Lene Bjerke Laborie

Prevalence of radiographic findings thought to be associated with femoroacetabular impingement in a population-based cohort of 2081 healthy young adults.

PURPOSE To report the prevalence of qualitative radiographic findings for femoroacetabular impingement (FAI) and associations among them and to characterize the inter- and intraobserver variability of these interpretations. MATERIALS AND METHODS This study is part of an institutional review board-approved population-based prospective follow-up of 2081 of 4006 (participation rate, 51.9%) young adults (874 [42.0%] male participants, 1207 [58.0%] female participants; mean age, 18.6 years) who took part in a randomized hip trial on developmental dysplasia of the hip. All participants gave informed consent. Two pelvic radiographs were obtained. Pistol-grip deformity, focal femoral neck prominence, and flattening of the lateral head, all suggestive of cam-type impingement, and the posterior wall sign, excessive acetabular coverage, and crossover sign, all suggestive of pincer-type impingement, were assessed subjectively by an experienced radiologist. To assess inter- and intraobserver agreement, images from 350 examinations were read independently twice by two observers. RESULTS Cam-type deformities were seen in 868 male and 1192 female participants, respectively, as follows: pistol-grip deformity, 187 (21.5%) and 39 (3.3%); focal femoral neck prominence, 89 (10.3%) and 31 (2.6%); and flattening of the lateral femoral head, 125 (14.4%) and 74 (6.2%). Pincer-type deformities were seen in the same numbers of male and female participants, respectively, as follows: posterior wall sign, 203 (23.4%) and 131 (11.0%); and excessive acetabular coverage, 127 (14.6%) and 58 (4.9%) (all P < .001, according to sex distribution). The crossover sign was seen in 446 (51.4%) and 542 (45.5%) of the male and female participants, respectively (P = .004). There was a high degree of coexistence (odds ratio [OR] > 2) among most FAI findings. Interobserver agreement was good to very good (κ = 0.74-0.84) in rating cam- and pincer-type findings. Intraobserver agreement was moderate or good (κ = 0.49-0.80) for all findings for both observers. CONCLUSION Overall, radiographic FAI findings are quite common in a population of healthy young adults, especially in males, with a high degree of coexistence among most findings (OR > 2).

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.

The spectrum of ABCC8 mutations in Norwegian patients with congenital hyperinsulinism of infancy.

Potassium channels in the plasma membrane of the pancreatic beta cells are critical in maintaining glucose homeostasis by responding to ATP and coupling metabolic changes to insulin secretion. These channels consist of subunits denoted the sulfonylurea receptor SUR1 and the inwardly rectifying ion channel KIR6.2, which are encoded by the genes ABCC8 and KCNJ11, respectively. Activating mutations in the subunit genes can result in monogenic diabetes, whereas inactivating mutations are the most common cause of congenital hyperinsulinism of infancy (CHI). Twenty‐six Norwegian probands with CHI were analyzed for alterations in ABCC8 and KCNJ11. Fifteen probands (58%) had mutations in the ABCC8 gene. Nine patients were homozygous or compound heterozygous for the mutations, indicating diffuse pancreatic disease. In five patients, heterozygous and paternally inherited mutations were found, suggesting focal disease. One patient had a de novo mutation likely to cause a milder, dominant form of CHI. Altogether, 16 different ABCC8 mutations (including the novel alterations W231R, C267X, IVS6‐3C>G, I462V, Q917X and T1531A) were identified. The mutations IVS10+1G>T, R1493W and V21D occurred in five, three and two families, respectively. KCNJ11 mutations were not found in any patients. Based on our mutation screening, we estimate the minimum birth prevalence of ABCC8‐CHI in Norway to 1:70,000 during the past decade. Our results considerably extend the knowledge of the molecular genetics behind CHI in Scandinavia.

DNA hypomethylation, transient neonatal diabetes, and prune belly sequence in one of two identical twins.

One known genetic mechanism for transient neonatal diabetes is loss of methylation at 6q24. The etiology of prune belly sequence is unknown but a genetic defect, affecting the mesoderm from which the triad abdominal muscle hypoplasia, urinary tract abnormalities, and cryptorchidism develop, has been suggested. We investigated a family, including one twin, with transient neonatal diabetes and prune belly sequence. Autoantibody tests excluded type 1 diabetes. Microsatellite marker analysis confirmed the twins being monozygotic. We identified no mutations in ZFP57, KCNJ11, ABCC8, GCK, HNF1A, HNF1B, HNF3B, IPF1, PAX4, or ZIC3. The proband had loss of methylation at the 6q24 locus TNDM and also at the loci IGF2R, DIRAS3, and PEG1, while the other family members, including the healthy monozygotic twin, had normal findings. The loss of methylation on chromosome 6q24 and elsewhere may indicate a generalized maternal hypomethylation syndrome, which accounts for both transient neonatal diabetes and prune belly sequence.

The alpha angle in cam-type femoroacetabular impingement

We report on gender-specific reference intervals of the alpha angle and its association with other qualitative cam-type findings in femoroacetabular impingement at the hip, according to a population-based cohort of 2038 19-year-olds, 1186 of which were women (58%). The alpha angle was measured on standardised frog-leg lateral and anteroposterior (AP) views using digital measurement software, and qualitative cam-type findings were assessed subjectively on both views by independent observers. In all, 2005 participants (837 men, 1168 women, mean age 18.6 years (17.2 to 20.1) were included in the analysis. For the frog-leg view, the mean alpha angle (right hip) was 47° (26 to 79) in men and 42° (29 to 76) in women, with 97.5 percentiles of 68° and 56°, respectively. For the AP view, the mean values were 62° (40 to 105) and 52° (36 to 103) for men and women, respectively, with 97.5 percentiles of 93° and 94°. Associations between higher alpha angles and all qualitative cam-type findings were seen for both genders on both views. The reference intervals presented for the alpha angle in this cross-sectional study are wide, especially for the AP view, with higher mean values for men than women on both views.

Radiological findings for hip dysplasia at skeletal maturity. Validation of digital and manual measurement techniques

ObjectiveTo report on intra-observer, inter-observer, and inter-method reliability and agreement for radiological measurements used in the diagnosis of hip dysplasia at skeletal maturity, as obtained by a manual and a digital measurement technique.Materials and methodsPelvic radiographs from 95 participants (56 females) in a follow-up hip study of 18- to 19-year-old patients were included. Eleven radiological measurements relevant for hip dysplasia (Sharp’s, Wiberg’s, and Ogata’s angles; acetabular roof angle of Tönnis; articulo-trochanteric distance; acetabular depth-width ratio; femoral head extrusion index; maximum teardrop width; and the joint space width in three different locations) were validated. Three observers measured the radiographs using both a digital measurement program and manually in AgfaWeb1000. Inter-method and inter- and intra-observer agreement were analyzed using the mean differences between the readings/readers, establishing the 95% limits of agreement. We also calculated the minimum detectable change and the intra-class correlation coefficient.ResultsLarge variations among different radiological measurements were demonstrated. However, the variation was not related to the use of either the manual or digital measurement technique. For measurements with greater absolute values (Sharp’s angle, femoral head extrusion index, and acetabular depth-width ratio) the inter- and intra-observer and inter-method agreements were better as compared to measurements with lower absolute values (acetabular roof angle, teardrop and joint space width).ConclusionThe inter- and intra-observer variation differs notably across different radiological measurements relevant for hip dysplasia at skeletal maturity, a fact that should be taken into account in clinical practice. The agreement between the manual and digital methods is good.

Prevalence of radiographic findings associated with hip dysplasia in a population-based cohort of 2081 19-year-old Norwegians.

In Norway total joint replacement after hip dysplasia is reported more commonly than in neighbouring countries, implying a higher prevalence of the condition. We report on the prevalence of radiological features associated with hip dysplasia in a population of 2081 19-year-old Norwegians. The radiological measurements used to define hip dysplasia were Wibergs centre-edge (CE) angle at thresholds of < 20° and < 25°, femoral head extrusion index < 75%, Sharps angle > 45°, an acetabular depth to width ratio < 250 and the sourcil shape assessed subjectively. The whole cohort underwent clinical examination of their range of hip movement, body mass index (BMI), and Beighton hypermobility score, and were asked to complete the EuroQol (EQ-5D) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The prevalence of hip dysplasia in the cohort varied from 1.7% to 20% depending on the radiological marker used. A Wibergs CE angle < 20° was seen in 3.3% of the cohort: 4.3% in women and 2.4% in men. We found no association between subjects with multiple radiological signs indicative of dysplasia and BMI, Beighton score, EQ-5D or WOMAC. Although there appears to be a high prevalence of hip dysplasia among 19-year-old Norwegians, this is dependent on the radiological parameters applied.

In situ fixation of slipped capital femoral epiphysis with Steinmann pins

Background and purpose Slipped capital femoral epiphysis (SCFE) is often treated by surgical fixation; however, no agreement exists regarding technique. We analyzed the outcome of in situ fixation with Steinmann pins. Patients and methods All 67 subjects operated for slipped capital femoral epiphysis at Haukeland University Hospital during the period 1990–2007 were included. All were treated by in situ fixation with 2 or 3 parallel Steinmann pins (8 mm threads at the medial end). The follow-up evaluation consisted of clinical examination and hip radiographs. Radiographic outcome was based on measurements of slip progression, growth of the femoral neck, leg length discrepancy, and signs of avascular necrosis and chondrolysis. Results 67 subjects (41 males) were operated due to unilateral slips (n = 47) or bilateral slips (n = 20). Mean age at time of diagnosis was 13 (7.2–16) years. Mean age at follow-up was 19 (14–30) years, with a mean postoperative interval of 6.0 (2–16) years. The operated femoral neck was 9% longer at skeletal maturity than at surgery, indicating continued growth of the femoral neck. At skeletal maturity, 12 subjects had radiographic features suggestive of a previous asymptomatic slip of the contralateral hip. The total number of bilateral cases of SCFE was 32, i.e half of the children had bilateral SCFE. 3 subjects required additional surgery and mild avascular necrosis of the femoral head was seen in 1 patient. None had slip progression or chondrolysis. Interpretation In situ pinning of SCFE with partly threaded Steinmann pins appears to be a feasible and safe method, with few complications. The technique allows further growth of the femoral neck.

Screening Strategies for Hip Dysplasia: Long-term Outcome of a Randomized Controlled Trial

OBJECTIVE: Screening for hip dysplasia is controversial. A previous randomized controlled trial revealed that adding universal or selective ultrasound to routine clinical examination gave a nonsignificant reduction in rates of late presenting cases, but with higher treatment rates. This study assesses differences in outcome at skeletal maturity for the 3 newborn screening strategies in terms of radiographic markers of acetabular dysplasia and early degenerative change and avascular necrosis (AVN) secondary to neonatal treatment. METHODS: From the initial trial including 11 925 newborns, a population-based sample of 3935 adolescents was invited for follow-up at age 18 to 20 years. A standardized weight-bearing anteroposterior view was obtained. The outcomes evaluated were the radiographic findings of dysplasia (center-edge angle, femoral head extrusion-index, acetabular depth-width ratio, Sharp’s angle, subjective evaluation of dysplasia) and degenerative change (joint-space width). Signs of AVN were documented. RESULTS: Of the 3935 subjects invited, 2038 (51.8%) attended the maturity review, of which 2011 (58.2% female patients) were included: 551, 665, and 795 subjects from the universal, selective, and clinical groups, respectively. Rates per group of positive radiographic findings associated with dysplasia or degenerative change varied depending on radiographic marker used. No statistically significant differences were detected between groups. No AVN was seen. CONCLUSIONS: Although both selective and universal ultrasound screenings gave a nonsignificant reduction in rates of late cases when compared with expert clinical programs, we were unable to demonstrate any additional reduction in the rates of radiographic findings associated with acetabular dysplasia or degenerative change at maturity. Increased treatment rates were not associated with AVN.

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

BackgroundTo 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 methodsIn 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.ResultsTwenty-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.ConclusionGAD, 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.