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1.
  • Abtahi, Jahan, et al. (author)
  • A bisphosphonate-coating improves the fixation of metal implants in human bone. A randomized trial of dental implants
  • 2012
  • In: Bone. - : Elsevier. - 8756-3282 .- 1873-2763. ; 50:5, s. 1148-1151
  • Journal article (peer-reviewed)abstract
    • Many surgical procedures use metal implants in bone. The clinical results depend on the strength of the bone holding these implants. Our objective was to show that a drug released from the implant surface can improve parameters reflecting the quality or amount of this bone. Sixteen patients received paired dental titanium implants in the maxilla, in a randomized, double-blinded fashion. One implant in each pair was coated with a thin fibrinogen layer containing 2 bisphosphonates. The other implant was untreated. Fixation was evaluated by measurement of resonance frequency (implant stability quotient; ISQ) serving as a proxy for stiffness of the implant-bone construct. Increase in ISQ at 6 months of follow-up was the primary variable. None of the patients had any complications. The resonance frequency increased 6.9 ISQ units more for the coated implants (p = 0.0001; Cohens d = 1.3). The average difference in increase in ISQ and the effect size, suggested a clinically relevant improvement. X-ray showed less bone resorption at the margin of the implant both at 2 months (p = 0.012) and at 6 months (p = 0.012). In conclusion, a thin, bisphosphonate-eluting fibrinogen coating might improve the fixation of metal implants in human bone. This might lead to new possibilities for orthopedic surgery in osteoporotic bone and for dental implants.
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2.
  • Abtahi, Jahan, et al. (author)
  • Bisphosphonate coating might improve fixation of dental implants in the maxilla: A pilot study
  • 2010
  • In: International Journal of Oral and Maxillofacial Surgery. - : Elsevier Science B.V., Amsterdam. - 0901-5027 .- 1399-0020. ; 39:7, s. 673-677
  • Journal article (peer-reviewed)abstract
    • This pilot study evaluates the clinical stability of bisphosphonate-coated dental implants placed using a two-stage surgical procedure in five patients. Each patient received seven regular Brånemark implants, one of which was coated with bisphosphonate in a fibrinogen matrix. The coated implant was inserted where the bone was expected to have the least favourable quality. The level of the marginal bone around each implant was measured by intraoral periapical radiographs and implant stability was recorded using resonance frequency measurements. Frequency values (ISQ) were obtained peroperatively before flap closure and after 6 months at abutment connection. At abutment connection the bisphosphonate-coated implants were removed en bloc in two patients for histological examination. An animal experiment had previously confirmed that gamma-sterilization did not reduce bioactivity of the bisphosphonate coating. In each patient, the bisphosphonate-coated implant showed the largest improvement in ISQ level of all implants. Their values at the start tended to be lower, and the absolute value at 6 months did not differ. No complications occurred with the coated implants. Histology showed no abnormalities. Improvement in ISQ values was an expected effect of the bisphosphonate coating, but could be due to the choice of insertion site. This finding warrants a randomized, blinded study.
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3.
  • Abtahi, Jahan, et al. (author)
  • Bisphosphonate-induced osteonecrosis of the jaw in a rat model arises first after the bone has become exposed. No primary necrosis in unexposed bone
  • 2012
  • In: Journal of Oral Pathology & Medicine. - : John Wiley and Sons. - 0904-2512 .- 1600-0714. ; 41:6, s. 494-499
  • Journal article (peer-reviewed)abstract
    • J Oral Pathol Med (2012) 41: 494499 Background: Bisphosphonate-related osteonecrosis of the jaw was first described to start with sterile osteocyte death, similar to osteonecrosis in other parts of the skeleton. The typical chronic osteomyelitis was thought to develop when the dead bone was exposed to the oral cavity. An alternative explanation would be that the chronic osteomyelitis is a result of a bisphosphonate-related inability of infected bony lesions to heal. We tested the hypothesis that primary osteocyte death is not necessary for the development of jaw osteonecrosis. Material and methods: Forty rats were randomly allocated to four groups of 10. All animals underwent unilateral molar extraction and received the following drug treatments: Group I, controls with no drug treatment; Group II, 200 mu g/kg per day alendronate; Groups III and IV, 200 mu g/kg per day alendronate and 1 mg/kg of dexamethasone. All rats were euthanized after 14 days. Presence of osteonecrosis was determined by clinical and histological observations for groups IIII. For group IV, osteocyte viability at the contralateral uninjured site was examined using lactate dehydrogenase histochemistry (LDH). Results: All animals in the alendronate plus dexamethasone groups developed large ONJ-like lesions. Lactate dehydrogenase staining showed viable osteocytes in the contralateral jaw with no tooth extraction. No signs of osteonecosis were seen in the other groups. Conclusion: Bisphosphonates and dexamethasone caused no osteocyte death in uninjured bone, but large ONJ-like lesions after tooth extraction. Osteonecrosis of the jaw appears to arise first after the bone has been exposed. Possibly, bisphosphonates hamper the necessary resorption of bone that has become altered because of infection.
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4.
  • Abtahi, Jahan, 1965- (author)
  • Bisphosphonates and implants in the jaw bone
  • 2013
  • Doctoral thesis (other academic/artistic)abstract
    • Insertion of metal implants in bone is one of the commonest of all surgical procedures. The success of these operations is dependent on the fixation of the implants, which, in turn, depends on the strength of the bone that holds them. If the quality of the bone holding the implant could be improved locally, surgical procedures would become simpler and rehabilitation would become faster. Bisphosphonates are anti-resorptive drugs that act specifically on osteoclasts, thereby maintaining bone density and strength. Once released from the surface of a coated implant, bisphosphonates reduce osteoclast activity, thereby changing the balance of bone turnover in favor of bone formation, leading to a net gain in local bone density. During the last decades, the effects of bisphosphonate treatment on the stability of implants have been tested in several clinical and animal studies, but not in human jaws. This may be because it has been suggested that there is a link between the use of bisphosphonates (especially those given intravenously) and a condition called osteonecrosis of the jaw (ONJ). The pathophysiology and treatment of ONJ is controversial. The difficulty in treating ONJ has highlighted the importance of prevention.The overall aim of the present thesis was to evaluate the effect of local and systemic use of bisphosphonates on bone tissue. Could a thin, bisphosphonate-eluting fibrinogen coating improve the fixation of metal implants in the human jaw? Would it be possible to reproduce ONJ and prevent the development of this condition in an animal model?In two clinical studies, a total number of 96 implants were inserted in 21 patients. In a randomized trial with a paired design, one implant in each pair was coated with a thin fibrinogen layer containing two bisphosphonates (pamidronate and ibandronate). The bisphosphonate-coated implants showed better stability as measured by resonancefrequency analysis. Radiographic intraoral films also showed less bone loss. Three animal models were developed. In a study comparing local and systemic effects of bisphosphonates, zoledronate-coated screws inserted in rats showed better fixation in spite of a drug treatment that is known to induce ONJ-like lesions when given systemically. In another rat model, ONJ-like lesions were reproducibly induced at sites of tooth extraction whereas there were no signs of bone cell death in uninjured sites. Finally, rat experiments showed that the development of ONJ-like lesions after tooth extraction could be prevented by early mucoperiosteal coverage.In conclusion, a thin, bisphosphonate-eluting fibrinogen coating can improve the fixation of dental implants in human bone. This may lead to new possibilities in orthopaedic surgery and dentistry. The pathophysiology of ONJ is strongly linked to bone exposure in combination with drugs that reduce resorption.
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5.
  • Abtahi, Jahan, et al. (author)
  • Effect of Local vs. Systemic Bisphosphonate Delivery on Dental Implant Fixation in a Model of Osteonecrosis of the Jaw
  • 2013
  • In: Journal of Dental Research. - : Sage Publications. - 0022-0345 .- 1544-0591. ; 92:3, s. 279-283
  • Journal article (peer-reviewed)abstract
    • Locally applied bisphosphonates may improve the fixation of metal implants in bone. However, systemic bisphosphonate treatment is associated with a risk of osteonecrosis of the jaw (ONJ). We hypothesized that local delivery of bisphosphonate from the implant surface improves the fixation of dental implants without complications in a setting where systemic treatment induces ONJ. Forty rats were randomly allocated to 4 groups of 10. All groups received a titanium implant inserted in an extraction socket. Group I received the implants only. Group II received dexamethasone (0.5 mg/kg). Group III received dexamethasone as above plus alendronate (200 µg/kg). Group IV received zoledronate-coated implants and dexamethasone as above. The animals were sacrificed 2 weeks after tooth extraction. All 10 animals with systemic alendronate treatment developed large ONJ-like changes, while all with local treatment were completely healed. Implant removal torque was higher for the bisphosphonate-coated implants compared with the other groups (p < 0.03 for each comparison). Micro-computed tomography of the maxilla showed more bone loss in the systemic alendronate group compared with groups receiving local treatment (p = 0.001). Local bisphosphonate treatment appears to improve implant fixation in a setting where systemic treatment caused ONJ.
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6.
  • Abtahi, Jahan, 1965-, et al. (author)
  • Ibandronate Reduces the Surface Bone Resorption of Mandibular Bone Grafts : A Randomized Trial With Internal Controls
  • 2021
  • In: JBMR Plus. - : Wiley. - 2473-4039. ; 5:3
  • Journal article (peer-reviewed)abstract
    • Autologous bone grafts are considered the gold standard for reconstruction of the edentulous alveolar ridges. However, this procedure is associated with unpredictable bone loss caused by physiological bone resorption. Bisphosphonates are antiresorptive drugs that act specifically on osteoclasts, thereby maintaining bone density, volume, and strength. It was hypothesized that the resorption of bone grafts treated with an ibandronate solution would be less advanced than bone grafts treated with saline. Ten patients who underwent bilateral sagittal split osteotomy were included in a randomized double-blind trial with internal controls. Each patient received a bone graft treated with a solution of ibandronate on one side and a graft treated with saline (controls) contralaterally. Radiographs for the measurement of bone volume were obtained at 2 weeks and at 6 months after surgery. The primary endpoint was the difference in the change of bone volume between the control and the ibandronate bone grafts 6 months after surgery. All of the bone grafts healed without complications. One patient was excluded because of reoperation. In eight of the nine patients, the ibandronate bone grafts showed an increase in bone volume compared with baseline, with an average gain of 126 mm(3) (40% more than baseline) with a range of +27 to +218 mm(3). Only one ibandronate-treated graft had a decrease in bone volume (8%). In the controls, an average bone volume loss of -146 mm(3) (58% of baseline) with a range of -29 to -301 mm(3) was seen. In the maxillofacial field, the reconstructions of atrophic alveolar ridges, especially in the esthetical zones, are challenging. These results show that bone grafts locally treated with ibandronate solution increases the remaining bone volume. This might lead to new possibilities for the maxillofacial surgeons in the preservation of bone graft volumes and for dental implant installations.
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7.
  • Abtahi, Jahan, 1965-, et al. (author)
  • Impact of a zoledronate coating on early post-surgical implant stability and marginal bone resorption in the maxilla-A split-mouth randomized clinical trial.
  • 2019
  • In: Clinical Oral Implants Research. - : John Wiley & Sons. - 0905-7161 .- 1600-0501. ; 30:1, s. 49-58
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: The objective of this clinical study was to evaluate the effect of a bisphosphonate coating on a titanium implant on the implant stability quotient (ISQ) and the radiographic marginal bone levels at implants during early healing (2-8 weeks).MATERIALS AND METHODS: In a randomized double-blind trial with internal controls, 16 patients received a dental implant coated with zoledronate and one uncoated implant as a control. The coated and uncoated implants which were visually indistinguishable were bone level titanium implants with a moderately rough surface and a microthreaded neck. ISQ values were obtained at insertion and at 2, 4, 6, and 8 weeks. Radiographs were obtained at insertion and at 8 weeks. The primary outcome was the difference in ISQ values between the coated implants and the control implants at 4 and 6 weeks, corrected for insertion values. The secondary outcome was loss of marginal bone level from insertion to 8 weeks.RESULTS: Implant stability quotient values remained largely constant over the 8 weeks, and there was no significant difference between coated and uncoated implants at any time point. There was 0.12 (SD 0.10) mm marginal bone loss at the control implants and 0.04 (SD 0.08) mm at the coated implants. The difference was 0.17 mm; SD 0.14; p < 0.006). On blind qualitative scoring, 13 of the 15 control implants and two of 15 coated implants showed small marginal bone defects (p = 0.003).CONCLUSIONS: There were no statistically significant differences observed in ISQ values between the coated and uncoated implants during the early healing. There was less marginal bone loss at the coated implants.
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8.
  • Abtahi, Jahan, 1965-, et al. (author)
  • Malignant Transformation of Ossifying Fibroma into Parosteal Osteosarcoma with High-grade Component: Presentation of an Unusual Case and Review of the Literature
  • 2018
  • In: The Open Dentistry Journal. - : Bentham Open. - 1874-2106. ; 12, s. 1059-1068
  • Journal article (peer-reviewed)abstract
    • Background: Parosteal Osteosarcoma of the Jaw (POSJ) is a rare entity that is associated with a high survival rate. Several case reports and case series of POSJ have been published in the literature, but few authors have described development of this tumor by possible transformation from a fibro-osseous neoplasm. Objective: We present a rare occurrence of parosteal osteosarcoma with involvement of the posterior maxilla, orbit floor, and infra-temporal fossa in a 20-year-old man. Furthermore, we performed a literature review regarding clinical, radiological, and histological features; treatment strategies; and etiology/pathophysiology. Methods: A PubMed search yielded a total of 74 articles and the articles were sorted according to their corresponding key area of focus. Results: This was a case of POSJ with high-grade component in the maxillofacial region of a 20-year old male. Co-expression of MDM2 and CDK4 was confirmed. At 2.5-year follow-up, the patient had died. The literature review revealed 18 articles including 20 cases of POSJ. Four cases represent the possible development of this tumor by transformation from a fibro-osseous neoplasm: Two cases of fibrous dysplasia, one case of cemento-ossifying fibroma, and the case of Ossifying Fibroma (OF) in the present study. Conclusion: In conclusion, we found an unusual case of POSJ of the midface in a patient with a previous diagnosis of OF in the same region. To our knowledge, there have been no previous reports of development of POSJ in OF. Furthermore, this is the first described case of high-grade surface osteosarcoma in the craniofacial region.
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9.
  • Abtahi, Jahan, et al. (author)
  • Prevention of osteonecrosis of the jaw by mucoperiosteal coverage in a rat model
  • 2013
  • In: International Journal of Oral and Maxillofacial Surgery. - : Elsevier BV. - 0901-5027 .- 1399-0020. ; 42:5, s. 632-636
  • Journal article (peer-reviewed)abstract
    • There is evidence for a link between the use of systemic bisphosphonates and osteonecrosis of the jaw (ONJ). This condition has the appearance of chronic osteomyelitis, and antibiotics prevent the development of ONJ in animal models. Clinically, ONJ can sometimes be successfully treated by mucoperiosteal coverage. If ONJ is indeed primarily caused by bacterial infection, immediate coverage of the extraction alveolus might reduce the risk of ONJ development in risk patients. Therefore, we studied whether immediate mucoperiosteal coverage after tooth extraction could prevent ONJ development in a rat model. Thirty rats were randomly allocated to three groups of 10. Group I (controls): extraction, no drug treatment; Group II (non-coverage): extraction, dexamethasone plus alendronate; Group III (coverage): dexamethasone plus alendronate, plus coverage by a mucoperiosteal flap. Rats were examined for macroscopic ONJ-like wounds after 2 weeks. All animals in the non-coverage group developed large ONJ-like changes. The coverage and control groups showed an intact overlying mucosa in all rats. Findings were confirmed with histology. Bisphosphonates and dexamethasone caused ONJ-like lesions after tooth extraction in a rat model. This was prevented by immediate mucoperiosteal coverage. The risk of ONJ in patients using bisphosphonates might be reduced by mucoperiosteal coverage after tooth extraction.
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10.
  • Abtahi, Jahan, et al. (author)
  • Randomised trial of bisphosphonate-coated dental implants: Radiographic follow-up after five years of loading
  • 2016
  • In: International Journal of Oral and Maxillofacial Surgery. - : CHURCHILL LIVINGSTONE. - 0901-5027 .- 1399-0020. ; 45:12, s. 1564-1569
  • Journal article (peer-reviewed)abstract
    • The results of a randomised trial with bisphosphonate-coated dental implants have been reported previously. Each patient received one coated and one uncoated implant in a double-blind split-mouth design study. After 6 months of osseointegration, resonance frequency analysis indicated better fixation of the coated implants. Reduced marginal bone resorption was also shown. However, it was not known whether the advantage of the bisphosphonate coating would persist over time. The radiographic results at 5 years after implant installation are reported herein. A blinded investigator measured marginal resorption on fresh radiographs obtained for 14 of the 16 patients (two had died) and compared these with the post-implantation images. Non-parametric statistics were used. All implants functioned well. The median marginal bone loss for control implants was found to be 0.70 mm, which is less than usually reported in the literature. The bisphosphonate-coated implants showed even less resorption (median 0.20 mm). The median difference within each pair of implants after 5 years of use was 0.34 mm (95% confidence interval 0.00-0.75 mm; P = 0.04). The present data suggest that bisphosphonate-coated implants enable prolonged preservation of the marginal bone.
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