An insight into rheumatology resources available on the World Wide Web (http://www.ilar.org)
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Humans↗
Biomedical subjects
J Dequeker
Publications and source records attributed to J Dequeker.
Down-regulation of the serum stimulatory components of the insulin-like growth factor (IGF) system (IGF-I, IGF-II, IGF binding protein [BP]-3, and IGFBP-5) in age-related (type II) femoral neck osteoporosis.
Both a decrease in bone formation and an increase in bone resorption have been implicated in the pathogenesis of age-related (type II) femoral neck osteoporosis. While the increase in the bone resorption rate has been shown to be partially related to secondary hyperparathyroidism, the mechanisms underlying the decline in bone formation have not yet been identified. The aim of the present study was to test the hypothesis that the bone formation deficit associated with type II osteoporosis might be due to secondary hyperparathyroidism and/or to a deficiency of the insulin-like growth factor (IGF) system. Circulating concentrations of IGF-I, IGF-II, IGF binding protein (IGFBP)-3, IGFBP-4, IGFBP-5, 25-hydroxycholecalciferol (25(OH)D3), and intact parathyroid hormone (PTH) were measured in 50 elderly women after sustaining a hip fracture and in 50 healthy age-matched controls. In addition, serum levels of osteocalcin (OC), skeletal alkaline phosphatase, and N-terminal procollagen peptide and urinary pyridinium cross-links were determined as markers of bone remodeling, and bone mineral density (BMD) was assessed at the proximal femur. In the patient group, serum was drawn within 18 h of the fracture and prior to surgery. Circulating protein concentrations did not change over this time frame. No difference was found between mean IGFBP-4 serum levels in the two groups studied, while mean levels of IGF-I, IGF-II, IGFBP-3, IGFBP-5, 25(OH)D3, and markers of bone formation were significantly lower (p < 0.006) in patients as compared with healthy subjects. Serum PTH and urinary pyridinium cross-links, however, were markedly increased (p < 0.001) in the osteoporotic group. In pooled data from the normal and osteoporotic populations, age-adjusted multiple regression models based on IGF-I, IGF-II, IGFBP-3, and IGFBP-5 were found to be highly predictive of serum OC (R2 = 19%, p < 0.001) and BMD of femoral neck (R2 = 49%, p < 0.0001), consistent with an effect of the anabolic IGF components on overall bone formation rate. Similar models based on 25(OH)D3 and PTH, however, were statistically unrelated to OC. To address further the potential impact of trauma on circulating IGF system components, we measured IGF system component levels in 10 male patients within 18 h following tibial fracture and in 10 age-matched normal male subjects. There was no significant difference in serum level of any of the IGF system components between the two groups. Although limited by its cross-sectional design, the present study suggests that, in addition to bone resorption resulting from secondary hyperparathyroidism, impaired bone formation associated with deficiency of the IGF system might predispose elderly women to fragility fracture of the proximal femur.
Age Factors↗
Direct three-dimensional morphometric analysis of human cancellous bone: microstructural data from spine, femur, iliac crest, and calcaneus.
The appearance of cancellous bone architecture is different for various skeletal sites and various disease states. During aging and disease, plates are perforated and connecting rods are dissolved. There is a continuous shift from one structural type to the other. So traditional histomorphometric procedures, which are based on a fixed model type, will lead to questionable results. The introduction of three-dimensional (3D) measuring techniques in bone research makes it possible to capture the actual architecture of cancellous bone without assumptions of the structure type. This requires, however, new methods that make direct use of the 3D information. Within the framework of a BIOMED I project of the European Union, we analyzed a total of 260 human bone biopsies taken from five different skeletal sites (femoral head, vertebral bodies L2 and L4, iliac crest, and calcaneus) from 52 donors. The samples were measured three-dimensionally with a microcomputed tomography scanner and subsequently evaluated with both traditional indirect histomorphometric methods and newly developed direct ones. The results show significant differences between the methods and in their relation to the bone volume fraction. Based on the direct 3D analysis of human bone biopsies, it appears that samples with a lower bone mass are primarily characterized by a smaller plate-to-rod ratio, and to a lesser extent by thinner trabecular elements.
Adult↗
Molecular signaling in bone fracture healing and distraction osteogenesis.
The process of fracture healing has been described in detail in many histological studies. Recent work has focused on the mechanisms by which growth and differentiation factors regulate the fracture healing process. Rapid progress in skeletal cellular and molecular biology has led to the identification of many signaling molecules associated with the formation of skeletal tissues, including members of the transforming growth factor-beta (TGF-beta) superfamily and the insulin-like growth factor (IGF) family. Increasing evidence indicates that they are critical regulators of cellular proliferation, differentiation, extracellular matrix biosynthesis and mineralization. Limb lengthening procedure (distraction osteogenesis) is a relevant model to investigate the in vivo correlation between mechanical stimulation and biological responses as the callus is stretched by a proper rate and rhythm of mechanical strain. This model also provides additional insights into the molecular and cellular events during bone fracture repair. TGF-beta 1 was significantly increased in both the distracted callus and the fracture callus. The increased level of TGF-beta 1, together with a low concentration of calcium and an enhanced level of collagen synthesis, was maintained in the distracted callus as long as mechanical strain was applied. Less mineralization is also associated with a low level of osteocalcin production. These observations provide further insights into the molecular basis for the cellular events during distraction osteogenesis.
Animals↗
[The plague and the art of painting: some examples].
The author gives four examples of pictures representing the plague: "The Plague of Asdod" by Nicolas Poussin, a picture of Saint Roch by the Master of Frankfort, "Saint Roch Interceding for the Plague-stricken" by Peter Paul Rubens and "The Sisters of Saint Elisabeth Hospital in Antwerp and the Works of Mercy" by Jacob Jordaens.
Europe↗
NSAIDs/corticosteroids--primum non nocere.
NSAIDs/Corticosteroids are the most used and maybe misused drugs against "aches and pains of the musculoskeletal system". Their effectiveness to reduce (not cure) inflammation and related pain is without doubt. The problem is that of their side effects in particular of the GI-tract and other body systems. It is clear that these side effects occur more often and more seriously in a number of patients, the so-called high risk group: elderly women, patients with previous history of gastro-intestinal ulcer and corticosteroid users. The discovery that there are two pathways to influence cyclooxygenase activity and prostaglandin production and that some NSAIDs have a more marked COX-2 and COX-1 inhibition opens new perspectives. COX-1 is present in normal tissues and is responsible for the production of protective prostaglandins in the gastric mucosa and other tissues. COX-2 is induced by inflammatory cytokines and plays a role in the inflammatory cascade. Therefore more specific COX-2 antagonists should be safer for the gastro-intestinal mucosa and kidney function. The risk of hip fracture is 50% higher in patients receiving long-term corticosteroid therapy, and 30-35% of corticosteroid patients have vertebral fractures. The renewed interest in osteoporosis and increased number of papers on bone loss in RA reflect on the one hand the advances in technology to measure bone mineral density (BMD) accurately and precisely, and on the other hand the availability of effective drugs to stop bone loss and reverse the process. The possible deleterious effect of low dose corticosteroids continues to be a subject of concern, particularly in rheumatology where serum levels of free cortisone may be higher because of low albumen and other protein changes. Recently, several editorials and conflicting data obtained from cross-sectional and longitudinal studies in RA on steroid-induced osteoporosis have been published. Because the pathogenesis of steroid osteoporosis is distinct from that of entities such as postmenopausal osteoporosis, each therapy requires specific assessment in steroid treated patients. In recent years a wide variety of therapies, for example hormone replacement therapy, calcium supplements administered with vitamin D metabolites, thiazides, diuretics, anabolic steroids, tibolone, calcitonin and bisphosphonates, have been proposed to prevent osteoporosis in patients receiving longterm corticosteroid therapy, but there have been few carefully controlled trials, except for vitamin D and bisphosphonates.
Adrenal Cortex Hormones↗
Undergraduate education in rheumatology: challenges for the millennium.
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Curriculum↗
Learning objectives of undergraduate medical education in rheumatology.
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Curriculum↗
Video supported small group learning: problem solving and clinical reasoning.
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Audiovisual Aids↗
Lack of association between osteoarthritis of the hip and gene polymorphisms of VDR, COL1A1, and COL2A1 in postmenopausal women.
OBJECTIVE: To evaluate whether DNA polymorphisms of the VDR (vitamin D receptor), COL1A1 (alpha1 type I collagen), and COL2A1 (alpha1 type II collagen) genes, which have previously been linked to bone mineral density (BMD) and/or osteoarthritis (OA), are also associated with OA of the hip (OAH). METHODS: Genotype frequency distributions were compared between a group of 239 elderly healthy female controls and a group of 75 female OAH patients who underwent total hip replacement. All participants underwent BMD measurements of the total body, lumbar spine, and femoral neck. Mutation detection was done using polymerase chain reaction followed by restriction enzyme digestion. Polymorphisms were detected by digestion with Bsm I for VDR, Acc B7I for COL1A1, and Pvu II for COL2A1. RESULTS: None of the genotype frequency distributions of any of the examined polymorphisms was significantly different between the OAH group and the control group. No significant differences in BMD variables were observed after stratification of the subjects according to the examined genotypes within each study group. CONCLUSION: In Belgian postmenopausal women, the examined polymorphisms of the candidate genes VDR, COL1A1, and COL2A1 do not significantly contribute to an increased prevalence of OAH or to differences in BMD.
Aged↗
Low frequency of HLA-B27 and scarcity of ankylosing spondylitis in a Zairean Bantu population.
Ankylosing spondylitis (AS) is an inflammatory rheumatic disease which is thought to be rarely seen in African Blacks. Its genetic predisposition has been stressed in Caucasians where the HLA-B27 antigen is firmly linked to the disease. In the present study, HLA-B27 antigen was determined in 146 individuals of Bantu root. Only one of these subjects was found to possess HLA-B27 antigen. This study correlates the low frequency of HLA-B27 with the observed scarcity of AS in patients attending a clinic in Kinshasa for osteoarticular diseases.
Adult↗
Effects of menstrual history and use of medications on bone mineral density: the EVOS Study.
We have previously shown considerable between-center variation in bone mineral density (BMD) in the 13 EVOS centers that performed bone densitometry on their sex- and age-stratified population samples, after adjusting for weight and age. We have now investigated whether part of the between-center variability may be attributed to between-center variations in the use of medications. Information was collected from 2088 women and 1908 men at baseline on whether the subjects had ever been prescribed calcium, calcitonin, anabolic steroids, fluoride, vitamin D, or glucocorticoids and, for the women, whether they had ever used the oral contraceptive pill (OCP) or hormone replacement therapy (HRT). Each of these variables was fitted into a regression model adjusted for age, height, weight, and center. Only OCP and HRT significantly affected BMD. Those who had ever used OCPs had spinal BMD 0.029 g/cm2 greater than those who had never used them. Users of HRT had higher BMD than nonusers: 0. 037 g/cm2 at the spine, 0.018 g/cm2 at the trochanter, and 0.018 g/cm2 at the femoral neck. As expected, there was a great variation between centers in the use of OCP and HRT, but there were no significant correlations between mean BMD at any site in a given center and the prevalence of OCP or HRT use in that center. The between-center variance in BMD at all three sites remained highly significant after adjusting for treatment (P < 0.001). We conclude that HRT and OCP use are associated with moderate increases in BMD. The geographical variability of BMD in Europe was not explained by treatment with pharmaceuticals.
Absorptiometry, Photon↗
Measurements of vertebral shape by radiographic morphometry: sex differences and relationships with vertebral level and lumbar lordosis.
OBJECTIVE: To examine sex-related and vertebral-level-specific differences in vertebral shape and to investigate the relationships between the lumbar lordosis angle and vertebral morphology. DESIGN AND PATIENTS: Lateral thoracic and lumbar spine radiographs were obtained with a standardized protocol in 142 healthy men and 198 healthy women over 50 years old. Anterior (Ha), central (Hc) and posterior (Hp) heights of each vertebra from T4 to L4 were measured using a digitizing technique, and the Ha/Hp and Hc/Hp ratios were calculated. The lumbar lordosis angle was measured on the lateral lumbar spine radiographs. RESULTS: Ha/Hp and Hc/Hp ratios were smaller in men than women by 1.8% and 0.7%, respectively, and these ratios varied with vertebral level. Significant correlations were found between vertebral shape and the lumbar lordosis angle. CONCLUSIONS: These results demonstrate that vertebral shape varies significantly with sex, vertebral level and lumbar lordosis angle. Awareness of these relationships may help prevent misdiagnosis in clinical vertebral morphometry.
Aged↗
Bone mineral density and biomechanical properties of spine and femur of ovariectomized rats treated with naproxen.
Prostaglandins have been reported to mediate the effects of ovariectomy on bone loss. We studied the effect of naproxen, an inhibitor of production of prostaglandins, on ovariectomy-induced bone loss. One hundred forty female Wistar rats 4.5 months of age were divided into groups of baseline, sham operation (sham), sham treated with naproxen at 10 mg/kg per day (in food), and ovariectomy treated with naproxen or estrogen as intramuscular injection of estradiol at 0.2 mg/kg body weight per week. They were killed 3, 6, and 9 months postsurgery. Bone mineral density (BMD) of the lumbar spine (L1-4), femoral neck, midshaft, and distal metaphysis was determined using dual-energy X-ray absorptiometry (DXA) in vitro. The compressive test of the L1 vertebral body and torsional test of the left femur were performed. The right femoral neck and femoral midshaft were processed undecalcified for determining cross-sectional moments of inertia. Naproxen treatment partially prevented ovariectomy-induced loss or less gain in BMD, in a significant manner, in the femoral neck cortical area, and also in L1 compressive strength and stiffness. Estrogen fully prevented these ovariectomy-induced effects. Naproxen showed no effect on ovariectomy-induced improvement in femoral torsional strength and stiffness and cross-sectional moments of inertia. No statistically significant difference was found between naproxen-treated sham rats and untreated sham rats. The data suggest that naproxen partially prevents ovariectomy-induced osteopenia.
Absorptiometry, Photon↗
Diagnostic sensitivity of peripheral quantitative computed tomography measurements at ultradistal and proximal radius in postmenopausal women.
Peripheral quantitative computed tomography (pQCT) is a bone densitometry technique that is able to provide real volumetric bone density values not only of the total but also of trabecular and cortical bone separately. Normal reference curves were constructed with cross-sectional data obtained in 275 postmenopausal women (50-85 years), measured at 4% of the ulnar length (ultradistal region), and data for total, trabecular, and cortical bone density were obtained. In these postmenopausal subjects, continuously significant (p < 0.0001) age-dependent declines in bone density of 1.14%, 1.1%, and 0.57% for total, trabecular, and cortical bone, respectively, were observed while similar declines of 0.9%, 0.9%, and 0.4% per year since menopause, respectively, were found. The estimated mechanical stability index also showed linear dependencies with decreases of 0.84%/year and 0.6%/year since menopause (p < 0.0001). A more proximal acquisition at 15% of the ulnar length, an almost pure cortical region, resulted in linear declines of 0.41%/year and 0.27%/year (p < 0.0001) for the cortical bone and the mechanical stability index with significant changes of -0.27% and -0.23% per year, respectively, since menopause. Covariance analysis showed similar age dependencies of the different bone indices obtained in both regions of interest except for the stability index. A significant size adaptation of the bone with age was also observed, which was seen in the relationships of the trabecular and cortical bone areas to age and to bone density. Diagnostic sensitivity of all parameters for established osteoporosis was assessed by receiver operating characteristic (ROC) curves, comparing 99 patients with at least one fracture to the reference population. The area under these curves was highest in the ultradistal pure trabecular density of the radius (75%), followed by stability index (72%) and the area of cortical bone (65%) of the proximal site. No distinguishing power was seen for the cortical bone density values obtained in either the ultradistal (51%) or proximal radius (52%).
Age Factors↗
Morphometric analysis of human bone biopsies: a quantitative structural comparison of histological sections and micro-computed tomography.
As a part of the European Union BIOMED I study "Assessment of Bone Quality in Osteoporosis," the trabecular structure of transiliac bone biopsies was assessed by conventional histomorphometry and by three-dimensional microcomputed tomography (microCT). Sixty-three cylindrical human transiliac bone specimens were obtained post mortem from 27 women and 36 men (age 23-92 years) and evaluated morphometrically in this study. For the conventional histomorphometric analysis, a pair of four undecalcified sections were prepared from two regions in the mediolateral plane of the bone cores. The sections were stained with the von Kossa technique to obtain high-contrast two-dimensional images. Prior to the histologic sectioning the samples were measured with a desktop microCT, providing a 14 microm nominal resolution. The morphometric parameters computed by both methods in two or three dimensions, respectively, were bone volume density (BV/TV), bone surface density (BS/TV), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp). Results showed highly significant (p < 0.0001) correlations between conventional histology and microCT for BV/TV (r = 0.93), BS/TV (r = 0.91), Tb.Th (r = 0.84), and Tb.Sp (r = 0.91). The mean percentage differences between histology and microCT ranged from 2.5% (BV/TV) to 6.1% (Tb.Th). The high correlations and the low differences in terms of absolute numbers between conventional histomorphometric and microtomographic analysis are very promising for the use of micro-tomographic imaging. MicroCT is a nondestructive, fast, and very precise procedure that allows the measurement of cancellous and compact bone in unprocessed biopsies or small bones, as well as a fully automatic determination of three-dimensional morphometric indices.
Adult↗
Do quantitative ultrasound measurements reflect structure independently of density in human vertebral cancellous bone?
Ultrasonic measurements were made in three orthogonal directions on 70 vertebral bone cubes. Apparent density (rho) was determined, and microcomputed tomography was used to derive a range of microstructural parameters. Qualitatively different ultrasonic behavior was observed in the craniocaudal (CC) axis, in which two distinct waves propagated. In this direction, only attenuation correlated strongly with rho (r2 = 80%), whereas, in the anteroposterior (AP) and mediolateral (ML) axes, there were significant correlations between all ultrasonic parameters and rho (r2 = 57%-79%). Microstructural parameters were, in general, correlated with ultrasonic properties, but when adjusted for rho, few significant relationships remained and the additional variance explained by individual microstructural parameters was relatively small (< 25% for CC axis, < 3% for AP, 0% for ML). In stepwise regression analysis including rho and all of the microstructural parameters, rho remained the primary determinant of ultrasonic properties in the transverse axes: Combinations of structural parameters explained, at most, an additional of 6% of the variability in ultrasonic properties in the AP axis, but failed to contribute significantly in the ML axis. In the CC axis, structural parameters played a greater role, but the pattern of associations was complex and the predictive power of the models was generally much less than that for the transverse axes. These data indicate that the ability of ultrasound to reflect aspects of trabecular structure is strongly dependent on the direction in which ultrasonic measurements are made, and provide only qualified support for the hypothesis that ultrasound reflects cancellous bone structure independently of bone density.
Absorptiometry, Photon↗
Teaching problem-solving and clinical reasoning: 20 years experience with video-supported small-group learning.
In the context of a curriculum reform the Faculty of Medicine of the University of Leuven, Belgium, introduced a new teaching project: video-supported small-group learning on problem-solving and clinical reasoning. The aim of this study is to reflect 20 years experience. The video-supported sessions for sixth-year medical students during their practical year in peripheral hospitals were constructed in four stages. The first stage is the video presentation of a case with history-taking and physical examination. The student and three tutors of internal medicine make notes and can ask further questions and perform additional physical examination acts after the video presentation. The coordinator of the course, who knows the patient, then simulates the patient and the doctor to answer the questions. The second stage consists of making up individually a synoptic problem list, integrating history and physical examination; a differential diagnosis list with the most likely diagnosis fitting the problem list; and a list with investigations to be asked for confirming the diagnosis. The third stage consists of three small student groups discussing the three lists requested in stage 2. Each small group of students, passively assisted by a tutor, has to come to the consensus lists. The fourth stage is the confrontation of the consensus lists of the three groups with the aim of coming to an overall agreement. At this stage tutors are more actively involved in the discussion. Several learning processes are involved in this way of teaching. During the first stage the students learn the traditional teaching 'see one, do one and teach one', a demonstration of a full history and physical examination. By asking for additional information they learn by a critical attitude and by developing a strategy of fact-finding. During the second and third stages, by making their lists and during the consensus processes, they learn the significance of individual findings, problem-framing and the synthesis of history and physical examination data in medical concepts. The third and fourth parts of the sessions bring up the process of clinical reasoning, formulation of a working hypothesis, the discussion of the pathophysiology of findings, clustering of problems and epidemiological considerations as incidence and prevalence. Finally, the exercise to select diagnostic tests gives the students the possibility of appreciating the value of sensitivity/specificity and risks, benefits and costs of diagnostic procedures. These video-supported clinical problem-solving and reasoning sessions were positively appraised by students, teachers and medical faculty over the years. Over 20 years, more than 90 cases have been recorded on video, with a widespread variation in diagnoses and clinical presentations. Small-group teaching with the aid of a video case, as described in this paper, can promote enjoyable learning for students and teachers.
Clinical Competence↗