| 1. |
- Dieppe, Paul, et al.
(författare)
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Variations in the pre-operative status of patients coming to primary hip replacement for osteoarthritis in European orthopaedic centres
- 2009
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Total hip joint replacement (THR) is a high volume, effective intervention for hip osteoarthritis (OA). However, indications and determinants of outcome remain unclear. The 'EUROHIP consortium' has undertaken a cohort study to investigate these questions. This paper describes the variations in disease severity in this cohort and the relationships between clinical and radiographic severity, and explores some of the determinants of variation. Methods: A minimum of 50 consecutive, consenting patients coming to primary THR for primary hip OA in each of the 20 participating orthopaedic centres entered the study. Pre-operative data included demographics, employment and educational attainment, drug utilisation, and involvement of other joints. Each subject completed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC - Likert version 3.1). Other data collected at the time of surgery included the prosthesis used and American Society of Anaesthesiologists (ASA) status. Preoperative radiographs were read by the same three readers for Kellgren and Lawrence (K&L) grading and Osteoarthritis Research Society International (OARSI) atlas features. Regression analyses were carried out. Results: Data from 1327 subjects has been analysed. The mean age of the group was 65.7 years, and there were more women (53.4%) than men. Most (79%) were ASA status 1 or 2. Reported disease duration was 5 years or less in 69.2%. Disease in other joint sites was common. Radiographs were available in 1051 subjects and the K&L grade was 3 or 4 in 95.8%. There was much more variation in clinical severity (WOMAC score); the mean total WOMAC score was 59.2 (SD 16.1). The radiographic severity showed no correlation with WOMAC scores. Significantly higher WOMAC scores (worse disease) were seen in older people, women, those with obesity, those with worse general health, and those with lower educational attainment. Conclusion: 1. Clinical disease severity varies widely at the time of THR for OA. 2. In advanced hip OA clinical severity shows no correlation with radiographic severity. 3. Simple scores of pain and disability do not reflect the complexity of decision-making about who should have a THR.
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| 2. |
- Estrada, Karol, et al.
(författare)
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Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
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Tidskriftsartikel (refereegranskat)abstract
- Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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| 3. |
- Evangelou, Evangelos, et al.
(författare)
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A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip
- 2014
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 73:12, s. 2130-2136
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects. Methods We performed a two-stage meta-analysis on more than 78 000 participants. In stage 1, we synthesised data from eight GWAS whereas data from 10 centres were used for 'in silico' or 'de novo' replication. Besides the main analysis, a stratified by sex analysis was performed to detect possible sex-specific signals. Meta-analysis was performed using inverse-variance fixed effects models. A random effects approach was also used. Results We accumulated 11 277 cases of radiographic and symptomatic hip OA. We prioritised eight single nucleotide polymorphism (SNPs) for follow-up in the discovery stage (4349 OA cases); five from the combined analysis, two male specific and one female specific. One locus, at 20q13, represented by rs6094710 (minor allele frequency (MAF) 4%) near the NCOA3 (nuclear receptor coactivator 3) gene, reached genome-wide significance level with p=7.9x10(-9) and OR=1.28 (95% CI 1.18 to 1.39) in the combined analysis of discovery (p= 5.6x10(-8)) and follow-up studies (p=7.3x10(-4)). We showed that this gene is expressed in articular cartilage and its expression was significantly reduced in OA-affected cartilage. Moreover, two loci remained suggestive associated; rs5009270 at 7q31 (MAF 30%, p=9.9x10(-7), OR=1.10) and rs3757837 at 7p13 (MAF 6%, p=2.2x10(-6), OR=1.27 in male specific analysis). Conclusions Novel genetic loci for hip OA were found in this meta-analysis of GWAS.
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| 4. |
- Evangelou, Evangelos, et al.
(författare)
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Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22
- 2011
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70:2, s. 349-355
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Osteoarthritis (OA) is the most prevalent form of arthritis and accounts for substantial morbidity and disability, particularly in older people. It is characterised by changes in joint structure, including degeneration of the articular cartilage, and its aetiology is multifactorial with a strong postulated genetic component. Methods A meta-analysis was performed of four genome-wide association (GWA) studies of 2371 cases of knee OA and 35 909 controls in Caucasian populations. Replication of the top hits was attempted with data from 10 additional replication datasets. Results With a cumulative sample size of 6709 cases and 44 439 controls, one genome-wide significant locus was identified on chromosome 7q22 for knee OA (rs4730250, p = 9.2 x 10(-9)), thereby confirming its role as a susceptibility locus for OA. Conclusion The associated signal is located within a large (500 kb) linkage disequilibrium block that contains six genes: PRKAR2B (protein kinase, cAMP-dependent, regulatory, type II, beta), HPB1 (HMG-box transcription factor 1), COG5 (component of oligomeric golgi complex 5), GPR22 (G protein-coupled receptor 22), DUS4L (dihydrouridine synthase 4-like) and BCAP29 (B cell receptor-associated protein 29). Gene expression analyses of the (six) genes in primary cells derived from different joint tissues confirmed expression of all the genes in the joint environment.
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| 5. |
- Franklin, Jonas, et al.
(författare)
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Association between occupation and knee and hip replacement due to osteoarthritis: a case-control study
- 2010
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The objective of this study was to examine the association between occupation and osteoarthritis (OA) leading to total knee (TKR) or hip (THR) joint replacement. Methods: The following is the case-control study design. All patients still living in Iceland who had had a TKR or THR due to OA as of the end of 2002 were invited to participate. First degree relatives of participating patients served as controls. N = 1,408 cases (832 women) and n = 1,082 controls (592 women), 60 years or older and who had adequately answered a questionnaire were analyzed. Occupations were classified according to international standards. Inheritance of occupations was calculated by using the Icelandic Genealogy Database. Results: The age adjusted odds ratio (OR) for male farmers getting a TKR due to OA was 5.1 (95% confidence interval (CI) 2.1 to 12.4) and for a male farmer getting a THR due to OA the OR was 3.6 (95% CI 2.1 to 6.2). The OR for a fisherman getting a TKR was 3.3 (95% CI 1.3 to 8.4). No other occupations showed increased risk for men. For women there was no increased risk for any occupation. Farming and fishing were also the occupations that showed the greatest degree of inheritance. Conclusions: These results support an association in males between occupations with heavy physical load and both TKR and THR for OA.
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| 6. |
- Franklin, Jonas, et al.
(författare)
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Natural history of radiographic hip osteoarthritis: A retrospective cohort study with 11-28 years of followup.
- 2011
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Ingår i: Arthritis Care and Research. - : Wiley. - 2151-4658 .- 2151-464X. ; 63:5, s. 689-695
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Tidskriftsartikel (refereegranskat)abstract
- Abstract OBJECTIVE: To evaluate the association between radiographic hip osteoarthritis (OA) and future total hip replacement (THR) due to OA or hip fracture. METHODS: We studied a cohort of individuals who had colon radiography from 1980-1997. Minimal joint space (MJS) was measured and each hip was graded for radiographic OA according to the Kellgren/Lawrence scale. Subjects were followed until the end of 2008. A Cox proportional hazards model, adjusted for age and sex, was used to evaluate factors associated with THR and hip fracture. RESULTS: A total of 2,953 hips were studied (57% women). The cumulative incidence of THR was 2.5% and the cumulative incidence of hip fracture was 2.6%. For hips with radiographic hip OA (MJS of 2.5 mm or less), the cumulative incidence of THR was 16.9% and the hazard ratio (HR) for THR was 13.2 (95% confidence interval [95% CI] 8.1-21). Using Kellgren/Lawrence grading, the HR for THR was 12.9 (95% CI 7.9-21) for hips with radiographic OA compared to those without. The HR for all types of hip fracture for hips with radiographic OA (MJS of 2.5 mm or less) was 0.47 (95% CI 0.15-1.5), for intracapsular fractures was 0.29 (95% CI 0.04-2.1), and for extracapsular fractures was 0.67 (95% CI 0.16-2.8). CONCLUSION: The risk of THR due to OA is substantially increased in patients with radiographic hip OA, regardless of symptoms, and increases with decreasing MJS. However, 11-28 years after having had radiographic hip OA, more than 4 of 5 of those having radiographic signs of hip OA had not had a THR for OA.
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| 7. |
- Franklin, Jonas, et al.
(författare)
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Revision and complication rates in 654 Exeter total hip replacements, with a maximum follow-up of 20 years.
- 2003
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 4:1, s. 1-5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Iceland's geographical isolation with a stable and small population gives a rare opportunity for follow-up studies of medical interventions. Total hip replacements (THR) have been done at FSA Central Hospital in Akureyri, Iceland since 1982 with the Exeter hip implant being in use from the beginning. Methods: Hospital records for all patients operated on with THR between 1982 and the end of 1999 were reviewed and the patients were followed until the end of 2001. Information was gathered regarding the indication for primary surgery, the reason for revision if needed, as well as that of any complications. Survival statistics were used to calculate the cumulative revision rate. Results: The mean age at primary THR was 68.4 years for males and 68.8 years for females. 654 primary THRs were done; of which 571 (87 %) were due to osteoarthritis. 37 of the primary arthroplasties had been revised before the end of year 2001. Conclusion: We have in this unique 2-20 year study of 654 THRs with no loss to follow-up for the patients, found revision rates that conform with the large Swedish THR registry. Complication rates in general are in agreement with that reported for other comparable patient groups, while infection rates appear lower.
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| 8. |
- Ingvarsson, Thorvaldur
(författare)
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Prevalence and Inheritance of Hip Osteoarthritis in Iceland
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hereditary factors are suggested to contribute to osteoarthritis (OA), but their relative importance is uncertain. Moreover, the underlying specific variations at the genome level remain unknown. The prevalence of hip OA in Iceland was assessed by examining colon radiographs and was found to be at least 5-fold higher compared to Sweden and Denmark. The age-standardized incidence of total hip replacement (THR) for primary hip OA in Iceland between 1982 and 1996 was determined and found to be 50 percent higher than in Sweden. A comparison of two methods for estimating hip OA from colon radiographs showed that a simple quantitative method of measuring joint space was more reliable than a qualitative method. The contribution of heritability to hip OA leading to THR was investigated by combining information from two population-wide databases in Iceland: a national register of all THR and a database of all Icelandic genealogy records. A genetic contribution to THR for OA was shown by (a) identifying a large number of familial clusters of THR for OA, and by showing that (b) OA patients descended from fewer founders than matched controls, (c) the kinship coefficient among patients with THR for OA was greater for than matched controls, and (d) the relative risk for siblings of THR for OA patients was 3.1 (2.5, 3.1). Icelandic patients with THR for OA are thus significantly more related to each other than the general Icelandic population. Finally, a genome locus with a lod score of 2.58 was identified on chromosome 16p by a genome wide scan of a large Icelandic family with primary hip OA. These findings support a significant genetic contribution to a common form of OA and encourages the continued search for genes conferring an increased susceptibility to OA.
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| 9. |
- Ingvarsson, Thorvaldur, et al.
(författare)
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Prevalence of hip osteoarthritis in Iceland
- 1999
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Ingår i: Annals of the Rheumatic Diseases. - 1468-2060. ; 58:4, s. 201-207
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess the prevalence of primary hip osteoarthritis (OA) in Iceland. To compare the prevalence of primary hip OA in Iceland with published rates of primary hip OA for related Scandinavian populations.METHODS: Roentgenographs were examined of 1530 Icelandic people 35 years or older (653 males, 877 females) subjected to colon radiography during the years 1990-1996. The radiographs examined represent approximately 40 of all colon radiographs taken in Iceland during this period. After exclusion of non-primary hip OA cases, the minimum hip joint space was measured with a mm ruler. Presence of hip OA was defined as a minimum joint space of 2.5 mm or less on an anteroposterior radiograph. Intraclass correlation coefficients for inter and intraobserver variability of assessment of mm joint space were 0.91 and 0.95, respectively.RESULTS: Of the 1517 people included, 227 hips in 165 patients (77 men, 88 women) were diagnosed as having radiological primary hip OA. The mean age at colon examination for these patients was 68 (35-89) years. The overall prevalence of coxarthrosis among all examined patients 35 years and older was 10.8 (12 for men, 10 for women), rising from 2 at 35-39 years to 35.4 for those 85 years or older. If the population structure (age and sex distribution) for those older than 35 years in Iceland was used to standardise prevalence for both Iceland and south Sweden (using previously published data for south Sweden), the age and sex standardised prevalence of hip OA for those older than 35 years in Iceland was 8, compared with 1.2 for south Sweden.CONCLUSIONS: The prevalence of radiological primary hip OA is very high in Iceland, and in excess of fivefold higher than the prevalence found by using similar techniques in studies on related populations in southern Scandinavia. The rate difference is particularly notable for those younger than 70 years.
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| 10. |
- Ingvarsson, Thorvaldur, et al.
(författare)
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sländskt släktregister ger kunskap om arvets betydelse vid artros
- 2002
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Ingår i: Läkartidningen. - 0023-7205. ; 99:47, s. 4724-4728
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Tidskriftsartikel (refereegranskat)abstract
- Osteoarthritis is a heterogeneous and multifactorial disease with many pathogenic mechanisms implicated in its development and progression. Although osteoarthritis is a manifestation of certain metabolic, mechanical or inflammatory events, several distinct forms of osteoarthritis are inherited as dominantly acquired Mendelian traits. Gathering evidence is showing that inheritance and possible mutations in genes associated with osteoarthritis can play a major role in the common form of osteoarthritis in many joints. By the introduction of new biological methods for finding gene defects the search for possible gene defects have taken mainly three forms: (1) Parametric linkage analysis of rare families in which osteoarthritis segregates as a Mendelian trait; (2) model free linkage analysis of affected sibling pairs, and (3) association analysis of known candidate genes. Mutations today known to be associated with osteoarthritis all occur in relatively rare syndromes or diseases, which have osteoarthritis as a major component. In recent years many loci have been found associated with the "common osteoarthritis phenotype". Chromosomes 2, 4, 6, 11 and 16 were identified in multiple genome scans and are therefore the most likely to encode susceptibility. Ongoing studies will lead to classifications of the "common osteoarthritis" based on the exact causative gene defects, rather than on their variable clinical and radiographic phenotype. Hopefully, these studies will lead to future new therapy of osteoarthritis.
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