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2.
  • Abramo, Antonio, et al. (author)
  • Evaluation of a treatment protocol in distal radius fractures: a prospective study in 581 patients using DASH as outcome.
  • 2008
  • In: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3682 .- 1745-3674. ; 79:3, s. 376-385
  • Journal article (peer-reviewed)abstract
    • BACKGROUND AND PURPOSE: Distal radius fractures are most often treated nonoperatively, but sometimes they are treated surgically when deemed unstable. Based on the literature, a consensus protocol for treatment has been developed in southern Sweden to aid clinicians in their decision making. We evaluated the results of this protocol prospectively using a validated outcome instrument (DASH) in a large consecutive and population based series of unselected patients. METHODS: 581 patients were treated according the protocol. Age, sex, fracture side, and type of treatment were registered. The subjective outcome was measured by DASH. 133 patients were operated. RESULTS: 75% of the patients returned the questionnaire. The median DASH score at 3 months was 18.3 and at 12 months it was 7.5. All treatment groups had low DASH scores at the final follow-up. Reduced, nonoperated fractures had a worse score (11.6) than undisplaced (4.2) or operated fractures (6.0). Age was the only other predictor, with older patients having a worse score. A correlation was found between the short-version 11-item QuickDASH questionnaire and the full 30-item DASH, both at 3 months (r = 0.98) and at 1 year (r = 0.97) (p< 0.001 for both). INTERPRETATION: Most patients have residual symptoms at 3 months after the fracture but are normalized at 1 year. Good final subjective result was achieved with the proposed protocol regardless of initial severity and treatment of the fracture, as indicated by a low median DASH score in all groups. There was correlation between QuickDASH and the full DASH, and the former could be used in future studies.
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3.
  • Abramo, Antonio, et al. (author)
  • Open reduction and internal fixation compared to closed reduction and external fixation in distal radial fractures A randomized study of 50 patients
  • 2009
  • In: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3682 .- 1745-3674. ; 80:4, s. 478-485
  • Journal article (peer-reviewed)abstract
    • Background and purpose In unstable distal radial fractures that are impossible to reduce or to maintain in reduced position, the treatment of choice is operation. The type of operation and the choice of implant, however, is a matter of discussion. Our aim was to investigate whether open reduction and internal fixation would produce a better result than traditional external fixation. Methods 50 patients with an unstable or comminute distal radius fracture were randomized to either closed reduction and bridging external fixation, or open reduction and internal fixation using the TriMed system. The primary outcome parameter was grip strength, but the patients were followed for 1 year with objective clinical assessment, subjective outcome using DASH, and radiographic examination. Results At 1 year postoperatively, grip strength was 90% (SD 16) of the uninjured side in the internal fixation group and 78% (17) in the external fixation group. Pronation/supination was 150 degrees (15) in the internal fixation group and 136 degrees (20) in the external fixation group at 1 year. There were no differences in DASH scores or in radiographic parameters. 5 patients in the external fixation group were reoperated due to malunion, as compared to 1 in the internal fixation group. 7 other cases were classified as radiographic malunion: 5 in the external fixation group and 2 in the internal fixation group. Interpretation Internal fixation gave better grip strength and a better range of motion at 1 year, and tended to have less malunions than external fixation. No difference could be found regarding subjective outcome.
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4.
  • Abramo, Antonio, et al. (author)
  • Osteotomy of distal radius fracture malunion using a fast remodeling bone substitute consisting of calcium sulphate and calcium phosphate.
  • 2010
  • In: Journal of biomedical materials research. Part B, Applied biomaterials. - : Wiley. - 1552-4981 .- 1552-4973. ; 92:1, s. 281-6
  • Journal article (peer-reviewed)abstract
    • Malunion after a distal radius fracture can be treated with an osteotomy of the distal radius. Autologous iliac crest bone graft is often used to fill the gap, but the procedure is associated with donor site morbidity. In this study a novel fast resorbing biphasic bone substitute consisting of a mixture of calcium sulphate and calcium phosphate is used (Cerament BoneSupport AB, Sweden). Fifteen consecutive patients, with a mean age of 52 (27-71) years were included. All had a malunion after a distal radius fracture and underwent an osteotomy. A fragment specific fixation system, TriMed (TriMed, Valencia, CA), consisting of a Buttress Pin and a Radial Pin Plate were used for fixation and a calcium sulphate and calcium phosphate mixture as bone substitute. The patients were followed for 1 year. Grip strength increased from 61 (28-93)% of the contralateral hand to 85 (58-109)%, p < 0.001. DASH scores decreased from 37 (22-61) to 24 (2-49) p = 0.003. Radiographically all osteotomies healed. An increase of ulnar variance was noted during healing from 1.8 mm immediately postoperatively to 2.6 mm at final follow up. Osteotomy can increase grip strength and decease disability after a malunited fracture. In the present series the bone substitute was replaced by bone, but a minor loss of the achieved radiographic correction was noted in some patients during osteotomy healing. A more rigid fixation may improve the radiographic outcome with this kind of bone substitute.
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5.
  • Abramo, Antonio, et al. (author)
  • Osteotomy of dorsally displaced malunited fractures of the distal radius: no loss of radiographic correction during healing with a minimally invasive fixation technique and an injectable bone substitute.
  • 2008
  • In: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3682 .- 1745-3674. ; 79:2, s. 262-268
  • Journal article (peer-reviewed)abstract
    • BACKGROUND AND PURPOSE: Malunion after a distal radius fracture can be treated with an osteotomy of the distal radius. Often autologous iliac crest bone graft is used to fill the gap, but this is associated with donor site morbidity. Instead of bone graft, we have used a slow-resorbing bone substitute in combination with a minimally invasive fixation technique. PATIENTS AND METHODS: 25 consecutive patients with a dorsal malunion after a distal radius fracture underwent an osteotomy. A TriMed buttress pin and a radial pin plate were used for fixation, and Norian SRS as bone substitute. The patients were followed for a minimum of 1 year and range of motion, grip strength, DASH scores, and the radiographic correction were measured. RESULTS: Forearm rotation improved from 137 degrees to 155 degrees , flexion/extension from 102 degrees to 120 degrees , and radioul-nar deviation from 32 degrees to 43 degrees . Grip strength increased from 62% of the contralateral hand to 82%. DASH scores decreased from 36 to 23. Radiographically, all osteotomies but 1 healed and the radiographic correction achieved was consistent over the first year. INTERPRETATION: Osteotomy of the distal radius is effective in increasing motion and grip strength after a malunited distal radial fracture. Patient satisfaction is high and subjective results measured with DASH are good. Using a bone substitute, the operation can be performed as an outpatient procedure and donor-site pain avoided. No loss of the radiographic correction achieved was noted during osteotomy healing.
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6.
  • Afendras, G, et al. (author)
  • Hemi-hamate osteochondral transplantation in proximal interphalangeal dorsal fracture dislocations: a minimum 4 year follow-up in eight patients.
  • 2010
  • In: Journal of Hand Surgery: European Volume. - : SAGE Publications. - 2043-6289 .- 1753-1934. ; 35:8, s. 627-631
  • Journal article (peer-reviewed)abstract
    • Fracture dislocations of the PIP joint are challenging to treat. In hemi-hamate arthroplasty, the palmar lip joint surface is reconstructed using an osteochondral graft from the hamate and the immediate stability permits early movement. In the long term, collapse of non-vascularized osteochondral grafts might lead to degenerative arthritis. We examined the radiographic result after a minimum of 4 years with special reference to the development of osteoarthritis and its relation to clinical symptoms in eight patients, mean age 49 (25-66) years. After a mean of 60 (48-69) months, the arc of motion was 67 degrees (45 degrees -95 degrees ) at the PIP joint and grip strength was 91% of the uninjured side. The visual analogue score for pain (0-100) was 10 (0-70) mm. Severe arthritis (grade IV) was found in two and mild arthritis (grade II) in another two patients, but only one of these four cases had troublesome pain. The hemi-hamate technique is an attractive alternative to other treatment options, but some cases develop osteoarthritis in the medium term.
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7.
  • Arvidsson, Linnea, et al. (author)
  • Patients Aged 80 or More With Distal Radius Fractures Have a Lower One-Year Mortality Rate Than Age- and Gender-Matched Controls : A Register-Based Study
  • 2024
  • In: Geriatric Orthopaedic Surgery and Rehabilitation. - 2151-4585. ; 15
  • Journal article (peer-reviewed)abstract
    • Introduction: With a rapidly ageing population, the number of distal radius fractures (DRFs) in the elderly will increase dramatically. The aim of this retrospective register study was to examine the 1- and 5-year mortality in DRF patients aged 80 years or more and correlate the overall survival to factors not related to the fracture itself. Material and Methods: Patients aged ≥80 diagnosed with DRFs in Lund University Hospital in Sweden in the period 2010-2012 were extracted from the prospective Lund Distal Radius Fracture register. One- and 5-year standardised mortality rates (SMRs) were calculated using the Swedish standard population as a reference. Medical records were searched for non-fracture-related factors including comorbidity, medications, cognitive impairment and type of living. Cox proportional hazard regression models were used to identify prognostic factors for all-cause mortality. Results: The study cohort included 240 patients, with a mean age of 86. The overall 1-year mortality was 5% (n = 11/240) and the 5-year mortality was 44% (n = 105/240). The 1-year SMR was.44 (CI.18-.69, P <.01) when indirectly adjusted for age and gender and compared to the Swedish standard population. The 5-year SMR was.96 (CI.78-1.14). The patients’ ability to live independently in their own home had the highest impact on survival. Discussion: The 1-year mortality rate among the super-elderly DRF patients was only 44% of that expected. Possibly, a DRF at this age could be a sign of a healthier and more active patient. Conclusions: The DRF patients aged 80 or more had a substantially lower mortality rate 1 year after fracture compared to the age- and gender-matched standard population. Patients living independently in their own homes had the longest life expectancy. Treatment should not be limited solely because of old age, but individualised according to the patient’s ability and activity level.
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8.
  • Arvidsson, Linnea, et al. (author)
  • Virtual Follow up After Distal Radius Fracture Surgery — Patient Experiences During the COVID-19 Pandemic
  • 2023
  • In: Journal of Patient Experience. - Thousand Oaks, CA : Sage Publications. - 2374-3735 .- 2374-3743. ; 10
  • Journal article (peer-reviewed)abstract
    • The majority of patients with a distal radius fracture (DRF) are elderly, a group known to experience difficulties with new technology, partly due to a low level of digital literacy. At the beginning of the coronavirus disease 2019 pandemic, during the spring 2020, patients that underwent DRF surgery had regular follow-ups replaced by video calls from their surgeon and physiotherapist. Afterward, patients answered questionnaires regarding health and digital literacy and took part in semistructured interviews regarding the experience of the virtual follow-up. By systemic text condensation, 2 major categories were identified: (1) The video call—new, but surprisingly simple: All but 1 found it easier than expected, and (2) Video calls—the patient's choice: All but 1 patient preferred video calls to physical visits for follow-up. This is the first mixed methods study to assess patients’ experiences of digital follow-up after DRF surgery. This study indicates that digital follow-up was highly appreciated, even among patients with low levels of digital literacy. Digital technologies must be made suitable even for patients with inadequate levels of digital literacy. © The Author(s) 2023.
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9.
  • Aspenberg, Per, et al. (author)
  • Bone graft proteins influence osteoconduction. A titanium chamber study in rats
  • 1996
  • In: Acta Orthopaedica Scandinavica. - : Medical Journals Sweden AB. - 0001-6470. ; 67:4, s. 377-382
  • Journal article (peer-reviewed)abstract
    • Although it is often emphasized that the matrix of bone grafts contains several growth factors, it is not known if these factors become activated and play a role in bone grafting. We therefore compared ground defatted bone which had or had not been deproteinized by heating with water to 270 degrees C at an autogenic pressure of 55 bar. This is a careful ceramic procedure which leaves the mineral unchanged. Deproteinized and non-deproteinized bone granulae derived from cortical rat bone were placed in titanium bone conduction chambers implanted bilaterally in rat tibiae. Ingrowing bone could enter the cylindrical interior of the chamber only at one end. It then penetrated the material in the chamber, but due to the length of the cylinder, it never reached the other end. The mean distance which the ingrown bone had reached in the material was then measured on histological slides. The bone formation activity was measured by TcMDP scintimetry. With the protein-containing granulae, the mean bone ingrowth distance and the scintimetric activity were increased by 41% and 31%, respectively (p < 0.01). We conclude that there is a limited favourable effect of proteins in a graft. Our grounded material had a large fracture surface area with no osteoid lining. The leakage of growth factors from such areas may explain the extraordinarily good clinical incorporation of morselized compacted allografts.
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10.
  • Aspenberg, Per, et al. (author)
  • Reduced expression of BMP-3 due to mechanical loading: a link between mechanical stimuli and tissue differentiation
  • 2000
  • In: Acta Orthopaedica Scandinavica. - : Medical Journals Sweden AB. - 0001-6470. ; 71:6, s. 558-562
  • Journal article (peer-reviewed)abstract
    • Mechanical signaling and BMP expression appear to be involved in controlling the differentiation of cartilage in fracture repair, but the connection between mechanics and BMP signaling is not known. In this study of rats, we used a bone chamber to see how BMP gene expression was changed by a mechanical loading regime that induces cartilage formation in this model. We compared the still undifferentiated tissue in loaded and unloaded chambers in the same rat regarding the expression of TGFbeta-1, BMP-2, 3, 4, 5, 6, 7, CDMP-1, 2 and ALK-2 and 3 by using RT-PCR normalized against GAPDH. We found expression of TGFbeta-1, BMP-2 and 4 in all specimens, and BMP 5-7 and CDMPs in none. 1 week after loading started, BMP-3 was strongly expressed in the unloaded control specimens in 7 of 8 animals, but detectable in only I of the contralateral loaded ones. After 2 weeks of loading, the BMP-3 expression pattern was less clear, but with both time groups taken together, there was still less BMP-3 expression on the loaded side in 9 rats, more in 1 and no difference in 5 (p = 0.01). ALK-2 at 1 week was expressed in all specimens expressing BMP-3 and in none of the others. At 2 weeks, ALK-2 was expressed in all specimens. Thus, a loading regime, known to induce cartilage in this model, caused down-regulation of BMP-3 and ALK-2. The results are consistent with the view that BMP-3 inhibits differentiation, as recently described. This role appears to be linked to the ALK-2 receptor. Most importantly, the results indicate a link between mechanical signaling and BMP expression such that mechanically-induced down-regulation of the inhibiting BMP-3 enabled the induction of cartilage.
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12.
  • Belfrage, Ola, et al. (author)
  • Local treatment of a bone graft by soaking in zoledronic acid inhibits bone resorption and bone formation. A bone chamber study in rats.
  • 2012
  • In: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 13:Dec.,05
  • Journal article (peer-reviewed)abstract
    • ABSTRACT: BACKGROUND: Bone grafts are frequently used in orthopaedic surgery. Graft remodelling is advantageous but can occur too quickly, and premature bone resorption might lead to decreased mechanical integrity of the graft. Bisphosphonates delay osteoclastic bone resorption but may also impair formation of new bone. We hypothesize that these effects are dose dependent. In the present study we evaluate different ways of applying bisphosphonates locally to the graft in a bone chamber model, and compare that with systemic treatment. METHODS: Cancellous bone grafts were placed in titanium chambers and implanted in the tibia of 50 male rats, randomly divided into five groups. The first group served as negative control and the grafts were rinsed in saline before implantation. In the second and third groups, the grafts were soaked in a zoledronic acid solution (0.5 mg/ml) for 5 seconds and 10 minutes respectively before being rinsed in saline. In the fourth group, 8 μL of zoledronic acid solution (0.5 mg/ml) was pipetted onto the freeze-dried grafts without rinsing. The fifth group served as positive control and the rats were given zoledronic acid (0.1 mg/kg) systemically as a single injection two weeks after surgery. The grafts were harvested at 6 weeks and analysed with histomorphometry, evaluating the ingrowth distance of new bone into the graft as an equivalent to the anabolic osteoblast effect and the amount (bone volume/total volume; BV/TV) of remaining bone in the remodelled graft as equivalent to the catabolic osteoclast effect. RESULTS: In all chambers, almost the entire graft had been revascularized but only partly remodelled at harvest. The ingrowth distance of new bone into the graft was lower in grafts soaked in zoledronic acid for 10 minutes compared to control (p = 0.007). In all groups receiving zoledronic acid, the BV/TV was higher compared to control. CONCLUSIONS: This study found a strong inhibitory effect on bone resorption by bisphosphonates but also a limited inhibition of the ingrowth of new bone. Local treatment at surgery resulted in stronger inhibition of both resorption and bone formation compared to systemic treatment.
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14.
  • Belfrage, Ola, et al. (author)
  • Local treatment of cancellous bone grafts with BMP-7 and zoledronate increases both the bone formation rate and bone density.
  • 2011
  • In: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3682 .- 1745-3674. ; 82:2, s. 228-233
  • Journal article (peer-reviewed)abstract
    • Background and purpose The remodeling of morselized bone grafts in revision surgery can be enhanced by an anabolic substance such as a bone morphogenetic protein (BMP). On the other hand, BMPs boost catabolism and might cause a premature resorption, both of the graft and of the new-formed bone. Bisphosphonates inactivate osteoclasts and can be used to control the resorption. We studied a combination of both drugs as a local admix to a cancellous allograft. Methods Cancellous bone allografts were harvested and freeze-dried. Either saline, BMP-7, the bisphosphonate zoledronate, or a combination of BMP-7 and zoledronate were added in solution. The grafts were placed in bone conduction chambers and implanted in the proximal tibia of 34 rats. The grafts were harvested after 6 weeks and evaluated by histomorphometry. Results Bone volume/total volume (BV/TV) was 50% in the grafts treated with the combination of BMP-7 and zoledronate and 16% in the saline controls (p < 0.001). In the zoledronate group BV/TV was 56%, and in the BMP group it was 14%. The ingrowth distance of new bone into the graft was 3.5 mm for the combination of BMP-7 and zoledronate and 2.6 mm in the saline control (p = 0.002). The net amount of retained remodeled bone was more than 4 times higher when BMP-7 and zoledronate were combined than in the controls. Interpretation An anabolic drug like BMP-7 can be combined with an anti-catabolic bisphosphonate as local bone graft adjunct, and the combination increases the amount of remaining bone after remodeling is complete.
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15.
  • Belfrage, Ola, et al. (author)
  • Locally administered bisphosphonate in hip stem revisions using the bone impaction grafting technique : a randomised, placebo-controlled study with DXA and five-year RSA follow-up
  • 2019
  • In: HIP International. - : SAGE Publications. - 1120-7000 .- 1724-6067. ; 29:1, s. 26-34
  • Journal article (peer-reviewed)abstract
    • Background: Bisphosphonates have previously been shown to increase the density of impacted graft bone. In the present study we hypothesise that bisphosphonates also reduce early stem subsidence. We examined the effect of locally applied bisphosphonate to allografts on prosthetic micromotion and bone density in femoral stem revision with impaction grafting. Methods: 37 patients were randomised to either clodronate or saline as local adjunct to the morsellised allograft bone. 24 patients were finally analysed per protocol and evaluated by dual-energy x-ray absorptiometry (DXA) during the first year and with radiostereometric analysis (RSA) for 5 years. Results: There were no significant differences neither in bone density, nor in migratory behaviour between the groups. The femoral stems had subsided 3.6 mm in both groups (p = 0.99) at 5 years and there was no difference as measured over time with mixed models analysis. The clinical outcome was good in both groups. Conclusion: Clodronate as a local addendum to allograft bone in hip revision did not increase bone density or reduce micromotion of the implant.
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16.
  • Bergqvist, D, et al. (author)
  • Trends in civilian vascular trauma during 30 years. A Swedish perspective
  • 1987
  • In: Acta Chirurgica Scandinavica. - 0001-5482. ; 153:7-8, s. 417-422
  • Journal article (peer-reviewed)abstract
    • Vascular injuries operated on during a 30-year period (1955-1984) were analyzed. There has been significant increase of such injuries, particularly the iatrogenic types. The total incidence per 100,000 population and year rose from 11.0 to 26.6. Various angiographic and catheterization techniques were responsible for the iatrogenic increase. The noniatrogenic vascular injuries not infrequently were part of multiple trauma, with fractures and a variety of penetrating wounds. Numerous operative techniques were used, increasingly with reconstructive surgery. The mortality rate did not change in the study period, but the rate of amputations and of various long-term sequelae diminished.
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17.
  • Bosemark, Per, et al. (author)
  • Augmentation of autologous bone graft by a combination of bone morphogenic protein and bisphosphonate increased both callus volume and strength
  • 2013
  • In: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3682 .- 1745-3674. ; 84:1, s. 106-111
  • Journal article (peer-reviewed)abstract
    • Background and purpose Bone morphogenic proteins (BMPs) can be used in non-unions to replace autograft. BMPs induce osteoblasts and (less well known) also osteoclasts, which can in turn be controlled by a bisphosphonate. In the present study, our aim was to improve the biological effect of autologous bone graft by adding an anabolic BMP, with or without bisphosphonates, in an open-fracture model prone to non-union. Methods Rat femurs were osteotomized and fixed with an intramedullary K-wire. Autograft was placed at the osteotomy, mixed with either saline or BMP-7. After 2 weeks, the rats had a single injection of saline or of a bisphosphonate (zoledronate). The rats were killed after 6 weeks and the femurs were evaluated by radiography, micro-CT, histology, and 3-point bending test. Results All fractures healed. The callus volume was doubled in the BMP-treated femurs (p < 0.01) and increased almost 4-fold in the femurs treated with both BMP and systemic zoledronate (p < 0.01) compared to autograft. In mechanical testing, the autograft group reached approximately half the strength of the contralateral, non-osteotomized femur (p < 0.001). By adding BMP to the autograft, the strength was doubled (p < 0.001) and with both BMP and systemic zoledronate, the strength was increased 4-fold (p < 0.001) compared to autograft alone. Interpretation The combination of BMP and bisphosphonate as an adjunct to autograft is superior to autograft alone or combined with BMP. The combination may prove valuable in the treatment of non-unions.
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18.
  • Bosemark, Per, et al. (author)
  • Influence of systemic bisphosphonate treatment on mechanical properties of BMP-induced calluses in a rat fracture model: Comparison of three-point bending and twisting test.
  • 2014
  • In: Journal of Orthopaedic Research. - : Wiley. - 1554-527X .- 0736-0266. ; 32:5, s. 721-726
  • Journal article (peer-reviewed)abstract
    • The combination of autograft, BMP and bisphosphonate has been shown to produce strong calluses. In this study, without autograft we investigate the effect of bisphosphonate treatment on BMP-induced calluses, both in bending and in rotation. Sprague-Dawley rats (n = 42) underwent femoral osteotomy and BMP-7 treatment. At 2 weeks an injection of saline or bisphosphonate was administered. The animals were sacrificed after 6 weeks. Both femurs were tested in either three-point bending or twisting. All femurs healed. BMP + bisphosphonate-treatment led to larger calluses (p < 0.05) and in three-point bending, higher ultimate force (p < 0.01) and greater stiffness (p < 0.05) than BMP alone. The BMP + bisphosphonate group was nearly 60% stronger than controls, while the BMP group did not reach the strength (p < 0.05) nor stiffness (p < 0.01) of the controls. In the twisting test, similar trends were found but less pronounced. Three-point bending produced transverse callus associated fractures, whereas the twisting test produced spiral fractures, located in the structurally weaker distal femur. BMP + bisphosphonate-treatment produces calluses that are mechanically superior to calluses induced by BMP alone, when tested both in three-point bending and in twisting. For the mechanical evaluation of pharmacologically enhanced calluses with breaking strengths exceeding the native bone, the bending test is recommended. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.
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19.
  • Bosemark, Per, et al. (author)
  • The Masquelet Induced Membrane Technique with BMP and a Synthetic Scaffold Can Heal a Rat Femoral Critical Size Defect.
  • 2015
  • In: Journal of Orthopaedic Research. - : Wiley. - 1554-527X .- 0736-0266. ; 33:4, s. 488-495
  • Journal article (peer-reviewed)abstract
    • Long bone defects can be managed by the induced membrane technique together with autologous bone graft. However, graft harvest is associated with donor site morbidity. This study investigates if a tricalcium phosphate hydroxyapatite scaffold can be used alone or in combination with bone active drugs to improve healing. Sprague Dawley rats (n = 40) were randomized into four groups. (A) scaffold, (B) BMP-7, (C) BMP-7 + scaffold, and (D) BMP-7 + scaffold + systemic bisphosphonate at 2 weeks. Locked femoral nailing was followed by 6 mm segment removal and implantation of an epoxy spacer. At 4 weeks, the spacers were removed and the defects grafted. Eleven weeks later, the bones were explanted for evaluation with radiography, manual assessment, micro-CT, histology, and Fourier Transform Infrared spectroscopy (FTIR). Isolated scaffolds (A) did not heal any defects, whereas the other treatments led to healing in 7/10 (B), 10/10 (C), and 9/10 (D) rats. Group D had greater volume of highly mineralized bone (p < 0.01) and higher bone volume fraction (p < 0.01) compared to all other groups. A synthetic scaffold + BMP-7 combined with a bisphosphonate improved the callus properties in a rat femoral critical size defect, compared to both BMP-7 and scaffold alone or the two combined. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.
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21.
  • de Rooij, Philippe P., et al. (author)
  • The fate of mechanically induced cartilage in an unloaded environment
  • 2001
  • In: Journal of Biomechanics. - 1873-2380. ; 34:7, s. 961-966
  • Journal article (peer-reviewed)abstract
    • According to mechanobiologic theories, persistent intermittent mechanical stimulation is required to maintain differentiated cartilage. In a rat model for bone repair, we studied the fate of mechanically induced cartilage after unloading. In three groups of rats, regenerating mesenchymal tissue was submitted to different loading conditions in bone chambers. Two groups were immediately killed after loading periods of 3 or 6 weeks (the 3-group and the 6-group). The third group was loaded for 3 weeks and then kept unloaded for another 3 weeks (the (3 + 3)-group). Cartilage was found in all loaded groups. Without loading, cartilage does not appear in this model. In the 3-group there was no clear ongoing endochondral ossification, the 6-group showed ossification in 2 out of 5 cartilage containing specimens, and in the (3 + 3)-group all cartilage was undergoing ossification. These results suggest a tendency of the cartilage to be maintained also under unloaded conditions until it is reached by bone that can replace it through endochondral ossification.Additional measurements showed less amount of new bone in the loaded specimens. In most of the loaded specimens in the 3-group, necrotic bone fragments were seen embedded in the fibrous tissue layer close to the loading piston, indicating that bone tissue had been resorbed due to the hydrostatic compressive load. In some specimens, a continuous cartilage layer covered the end of the specimen and seemed to protect the underlying bone from pressure-induced resorption. We suggest that one of the functions of the cartilage forming in the compressive loaded parts of a bone callus is to protect the surrounding bone callus from pressure-induced fluid flow leading to resorption.
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22.
  • Gupta, Ankur, et al. (author)
  • Cell factory-derived bioactive molecules with polymeric cryogel scaffold enhance the repair of subchondral cartilage defect in rabbits.
  • 2017
  • In: Journal of Tissue Engineering and Regenerative Medicine. - : Hindawi Limited. - 1932-6254. ; 11:6, s. 1689-1700
  • Journal article (peer-reviewed)abstract
    • We have explored the potential of cell factory-derived bioactive molecules, isolated from conditioned media of primary goat chondrocytes, for the repair of subchondral cartilage defects. Enzyme-linked immunosorbent assay (ELISA) confirms the presence of transforming growth factor-β1 in an isolated protein fraction (12.56 ± 1.15 ng/mg protein fraction). These bioactive molecules were used alone or with chitosan-agarose-gelatin cryogel scaffolds, with and without chondrocytes, to check whether combined approaches further enhance cartilage repair. To evaluate this, an in vivo study was conducted on New Zealand rabbits in which a subchondral defect (4.5 mm wide × 4.5 mm deep) was surgically created. Starting after the operation, bioactive molecules were injected at the defect site at regular intervals of 14 days. Histopathological analysis showed that rabbits treated with bioactive molecules alone had cartilage regeneration after 4 weeks. However, rabbits treated with bioactive molecules along with scaffolds, with or without cells, showed cartilage formation after 3 weeks; 6 weeks after surgery, the cartilage regenerated in rabbits treated with either bioactive molecules alone or in combinations showed morphological similarities to native cartilage. No systemic cytotoxicity or inflammatory response was induced by any of the treatments. Further, ELISA was done to determine systemic toxicity, which showed no difference in concentration of tumour necrosis factor-α in blood serum, before or after surgery. In conclusion, intra-articular injection with bioactive molecules alone may be used for the repair of subchondral cartilage defects, and bioactive molecules along with chondrocyte-seeded scaffolds further enhance the repair. Copyright © 2015 John Wiley & Sons, Ltd.
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23.
  • Harding, Anna Kajsa, et al. (author)
  • A single bisphosphonate infusion does not accelerate fracture healing in high tibial osteotomies.
  • 2011
  • In: Acta orthopaedica. - : Medical Journals Sweden AB. - 1745-3682 .- 1745-3674.
  • Journal article (peer-reviewed)abstract
    • Background Bisphosphonates increase the callus size and strength in animal fracture studies. In a human non-randomized pilot study of high tibial osteotomies in knee osteoarthritis, using the hemicallotasis (HCO) technique, bisphosphonates shortened the healing time by 12 days. In the present randomized study, we wanted to determine whether a single infusion of zoledronic acid reduces the time to clinical osteotomy healing. Results from the same trial, showing improved pin fixation with zoledronate, have been published separately. Methods 46 consecutive patients (aged 35-65 years) were operated. At 4 weeks postoperatively, the patients were randomized to an intravenous infusion of either zoledronic acid or sodium chloride. Dual-energy X-ray absorptiometry (DEXA) was performed 10 weeks postoperatively. Radiographs were taken at 10 weeks and every second week until there was radiographic and clinical healing. Healing was evaluated blind, with extraction of the external fixator as the endpoint. At 1.5 years, an additional radiograph was taken and the hip-knee-ankle (HKA) angle measured to evaluate whether correction had been retained. Results All osteotomies healed with no difference in healing time between the groups (77 (SD 7) days). Bone mineral density and bone mineral content, as assessed with DEXA, were similar between the groups. Radiographically, both groups had retained the acquired correction at the 1.5-year follow-up. Interpretation In this randomized comparison, a single infusion of zoledronic acid increased the pin fixation of the external frame but did not shorten the healing time. In both groups, the external fixator was extracted almost 2 weeks earlier than in previous studies. The early extraction did not cause a loss of correction in either group.
  •  
24.
  • Harding, Anna Kajsa, et al. (author)
  • A single dose zoledronic acid enhances pin fixation in high tibial osteotomy using the hemicallotasis technique. A double-blind placebo controlled randomized study in 46 patients.
  • 2010
  • In: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 46:3, s. 649-654
  • Journal article (peer-reviewed)abstract
    • INTRODUCTION: Bisphosphonates have been shown to reduce osteoclastic activity and enhance pin fixation in both experimental and clinical studies. In this prospective, randomized study of high tibial osteotomy using the hemicallotasis (HCO) technique, we evaluate whether treatment by one single infusion of zoledronic acid can enhance the pin fixation. MATERIALS AND METHODS: 46 consecutive patients (35-65 years) were operated on for knee osteoarthritis by the HCO technique. After the osteotomy, two hydroxyapatite-coated pins were inserted in the metaphyseal bone and two non-coated pins in the diaphyseal bone. The insertion torque was measured by a torque force screw driver. Four weeks postoperatively, the patients were randomized to either one infusion of zoledronic acid or sodium chloride intravenously. At time for removal of the pins, the extraction torque forces of the pins were measured. RESULTS: All osteotomies healed and no difference was found in time to healing. The mean extraction torque force in the non-coated pins in the diaphyseal bone was doubled in the zoledronic treated group (4.5 Nm, SD 2.1) compared to the placebo group (2.4 (SD 1.0, p<0.0001). The mean extraction torque forces of the hydroxyapatite-coated pins in the metaphyseal bone were similar in the zoledronic acid group (4.7 Nm, SD 1.3) and in the placebo group (4.0 Nm, SD 1.3). DISCUSSION: A single infusion of zoledronic acid improved twofold the fixation of non-coated pins in diaphyseal bone. Bisphosphonates might be an alternative to hydroxyapatite-coated pins in nonosteoporotic bone.
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25.
  • Harding, Anna Kajsa, et al. (author)
  • Manipulating the anabolic and catabolic response in bone graft remodeling : Synergism by a combination of local BMP-7 and a single systemic dosis of zoledronate
  • 2008
  • In: Journal of Orthopaedic Research. - : Wiley. - 0736-0266 .- 1554-527X. ; 26:9, s. 1245-1249
  • Journal article (peer-reviewed)abstract
    • Remodeling of a bone graft can be influenced both by anabolic substances, such as a bone morphogenic protein (BMP) and by anticatabolic substances, such as the bisphosphonates. BMPs are potent bone anabolic substances, but also boost catabolism and cause resorption. Bisphosphonates inhibit osteoclast function and can be used to postpone resorption. In the present study a combination of both drugs was explored in a rat bone chamber model. Cancellous bone grafts were treated with either BMP-7 or saline and placed in a bone chamber implanted in the proximal tibia. After 2 weeks, an injection of either zoledronate 0.1 mg/kg or saline was given subcutaneously. The rats were killed after 6 weeks, and bone ingrowth distance into the graft and graft resorption were measured by histomorphometry. BMP-7 significantly (p = 0.007) increased new bone ingrowth distance into the graft from 2.0 mm (SD = 0.98 mm) in the controls to 3.1 mm (SD = 0.93 mm). If bisphosphonate was not given, most of the newly formed and old graft bone was resorbed. A single injection of zoledronate significantly (p< 0.001) increased the trabecular volume/total volume to 40% (SD = 9%) compared to 14% (SD = 10%) in the nonbisphosphonate treated. In total, the net amount of bone increased by 400% when BMP-7 and zoledronate combined was compared to saline. A bone graft can be treated with BMP-7 to increase new bone formation and at the same time be protected against premature catabolism by a single dose of a bisphosphonate. This combination might be useful in various conditions in orthopedic reconstruction. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
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26.
  •  
27.
  • Horstmann, Peter Frederik, et al. (author)
  • Composite biomaterial as a carrier for bone-Active substances for metaphyseal tibial bone defect reconstruction in rats
  • 2017
  • In: Tissue Engineering - Part A. - : Mary Ann Liebert Inc. - 1937-3341 .- 1937-335X. ; 23:23-24, s. 1403-1412
  • Journal article (peer-reviewed)abstract
    • Restoring lost bone is a major challenge in orthopedic surgery. Currently available treatment strategies have shortcomings, such as risk of infection, nonunion, and excessive resorption. Our primary aim was to study if a commercially available gentamicin-containing composite calcium sulfate/hydroxyapatite biomaterial (GBM) could serve as a carrier for local delivery of bone morphogenic protein-2 (BMP-2) and zoledronic acid (ZA) in a tibia defect model in rats. Empty and allograft-filled defects were used as controls. A 3 × 4-mm metaphyseal bone defect was created in the proximal tibia, and the rats were grouped according to defect filling: (1) Empty, (2) Allograft, (3) GBM, (4) GBM + ZA, and (5) GBM + ZA + BMP-2. In vivo microcomputed tomography (micro-CT) images at 4 weeks showed significantly higher mineralized tissue volume (MV) in the intramedullary defect region and the neocortical/callus region in all GBM-Treated groups. After euthanization at 8 weeks, ex vivo micro-CT showed that addition of ZA (GBM + ZA) and BMP-2 (GBM + ZA + BMP-2) mainly increased the neocortical and callus formation, with the highest MV in the combined ZA and BMP-2-Treated group. Qualitative histological analysis, verifying the increased neocortical/callus thickness and finding of trabecular bone in all GBM-Treated groups, supported that the differences in MV measured with micro-CT in fact represented bone tissue. In conclusion, GBM can serve as a carrier for ZA and BMP-2 leading to increased MV in the neocortex and callus of a metaphyseal bone defect in rats.
  •  
28.
  • Huang, Jintian, et al. (author)
  • A calcium sulphate/hydroxyapatite ceramic biomaterial carrier for local delivery of tobramycin in bone infections : Analysis of rheology, drug release and antimicrobial efficacy
  • 2023
  • In: Ceramics International. - 0272-8842. ; 49:21, s. 33725-33734
  • Journal article (peer-reviewed)abstract
    • Local targeted treatment of bone and joint infections using antibiotic-containing carriers is a common practice today. A recently FDA approved biphasic calcium sulphate/hydroxyapatite (CaS/HA) carrier containing gentamicin has been reported to give a sustained drug release, highly effective in eradicating bone infections. We present the first study evaluating the widely used aminoglycoside tobramycin (TOB) incorporated in the CaS/HA material with or without gentamycin (GEN) or vancomycin (VAN) with focus on rheology, drug release and antibacterial efficacy. In-vitro antibiotic release kinetics and biomaterial degradation were established by immersing the composites in phosphate buffered saline. The anti-bacterial effect of antibiotic containing CaS/HA composites as well as antibiotics release fractions were evaluated by Kirby-Bauer disk diffusion against S. aureus. The CaS/HA + GEN + TOB combination delayed setting to over 30 min whereas TOB + VAN slightly prolonged setting time (25 min vs. 15 min) still with good injectability. TOB was released from CaS/HA continuously for 35 days and during this period, the antibiotic loaded biomaterial could show a continuous anti-bacterial efficacy even at the last time point of day-35. After day-35, the pellets used for antibiotic release were taken out from release medium and broken into a paste. CaS/HA + TOB paste showed the largest ZOI (25 mm) against S. aureus ATCC 25923, while CaS/HA + VAN paste had no ZOI and CaS/HA + VAN + TOB paste had a ZOI of 18 mm. At the same time, the ZOI of CaS/HA + TOB against S. aureus P-3 was 14 mm compared to 0 mm in the other two groups. Adding TOB to CaS/HA containing VAN, extended the antimicrobial effect with a longer time and larger zone of inhibition, while no synergistic effect of the co-delivery was observed. Our in-vitro results indicate that CaS/HA could be used as a carrier for TOB as a local targeted delivery system in the treatment of bone infections.
  •  
29.
  •  
30.
  • Isaksson, Hanna, et al. (author)
  • Neutron tomographic imaging of bone-implant interface : Comparison with X-ray tomography
  • 2017
  • In: Bone. - : Elsevier BV. - 8756-3282. ; 103, s. 295-301
  • Journal article (peer-reviewed)abstract
    • Metal implants, in e.g. joint replacements, are generally considered to be a success. As mechanical stability is important for the longevity of a prosthesis, the biological reaction of the bone to the mechanical loading conditions after implantation and during remodelling determines its fate. The bone reaction at the implant interface can be studied using high-resolution imaging. However, commonly used X-ray imaging suffers from image artefacts in the close proximity of metal implants, which limit the possibility to closely examine the bone at the bone-implant interface. An alternative ex vivo 3D imaging method is offered by neutron tomography. Neutrons interact with matter differently than X-rays; therefore, this study explores if neutron tomography may be used to enrich studies on bone-implant interfaces. A stainless steel screw was implanted in a rat tibia and left to integrate for 6 weeks. After extracting the tibia, the bone-screw construct was imaged using X-ray and neutron tomography at different resolutions. Artefacts were visible in all X-ray images in the close proximity of the implant, which limited the ability to accurately quantify the bone around the implant. In contrast, neutron images were free of metal artefacts, enabling full analysis of the bone-implant interface. Trabecular structural bone parameters were quantified in the metaphyseal bone away from the implant using all imaging modalities. The structural bone parameters were similar for all images except for the lowest resolution neutron images. This study presents the first proof-of-concept that neutron tomographic imaging can be used for ex-vivo evaluation of bone microstructure and that it constitutes a viable, new tool to study the bone-implant interface tissue remodelling.
  •  
31.
  • Jeppsson, Charlotte, et al. (author)
  • A combination of bisphosphonate and BMP additives in impacted bone allografts
  • 2003
  • In: Acta Orthopaedica Scandinavica. - : Medical Journals Sweden AB. - 0001-6470. ; 74:4, s. 483-489
  • Journal article (peer-reviewed)abstract
    • OP-1 increases bone ingrowth distance of new bone into allografts (TΣgil et al. 2000), but the bone density after incorporation may be reduced by an increase in resorption (H÷stner et al. 2000). Bisphosphonates inactivate osteoclasts and can be used to increase allograft bone density after incorporation (Aspenberg and ┼strand 2002). A combination of locally-applied bisphosphonate and OP-1 in the graft could therefore be expected to increase both new bone ingrowth and density. We tested this by using a rat bone chamber model. OP-1 alone increased the ingrowth distance of bone. Clodronate increased final bone density greatly, but reduced the ingrowth distance of new bone into grafts that were extremely impacted. This reduction was improved by adding OP-1. Regardless of graft density, combinations of OP-1 and clodronate included a high final bone density, but the ingrowth distances were shorter than with OP-1 alone. These data indicate that new bone and tissue ingrowth into a compacted graft depends on resorption and that resorption is a prerequisite for the stimulating effect of OP-1 in this experimental set-up. Although the problems associated with the use of OP-1 in impaction grafting may be solved by adding a bisphosphonate, some of the benefits of OP-1 can be lost.
  •  
32.
  • Juréus, Jan, et al. (author)
  • The natural course of spontaneous osteonecrosis of the knee (SPONK) A 1-to 27-year follow-up of 40 patients
  • 2013
  • In: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3682 .- 1745-3674. ; 84:4, s. 410-414
  • Journal article (peer-reviewed)abstract
    • Background and purpose Spontaneous osteonecrosis of the knee (SPONK) is a painful lesion in the elderly, frequently leading to osteoarthritis and subsequent knee surgery. We evaluated the natural course and long-term consequences of SPONK in terms of need for major knee surgery. Methods Between 1982 and 1988, 40 consecutive patients were diagnosed with SPONK. The short-term outcome has been reported previously (1991). After 1-7 years, 10 patients had a good radiographic outcome and 30 were considered failures, developing osteoarthritis. In 2012, all 40 of the patients were matched with the Swedish Knee Arthroplasty Register (SKAR) and their medical records were reviewed to evaluate the long-term need for major knee surgery. Results At the 2012 review, 33 of the 40 patients had died. The mean follow-up time from diagnosis to surgery, death, or end of study was 9 (1-27) years. 17 of 40 patients had had major knee surgery with either arthroplasty (15) or osteotomy (2). All operated patients but 1 were in the radiographic failure group and had developed osteoarthritis in the study from 1991. 6 of 7 patients with large lesions (> 40% of the AP radiographic view of the condyle) at the time of the diagnosis were operated. None of the 10 patients with a lesion of less than 20% were ever operated. Interpretation It appears that the size of the osteonecrotic lesion can be used to predict the outcome. Patients showing early signs of osteoarthritis or with a large osteonecrosis have a high risk of later major knee surgery.
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33.
  • Juréus, Jan, et al. (author)
  • Treatment of spontaneous osteonecrosis of the knee (SPONK) by a bisphosphonate A prospective case series with 17 patients
  • 2012
  • In: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3682 .- 1745-3674. ; 83:5, s. 511-514
  • Journal article (peer-reviewed)abstract
    • Background and purpose Primary spontaneous osteonecrosis of the knee is a painful lesion in the elderly without any known cause. The onset of pain is usually acute. The prognosis is poor with high frequency of osteoarthritis, joint surface collapse, and subsequent knee surgery. In the present study, we determined whether bisphosphonates can prevent the joint surface collapse by delaying the post-necrotic remodeling. Patients and methods Between 2006 and 2009, 17 consecutive patients (mean age 68 years) with clinical and radiographic signs of knee osteonecrosis were identified and given alendronate, 70 mg perorally, once a week for a minimum of 6 months. The patients were followed clinically, radiographically, and by MRI. Results 10 of the 17 patients did not develop osteoarthritis (group A), 4 patients developed mild osteoarthritis but no knee joint surface collapse (group B), and 3 patients had a joint surface collapse (group C). 2 of the 3 patients in group C-as compared to none in the other groups-stopped medication prematurely, due to side effects. Interpretation Compared to a previous, untreated series of osteonecrosis patients at our hospital, the clinical results in the present series appeared better. 59% of the patients had a complete radiographic recovery, as compared to 25% in the original study. 12% were failures regarding need to undergo surgery when bisphosphonates were given, as compared to 32% in the previous untreated series. An anticatabolic drug delaying the remodeling might be an effective treatment in osteonecrosis of the knee but further (preferably randomized) studies are necessary.
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34.
  • Juréus, Jan, et al. (author)
  • Vascular evaluation after cervical hip fractures in children: a case series of eight children examined by scintigraphy after surgery for cervical hip fracture and evaluated for development of secondary radiological changes.
  • 2016
  • In: Journal of Pediatric Orthopedics. Part B. - 1473-5865. ; 25:1, s. 17-23
  • Journal article (peer-reviewed)abstract
    • Femoral neck fractures in children and young adults are rare, but have a high risk of avascular necrosis (AVN) and subsequent gradual collapse of the femoral head. In 2006, we initiated the use of scintigraphy for the diagnosis of vascular impairment after a cervical fracture in children. In the present retrospective case study, we evaluated the effect of the remaining postoperative circulation in the femoral head after fracture in terms of the development of AVN and secondary degenerative changes of the hip joint. Eight children, four girls and four boys [mean age 11.5 years (7-16)], had been operated for a cervical or a basocervical hip fracture between 2006 and 2012. The femoral head circulation was evaluated postoperatively with scintigraphy and all children had been followed radiographically for a minimum of 1 year. The Ficat classification was used to stage the AVN and the Stulberg classification was used to stage the sphericity of the femoral head at follow-up. In two patients, the femoral head had normal circulation postoperatively and they also had normal radiographs at follow-up. In two patients, the entire femoral head was avascular postoperatively and at follow-up, one patient had normal radiographs and one had both subchondral sclerosis and flattening. These two patients had been treated with bisphosphonates and prolonged non-weight-bearing. Four patients had postoperatively retained circulation in parts of the femoral head. Three of these four patients had normal radiographs at follow-up. Evaluation of the remaining circulation after surgery may help to predict the outcome and guide the postoperative regime in children with a femoral neck fracture.
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35.
  • Kanakaris, Nikolaos K., et al. (author)
  • Is there a role for bone morphogenetic proteins in osteoporotic fractures?
  • 2009
  • In: Injury. - 1879-0267. ; 40, s. 21-26
  • Journal article (peer-reviewed)abstract
    • The central role of bone morphogenetic proteins (BMPs) in the remodelling process of the human skeleton has been identified in numerous experimental and clinical studies. BMPs appear to be key agents in the osteoblastic differentiation of mesenchymal stem cells, and more recent evidence implicates them with the cells of the osteoclastic lineage. BMP-2, BMP-4, BMP-6 and BMP-7 have been studied in the context of osteoporosis and have been associated with its pathophysiological pathways. The theoretical advantages of local or systemic treatment of osteoporotic fractures with BMPs include the potential of inducing a rapid increase in bone strength locally at the fractured area and systemically in the entire skeleton, as well as accelerating the bone-healing period. Animal models of osteoporotic fractures suggested that the induction of new bone by local or systemic use of BMP-7 should be investigated as potential bone augmentation therapy to improve bone quality in symptomatic spinal osteoporosis. As our knowledge expands, new innovations may provide clinicians with advanced biologically-based therapies for the successful treatment of osteoporotic fractures. (C) 2009 Elsevier Ltd. All rights reserved.
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36.
  • Khayyeri, Hanifeh, et al. (author)
  • Corroboration of mechanobiological simulations of tissue differentiation in an in vivo bone chamber using a lattice-modeling approach
  • 2009
  • In: Journal of Orthopaedic Research. - : Wiley. - 1554-527X .- 0736-0266. ; 27:12, s. 1659-1666
  • Journal article (peer-reviewed)abstract
    • It is well established that the mechanical environment modulates tissue differentiation, and a number of mechanoregulatory theories for describing the process have been proposed. In this study, simulations of an in vivo bone chamber experiment were performed that allowed direct comparison with experimental data. A mechanoregulation theory for mesenchymal stem cell differentiation based on a combination of fluid flow and shear strain (computed using finite element analysis) was implemented to predict tissue differentiation inside mechanically controlled bone chambers inserted into rat tibae. To simulate cell activity, a lattice approach with stochastic cell migration, proliferation, and selected differentiation was adopted; because of its stochastic nature, each run of the simulation gave a somewhat different result. Simulations predicted the load-dependency of the tissue differentiation inside the chamber and a qualitative agreement with histological data; however, the full variability found between specimens in the experiment could not be predicted by the mechanoregulation algorithm. This result raises the question whether tissue differentiation predictions can be linked to genetic variability in animal populations.
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37.
  • Khayyeri, Hanifeh, et al. (author)
  • Tissue differentiation in an in vivo bioreactor: in silico investigations of scaffold stiffness
  • 2010
  • In: Journal of Materials Science: Materials in Medicine. - : Springer Science and Business Media LLC. - 1573-4838 .- 0957-4530. ; 21:8, s. 2331-2336
  • Journal article (peer-reviewed)abstract
    • Scaffold design remains a main challenge in tissue engineering due to the large number of requirements that need to be met in order to create functional tissues in vivo. Computer simulations of tissue differentiation within scaffolds could serve as a powerful tool in elucidating the design requirements for scaffolds in tissue engineering. In this study, a lattice-based model of a 3D porous scaffold construct derived from micro CT and a mechano-biological simulation of a bone chamber experiment were combined to investigate the effect of scaffold stiffness on tissue differentiation inside the chamber. The results indicate that higher scaffold stiffness, holding pore structure constant, enhances bone formation. This study demonstrates that a lattice approach is very suitable for modelling scaffolds in mechano-biological simulations, since it can accurately represent the micro-porous geometries of scaffolds in a 3D environment and reduce computational costs at the same time.
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38.
  • Khayyeri, Hanifeh, et al. (author)
  • Variability observed in mechano-regulated in vivo tissue differentiation can be explained by variation in cell mechano-sensitivity
  • 2011
  • In: Journal of Biomechanics. - : Elsevier BV. - 1873-2380 .- 0021-9290. ; 44:6, s. 1051-1058
  • Journal article (peer-reviewed)abstract
    • Computational simulations of tissue differentiation have been able to capture the main aspects of tissue formation/regeneration observed in animal experiments—except for the considerable degree of variability reported. Understanding and modelling the source of this variability is crucial if computational tools are to be developed for clinical applications. The objective of this study was to test the hypothesis that differences in cell mechano-sensitivity between individuals can explain the variability of tissue differentiation patterns observed experimentally. Simulations of an experiment of tissue differentiation in a mechanically loaded bone chamber were performed. Finite element analysis was used to determine the biophysical environment, and a lattice-modelling approach was used to simulate cell activity. Differences in cell mechano-sensitivity among individuals were modelled as differences in cell activity rates, with the activation of cell activities regulated by the mechanical environment. Predictions of the tissue distribution in the chambers produced the two different classes of results found experimentally: (i) chambers with a layer of bone across the chamber covered by a layer of cartilage on top and (ii) chambers with almost no bone, mainly fibrous tissue and small islands of cartilage. This indicates that the differing cellular response to the mechanical environment (i.e., subject-specific mechano-sensitivity) could be a reason for the different outcomes found when implants (or tissue engineered constructs) are used in a population.
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39.
  • Kok, Joeri, et al. (author)
  • Augmenting a dynamic hip screw with a calcium sulfate/hydroxyapatite biomaterial
  • 2021
  • In: Medical Engineering and Physics. - : Elsevier BV. - 1350-4533. ; 92, s. 102-109
  • Journal article (peer-reviewed)abstract
    • Internal fixation failure in hip fractures can lead to reoperation. Calcium sulfate/hydroxyapatite (CaS/HA) is a biomaterial that can be used for augmenting fracture fixation. We aimed to determine whether an injection of 2 ml CaS/HA increases the fixation of a dynamic hip screw inserted in synthetic and human trabecular bone. The study consists of two parts: 1) synthetic bone blocks (n = 74), with three subgroups: empty (cannulated screw, no injection), cannulated, and fenestrated; and 2) osteoporotic human femoral heads (n = 29), with the same subgroups. The heads were imaged using µCT. Bone volume fraction, insertion angle, and head diameter were measured. Pullout tests were performed and peak force, stiffness, and work were measured. The fenestrated group showed increases in pullout strength compared to no injection in the synthetic blocks. The cannulated group showed a higher pullout strength in low-density blocks. In the femoral heads, the variation was larger and there were no significant differences between groups. The bone volume fraction correlated with the peak force and work, and the insertion angle correlated with the stiffness. CaS/HA can improve the fixation of a dynamic hip screw. For clinical use, spreading of the material around the threads of the screw must be ensured.
  •  
40.
  • Kok, Joeri, et al. (author)
  • Fracture strength of the proximal femur injected with a calcium sulfate/hydroxyapatite bone substitute
  • 2019
  • In: Clinical Biomechanics. - : Elsevier BV. - 0268-0033. ; 63, s. 172-178
  • Journal article (peer-reviewed)abstract
    • Background: Available interventions for preventing fragility hip fractures show limited efficacy. Injection of a biomaterial as bone substitute could increase the fracture strength of the hip. This study aimed to show the feasibility of injecting a calcium sulfate/hydroxyapatite based biomaterial in the femoral neck and to calculate the consequent change in strength using the finite element method. Methods: Five patients were injected with 10 ml calcium sulfate/hydroxyapatite in their femoral neck. Quantitative CT scans were taken before and after injection. Five additional patients with fragility hip fractures were also scanned and the images from the non-fractured contralateral sides were used. Finite element models were created for all proximal femora with and without injection and the models were tested under stance and sideways fall loading until fracture. The change in fracture strength caused by the injection was calculated. Additionally, perturbations in volume, location, and stiffness of the injected material were created to investigate their contribution to the fracture strength increase. Findings: The 10 ml injection succeeded in all patients. Baseline simulations showed theoretical fracture strength increases of 0–9%. Volume increase, change in location and increase in stiffness of the material led to increases in fracture strength of 1–27%, −8-26% and 0–17%, respectively. Altering the location of the injection to a more lateral position and increasing the stiffness of the material led to increases in fracture strength of up to 42%. Interpretation: This study shows that an injection of calcium sulfate/hydroxyapatite is feasible and can theoretically increase the hip's fracture strength.
  •  
41.
  • Kopylov, Philippe, et al. (author)
  • Delayed surgery does not reduce the interface strength between the surface of a bone fracture and a self-curing injectable hydroxyapatite (Norian SRS)
  • 2001
  • In: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery. - : Informa UK Limited. - 1651-2073 .- 0284-4311. ; 35:2, s. 129-133
  • Journal article (peer-reviewed)abstract
    • The shear strength of the interface between bone and an injectable calcium phosphate bone substitute that cures to form a carbonated apatite (Norian SRS) was measured and related to the time that elapsed between injury and surgery. Eleven rabbits had a 3 mm drill hole made in the retropatellar aspect of the distal femur. After one week, the rabbits were reoperated on and the hole filled with Norian SRS after it had been cleaned gently with a sponge. During the same procedure a similar hole was burred in the opposite femur and filled with Norian SRS after a few minutes ("immediate injection"). Four other rabbits had only one side operated on with immediate injection of Norian SRS to compare with the opposite untreated side. The rabbits were killed four days after the injection of Norian SRS. The femurs were prepared and sawed perpendicularly to the burr channels to produce discs 3.5 mm thick. A push out test of the Norian SRS plug within the bone disc was done to measure the force at failure. In the immediately injected specimens the failure occurred at a mean of 28 N (range 5-57) compared with 42 N (range 25-65) in the specimens injected after a one week delay. There was no significant difference between delayed and immediate treatment (95% confidence interval -5 to 133). The histological examination showed that 9 of the 12 specimens had Norian SRS still adherent to half or more of the circumference of the hole. This indicates that the failure occurred in the Norian SRS rather than in the bone or at the interface.
  •  
42.
  • Kopylov, Philippe, et al. (author)
  • Distal radioulnar joint replacement
  • 2007
  • In: Techniques in Hand & Upper Extremity Surgery. - 1089-3393. ; 11:1, s. 109-114
  • Journal article (peer-reviewed)abstract
    • The resection of the ulnar head, as described by Darrach, has unfortunately become the standard of care despite the frequent problems of ulnar stump instability following this procedure. To offer better treatment to our patients, we have to appreciate the various roles and the importance of the ulnar head for the function of the distal radioulnar joint (DRUJ) in mechanically loaded forearm rotation. The ulnar head forms the load-bearing keystone of the DRUJ and the distal forearm, important for maintaining adequate tension within the radioulnar ligaments and the interosseous membrane. A DRUJ implant replacing the ulnar head should and has to be the fixed point and load-bearing part of the joint and will be exerted to large mechanical loads making a neutralization of these forces necessary. A partial resurfacing implant for the DRUJ can be used for primary procedures. The resection is minimal, and further, the attachments of the stabilizing ligaments, the triangular fibrocartilage complex in particular, are preserved with a maintained anatomy and stability. For revision and salvage procedure, a modular ulnar head can be used, which restores the ulnar head offset and stabilizes the ulnar stump, restoring a pain-free DRUJ. The modularity of these 2 implants addresses the majority of indications for prosthesis in the DRUJ.
  •  
43.
  • Kopylov, Philippe, et al. (author)
  • The rheumatoid finger : Treatment concepts and indications for surgery
  • 2016
  • In: Clinical Management of the Rheumatoid Hand, Wrist, and Elbow. - Cham : Springer International Publishing. - 9783319266602 - 9783319266589 ; , s. 185-194
  • Book chapter (peer-reviewed)abstract
    • Synovial proliferation in rheumatoid arthritis causes capsular distension, destruction of tendons and ligaments, and erosion of bone. The classic deformities in rheumatoid arthritis, like boutonnière or swan neck, are not consistent, and each patient may have his or her own pattern of deformities. The anatomic arrangement of the tendons enables motion of the proximal interphalangeal (PIP) joint isolated and separated from the distal interphalangeal (DIP) joint. The central band of the extensor mechanism and the flexor digitorum superficialis (FDS) both insert on the middle phalanx and both contribute to the control of the PIP joint. In contrast, the flexor digitorum profundus (FDP) tendon runs along the whole finger and acts on both the PIP and DIP joints. In a similar fashion, the conjoined lateral bands insert on the distal phalanx but influence the motion of the PIP joint as well. A change in length, by distention, rupture, or inability to glide one or several of these tendons, will provoke an imbalance, which may lead to a boutonnière or swan-neck deformity. A boutonnière deformity is often identified as a substantial problem to the patient, especially when the DIP joint has gone into hyperextension. Also the swan-neck deformity most often is identified by the patient as a source of severe subjective hand and finger functional impairment because of impaired grip. If a moderate lack of extension after treatment is accepted by the patient, surgical treatment offers an acceptable solution. Implants may be used in stiff joints to regain some mobility of the PIP joint but rebalancing of the extensor mechanism is difficult.
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44.
  • Landgren, Marcus, et al. (author)
  • External or internal fixation in the treatment of non-reducible distal radial fractures? A 5-year follow-up of a randomized study involving 50 patients
  • 2011
  • In: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3682 .- 1745-3674. ; 82:5, s. 610-613
  • Journal article (peer-reviewed)abstract
    • Background and purpose We have previously shown in a randomized study that in the first year after treatment, open reduction and internal fixation resulted in better grip strength and forearm rotation than closed reduction and bridging external fixation. In the present study, we investigated whether this difference persists over time. Patients and methods The 50 patients included in the original study (mean age 53 years, 36 women) were sent a QuickDASH questionnaire and an invitation to a radiographic and clinical examination after a mean of 5 (3-7) years. Results All 50 patients returned the QuickDASH questionnaire and 45 participated in the clinical and radiographic examination. In the internal fixation group, the grip strength was 95% (SD 12) of the uninjured side and in the external fixation group it was 90% (SD 21) of the uninjured side (p = 0.3). QuickDASH score, range of motion, and radiographic parameters were similar between the groups. Interpretation The difference originally found between internal and external fixation in distal radial fractures at 1 year regarding grip strength and range of motion was found to diminish with time. At 5 years, both groups had approached normal values.
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45.
  • Landgren, Marcus, et al. (author)
  • Fragment-Specific Fixation Versus Volar Locking Plates in Primarily Nonreducible or Secondarily Redisplaced Distal Radius Fractures : A Randomized Controlled Study
  • 2017
  • In: The Journal of Hand Surgery. - : Elsevier BV. - 0363-5023. ; 42:3, s. 1-165
  • Journal article (peer-reviewed)abstract
    • Purpose: To compare the patient-reported, clinical, and radiographic outcome of 2 methods of internal fixation in distal radius fractures. Methods: Fifty patients, mean age 56 years (range, 21-69 years) with primarily nonreducible or secondarily redisplaced distal radius fractures were randomized to open reduction internal fixation using volar locking plates (n = 25) or fragment-specific fixation (n = 25). The patients were assessed on grip strength, range of motion, patient-reported outcome (Quick Disabilities of the Arm, Shoulder, and Hand), pain (visual analog scale), health-related quality of life (Short Form-12 [SF-12]), and radiographic evaluation. Grip strength at 12 months was the primary outcome measure. Results: At 12 months, no difference was found in grip strength, which was 90% of the uninjured side in the volar plate group and 87% in the fragment-specific fixation group. No differences were found in range of motion and the median Quick Disabilities of the Arm, Shoulder, and Hand score was 5 in both groups. The overall complication rate was significant, 21% in the volar locking plate group, compared with 52% in the fragment-specific group. Conclusions: In treatment of primarily nonreducible or secondarily redisplaced distal radius fractures, volar locking plates and fragment-specific fixation both achieve good and similar patient-reported outcomes, although more complications were recorded in the fragment-specific group. Type of study/level of evidence: Therapeutic II.
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46.
  • Landgren, Marcus, et al. (author)
  • Intermediate-Term Outcome After Distal Radius Fracture in Patients With Poor Outcome at 1 Year : A Register Study With a 2- to 12-Year Follow-Up
  • 2019
  • In: The Journal of Hand Surgery. - : Elsevier BV. - 0363-5023 .- 1531-6564. ; 44:1, s. 39-45
  • Journal article (peer-reviewed)abstract
    • Purpose: Most patients recover well from a distal radius fracture (DRF). However, approximately one-fifth have severe disability after 1 year when evaluated using the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire. In the present study, we evaluated this subgroup of patients in our register with an inferior outcome. We hypothesized that the patient-reported outcome would improve with time. Methods: Since 2001, patients 18 years and older with a DRF, at the Department of Orthopedics, Skåne University Hospital (Lund, Sweden) are prospectively registered in the Lund Wrist Fracture Register. We have previously defined a DASH score above 35 at the 1-year follow-up as the cutoff of major disability. Between 2003 and 2012, 17% of the patients (445 of 2,571) in the register exceeded this cutoff. Three hundred eighty-eight were women and 57 men and the mean age was 69 years (range, 18–95 years). One-fourth had been surgically treated. In December 2014, 2 to 12 years after the fracture, a follow-up DASH questionnaire was sent to the 346 of 445 patients still alive. Results: Seventy-three patients (27%) had initially been treated surgically and 196 (73%) nonsurgically for their DRF. Two hundred sixty-nine of 346 patients (78%) returned the follow-up DASH questionnaire at 2 to 12 years (mean, 5.5 years) after the fracture. The overall median DASH score improved from 50 at 1 year to 36 at the 2- to 12-year follow-up, (P <.05). Forty-seven percent had improved to a score below the cutoff 35, but 53% remained at a high suboptimal level. Conclusions: The subjective outcome after a DRF improves over time for patients with an inferior result at 1 year, but more than half of the patients continue to have major disability. Type of study/level of evidence: Prognostic II.
  •  
47.
  • Landgren, Marcus, et al. (author)
  • Similar 1-year subjective outcome after a distal radius fracture during the 10-year-period 2003-2012 : A longitudinal register-based study involving 3,666 patients
  • 2017
  • In: Acta Orthopaedica. - : Taylor & Francis Group. - 1745-3674 .- 1745-3682. ; 88:4, s. 451-456
  • Journal article (peer-reviewed)abstract
    • Background and purpose: During the last decades, treatment of distal radius fractures (DRFs) has changed, with surgical intervention being more common and with new techniques. We investigated whether this change has influenced the subjective outcome. Here we report, year by year, the 1-year score after a DRF over a 10-year-period, using a patient-reported outcome measure.Patients and methods: Patients aged 18 years or more with a DRF between 2003 and 2012 were prospectively and consecutively registered in a longitudinal outcome database. 1 year after the fracture, all the patients were sent a validated subjective outcome questionnaire, the Disabilities of the Arm, Shoulder, and Hand (DASH). The lower the score (0-100), the better the outcome.Results: Between 2003 and 2012, 3,666 patients (2,833 of them women; mean age 62 (18-98) years) were included. 22% were operated and the rate remained constant over the years. The surgical methods shifted from external fixators (42%) and fragment-specific plates (45%) in 2003, to mainly volar locking plates (65%) in 2012. 70% of the patients responded to the 1-year DASH questionnaire. The median DASH score was 9 (IQR: 2-25) for the cohort, both in surgically treated patients (9 (IQR: 3-25)) and in non-surgically treated patients (9 (IQR 2-27)). Subgroup analysis showed a higher median DASH score for women than for men; for patients with AO type C fractures rather than type B or type A fractures; for patients with external fixation or fragment-specific fixation than for those who underwent surgery using volar locking plates; and for patients who were operated by a general orthopedic surgeon rather than a hand surgeon.Interpretation: The shift in surgical treatment had no influence on the subjective outcome for the cohort.
  •  
48.
  • Le Cann, Sophie, et al. (author)
  • Bone Damage Evolution Around Integrated Metal Screws Using X-Ray Tomography : In situ Pullout and Digital Volume Correlation
  • 2020
  • In: Frontiers in Bioengineering and Biotechnology. - : Frontiers Media SA. - 2296-4185. ; 8
  • Journal article (peer-reviewed)abstract
    • Better understanding of the local deformation of the bone network around metallic implants subjected to loading is of importance to assess the mechanical resistance of the bone-implant interface and limit implant failure. In this study, four titanium screws were osseointegrated into rat tibiae for 4 weeks and screw pullout was conducted in situ under x-ray microtomography, recording macroscopic mechanical behavior and full tomographies at multiple load steps before failure. Images were analyzed using Digital Volume Correlation (DVC) to access internal displacement and deformation fields during loading. A repeatable failure pattern was observed, where a ∼300–500 μm-thick envelope of bone detached from the trabecular structure. Fracture initiated close to the screw tip and propagated along the implant surface, at a distance of around 500 μm. Thus, the fracture pattern appeared to be influenced by the microstructure of the bone formed closely around the threads, which confirmed that the model is relevant for evaluating the effect of pharmacological treatments affecting local bone formation. Moreover, cracks at the tibial plateau were identified by DVC analysis of the tomographic images acquired during loading. Moderate strains were first distributed in the trabecular bone, which localized into higher strains regions with subsequent loading, revealing crack-formation not evident in the tomographic images. The in situ loading methodology followed by DVC is shown to be a powerful tool to study internal deformation and fracture behavior of the newly formed bone close to an implant when subjected to loading. A better understanding of the interface failure may help improve the outcome of surgical implants.
  •  
49.
  •  
50.
  • Le Cann, Sophie, et al. (author)
  • Characterization of the bone-metal implant interface by Digital Volume Correlation of in-situ loading using neutron tomography
  • 2017
  • In: Journal of the Mechanical Behavior of Biomedical Materials. - : Elsevier BV. - 1751-6161. ; 75, s. 271-278
  • Journal article (peer-reviewed)abstract
    • Metallic implants are commonly used as surgical treatments for many orthopedic conditions. The long-term stability of implants relies on an adequate integration with the surrounding bone. Unsuccessful integration could lead to implant loosening. By combining mechanical loading with high-resolution 3D imaging methods, followed by image analysis such as Digital Volume Correlation (DVC), we aim at evaluating ex vivo the mechanical resistance of newly formed bone at the interface. X-rays tomography is commonly used to image bone but induces artefacts close to metallic components. Utilizing a different interaction with matter, neutron tomography is a promising alternative but has not yet been used in studies of bone mechanics. This work demonstrates that neutron tomography during in situ loading is a feasible tool to characterize the mechanical response of bone-implant interfaces, especially when combined with DVC. Experiments were performed where metal screws were implanted in rat tibiae during 4 weeks. The screws were pulled-out while the samples were sequentially imaged in situ with neutron tomography. The images were analyzed to quantify bone ingrowth around the implants. DVC was used to track the internal displacements and calculate the strain fields in the bone during loading. The neutron images were free of metal-related artefacts, which enabled accurate quantification of bone ingrowth on the screw (ranging from 60% to 71%). DVC allowed successful identification of the deformation and cracks that occurred during mechanical loading and led to final failure of the bone-implant interface.
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