Determinants of the size of incident vertebral deformities in European men and women in the sixth to ninth decades of age: the European Prospective Osteoporosis Study (EPOS).

UNLABELLED: More severe vertebral fractures have more personal impact. In the European Prospective Osteoporosis Study, more severe vertebral collapse was predictable from prior fracture characteristics. Subjects with bi-concave or crush fractures at baseline had a 2-fold increase in incident fracture size and thus increased risk of a disabling future fracture. INTRODUCTION: According to Euler's buckling theory, loss of horizontal trabeculae in vertebrae increases the risk of fracture and suggests that the extent of vertebral collapse will be increased in proportion. We tested the hypothesis that the characteristics of a baseline deformity would influence the size of a subsequent deformity. METHODS: In 207 subjects participating in the European Prospective Osteoporosis Study who suffered an incident spine fracture in a previously normal vertebra, we estimated loss of volume (fracture size) from plane film images of all vertebral bodies that were classified as having a new fracture. The sum of the three vertebral heights (anterior, mid-body, and posterior) obtained at follow-up was subtracted from the sum of the same measures at baseline. Each of the summed height loss for vertebrae with a McCloskey-Kanis deformity on the second film was expressed as a percentage. RESULTS AND CONCLUSIONS: In univariate models, the numbers of baseline deformities and the clinical category of the most severe baseline deformity were each significantly associated with the size of the most severe incident fracture and with the cumulated sum of all vertebral height losses. In multivariate modeling, age and the clinical category of the baseline deformity (crush > bi-concave > uni-concave > wedge) were the strongest determinants of both more severe and cumulative height loss. Baseline biconcave and crush fractures were associated at follow-up with new fractures that were approximately twice as large as those seen with other types of deformity or who previously had undeformed spines. In conclusion, the characteristics of a baseline vertebral deformity determines statistically the magnitude of vertebral body volume lost when a subsequent fracture occurs. Because severity of fracture and number of fractures are determinants of impact, the results should improve prediction of the future personal impact of osteoporosis once a baseline prevalent deformity has been identified.

Determinants of incident vertebral fracture in men and women: results from the European Prospective Osteoporosis Study (EPOS).

The aim of this analysis was to determine the influence of lifestyle, anthropometric and reproductive factors on the subsequent risk of incident vertebral fracture in men and women aged 50-79 years. Subjects were recruited from population registers from 28 centers across Europe. At baseline, they completed an interviewer-administered questionnaire and had lateral thoraco-lumbar spine radiographs performed. Repeat spinal radiographs were performed a mean of 3.8 years later. Incident vertebral fractures were defined morphometrically and also qualitatively by an experienced radiologist. Poisson regression was used to determine the influence of the baseline risk factor variables on the occurrence of incident vertebral fracture. A total of 3173 men (mean age 63.1 years) and 3402 women (mean age 62.2 years) contributed data to the analysis. In total there were 193 incident morphometric and 224 qualitative fractures. In women, an age at menarche 16 years or older was associated with an increased risk of vertebral fracture (RR = 1.80; 95%CI 1.24, 2.63), whilst use of hormonal replacement was protective (RR = 0.58; 95%CI 0.34, 0.99). None of the lifestyle factors studied including smoking, alcohol intake, physical activity or milk consumption showed any consistent associations with incident vertebral fracture. In men and women, increasing body weight and body mass index were associated with a reduced risk of vertebral fracture though, apart from body mass index in men, the confidence intervals embraced unity. For most variables the strengths of the associations observed were similar using the qualitative and morphometric approaches to fracture definition. In conclusion our data suggest that modification of other lifestyle risk factors is unlikely to have a major impact on the population occurrence of vertebral fractures. The important biological mechanisms underlying vertebral fracture risk need to be explored using new investigational strategies.

Is the predictive power of previous fractures for new spine and non-spine fractures associated with biochemical evidence of altered bone remodelling? The EPOS study. European Prospective Osteoporosis Study.

BACKGROUND: In the European Prospective Osteoporosis Study (EPOS), a past spine fracture increased risk of an incident fracture 3.6 - 12-fold even after adjusting for BMD. We examined the possibility that biochemical marker levels were associated with this unexplained BMD-independent element of fracture risk. METHODS: Each of 182 cases in EPOS of spine or non-spine fracture that occurred in 3.8 years of follow-up was matched by age, sex and study centre with two randomly assigned never-fractured controls and one case of past fracture. Analytes measured blind were: osteocalcin, bone-specific alkaline phosphatase, total alkaline phosphatase, serum creatinine, calcium, phosphate and albumin, together with the collagen cross-links degradation products serum CTS and urine CTX. Most subjects also had bone density measured by DXA. RESULTS: Cases who had recent fractures did not differ in marker levels from cases who had their last fracture more than 3 years previously. No statistically significant effect of recent fracture was found for any marker except osteocalcin, which was 17.6% lower in recent peripheral cases compared to unfractured controls (p<0.05) and this was independent of BMD. CONCLUSION: Past fracture as a risk indicator for future fracture is not strongly mediated through increased bone turnover.

Incidence of vertebral fracture in europe: results from the European Prospective Osteoporosis Study (EPOS).

Vertebral fracture is one of the major adverse clinical consequences of osteoporosis; however, there are few data concerning the incidence of vertebral fracture in population samples of men and women. The aim of this study was to determine the incidence of vertebral fracture in European men and women. A total of 14,011 men and women aged 50 years and over were recruited from population-based registers in 29 European centers and had an interviewer-administered questionnaire and lateral spinal radiographs performed. The response rate for participation in the study was approximately 50%. Repeat spinal radiographs were performed a mean of 3.8 years following the baseline film. All films were evaluated morphometrically. The definition of a morphometric fracture was a vertebra in which there was evidence of a 20% (+4 mm) or more reduction in anterior, middle, or posterior vertebral height between films--plus the additional requirement that a vertebra satisfy criteria for a prevalent deformity (using the McCloskey-Kanis method) in the follow-up film. There were 3174 men, mean age 63.1 years, and 3,614 women, mean age 62.2 years, with paired duplicate spinal radiographs (48% of those originally recruited to the baseline survey). The age standardized incidence of morphometric fracture was 10.7/1,000 person years (pyr) in women and 5.7/1,000 pyr in men. The age-standardized incidence of vertebral fracture as assessed qualitatively by the radiologist was broadly similar-12.1/1,000 pyr and 6.8/1,000 pyr, respectively. The incidence increased markedly with age in both men and women. There was some evidence of geographic variation in fracture occurrence; rates were higher in Sweden than elsewhere in Europe. This is the first large population-based study to ascertain the incidence of vertebral fracture in men and women over 50 years of age across Europe. The data confirm the frequent occurrence of the disorder in men as well as in women and the rise in incidence with age.

Prevalent vertebral deformity predicts incident hip though not distal forearm fracture: results from the European Prospective Osteoporosis Study.

The presence of a vertebral deformity increases the risk of subsequent spinal deformities. The aim of this analysis was to determine whether the presence of vertebral deformity predicts incident hip and other limb fractures. Six thousand three hundred and forty-four men and 6788 women aged 50 years and over were recruited from population registers in 31 European centers and followed prospectively for a median of 3 years. All subjects had radiographs performed at baseline and the presence of vertebral deformity was assessed using established morphometric methods. Incident limb fractures which occurred during the follow- up period were ascertained by annual postal questionnaire and confirmed by radiographs, review of medical records and personal interview. During a total of 40348 person-years of follow-up, 138 men and 391 women sustained a limb fracture. Amongst the women, after adjustment for age, prevalent vertebral deformity was a strong predictor of incident hip fracture, (rate ratio (RR) = 4.5; 95% CI 2.1-9.4) and a weak predictor of 'other' limb fractures (RR = 1.6; 95% CI 1.1-2.4), though not distal forearm fracture (RR = 1.0; 95% CI 0.6-1.6). The predictive risk increased with increasing number of prevalent deformities, particularly for subsequent hip fracture: for two or more deformities, RR = 7.2 (95% CI 3.0-17.3). Amongst men, vertebral deformity was not associated with an increased risk of incident limb fracture though there was a nonsignificant trend toward an increased risk of hip fracture with increasing number of deformities. In summary, prevalent radiographic vertebral deformities in women are a strong predictor of hip fracture, and to a lesser extent humerus and 'other' limb fractures; however, they do not predict distal forearm fractures.

Hip geometry, bone mineral distribution, and bone strength in European men and women: the EPOS study.

Hip geometry and bone mineral density (BMD) have been shown previously to relate, independently of each other, to risk of hip fracture. We used Lunar DPX "beta" versions of hip strength analysis (HSA) and hip axis length (HAL) software to analyze scans from ten representative age-stratified population samples in the European Prospective Osteoporosis Study (EPOS). All 1617 subjects were >50 years of age, and 1033 were women. The data were modeled with gender and center as categorical variables. The bone mineral density of the upper half of the femoral neck declined at a faster rate with age than that in the lower half. Femoral neck cross-sectional moment of inertia (CSMI), a measure of resistance to bending, showed no significant age reduction in either gender. However, height and weight effects on CSMI were significantly more beneficial in men than in women (0.002 < p < 0.012) and the weight effect appeared to be mediated by bone mineral content (BMC). Compressive stress (Cstress), defined as the stress in the femoral neck at its weakest cross section arising from a standardized fall, was higher in women. Although Cstress increased with body weight when BMC was held constant, in practice it fell through the association and statistical interaction of rising body weight with rising BMC. HAL, as expected, was strongly positively associated with male gender and also height (p < 0.0001). Hip strength-related indices were markedly center-dependent. Significant differences (p < 0.0001) were noted between the centers for all the variables investigated that related to hip geometry. Adjustment for femoral neck bone mineral content (totBMC) showed these center differences to account for >50% of center variation in hip strength, which remained highly significant (p < 0.0001). We conclude that there are substantial geographical differences in femoral neck geometry as well as in BMD. These geometric variations may contribute to the large variations in hip fracture risk across Europe. The effects of aging on hip strength need to be explored in longitudinal studies.

[Economic aspects of osteoporosis]. / Ekonomické aspekty osteoporózy.

BACKGROUND: The objective of this study was to evaluate expenditures and efficacy of osteoporosis treatment in the Czech Republic (CZ) (1.38 million women and 0.99 million men > 55 years of age). METHODS AND RESULTS: Demographic data, incidence of hip fractures and prevalence of osteoporosis and osteopenia in Czech women and men, cost burden to healthcare agencies due to hip fractures and costs of diagnostic procedures, preventive measures and therapies of osteoporosis were obtained from published data and from database of the main health insurance agency (VZP) and the State Institute for Drug Control. The direct costs for treatment of hip fractures in the CZ in 1997 averaged Kc (Czech Crown) 2.5 billion, diagnosis of osteoporosis, Kc 150 million, prevention of osteoporosis using hormone replacement therapy, Kc 66 million, and treatments of osteoporosis which has been applied to less than 5% of osteoporosis patients, 482 million. However, despite the continuously increasing expenditures for treatments of osteoporosis, the incidence of hip fractures doubled in the last 10 years. This is mainly due to increased life expectancy in Czech women and men. CONCLUSIONS: The results of this first economic evaluation of diagnosis, treatment and consequences of osteoporosis in the CZ indicate a need for conceptual decisions in both treatment and prevention of osteoporosis.

Role of hydrophobic amino acids at position 74 of DRB1 chain in rheumatoid arthritis.

We have analyzed HLA class II alleles in a group of 153 Czech children with rheumatoid arthritis by PCR and hybridization with oligonucleotide probes. When we try to find a common sequence for all DRB1 alleles involved in juvenile and adult arthritis, we can notice hydrophobic amino acid at position 74, which is present in all these alleles, but not in nonsusceptible alleles, where is the hydrophilic amino acid at position 74. In our model, we speculate that the hydrophilic amino acid at position 74 creates a such kind of epitope which is not suitable for rheumatoid-associated peptides or T cells, and only hydrophobic amino acid can permit binding of these peptides or recognition by certain T cells. Analyses of the DPB1 sequences have shown that alleles which have a negatively charged amino acid at position 69, are more frequent in pauciarticular patients while those with a positively charged amino acid are more frequent in polyarticular patients. A positively charged amino acid at position 69 might present the same rheumatoid associated peptide as susceptible DRB1 alleles. The presence of more rheumatoid-associated peptide on the cell surface may cause conversion to more severe polyarticular forms. A negatively charged amino acid at position 69 could not present this peptide and a low concentration of the peptide on the cell surface presented just by DRB1 molecules keeps disease in a relatively benign condition of pauciarticular forms.

Metabolic bone status in young women with JCA.

The study was based on clinical, densitometric and biochemical evaluations and on a life-style questionnaire, applied in a cohort of 41 individuals. The mean age of the young women was 24.2 (18-36) years. The main point was to compare subgroups with (CS) an without (NCS) corticosteroid treatment (19 and 22 patients, respectively). There was no significant difference in age, weight and duration of JCA. Of the densitometric examinations, spine DXA (DPX-L LUNAR apparatus) yielded values significantly lower in CS than in NCS individuals (p = 0.05). Much more apparent was the difference in stiffness measurements in the calcanei performed by Achilles-LUNAR ultrasound instrument, again with lower values in CS women (p = 0.001) (Fig. 1, 2, 3). No significant differences were found between the two subgroups as regards blood levels of bone alkaline phosphatase, osteocalcin and tartrate-resistant acidic phosphatase, and urine hydroxyproline output. Menarche occurred at a mean age of 14.37 years in the CS subgroup (p = 0.01, against healthy population) and of 13.32 years in the NCS subgroup (not significant). The prevalence of fractures was enconsiderable in both subgroups. These findings are to be understood from the viewpoint of combined influences of both disease activity and corticotherapy in the CS patients with JCA.

Class II alleles in juvenile arthritis in Czech children.

OBJECTIVE: Patients with pauciarticular and polyarticular onset rheumatoid factor (RF) negative juvenile arthritis (JA) have been reported to have a variety of HLA associations. The reason for the differences found in several recent studies is not known. We compare a new series of patients investigated in Prague, Czechoslovakia with those we reported from Dallas. METHODS: Czech patients with JA (N = 153) were classified clinically using the same criteria as in our studies in Dallas. The RF negative group included 56 patients that had persistent pauciarticular disease, 42 pauciarticular with polyarticular course and 39 with polyarticular onset. RF was present in 13 additional patients. HLA class II alleles were determined by oligotyping as previously described from our laboratory. RESULTS: DRB1*0801 was increased and DRB1*0701 was decreased in all the RF negative groups. The persistent pauciarticular group was associated with DRB1*11 and DPB1*0201 and lacked the association with DRB1*1301 seen in Dallas. Also found in Prague and not in Dallas were an increase in the frequency of DR2 in pauciarticular patients with early conversion and of DRB1*1201 in patients with iritis. Certain HLA associations (DRB1*0801, DPB1*0201) appear to be present in patients with JA in most studies; others (DRB1*1301, DPB1*0301) are more variable. CONCLUSION: The reason for differences in the HLA risk factors observed in our 2 populations is not known. Clinical heterogeneity not detected by our method seems the most likely explanation. Genetic and environmental factors may also play a role.

HLA and juvenile rheumatoid arthritis.

HLA class II analysis in a group of 153 Czech children with juvenile rheumatoid arthritis by PCR and oligonucleotide hybridization demonstrated associations with several alleles. DRB1*0801 (RR = 5.3, p < 0.005) and DRB1 * 11 (RR = 2.2, p < 0.01) including all subtypes were shown to be increased in the rheumatoid factor-negative group (N = 137). The same results were observed in Italy, England and Norway. In patients with the pauciarticular onset with conversion to polyarticular within 3 years, a statistically significant increase in DR2 (RR = 10.1, p < 0.00005), mostly due to DRB1*1501, was found. In the iridocyclitis and antinuclear factor groups, susceptibility to DRB1*1201 was observed. There was a striking decrease in DRB1*0701 (RR = 0.3, p < 0.00005) in all groups. There was neither an increase in DRB1*1301 or DPB1*0301 nor a decrease in DRB1*04, as reported from other studies in Texas and Norway. The rheumatoid factor-positive group with polyarticular onset (N = 13) was associated with DRB1*04 (RR = 7.1, p < 0.005), as observed in adults. DPB1*0201 was increased in the persistent pauciarticular group (RR = 3.7, p < 0.0005). DPB1*0402 was decreased in all pauciarticular groups with or without conversion (RR = 0.3, p < 0.005). Taken together, there are not only genetic differences and clinical heterogeneity in juvenile rheumatoid arthritis patients but, also, common predisposing factors.

Metabolic bone status in young women with juvenile chronic arthritis.

A group of 26 young women (18-36 years of age) with juvenile chronic arthritis (JCA, duration 8-33 years) was investigated for bone metabolism and mineral status. Six of the patients were receiving longterm corticosteroid therapy, and 5 had received corticosteroid treatment in the past. Serum osteocalcin and urinary hydroxyproline were significantly elevated in 17 and 14 of the 26 patients, respectively, compared with healthy controls. Compared to controls, bone mineral density (BMD) in the lumbar spine was significantly lowered in 6 of 26 patients, all of whom were in the corticosteroid treated subgroup. No correlation was evident between any of the variables measured, except for the association of corticosteroid therapy with low BMD.

HLA class II alleles in juvenile dermatomyositis.

HLA class II alleles were investigated in 27 Czech patients (11 females and 16 males) with juvenile dermatomyositis. The immunogenetic investigation comprised determination of DRB1, DRB3, DRB5, DQA1, DQB1, and DPB1 alleles. Their prevalence was compared with that found in healthy Czech controls. No allele was found significantly more frequently in patients than in controls.

Clinical practice in pediatric rheumatology: a review of the Czechoslovak experience.

The use of corticosteroid therapy in the treatment of juvenile chronic arthritis in Czechoslovakia is summarized. The indispensability of corticosteroids in pediatric rheumatology is confirmed and some practical aspects of their application are discussed.

Sequences of HLA alleles associated with arthritis in adults and children.

Adult rheumatoid factor (RF) positive rheumatoid arthritis (RA) and RF positive arthritis of childhood are associated with DRB1*0401 in Caucasians, and DRB1*0405 in Orientals, and in Ashkenazi and nonAshkenazi Jews. Certain other DRB1 alleles (DRB1*0101,1001) which have a similar sequence in the 3rd hypervariable region of the 1st domain are also associated with RA, but they appear to function as weaker risk factors. The difference in the relative strength of the associations is likely to be due to structural differences in the 1st and 2nd variable regions of the first domain of these alleles. Similarities and differences in the HLA associations between North American Caucasoid patients with juvenile arthritis in Dallas, TX, USA, and in Prague, Czechoslovakia, are discussed.

[Factors affecting the development of para-articular ossification in total hip replacement]. / Faktory ovlivnující tvorbu paraartikulárních osifikací u totálních náhrad kycelního kloubu.

The authors evaluated the prevalence of paraarticular ossifications in three groups of patients after a minimum interval of one year following the administration of a total prosthesis. For evaluation they used Brooker's classification. The first group comprised 40 patients who during the first six weeks after administration of a cemented prosthesis of the hip joint took 75 mg of Indomethacin per day in three doses. The second control group comprised 50 patients, i.e. 61 operated hip joints (11 bilateral prostheses) to whom Indomethacin was not administered during the postoperative period, nor any other antiphlogistic preparations. The third group comprised 40 patients to whom a non-cemented prosthesis of the hip joint was implanted and who did not use any antiphlogistic preparations after operation. In the first group, i.e. patients after total endoprostheses of the hip joint with preventive administration of Indomethacin, ectopic ossifications were recorded in 32.5% of the operated patients. In the second group, i.e. without preventive Indomethacin administration, ectopic ossifications of various grades were recorded in 51%. In patients with non-cemented prostheses of the hip joint the prevalence of ectopic ossifications was only 18%. The authors selected from the control group a sub-group with bilateral prostheses of the hip joint where an ectopic bone was found. This sub-group comprised 9 operated patients and bilateral ectopic ossifications developed only in 33.3%. From the results ensues that Indomethacin administration is an expedient prevention of development of paraarticular ossifications. Marked reduction of development of ectopic bone formation occurs when bone cement is not used as a fixation medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Class I associations and frequencies of class II HLA-DRB alleles by RFLP analysis in children with rheumatoid-factor-negative juvenile chronic arthritis.

A total of 94 patients with juvenile chronic arthritis (JCA) was tested for HLA class I by serology and for class II by RFLP typing. Early onset JCA (EOPA) is associated with HLA-A2, DR5 and DR8 in both males and females. The combination (joint occurrence) of these JCA associated alleles (A2, DR5, DR8) is frequently seen in patients with chronic iridocyclitis. Late onset pauciarticular disease has an increased frequency of HLA-B27, especially in males. Our data confirm that polyarticular JCA with early childhood onset (< or = 4 years) is associated with DR5 and DR8 and has a different immunogenetic background from polyarticular JCA with later childhood (> 4 years) onset (associated with DR4).