD2858 at a dose of 30μmol/kg (20mg/kg) daily for up to 3weeks, while control animals were administered vehicle. At 4days, and at 1, 2 and 3weeks, histological analysis was performed, and at the 2 and 3week time points, we performed peripheral quantitative computed tomography (pQCT), X-rays, and four-point bending tests. Peripheral QCT showed an increase in both mineral density (of 28% at 2weeks and 38% at 3weeks) and mineral content (of 81% at 2weeks and 93% at 3weeks) in the calluses from AZD2858 treated animals as compared to vehicle treated animals. Histological analysis demonstrated that rats treated with GSK3 inhibitor healed their fractures rapidly, but without the pre-formation of cartilage tissue. Furthermore, four-point bending tests of fractured femora from animals treated for 2 and 3weeks showed an increase in strength in treated animals compared to their vehicle-treated controls. In conclusion, AZD2858, a potent GSK3 inhibitor, has a substantial impact on fracture healing. The fractures healed with a bony callus without an obvious endochondral component, suggesting that AZD2858 drives mesenchymal cells into the osteoblastic pathway. This leads to direct bone repair in an unstable fracture milieu.

  • 94.
    Staaf, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Åkerström, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Ljungström, Viktor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Karlsson, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Bergsten, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Hög tid att söka till nya MD/PhD-programmet vid Uppsala universitet: Tidig bro mellan preklinisk forskning och klinik2012In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, no 17-18, p. 898-898Article in journal (Refereed)
  • 95.
    Stenfelt, Sonya
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry, Polymer Chemistry.
    Hulsart-Billström, Gry
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Gedda, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Bergman, Kristoffer
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hilborn, Jöns
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry, Polymer Chemistry.
    Bowden, Tim
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry, Polymer Chemistry.
    Pre-incubation of chemically crosslinked hyaluronan-based hydrogels, loaded with BMP-2 and hydroxyapatite, and its effect on ectopic bone formation2014In: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 25, no 4, p. 1013-1023Article in journal (Refereed)
    Abstract [en]

    The effects of pre-incubation of hyaluronan hydrogels, for different lengths of time after the initiation of chemical crosslinking and prior to injection, were explored both by investigating the in vitro BMP-2 release kinetics from the hydrogel and by studying the ectopic bone formation in rats. From the curing profile, obtained from rheological analysis, appropriate pre-incubation times (1 min, 5 h and 3 days) were selected, to prepare slightly, moderately and fully cured hydrogels. Comparable release profiles were observed for all three test groups in vitro. Furthermore, radiography, pQCT and histology of the explanted grafts showed cancellous bone formation in all groups after 5 weeks in vivo. However, longer pre-incubation times gave rise to an increase in bone volume, but a decrease in bone density. Moreover, the 5 h and the 3 days grafts appeared to be more ordered and resistant to deformation from the surrounding tissue than the 1 min grafts. The observed variations in mechanical and biological properties could potentially be used to adapt the treatment for a specific indication.

  • 96.
    Ström, Håkan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Nilsson, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Milbrink, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Early migration pattern of the uncemented CLS stem in total hip arthroplasties2007In: Clinical Orthopaedics and Related Research, ISSN 0009-921X, E-ISSN 1528-1132, no 454, p. 127-132Article in journal (Refereed)
    Abstract [en]

    We performed this investigation to determine the possible migration starting immediately after surgery and the effect of different weightbearing regimens on the migration pattern of an uncemented hip stem (CLS). Stem migration was determined with radiostereometry analysis with baseline when the patients still were anesthetized. Subsequent examinations were done up to 1 year. Twenty-nine patients (mean age, 55 years; range, 26-63 years) were randomized to either unrestricted weightbearing combined with intensive physiotherapy from the first day after surgery or to partial weightbearing and a conservative training regimen for the first 3 months after surgery. At 1 week, subsidence was -0.03 mm in the unrestricted weightbearing group and 0.01 mm in the partial weightbearing group. At 1 year, subsidence was 1.01 mm in the unrestricted weightbearing group and 0.51 mm in the partial weightbearing group. One patient in the unrestricted weightbearing group had revision surgery because of aseptic loosening at 1.5 years after surgery. The CLS stem did not have any migration from the end the surgery until 1 week, but there was small migration from 1 week to 3 months after which the stem remained stable. The degree of early weightbearing did not affect the migration pattern.

  • 97.
    Ström, Håkan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Nilsson, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Milbrink, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    The effect of early weight bearing on migration pattern of the uncemented CLS stem in total hip arthroplasty2007In: The Journal of Arthroplasty, ISSN 0883-5403, E-ISSN 1532-8406, Vol. 22, no 8, p. 1122-1129Article in journal (Refereed)
    Abstract [en]

    Forty-two patients (younger than 65 years) with osteoarthritis were operated on with an uncemented CLS stem and randomized to early unrestricted weight bearing combined with intensive physiotherapy or to partial weight bearing combined with self-training. Radiostereometric analysis showed 1.2 (+0.11 to -6.76) mm subsidence of the stem at 24 months in both groups. There was no significant difference in the migration pattern between the unrestricted and partial weight bearing groups. Actual loading on the operated leg, measured with the F-scan system, did not influence the migration of the stem. There was a strong correlation between the average subsidence at 3 and 24 months (r = 0.96). Early full weight bearing and active rehabilitation can be used for the uncemented CLS stem without increased risk of early loosening.

  • 98.
    Thor, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Farzad, Payam
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Fracture of the tibia: Complication of bone grafting to the anterior maxilla2006In: British Journal of Oral & Maxillofacial Surgery, ISSN 0266-4356, E-ISSN 1532-1940, Vol. 44, no 1, p. 46-48Article in journal (Refereed)
    Abstract [en]

    Autogenous tibial cancellous bone has been used for reconstructive operations in oral and maxillofacial surgery for over 10 years, and has reduced many of the problems associated with conventional sites of autogenous grafts such as the iliac crest. The ease of access for harvesting, the speed of the operation, and the abundance of bone, are advantages of this donor site. We report a patient who had a graft taken from the proximal tibia and had a displaced fracture 2 weeks later after a fall. Five similar cases have been reported previously, of which none has required surgical intervention.

  • 99. Vuong, Vicky
    et al.
    Pettersson, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Grandfield, Kathryn
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Surface and Subsurface Analyses of Metal-on-Polyethylene Total Hip Replacement Retrievals2016In: Annals of Biomedical Engineering, ISSN 0090-6964, E-ISSN 1573-9686, Vol. 44, no 5, p. 1685-1697Article in journal (Refereed)
    Abstract [en]

    Metal-on-polyethylene (MoP) articulations are one of the most reliable implanted hip prostheses. Unfortunately, long-term failure remains an obstacle to the service life. There is a lack of higher resolution research investigating the metallic surface component of MoP hip implants. This study investigates the surface and subsurface features of metallic cobalt chromium molybdenum alloy (CoCrMo) femoral head components from failed MoP retrievals. Unused prostheses were used for comparison to differentiate between wear-induced defects and imperfections incurred during implant manufacturing. The predominant scratch morphology observed on the non-implanted references was shallow and linear, whereas the scratches on the retrievals consisted of largely nonlinear, irregular scratches of varying depth (up to 150 nm in retrievals and up to 60 nm in reference samples). Characteristic hard phases were observed on the surface and subsurface material of the cast samples. Across all samples, a 100-400 nm thick nanocrystalline layer was visible in the immediate subsurface microstructure. Although observation of the nanocrystalline layer has been reported in metal-on-metal articulations, its presence in MoP retrievals and unimplanted prostheses has not been extensively examined. The results suggest that manufacturing-induced surface and subsurface microstructural features are present in MoP hip prostheses prior to implantation and naturally, these imperfections may influence the in vivo wear processes after implantation.

  • 100. Wejheden, Carolina
    et al.
    Brunnberg, Sara
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lind, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Andersson, Göran
    Hanberg, Annika
    Transgenic mice with a constitutively active aryl hydrocarbon receptor (CA-AhR) display a gender specific bone phenotype2010In: Toxicological Sciences, ISSN 1096-6080, E-ISSN 1096-0929, Vol. 114, no 1, p. 48-58Article in journal (Refereed)
    Abstract [en]

    Bone tissue homeostasis is governed by hormones, growth factors and cytokines and can be distorted by environmental pollutants such as ligands to the aryl hydrocarbon receptor (AhR). A transgenic mouse expressing a constitutively active AhR (CA-AhR), mimicking continuous low-dose exposure to AhR-ligands, was used to explore potential long-term effects of these ligands on bone The density, content and dimensions of cortical and trabecular bone, as well as physical properties, were significantly altered in female transgenic mice, while almost no alterations were detected in males. Osteoclast volume density and serum level of CTX, reflecting osteoclast activity, were both increased by approximately 60% in female CA-AhR mice, while serum TRAP 5b, reflecting osteoclast numbers, was unchanged. Subsequently, the resorption index (CTX/TRAP 5b) was increased by 90% indicating increased osteoclast activity in female CA-AhR. Moreover, the protein level of the osteoclast collagenase cathepsin K was increased by 40 % in bone extracts of female CA-AhR mice. The mRNA expression of several osteoclast and osteoblast associated genes were altered in female transgenic mice, but not in males. Notably, early markers for osteoclast and osteoblast differentiation were normal, while the expression of functional markers of osteoclasts and osteoblasts were reduced. In conclusion, a low continuous activation of the AhR leads to a skeletal phenotype with increased bone resorption associated with more ductile bones in females but not in males. The results indicate the presence of an interaction between the AhR and a female specific mechanism implicated in inhibition of osteoclast development and function. Female bone tissue appears more susceptible to dioxins and other AhR-ligands than male bone tissue.

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