Vertebral Scheuermann's disease in Europe: prevalence, geographic variation and radiological correlates in men and women aged 50 and over.

UNLABELLED: In 27 centres across Europe, the prevalence of deforming spinal Scheuermann's disease in age-stratified population-based samples of over 10,000 men and women aged 50+ averaged 8% in each sex, but was highly variable between centres. Low DXA BMD was un-associated with Scheuermann's, helping the differential diagnosis from osteoporosis. INTRODUCTION: This study aims to assess the prevalence of Scheuermann's disease of the spine across Europe in men and women over 50 years of age, to quantitate its association with bone mineral density (BMD) and to assess its role as a confounder for the radiographic diagnosis of osteoporotic fracture. METHODS: In 27 centres participating in the population-based European Vertebral Osteoporosis Study (EVOS), standardised lateral radiographs of the lumbar and of the thoracic spine from T4 to L4 were assessed in all those of adequate quality. The presence of Scheuermann's disease, a confounder for prevalent fracture in later life, was defined by the presence of at least one Schmorl's node or irregular endplate together with kyphosis (sagittal Cobb angle >40° between T4 and T12) or a wedged-shaped vertebral body. Alternatively, the (rare) Edgren-Vaino sign was taken as diagnostic. The 6-point-per-vertebral-body (13 vertebrae) method was used to assess osteoporotic vertebral shape and fracture caseness. DXA BMD of the L2-L4 and femoral neck regions was measured in subsets. We also assessed the presence of Scheuermann's by alternative published algorithms when these used the radiographic signs we assessed. RESULTS: Vertebral radiographic images from 4486 men and 5655 women passed all quality checks. Prevalence of Scheuermann's varied considerably between centres, and based on random effect modelling, the overall European prevalence using our method was 8% with no significant difference between sexes. The highest prevalences were seen in Germany, Sweden, the UK and France and low prevalences were seen in Hungary, Poland and Slovakia. Centre-level prevalences in men and women were highly correlated. Scheuermann's was not associated with BMD of the spine or hip. CONCLUSIONS: Since most of the variation in population impact of Scheuermann's was unaccounted for by the radiological and anthropometric data, the search for new genetic and environmental determinants of this disease is encouraged.

Cost-effectiveness and cost-utility of add-on, low-dose prednisolone in patients with rheumatoid arthritis aged 65+: The pragmatic, multicenter, placebo-controlled GLORIA trial.

BACKGROUND: The GLORIA placebo-controlled trial found a favorable balance of benefit and harm for two years of prednisolone (5 mg/day) as add-on treatment for rheumatoid arthritis (RA) patients aged 65+. This study evaluated the cost-effectiveness of low-dose prednisolone in the treatment of RA. METHODS: The economic evaluation had a societal perspective with a time horizon of two years. Cost data were collected with questionnaires and from recorded events, and valued with standard Dutch unit prices of 2017. The primary effectiveness outcome was the disease activity score in 28 joints (DAS28). For cost-utility, quality-adjusted life years (QALYs) were estimated from the EuroQol-5 Dimension (EQ-5D) questionnaire. Bootstrapping assessed the uncertainty around the average differences in costs and health outcomes. RESULTS: In total, 444 of 451 randomized patients were included in the modified intention-to-treat analysis. Patients had median four active comorbidities at baseline. Mean total costs over two years were k€10.8 in the prednisolone group, k€0.5 (95% CI -4.0; 1.8) lower than in the placebo group. Total direct medical costs were k€0.5 (95% CI -4.0; 1.5) lower in the prednisolone group. The mean number of QALYs was similar in both groups (difference 0.02 [-0.03; 0.06] in favor of prednisolone). The DAS28 was 0.38 lower in the prednisolone group than in the placebo group (0.19; 0.56). CONCLUSION: With greater effectiveness (DAS28) at non-significantly lower costs, low-dose, add-on prednisolone is cost-effective for RA compared to placebo over two years. QALYs were equal in both groups, most likely due to the impact of multiple comorbidities.

[Gastroduodenal complications associated with non-steroidal anti-inflammatory drugs in Slovak Republic: results of one-year prospective study]. / Podiel gastroduodenálnych komplikácií vo vzt'ahu k liecbe nesteroidovými antiflogistikami v Slovenskei republike: rocná prospektívna stúdia.

The aim of the one-year prospective study was to estimate the prevalence of non-steroidal anti-inflammatory drugs using in patients with symptomatic gastroduodenal ulcers, the upper gastrointestinal bleeding and perforation (PUB--perforation, ulcer, bleeding). Among of 326 patients with PUB, prevalence of non-steroidal anti-inflammatory drugs using was 60%. In the group of 194 patients with non-steroidal antiinflammatory drugs induced PUB, 49% patients took aspirin, 38% non-aspirin non-steroidal anti-inflammatory drugs and 13% their combination. Low dosing aspirin (daily dosis < or =200 mg) was associated with PUB in 21% of patients. Age higher than 60 years and women had statisticaly signiticant higher prevalence of non-steroidal anti-inflammatory drugs induced PUB.

Low BMD is less predictive than reported falls for future limb fractures in women across Europe: results from the European Prospective Osteoporosis Study.

We have previously shown that center- and sex-specific fall rates explained one-third of between-center variation in upper limb fractures across Europe. In this current analysis, our aim was to determine how much of the between-center variation in fractures could be attributed to repeated falling, bone mineral density (BMD), and other risk factors in individuals, and to compare the relative contributions of center-specific BMD vs. center-specific fall rates. A clinical history of fracture was assessed prospectively in 2451 men and 2919 women aged 50-80 from 20 centers participating in the European Prospective Osteoporosis Study (EPOS) using standardized questionnaires (mean follow-up = 3 years). Bone mineral density (BMD, femoral neck, trochanter, and/or spine) was measured in 2103 men and 2565 women at these centers. Cox regression was used to model the risk of incident fracture as a function of the person-specific covariates: age, BMD, personal fracture history (PFH), family hip fracture history (FAMHIP), time spent walking/cycling, number of 'all falls' and falls not causing fracture ('fracture-free') during follow-up, alcohol consumption, and body mass index. Center effects were modeled by inclusion of multiplicative gamma-distributed random effects, termed center-shared frailty (CSF), with mean 1 and finite variance theta (theta) acting on the hazard rate. The relative contributions of center-specific fall risk and center-specific BMD on the incidence of limb fractures were evaluated as components of CSF. In women, the risk of any incident nonspine fracture (n = 190) increased with age, PFH, FAMHIP, > or =1 h/day walking/cycling, and number of 'all falls' during follow-up (all P < 0.074). 'Fracture-free' falls (P = 0.726) and femoral neck BMD did not have a significant effect at the individual level, but there was a significant center-shared frailty effect (theta = 0.271, P = 0.001) that was reduced by 4% after adjusting for mean center BMD and reduced by 19% when adjusted for mean center fall rate. Femoral trochanter BMD was a significant determinant of lower limb fractures (n = 53, P = 0.014) and the center-shared frailty effect was significant for upper limb fractures (theta = 0.271, P = 0.011). This upper limb fracture center effect was unchanged after adjusting for mean center BMD but was reduced by 36% after adjusting for center mean fall rates. In men, risk of any nonspine fracture (n = 75) increased with PFH, fall during follow-up (P < 0.026), and with a decrease in trochanteric BMD [RR 1.38 (1.08, 1.79) per 1 SD decrease]. There was no center effect evident (theta = 0.081, P = 0.096). We conclude that BMD alone cannot be validly used to discriminate between the risk of upper limb fractures across populations without taking account of population-specific variations in fall risk and other factors. These variations might reflect shared environmental or possibly genetic factors that contribute quite substantially to the risk of upper limb fractures in women.

Bone density variation and its effects on risk of vertebral deformity in men and women studied in thirteen European centers: the EVOS Study.

In Europe there is a 3-fold variation, according to geographical center, in risk of vertebral deformity in men and women over the age of 50. We investigated the relationship between bone density, as assessed by dual-energy X-ray absorptiometry (DEXA) of the spine and hip and prevalent vertebral deformities in 13 of the 36 centers participating in the European Vertebral Osteoporosis Study (EVOS). Each center recruited an age-stratified sample of men and women aged 50 years and over, and of those who agreed to densitometry, 288/2088 women and 233/1908 men were found to have one or more deformities of the vertebrae between T4 and L4 as assessed by the McCloskey algorithm. DEXA was in each case performed on L2-L4, the proximal femur, or both. Bone densitometry results were cross-calibrated between centers using the European Spine Phantom prototype and results expressed as bone mineral density (BMD, g/cm2). In both genders, subjects with deformities involving loss of anterior vertebral body height alone comprised over 20% of the total with deformities and these related poorly to BMD. Other classes of deformity were found by logistic regression to relate significantly to BMD in one or both genders, with odds ratios for the risk of any of these ranging from 1.67 to 2.11 for a 1 SD reduction in bone density at spine, femoral neck, or trochanter (p < 0.001). Adjusting for anthropometric variables and BMD did not remove the effect of age on risk which rose 1.67- to 1.78-fold per decade according to gender. The greater unadjusted rate of increase in deformity risk with age in women was attributable to their faster rate of bone loss with age; after adjusting for age, body mass index (BMI), and BMD at the trochanter in grams per square centimeter, men had a 2-fold higher risk of deformity than women. Analysis of the relationship between mean bone density and the prevalence of deformity in each center demonstrated no significant differences between centers in either gender, after adjusting for BMD, age, and BMI together with an a posteriori statistical adjustment for imperfect cross-calibration of densitometers. It is concluded that BMD is an important determinant of deformity risk in both genders. Together with age, BMD explains much of the differences in risk both between the sexes and between individual geographical centers in Europe.

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.

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.

Falls explain between-center differences in the incidence of limb fracture across Europe.

There is important geographic variation in the occurrence of the major osteoporotic fractures across Europe. The aim of this study was to determine whether between-center variation in limb fracture rates across Europe could be explained by variation in the incidence of falls. Men and women, aged 50-79 years, were recruited from population-based registers in 30 European centers. Subjects were followed by postal questionnaire to ascertain the occurrence of incident fractures, and were also asked about the occurrence and number of recent falls. Self-reported fractures were confirmed, where possible, by review of the radiographs, medical record, or subject interview. The age- and gender-adjusted incidence of falls was calculated by center using Poisson regression. Poisson regression was also used to assess the extent to which between-center differences in the incidence of limb fractures could be explained by differences in the age- and gender-adjusted incidence of falls at those centers. In all, 6302 men (mean age 63.9 years) and 6761 women (mean age 63.1 years) completed at least one questionnaire concerning fractures and falls. During a median follow-up time of 3 years, 3647 falls were reported by men and 4783 by women. After adjusting for age and gender, there was evidence of significant between-center differences in the occurrence of falls. There was also between-center variation in the occurrence of upper limb, lower limb, and distal forearm fractures. Variation in the age- and gender-adjusted center-specific fall rates explained 24%, 14%, and 6% of the between-center variation in incidence of distal forearm and upper and lower limb fractures, respectively. Given the constraints inherent in such an analysis, in men and women aged 50-79 years, variation in fall rates could explain a significant proportion of the between-center variation in the incidence of limb fracture across Europe.

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.

Nonsteroidal antiinflammatory drug-induced mucosal lesions of the upper gastrointestinal tract and their relationship to Helicobacter pylori.

The aim of the present study was to determine the prevalence of Helicobacter pylori infection in a group of patients hospitalized at the clinic of rheumatology who presented peptic ulcers and erosions associated with nonsteroidal antiinflammatory drugs (NSAIDs). Of a group of 4,256 hospitalized patients receiving therapy with NSAIDs, 221 patients with persistent dyspepsia underwent endoscopic examination of the upper segment of the gastrointestinal tract. Among them, mucosal abnormalities in the stomach and duodenum were confirmed in 69 patients. H. pylori was found in 42% (29/69) of the examined patients. Peptic ulcers were confirmed in 19 patients. Localization was gastric in 12 patients and duodenal in seven. H. pylori was found in only 17% of the patients (2/12) with gastric ulcers, but in as many as 86% (6/7) of those with duodenal ulcers. Patients with H. pylori taking NSAIDs were at higher risk of developing duodenal mucosal abnormalities, both ulcers (OR: 10.17; 95% CI: 1.08-23.88, p = 0.013) and erosions (OR: 2.67; 95 CI: 1.94-3.66, p = 0.001). Concomitant administration of corticoids and NSAIDs did not increase the risk of gastrotoxicity in patients with positive finding of H. pylori (OR: 0.32; 95% CI: 0.1-0.96). In conclusion, a close association was found between H. pylori infection and duodenal ulcers and erosions, but not between gastric ulcers and gastric erosions in a group of patients hospitalized for rheumatic diseases and undergoing NSAID therapy.

Eggshell calcium in the prevention and treatment of osteoporosis.

In this paper the most significant biological and clinical aspects of a biopreparation made of chicken eggshells are reviewed. Eggshell powder is a natural source of calcium and other elements (e.g. strontium and fluorine) which may have a positive effect on bone metabolism. Experimental and clinical studies performed to date have shown a number of positive properties of eggshell powder, such as antirachitic effects in rats and humans. A positive effect was observed on bone density in animal models of postmenopausal osteoporosis in ovariectomized female rats. In vitro eggshell powder stimulates chondrocyte differentiation and cartilage growth. Clinical studies in postmenopausal women and women with senile osteoporosis showed that eggshell powder reduces pain and osteoresorption and increases mobility and bone density or arrests its loss. The bioavailability of calcium from this source, as tested in piglets, was similar or better than that of food grade purified calcium carbonate. Clinical and experimental studies showed that eggshell powder has positive effects on bone and cartilage and that it is suitable in the prevention and treatment of osteoporosis.

[Prediction of changes in bone density during alendronate treatment in postmenopausal women]. / Predikcia zmien kostnej denzity pri liecbe alendronátom u postmenopauzálnych zien.

Alendronate is an aminobisphosphonate, a selective inhibitor of osteoclast-mediated bone resorption. Due to its influence a decline of markers of bone turnover occurs. The latter react much sooner than it is possible to detect significant changes of bone density. In the submitted trial the authors investigated changes of selected markers: total alkaline phosphatase (ALP), osteocalcin (OC), N-terminal telopeptide fragment of collagen type I (NTx) after 3 months' treatment with alendronate, the influence on bone density after one year's treatment in 50 postmenopausal women with densitometrically verified osteoporosis. After one-year treatment in the whole group a significant increase of bone density occurred in the area L2-L4 by 4.52% (SD = 3.9), neck of the femur by 2.24% (SD = 3.6), trochanter by 2.81% (SD = 3.0) and total by 1.89% (SD = 2.7). Total ALP and OC in serum, similarly as NTx in urine declined significantly already after 3 months treatment and the decline persisted also after one year of treatment. With the change of bone density after one year correlated significantly only NTx. A decline of NTx after 3 months by more than 30% as compared with the baseline value was recorded in 81% patients and this change predicted a significant rise of the bone density in the area of the neck of the femur, on average by 30. Urinary NTx is a promising predictor of the effect of alendronate treatment. Its drop by more than 30% after 3 months justifies the assumption that bone density increased after one year's treatment.

[Seroprevalence of Helicobacter pylori in rheumatoid arthritis and its relationship to pharmacotherapy]. / Séroprevalencia Helicobacter pylori pri reumatoidnej artritíde a jej vzt'ah k farmakoterapii.

GOAL: To find out a serology prevalence of Helicobacter pylori (Hp) infection in patients suffering from rheumatoid arthritis (RA) and to investigate its relationship to pharmacotherapy modes. METHOD: To determine Hp IgG class and IgA class antibodies by ELISA method in hospitalised patients with active RA according to ACR criteria (1987). RESULTS: 137 patients with RA were examined--20 men, 117 women, an average age was 54.6 +/- 13.1, an average length of RA in these patients was 12.46 +/- 9.75, positive RF/LFT had 88% of patients. Hp ELISA IgG antibodies were confirmed in 57% (78/137) of patients with RA, Hp ELISA IgA antibodies were confirmed in 60% of examined patients (82/137), and IgG + IgA antibodies simultaneously were found in 51% (70/137) of examined patients. A comparison of basic demographic data, specific parameters of the disease, and clinical signs has not confirmed any differences between groups of Hp positive and Hp negative patients. Patients with both types of Hp antibodies (IgG + IgA) had more frequent signs of RA in other places than joints (p = 0.046). RA patients with anti-Hp IgG antibodies more frequently used anticoagulation drugs (p = 0.029) while patients with anti-Hp IgA antibodies more frequently used methotrexate (p = 0.01). CONCLUSIONS: Results point out more frequent incidence of Hp IgA antibodies in RA patients treated with methotrexate and more frequent incidence of both IgG and IgA antibodies in patients with RA signs in other places than joints.

[Effect of alendronate therapy on bone turnover--results of a multicenter study]. / Vplyv liecby alendronátom na kostný obrat--výsledky multicentrickej stúdie.

Sodium alendronate is a bisphosphonate of the IInd generation with a strong antiresorptive effect. Its favourable effect on reduction of the incidence of vertebral and non-vertebral fractures was repeatedly confirmed. The objective of the multicentre study was to evaluate the effect of administration of 10 mg of sodium alendronate combined with 1000 mg of elemental calcium administered in the course of three months on the N-terminal telopeptide(NTx) a sensitive marker of bone resorption. The group comprised 275 postmenopausal women with densitometrically confirmed osteoporosis. After three months treatment a 53% decline of NTx values occurred as compared with baseline values. This finding confirms the favourable effect of sodium alendronate on bone remodelling. A decline of the concentration of bone markers is one of the good predictors of the effectiveness of treatment focused on reduction of atraumatic osteoporotic fractures.

Whom to treat? The contribution of vertebral X-rays to risk-based algorithms for fracture prediction. Results from the European Prospective Osteoporosis Study.

INTRODUCTION: Vertebral fracture is a strong risk factor for future spine and hip fractures; yet recent data suggest that only 5-20% of subjects with a spine fracture are identified in primary care. We aimed to develop easily applicable algorithms predicting a high risk of future spine fracture in men and women over 50 years of age. METHODS: Data was analysed from 5,561 men and women aged 50+ years participating in the European Prospective Osteoporosis Study (EPOS). Lateral thoracic and lumbar spine radiographs were taken at baseline and at an average of 3.8 years later. These were evaluated by an experienced radiologist. The risk of a new (incident) vertebral fracture was modelled as a function of age, number of prevalent vertebral fractures, height loss, sex and other fracture history reported by the subject, including limb fractures occurring between X-rays. Receiver Operating Characteristic (ROC) curves were used to compare the predictive ability of models. RESULTS: In a negative binomial regression model without baseline X-ray data, the risk of incident vertebral fracture significantly increased with age [RR 1.74, 95% CI (1.44, 2.10) per decade], height loss [1.08 (1.04, 1.12) per cm decrease], female sex [1.48 (1.05, 2.09)], and recalled fracture history; [1.65 (1.15, 2.38) to 3.03 (1.66, 5.54)] according to fracture site. Baseline radiological assessment of prevalent vertebral fracture significantly improved the areas subtended by ROC curves from 0.71 (0.67, 0.74) to 0.74 (0.70, 0.77) P=0.013 for predicting 1+ incident fracture; and from 0.74 (0.67, 0.81) to 0.83 (0.76, 0.90) P=0.001 for 2+ incident fractures. Age, sex and height loss remained independently predictive. The relative risk of a new vertebral fracture increased with the number of prevalent vertebral fractures present from 3.08 (2.10, 4.52) for 1 fracture to 9.36 (5.72, 15.32) for 3+. At a specificity of 90%, the model including X-ray data improved the sensitivity for predicting 2+ and 1+ incident fractures by 6 and 4 fold respectively compared with random guessing. At 75% specificity the improvements were 3.2 and 2.4 fold respectively. With the modelling restricted to the subjects who had BMD measurements (n=2,409), the AUC for predicting 1+ vs. 0 incident vertebral fractures improved from 0.72 (0.66, 0.79) to 0.76 (0.71, 0.82) upon adding femoral neck BMD (P=0.010). CONCLUSION: We conclude that for those with existing vertebral fractures, an accurately read spine X-ray will form a central component in future algorithms for targeting treatment, especially to the most vulnerable. The sensitivity of this approach to identifying vertebral fracture cases requiring anti-osteoporosis treatment, even when X-rays are ordered highly selectively, exceeds by a large margin the current standard of practice as recorded anywhere in the world.

The effects of lifestyle, dietary dairy intake and diabetes on bone density and vertebral deformity prevalence: the EVOS study.

The risk of low and moderate energy fracture is related to bone mineral density (BMD). Yet it is uncertain whether the epidemiologic determinants of fracture risk are the same as for low bone density. The European Vertebral Osteoporosis Study was a population-based prevalence study of vertebral deformity in 36 age-stratified population samples aged 50-80 years. In nearly 4000 subjects (13 centers), BMD measurements were also made at the spine, femoral neck and femoral trochanter. To investigate whether effects of reported physical activity on spine deformity risk were mediated through BMD, we modeled these and other risk factor data with BMD as the dependent variate after adjusting for age, center, sex and body mass index (BMI). The significant determinants of vertebral deformity risk were also entered into logistic models of deformity risk that included BMD measurements as covariates. Both current and lifetime physical activity were positively associated with BMD. This effect was stronger with hip BMD than with spine BMD. Lifetime smoking exposure was associated with reduced BMD. Type 2 diabetes mellitus was associated with increased BMD. Weak positive associations were found between consumption of dairy products and BMD at the three measured sites and these were strengthened by an interaction with measures of physical activity in men. Physical activity in women had the largest beneficial effect in lean women and in women exposed to hormone replacement therapy. When fracture risk was modeled with BMD as a covariate, the lifestyle and dietary determinants became less strongly related to vertebral deformity risk, suggesting that BMD may have acted as an intermediary variable. However, heavy physical activity in men still increased spine deformity risk after adjusting for BMD. It is concluded that physical activity in both genders and milk consumption in young women might protect against vertebral deformities in later life through their effects on bone density. The adverse effect of smoking on BMD was confirmed. Heavy physical activity in men might increase spine deformity risk even when BMD is normal.

Population-based geographic variations in DXA bone density in Europe: the EVOS Study. European Vertebral Osteoporosis.

The purpose of this study was to investigate variations in bone density between 16 European populations, 13 of which were participants in the European Vertebral Osteoporosis Study (EVOS). Men and women aged 50-80 years were recruited randomly from local population registers, stratified in 5-year age bands. The other three centres recruited similarly. Random samples of 20-100% of EVOS subjects were invited for dual-energy X-ray absorptiometry (DXA) densitometry of the lumbar spine and/or proximal femur using Hologic, Lunar or Norland pencil beam machines or, in one centre, a Sopha fan-beam machine. Cross-calibration of the different machines was undertaken using the European Spine Phantom prototype (ESPp). Highly significant differences in mean bone density were demonstrated between centres, giving rise to between centre SDs in bone density that were about a quarter of a population SD. These differences persisted when centres using Hologic machines and centres using Lunar machines were considered separately. The centres were ranked differently according to whether male or female subjects were being considered and according to site of measurement (L2-4, femoral neck or femoral trochanter). As expected, bone mineral density (BMD) had a curvilinear relationship with age, and apparent rates of decrease slowed as age advanced past 50 years in both sexes. In the spine, not only did male BMD usually appear to increase with age, but there was a highly significant difference between centres in the age effect in both sexes, suggesting a variability in the impact of osteoarthritis between centres. Weight was consistently positively associated with BMD, but the effects of height and armspan were less consistent. Logarithmic transformation was needed to normalize the regressions of BMD on the independent variates, and after transformation, all sites except the femoral neck in females showed significant increases in SD with age. Interestingly, the effect of increasing weight was to decrease dispersion in proximal femur measurements in both sexes, further accentuating the tendency in women for low body mass index to be associated with osteoporosis as defined by densitometry. It is concluded that there are major differences between BMD values in European population samples which, with variations in anthropometric variables, have the potential to contribute substantially to variations in rates of osteoporotic fracture risk in Europe.

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.

Health-related quality of life and radiographic vertebral fracture.

BACKGROUND: Vertebral fractures are associated with back pain and disability; however, relatively little is known about the impact of radiographic vertebral fractures on quality of life in population samples. The aim of this study was to determine the impact of a recent radiographic vertebral fracture on health-related quality of life (HRQoL). METHODS: Men and women aged 50 years and over were recruited from population registers in 12 European centers. Subjects completed an interviewer-administered questionnaire and had lateral spine radiographs performed. Subjects in these centers were followed prospectively and had repeat spinal radiographs performed a mean of 3.8 years later. Prevalent deformities were defined using established morphometric criteria, and incident vertebral fractures by both morphometric criteria and qualitative assessment. For each incident fracture case, three controls matched for age, gender, and center were selected: one with a prevalent deformity (at baseline) and two without prevalent deformities. All subjects were interviewed or completed a postal questionnaire instrument which included Short Form 12 (SF-12), the EQ-5D (former EuroQol), and the quality of life questionnaire of the International Osteoporosis Foundation (QUALEFFO). The median time from the second spinal radiograph until the quality of life survey was 1.9 years. Comparison between cases and their matched controls was undertaken using the signed rank test. RESULTS: 73 subjects with incident vertebral fracture (cases), mean age 64.8 years (of whom 23 had a baseline deformity), and 196 controls, mean age 63.9 years (of whom 60 had a baseline deformity), were studied. There were strong correlations between the domain scores for each of the three instruments. There was no statistically significant difference in any of the domain scores between cases and those controls with a prevalent deformity. However, compared with the controls without a prevalent deformity the cases had significantly impaired quality of life as determined using the total QUALEFFO score (38.2 vs 33.7), the physical component score of the SF-12 (39.9 vs 43.7) and the health status score of the EQ-5D (62.3 vs 69.9). When the analysis was repeated after stratification of the cases by baseline deformity status (i.e., cases with and without a prevalent deformity at baseline), cases with a prevalent deformity had impaired quality of life compared with their matched controls, both with and without a prevalent deformity. In contrast there was no significant difference in quality of life among the cases without a prevalent deformity and either control group. CONCLUSIONS: In this population-based study a recent vertebral fracture was associated with impairment in quality of life, though this was mainly among those who had sustained a previous vertebral deformity.