Total hip replacement in young adults with hip dysplasia: Age at diagnosis, previous treatment, quality of life, and validation of diagnoses reported to the Norwegian Arthroplasty Register between 1987 and 2007

Background and purpose: Dysplasia of the hip increases the risk of secondary degenerative change and subsequent total hip replacement. Here we report on age at diagnosis of dysplasia, previous treatment, and quality of life for patients born after 1967 and registered with a total hip replacement due to dysplasia in the Norwegian Arthroplasty Register. We also used the medical records to validate the diagnosis reported by the orthopedic surgeon to the register. Methods: Subjects born after January 1, 1967 and registered with a primary total hip replacement in the Norwegian Arthroplasty Register during the period 1987–2007 (n = 713) were included in the study. Data on hip symptoms and quality of life (EQ-5D) were collected through questionnaires. Elaborating information was retrieved from the medical records. Results: 540 of 713 patients (76%) (corresponding to 634 hips) returned the questionnaires and consented for additional information to be retrieved from their medical records. Hip dysplasia accounted for 163 of 634 hip replacements (26%), 134 of which were in females (82%). Median age at time of diagnosis was 7.8 (0–39) years: 4.4 years for females and 22 years for males. After reviewing accessible medical records, the diagnosis of hip dysplasia was confirmed in 132 of 150 hips (88%). Interpretation: One quarter of hip replacements performed in patients aged 40 or younger were due to an underlying hip dysplasia, which, in most cases, was diagnosed during late childhood. The dysplasia diagnosis reported to the register was correct for 88% of the hips

Disease progression and search for monogenic diabetes among children with new onset type 1 diabetes negative for ICA, GAD- and IA-2 Antibodies

Background: To investigate disease progression the first 12 months after diagnosis in children with type 1 diabetes negative (AAB negative) for pancreatic autoantibodies [islet cell autoantibodies(ICA), glutamic acid decarboxylase antibodies (GADA) and insulinoma-associated antigen-2 antibodies (IA-2A)]. Furthermore the study aimed at determining whether mutations in KCNJ11, ABCC8, HNF1A, HNF4A or INS are common in AAB negative diabetes. Materials and methods: In 261 newly diagnosed children with type 1 diabetes, we measured residual β-cell function, ICA, GADA, and IA-2A at 1, 6 and 12 months after diagnosis. The genes KCNJ11, ABCC8, HNF1A, HNF4A and INS were sequenced in subjects AAB negative at diagnosis. We expressed recombinant K-ATP channels in Xenopus oocytes to analyse the functional effects of an ABCC8 mutation. Results: Twenty-four patients (9.1%) tested AAB negative after one month. Patients, who were AAB-negative throughout the 12-month period, had higher residual β-cell function (P = 0.002), lower blood glucose (P = 0.004), received less insulin (P = 0.05) and had lower HbA1c (P = 0.02) 12 months after diagnosis. One patient had a heterozygous mutation leading to the substitution of arginine at residue 1530 of SUR1 (ABCC8) by cysteine. Functional analyses of recombinant K-ATP channels showed that R1530C markedly reduced the sensitivity of the K-ATP channel to inhibition by MgATP. Morover, the channel was highly sensitive to sulphonylureas. However, there was no effect of sulfonylurea treatment after four weeks on 1.0-1.2 mg/kg/24 h glibenclamide. Conclusion: GAD, IA-2A, and ICA negative children with new onset type 1 diabetes have slower disease progression as assessed by residual beta-cell function and improved glycemic control 12 months after diagnosis. One out of 24 had a mutation in ABCC8, suggesting that screening of ABCC8 should be considered in patients with AAB negative type 1 diabetes

Radiographic markers of hip dysplasia in young adults: predictive effect of factors in early life

Abstrac Background and objectives Acetabular dysplasia in young adults occurs, despite screening for developmental hip dysplasia (DDH) in the neonatal period. We aimed to examine how early life factors predict radiographic measurements of acetabular dysplasia at 18–19 years of age. Methods From a previous randomized trial (n = 12,014; 1988–90) evaluating the role of hip ultrasound in newborn screening of DDH, 4469 participants (2193 males) were invited to a follow-up 18 years later (2007–09), of which 2370 (53% attendance; 932 males) met. We examined associations between early life factors and four radiographic measurements for acetabular dysplasia at skeletal maturity. Hierarchical regressions, with addition of variables observed/measured consecutively in time, were analyzed using mixed effects models considering hip as the unit in the analyses. The study is approved by the Regional Ethics Committee. Results In total, 2340 participants (921 boys), mean age 18.7 years, (SD 0.6) had hip radiographs performed at follow-up and were included. Early life factors significantly predicting radiographic acetabular dysplasia at age 18–19-years included female gender, breech, low acetabular inclination (alpha) angle and sonographic instability, abduction treatment, as well as the velocity of growth during childhood. A positive family history of DDH was not associated with acetabular dysplasia at skeletal maturity. Conclusion The acetabular inclination (alpha) angle as measured on ultrasound at birth turned out to be a significant predictor of dysplasia at 18–19 years of age. The discordant role of a positive family history in early versus adult hip dysplasia is intriguing, warranting further studies on the genetic mechanisms of DDH. </jats:sec

Additional file 1 of Radiographic markers of hip dysplasia in young adults: predictive effect of factors in early life

Additional file 1: Table 1. a-d The statistical five-step hierarchic model examine if early life factors can predict four radiographic measurements (a-d) of acetabular dysplasia at 18-19 years of age. In total 2340 individuals were included for analysis. Table 2. Inverse probability weights (IPW) were applied in the final five-step model for each of the radiographic measurements, as a sensitivity analysis to account for the sampling from those from the original RCT who were invited to the maturity review (n=4469)

Is a Positive Femoroacetabular Impingement Test a Common Finding in Healthy Young Adults?

BACKGROUND: Femoroacetabular impingement (FAI) is an incompletely understood clinical concept that implies pathomechanical changes in the hip as a cause for hip-related pain in young adults. While a positive anterior impingement test is suggestive of FAI, its association with clinical and radiographic findings remain unconfirmed in healthy young adults. QUESTIONS/PURPOSES: We determined the prevalence of a positive test in 1170 young adults and examined its possible associations with (1) self-reported hip discomfort for the past 3 months; (2) weekly physical exercise; (3) hip ROM; and (4) radiographic findings associated with femoroacetabular impingement. METHODS: We invited 2344 healthy 19-year-olds to a population-based hip study between 2008 and 2009; 1170 patients (50%) consented. The study included questionnaires on medical and functional status, a clinical hip examination including the impingement test and hip ROM, and two pelvic radiographs (AP and frog-leg views). RESULTS: Based on at least one affected hip, 35 of 480 (7.3%) men and 32 of 672 (4.8%) women had positive impingement tests. Eighteen of the 1170 patients were excluded owing to suboptimal or missing radiographs. Self-reported hip discomfort in the women and increased physical exercise in the men were strongly associated with the positive impingement tests. Decreased abduction and internal rotation in the men, decreased flexion in both genders, and radiographic cam type findings in the men also were associated with positive tests. CONCLUSION: A positive test for anterior impingement is not uncommon in healthy young adults, especially in males. We believe it always should be performed along with pelvic radiographs in young, active patients presenting with hip pain. LEVEL OF EVIDENCE: Level II, diagnostic study. See the Guidelines for Authors for a complete description of level of evidence

COL11A1 is associated with developmental dysplasia of the hip and secondary osteoarthritis in the HUNT study

Objective: Developmental dysplasia of the hip (DDH) is a congenital condition affecting 2–3% of all infants. DDH increases the risk of osteoarthritis, is the cause of 30 ​% of all total hip arthroplasties (THAs) in adults <40 years of age and can result in loss of life quality. Our aim was to explore the genetic background of DDH in order to improve diagnosis, management and longterm outcome. Design: We used the large, ongoing, longitudinal Trøndelag Health Study (HUNT) database. Case definition was based on ICD-9/-10 diagnoses of DDH, or osteoarthritis secondary to DDH. Analyses were performed using SAIGE software, with covariates including sex, batch, birth year and principal components. We included only single nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) ≥ 0.01, R2 ≥ 0.8 and Hardy-Weinberg equilibrium (HWE) P-value ≥ 0.0001. Significance level was set at p ​< ​5 ​× ​10−8. Meta-analysis using data from DDH and primary osteoarthritis genome-wide association studies (GWASs) was done using METAL software. The study was approved by the regional ethical committee. Results: Analysis included 69,500 individuals, of which 408 cases, and 8,531,386 SNPs. Two SNPs near COL11A1 were significantly associated with DDH; rs713162 (β ​= ​−0.43, SE ​= ​0.07, p ​= ​8.4 ​× ​10−9) and rs6577334 (β ​= ​−0.43, SE ​= ​0.08, p ​= ​8.9 ​× ​10−9). COL11A1 has previously been associated with acetabular dysplasia and osteoarthritis. Meta-analysis supported previous GWAS findings of both DDH and primary osteoarthritis. Conclusions: This large, genome-wide case-control study indicates an association between COL11A1 and DDH and is an important contribution to investigating the etiology of DDH, with further research needed