| 1. |
- Aspenberg, Per, et al.
(författare)
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Atypical femoral fractures, bisphosphonates, and mechanical stress
- 2014
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Ingår i: Current osteoporosis reports. - : Springer. - 1544-1873 .- 1544-2241. ; 12:2, s. 189-193
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Tidskriftsartikel (refereegranskat)abstract
- Atypical fractures are stress fractures occurring in the femoral shaft and closely related to bisphosphonate use. We here discuss their radiographic definition and different putative etiologies, apart from mechanical stress. Long time reduction of skeletal remodeling because of bisphosphonate use is thought to allow time for the bone to deteriorate mechanically, resulting in reduced toughness. However, the risk of atypical fracture diminishes rapidly after cessation of treatment, which suggests more acute effects of bisphosphonate use. Microdamage normally accumulates at areas of high stress. Possibly, ongoing bisphosphonate use reduces the ability to resorb and replace areas of microdamage by targeted remodeling. This could lead to crack propagation beyond a point of no return, ending in macroscopic stress fracture.
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| 2. |
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| 3. |
- Aspenberg, Per, et al.
(författare)
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Stressfrakturer : hjulaxlar och idrottskarriärer brister
- 2014
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Ingår i: Läkartidningen. - Stockholm : Sveriges läkarförbund. - 0023-7205 .- 1652-7518. ; 111:36, s. 1436-1439
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Tidskriftsartikel (refereegranskat)abstract
- Stress fractures are caused by material fatigue. Microcracks appear normally in bone, and are dealt with by remodeling, specifically targeting areas of microdamage. Inhibition of targeted remodeling can allow microcracks to grow and form fractures. Intensive athletic training can lead to an increased microcrack formation rate, which exceeds what can be balanced by remodeling. Stress fractures often heal poorly, possibly because they are so thin: normal deformation of the bone during loading has been shown to lead to strains within thin cracks that are incompatible with cell survival. If the patient can't reduce loading sufficiently to allow healing, surgical stabilization will therefore be required. If the crack is transformed into a larger defect, e.g. by drilling a hole, strains will be reduced and healing facilitated by a simple procedure.
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| 4. |
- Bernhardsson, Magnus, 1989-
(författare)
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Healing Processes in Cancellous Bone
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Most of what is known about the biological response during fracture healing comes from numerous animal studies with shaft fractures in the long bone. However, most patients suffer from fractures closer to the ends of the long bones, in the hip, or in the vertebrae. These types of fractures mainly involve cancellous bone, while shaft fractures concern cortical bone. Compared to cortical bone whose structure is dense and compact, cancellous bone is of spongy and porous structure. A growing number of studies point towards that cortical and cancellous bone heal differently. To even this imbalance in knowledge between these two types of bone tissue, further studies in cancellous bone are justified.In this thesis we delved into the quiet unknown processes behind cancellous bone healing.In the first study we characterized and compared two models for cancellous bone healing in mice and rats: the first model can be used to analyze the morphology and morphometry of the regenerating bone; the second model can measure the mechanical properties of cancellous bone. The two models correspond in their developing patterns during the first week before they diverge. This suggests that these models can be utilized together to evaluate the initial healing in cancellous bone. Furthermore, we saw in the drill hole model that the bone formation is strictly restricted to the traumatized region, with a distinct interface to the adjacent uninjured tissue.The second study characterized the cellular response during the initial healing phase in cancellous bone. The focus was to follow the spatial location of inflammatory and osteogenic cells over time in a cancellous bone injury. In contrast to shaft fractures (cortical bone), where healing is described as sequential events where inflammatory cells are the first to arrive to the trauma before osteogenic cells are recruited and initiate healing, we could see how inflammatory and osteogenic cells appeared early, simultaneously after a cancellous bone injury. This study showed that cancellous bone differs from how fracture healing is normally described.In the third study we explored the role of a subpopulation of lymphocytes (CD8 positive cells), earlier studied in shaft fractures. We wanted to see how their absence would affect the healing in a cancellous bone injury. Without CD8+ cells, cancellous bone healing was impaired as expressed via poorer mechanical properties of the regenerated bone tissue.The fourth and last study issued the influence of uninjured bone marrow on cortical bone healing. We developed a cortical defect model which blocked uninjured marrow from reaching the defect. Without the presence of marrow, the cortical defects ability to regenerate was significantly impaired. This implies that the marrow is important for cortical bone healing.In conclusion, cancellous bone healing is different from its cortical counterpart and the general perception of fracture healing. We have briefly discerned healing mechanisms in cancellous bone that might be of clinical importance: the restricted cancellous bone formation is something to take into consideration when performing arthrodeses; and importance of marrow in skeletal defects (e.g. pseudarthroses). With this thesis, we hope to promote that further investigating on cancellous bone healing is necessary.
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| 5. |
- Bernhardsson, Magnus, et al.
(författare)
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Marrow compartment contribution to cortical defect healing
- 2018
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Ingår i: Acta Orthopaedica. - : TAYLOR & FRANCIS LTD. - 1745-3674 .- 1745-3682. ; 89:1, s. 119-123
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose - Healing of shaft fractures is commonly described as regards external callus. We wanted to clarify the role of the bone marrow compartment in the healing of stable shaft fractures. Patients and methods - A longitudinal furrow was milled along the longitudinal axis of the femoral shaft in mice. The exposed bone marrow under the furrow was scooped out. The mice were then randomized to no further treatment, or to receiving 2 silicone plugs in the medullary canal distal and proximal to the defect. The plugs isolated the remaining marrow from contact with the defect. Results were studied with histology and flow cytometry. Results - Without silicone plugs, the marrow defect was filled with new bone marrow-like tissue by day 5, and new bone was seen already on day 10. The new bone was seen only at the level of the cortical injury, where it seemed to form simultaneously in the entire region of the removed cortex. The new bone seemed not to invade the marrow compartment, and there was a sharp edge between new bone and marrow. The regenerated marrow was similar to uninjured marrow, but contained considerably more cells. In the specimens with plugs, the marrow compartment was either filled with loose scar tissue, or empty, and there was only minimal bone formation, mainly located around the edges of the cortical injury. Interpretation - Marrow regeneration in the defect seemed to be a prerequisite for normal cortical healing. Shaft fracture treatment should perhaps pay more attention to the local bone marrow.
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| 6. |
- Brandt, Jonathan, et al.
(författare)
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Single postoperative infusion of zoledronic acid to improve patient-reported outcome after hip or knee replacement : study protocol for a randomised, controlled, double-blinded clinical trial
- 2020
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 10:9
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: In Sweden, roughly 3000 patients are reoperated each year due to pain and loss of function related to a loosened hip or knee prosthesis. These reoperations are strenuous for the patient, technically demanding and costly for the healthcare system. Any such reoperation that can be prevented would be of great benefit. Bisphosphonates are drugs that inhibit osteoclast function. Several clinical trials suggest that bisphosphonates lead to improved implant fixation and one small study even indicates better functional outcome. Furthermore, in epidemiological studies, bisphosphonates have been shown to decrease the rate of revision for aseptic loosening by half. Thus, there are several indirect indications that bisphosphonates could improve patient-reported outcome, but no firm evidence. METHODS AND ANALYSIS: This is a pragmatic randomised, placebo-controlled, double-blinded, academic clinical trial of a single postoperative dose of zoledronic acid, in patients younger than 80 years undergoing primary total hip or knee replacement for osteoarthritis. Participants will be recruited from two orthopaedic departments. All surgeries will be performed, and study drugs given at Motala Hospital, Sweden. The primary endpoint is to investigate between-group differences in the Hip dysfunction and Osteoarthritis Outcome Score and the Knee injury and Osteoarthritis Outcome Score at 3-year follow-up. Secondary outcomes will be investigated at 1 year, 3 years and 6 years, and stratified for hip and knee implants. These secondary endpoints are supportive, exploratory or explanatory. A total of 1000 patients will be included in the study. ETHICS AND DISSEMINATION: The study has been approved by the Regional Ethical Review Board in Linköping (DNR 2015/286-31). The study will be reported in accordance with the Consolidated Standards of Reporting Trials statement for pharmacological trials. The results will be submitted for publication in peer-reviewed academic journals and disseminated to patient organisations and the media. TRIAL REGISTRATION NUMBER: EudraCT: No 2015-001200-55; Pre-results.
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| 7. |
- Bratengeier, Cornelia, 1983-, et al.
(författare)
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The release of osteoclast-stimulating factors on supraphysiological loading by osteoprogenitors coincides with expression of genes associated with inflammation and cytoskeletal arrangement
- 2022
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Ingår i: Scientific Reports. - : Springer. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Supraphysiological loading induced by unstable orthopedic implants initiates osteoclast formation, which results in bone degradation. We aimed to investigate which mechanosensitive cells in the peri-implant environment produce osteoclast-stimulating factors and how the production of these factors is stimulated by supraphysiological loading. The release of osteoclast-stimulating factors by different types of isolated bone marrow-derived hematopoietic and mesenchymal stem cells from six osteoarthritic patients was analyzed after one hour of supraphysiological loading (3.0 ± 0.2 Pa, 1 Hz) by adding their conditioned medium to osteoclast precursors. Monocytes produced factors that enhanced osteoclastogenesis by 1.6 ± 0.07-fold and mesenchymal stem cells by 1.4 ± 0.07-fold. Medium from osteoprogenitors and pre-osteoblasts enhanced osteoclastogenesis by 1.3 ± 0.09-fold and 1.4 ± 0.03-fold, respectively, where medium from four patients elicited a response and two did not. Next generation sequencing analysis of osteoprogenitors revealed that genes encoding for inflammation-related pathways and cytoskeletal rearrangements were regulated differently between responders and non-responders. Our data suggest that released osteoclast-stimulating soluble factors by progenitor cells in the bone marrow after supraphysiological loading may be related to cytoskeletal arrangement in an inflammatory environment. This connection could be relevant to better understand the aseptic loosening process of orthopedic implants.
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| 8. |
- Bögl, Hans Peter, 1969-
(författare)
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Atypical femoral fractures: Another brick in the wall : On aspects of healing, treatment strategies and surveillance
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Atypical femoral fractures are stress fractures of the femoral subtrochanteric and diaphyseal region. It is a common notion that these fractures heal poorly, if at all. In this thesis we show that patients with atypical femoral fractures have a good capacity to generate bone and therefore heal fractures. In daily practice, these patients have a higher risk for reoperation when compared with patients with a normal femoral fracture. However, this risk is less likely to be dependent on the type of fracture than other factors such as age, gender, comorbidities and survival. Using an implant that protects the fragile proximal femur, the risk for reoperations can be attenuated dramatically. An intramedullary nail with fixation of the femoral neck protects the femur from subsequent hip fractures – the most common complication in elderly patients with any type of femoral shaft fracture.Atypical femoral fractures are difficult to identify in the population. Erroneous diagnosis coding, poor reporting of adverse drug reactions and low accuracy of radiology reports make the identification and surveillance a difficult task. The Swedish Fracture Register has provided the option to register this special fracture since 2015. With its physician-based registration process, it enables researchers and treating physicians to identify and follow these rare fractures longitudinally.
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| 9. |
- Bögl, Hans Peter, 1969-, et al.
(författare)
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Increased rate of reoperation in atypical femoral fractures is related to patient characteristics and not fracture type : A nationwide cohort study
- 2020
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Ingår i: Osteoporosis International. - : SPRINGER LONDON LTD. - 0937-941X .- 1433-2965. ; 31:5, s. 951-959
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Tidskriftsartikel (refereegranskat)abstract
- Atypical femoral fractures are burdened with a high rate of reoperation. In our nationwide analysis, the increased rate of reoperation was related to patient background characteristics, such as age and health status, rather than fracture type. Introduction Patients with atypical fractures are complex to treat and burdened with a high risk of reoperation. We hypothesized that patients with surgically treated, complete atypical fractures have a higher risk of any reoperation and reoperation related to healing complications than patients with common femoral shaft fractures but that this increase would become insignificant when adjusted for predefined characteristics. Methods A cohort of 163 patients with atypical fractures and 862 patients with common femoral shaft or subtrochanteric fractures treated from 2008 to 2010 and who had follow-up radiographs and register data available until 31 December 2014 was included. Reoperations were identified by a complementary review of radiographs and register data and were used to calculate risks for any reoperation and reoperations related to healing complications. Results Patients with atypical fractures were more likely to be reoperated for any reason, age-adjusted OR 1.76 (95% CI, 1.08 to 2.86). However, patients with common fractures had a shorter follow-up due to a threefold higher death rate. Accordingly, in a multivariable-adjusted time-to-event model, the increased risk lost statistical significance for any reoperations, cause-specific HR 1.34 (95% CI, 0.85 to 2.13), and for reoperations related to healing complications, HR 1.32 (95% CI, 0.58 to 3.0). Continued use of bisphosphonate in the first year after the fracture did not affect the reoperation rate. Conclusions Our findings suggest that the increased risk of reoperation after an atypical femur fracture is largely explained by patient characteristics and not fracture type.
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| 10. |
- Bögl, Hans Peter, et al.
(författare)
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Reduced Risk of Reoperation Using Intramedullary Nailing with Femoral Neck Protection in Low-Energy Femoral Shaft Fractures
- 2020
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Ingår i: Journal of Bone and Joint Surgery. American volume. - : LIPPINCOTT WILLIAMS & WILKINS. - 0021-9355 .- 1535-1386. ; 102:17, s. 1486-1494
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Tidskriftsartikel (refereegranskat)abstract
- Background: In Sweden, approximately 1 in 4 women who are >= 50 years of age will sustain a hip fracture. Patients treated for a femoral shaft fracture are likely to have an even higher risk. We hypothesized that intramedullary nails protecting the femoral neck reduce the risk of subsequent hip fracture and allow the patient to avoid a challenging reoperation.Methods: Between 2008 and 2010, 5,475 fractures of the femoral shaft, in patients who were >= 55 years of age, were registered in a national registry in Sweden. Of these patients, 897 fulfilled the inclusion criteria. We used radiographs and register data to identify the reasons for and the types of reoperation that occurred between the index surgical procedure and December 31, 2014. The categories of implants were determined through a review of radiographs as intramedullary nails with and without femoral neck protection. Reoperations related to peri-implant fractures (including hip fractures) were analyzed as a subgroup of all major reoperations. Multivariable-adjusted, cause-specific hazard ratios (HRs) were calculated to compare the risk of reoperation between cases with nails with and without femoral neck protection.Results: Among the 897 patients, a total of 82 reoperations were performed. In 640 patients who were treated with intramedullary nails with femoral neck protection, there were 7 peri-implant fractures (no hip fractures) and 27 major reoperations. Among the 257 patients who were treated with intramedullary nails without femoral neck protection, 14 peri-implant hip fractures and 24 major reoperations were identified. Patients who received nails with femoral neck protection had a lower hazard for any peri-implant fracture (multivariable-adjusted cause-specific HR, 0.19 [95% confidence interval (CI), 0.07 to 0.5]) and major reoperation (multivariable-adjusted cause-specific HR, 0.51 [95% CI, 0.28 to 0.92]).Conclusions: Intramedullary nails with femoral neck protection in the treatment of low-energy femoral shaft fractures prevent secondary hip fractures and decrease the overall risk of reoperation for 4 to 6 years postoperatively.
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