Prevalent vertebral deformities: Relationship to bone mineral density and spinal osteophytosis in elderly men and women

The aims of this study were to ascertain vertebral deformity prevalence in elderly men and women and to describe the association between bone mineral density (BMD) at the lumbar spine and femoral neck, severity of spinal degenerative disease and vertebral deformity prevalence. We performed standardized spinal radiographs in a random sample of 300 elderly men and women participating in the Dubbo Osteoporosis Epidemiology Study, a population-based study of fracture risk factors. Radiographs were read independently by masked observers for the prevalence of vertebral deformity and severity of osteophytosis. BMD was measured by dual-energy X-ray absorptiometry. The prevalence of vertebral deformities was critically dependent on the criterion used. The less strict criteria seemed to overestimate deformities at either end of the spine region analysed. However, irrespective of the criterion used, prevalence of deformity was higher in men than in women (25% vs 20% for the 3 SD criterion, 17% vs 12% for the 4 SD criterion and 27% vs 25% for the 25% criterion). Femoral neck BMD was more strongly associated with vertebral deformities than spinal BMD for the 25% criterion (OR/SD change in BMD 1.39 (p=0.02) vs 1.20 (p=0.19)), 3 SD criterion (OR/SD change in BMD 1.45 (p=0.01) vs 1.10 (p=0.34)) and 4 SD criterion (OR/SD change in BMD 1.98 (p=0.0002) vs 1.68 (p=0.008)). BMD was also more strongly associated with biconcave deformities than either wedge or crush deformities and more so in men than in women. Severity of spinal osteophytosis was not associated with vertebral deformity. In conclusion, femoral neck BMD is at least equivalent to the lumbar spine BMD in strength of association with prevalent vertebral fractures. Spinal osteophytosis falsely elevates BMD without a concomitant decrease in fracture risk, indicating that any interpretation of spinal BMD needs to be adjusted for osteophytosis. These findings support the use of femoral neck bone densitometry in older men and women. Moreover, these data indicate that current criteria for radiological assessment of vertebral deformity are sufficiently loose to include a substantial proportion of non-fractures in the elderly, with important implications for the design of clinical trials. However, irrespective of the criterion used, vertebral deformities in men are at least as common, if not more so, than in women, suggesting that vertebral osteoporotic fractures are overlooked in men.     

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 40 348 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. Received: 23 February 2000 / Accepted: 11 August 2000     

Mortality Associated with Vertebral Deformity in Men and Women: Results from the European Prospective Osteoporosis Study (EPOS)

Clinically apparent vertebral deformities are associated with reduced survival. The majority of subjects with radiographic vertebral deformity do not, however, come to medical attention. The aim of this study was to determine the association between radiographic vertebral deformity and subsequent mortality. The subjects who took part in the analysis were recruited for participation in a multicentre population-based survey of vertebral osteoporosis in Europe. Men and women aged 50 years and over were invited to attend for an interviewer-administered questionnaire and lateral spinal radiographs. Radiographs were evaluated morphometrically and vertebral deformity defined according to established criteria. The participants have been followed by annual postal questionnaire – the European Prospective Osteoporosis Study (EPOS). Information concerning the vital status of participants was available from 6480 subjects, aged 50–79 years, from 14 of the participating centres. One hundred and eighty-nine deaths (56 women and 133 men) occurred during a total of 14 380 person-years of follow-up (median 2.3 years). In women, after age adjustment, there was a modest excess mortality in those with, compared with those without, vertebral deformity: rate ratio (RR) = 1.9 (95% confidence interval (CI) 1.0,3.4). In men, the excess risk was smaller and non-significant RR = 1.3 (95% CI 0.9,2.0). After further adjusting for smoking, alcohol consumption, previous hip fracture, general health, body mass index and steroid use, the excess risk was reduced and non-significant in both sexes: women, RR = 1.6 (95% CI 0.9,3.0); men RR = 1.2 (95% CI 0.7,1.8). Radiographic vertebral deformity is associated with a modest excess mortality, particularly in women. Part of this excess can be explained by an association with other adverse health and lifestyle factors linked to mortality. Received: 12 June 1997 / Accepted: 6 November 1997     

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. Received: 24 May 2002 / Accepted: 27 August 2002 RID="*" ID="*" For full listing of participants, please see appendix RID="*" ID="*" Project co-ordinators Acknowledgement The study was financially supported by a European Union Concerted Action Grant under Biomed-1 (BMH1CT920182), and also EU grants C1PDCT925102, ERBC1PDCT 930105 & 940229. The central coordination was also supported by the UK Arthritis Research Campaign, the Medical Research Council (G9321536), and the European Foundation for Osteoporosis and Bone Disease. The EU's PECO program linked to BIOMED 1 funded in part the participation of the Budapest, Warsaw, Prague, Piestany, Szczecin and Moscow centers. Data collection from Croatia was supported by a grant from the Wellcome Trust. The central X-ray evaluation was generously sponsored by the Bundesministerium für Forschung and Technologie, Germany. Individual centers acknowledge the receipt of locally acquired support for their data collection. We would like to thank the following individuals: Aberdeen, UK: Rita Smith; Cambridge & Harrow, UK: Anna Martin, Judith Walton; Truro, UK: Mrs Joanna Parsons; Oviedo, Spain : J Bernardino Diaz Lopez, Ana Rodriguez Rebollar.     

Sex Difference in the Validity of Vertebral Deformities as an Index of Prevalent Vertebral Osteoporotic Fractures: A Population Survey of Older Men and Women

Morphometric methods have been developed for standardized assessment of vertebral deformities in clinical and epidemiologic studies of spinal osteoporosis. However, vertebral deformity may be caused by a variety of other conditions. To examine the validity of morphometrically assessed vertebral deformities as an index of osteoporotic vertebral fractures, we developed an algorithm for radiological differential classification (RDC) based on a combination of quantitative and qualitative assessment of lateral spinal radiographs. Radiographs were obtained in a population of 50- to 80-year-old German women (n= 283) and men (n = 297) surveyed in the context of the European Vertebral Osteoporosis Study (EVOS). Morphometric methods (Eastell 3 SD and 4 SD criteria, McCloskey) were validated against RDC and against bone mineral density (BMD) at the femur and the lumbar spine. According to RDC 36 persons (6.2%) had at least one osteoporotic vertebral fracture; among 516 (88.9%) nonosteoporotics 154 had severe spondylosis, 132 had other spinal disease and 219 had normal findings; 14 persons (2.4%) could not be unequivocally classified. The prevalence of morphometrically assessed vertebral deformities ranged from 7.3% to 19.2% in women and from 3.5% to 16.6% in men, depending on the stringency of the morphometric criteria. The agreement between RDC and morphometric methods was poor. In men, 62–86% of cases with vertebral deformities were classified as nonosteoporotic (severe spondylosis or other spinal disease) by RDC, compared with 31–68% in women. Among these, most had wedge deformities of the thoracic spine. On the other hand, up to 80% of osteoporotic vertebral fractures in men and up to 48% in women were missed by morphometry, in particular endplate fractures at the lumbar spine. In the group with osteoporotic vertebral fractures by RDC the proportion of persons with osteoporosis according to the WHO criteria (T-score <−2.5 SD) was 90.0% in women and 86.6% in men, compared with 67.9–85.0% in women and 20.8–50.0% in men with vertebral deformities by various methods. Although vertebral deformities by most definitions were significantly and inversely related to BMD as a continuous variable in both sexes [OR; 95% CI ranged between (1.70; 1.07–2.70) and (3.69; 1.33–10.25)], a much stronger association existed between BMD and osteoporotic fractures defined by RDC [OR; 95% CI between (4.85; 2.30–10.24) and (15.40; 4.65–51.02)]. In the nonosteoporotic group individuals with severe spondylosis had significantly higher BMD values at the femoral neck (p <0.01) and lumbar spine (p <0.0004) compared with the normal group. On the basis of internal (RDC) and external (BMD) validation, we conclude that assessment of vertebral osteoporotic fracture by quantitative methods alone will result in considerable misclassification, especially in men. Criteria for differential diagnosis as used within RDC can be helpful for a standardized subclassification of vertebral deformities in studies of spinal osteoporosis. Received: 5 February 1999 / Accepted: 24 June 1999     

Quality of Life in Patients with Vertebral Fractures: Validation of the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO)

Vertebral fractures may be minor or lead to pain, decreased physical function, immobility, social isolation and depression, which together contribute to quality of life. A Working Party of the European Foundation for Osteoporosis has developed a specfic questionnaire for patients with vertebral fractures. This questionnaire, QUALEFFO, includes questions in the domains pain, physical function, social function, general health perception and mental function. QUALEFFO was validated in a multicenter study in seven countries. The study was done in 159 patients aged 55–80 years with clinical osteoporosis, i.e., back pain and other complaints with at least one vertebral fracture and lumbar bone mineral density T-score <−1. Patients with a recent vertebral fracture were excluded because of unstable disease. Controls were age- and sex-matched, and did not have chronic back pain or vertebral fractures. Subjects with conditions exerting a major influence on quality of life were excluded. The QUALEFFO was administered twice within 4 weeks and compared with a generic questionnaire, the Short Form 36 of the Medical Outcomes Study (SF-36). Standard spinal radiographs were made for assessment of vertebral height. Seven questions were removed from the analysis because of low response rate, linguistic ambiguities or redundancy. The 41 remaining questions were analyzed for repeatability, internal consistency and the capacity to discriminate between patients with vertebral fractures and controls. Comparison with the SF-36 was performed within similar domains by conditional logistic regression and by receiver operating characteristic (ROC) curves. The repeatability of QUALEFFO was good (kappa statistics 0.54–0.90) and 26 of 41 questions had a kappa score ≥0.70. The internal consistency of the five domains was adequate, with Crohnbach α around 0.80. All except five questions discriminated significantly between patients and controls. The median scores of QUALEFFO were significantly higher in patients with vertebral fractures than in controls in all five domain (p<0.001), which is consistent with decreased quality of life in patients with osteoporosis. Spinal radiographs were assessed using the McCloskey–Kanis algorithm. According to this, 124 patients (78%) had vertebral fractures of ≥3 SD severity, in contrast with 7 controls (4%). Significant correlations existed between scores of similar domains of QUALEFFO and the SF-36, especially for pain, physical function and mental function. All five domains within each questionnaire discriminated significantly between fracture cases and controls. The odds ratios for pain and social function were greater for QUALEFFO, while general health perception was more discriminating using the SF-36. The ROC curve analysis of QUALEFFO indicated that all five domains were significantly predictive of vertebral fractures. When comparing similar domains of the two questionnaires, QUALEFFO domains demonstrated significantly better performance for pain, physical function and social function. The QUALEFFO total score and SF-36 physical composite score showed similar performance. In conclusion, QUALEFFO is repeatable, coherent and discriminates well between patients with vertebral fractures and control subjects. The results of this study confirm the decreased quality of life in patients with vertebral fractures. Received: 4 August 1998 / Accepted: 28 December 1998     

Effects of 5-year treatment with elcatonin and alfacalcidol on lumbar bone mineral density and the incidence of vertebral fractures in postmenopausal women with osteoporosis: a retrospective study

 The purpose of this retrospective study was to compare the effects of long-term treatment (5 years) with elcatonin and alfacalcidol on bone mineral density (BMD) and the incidence of vertebral fractures in postmenopausal women with osteoporosis. Fifty-six osteoporotic women, more than 5 years after menopause and 58–79 years of age, were enrolled in the study and allocated to an elcatonin treatment group (20 units IM, weekly; n = 30) or an alfacalcidol treatment group (1 μg/day, daily; n = 26). BMD of the lumbar spine (L2-L4) was measured by dual energy X-ray absorptiometry at baseline and every year for 5 years. There were no significant differences in age, body mass index, years since menopause, BMD, or number of prevalent vertebral fractures at baseline between the two groups. One-way analysis of variance with repeated measurements showed no significant longitudinal changes in BMD in either group, suggesting that both treatments sustained the BMD over 5 years. Two-way analysis of variance with repeated measurements also showed no significant differences in longitudinal changes in BMD between the two groups, suggesting that the effects of the two treatments on BMD were similar. However, the number of incident vertebral fractures per patient was significantly lower in the alfacalcidol treatment group than in the elcatonin treatment group (0.80 ± 1.19 and 2.08 ± 2.73, respectively; P < 0.05). These findings indicate that both treatments appeared to sustain lumbar BMD similarly over a 5-year period in postmenopausal women with osteoporosis, but alfacalcidol treatment may be superior to elcatonin treatment regarding the incidence of vertebral fractures. Further study with prospective observations are needed to confirm the results of the present study. Received: April 2, 2002 / Accepted: July 13, 2002 Offprint requests to: J. Iwamoto     

Lifestyle factors are associated with osteoporosis in lean women but not in normal and overweight women: a population-based cohort study of 1222 women

The aim of the present population-based cohort study was to evaluate the contribution of lifelong lifestyle factors to calcaneal and distal forearm bone mass in elderly women. We studied 1222 of the 1689 eligible home-dwelling women aged 70–73 years. Lifelong occupational and leisure time physical activity, calcium intake, smoking, alcohol intake and medical history were obtained by a self-completed questionnaire. Main outcome measures were broadband ultrasound attenuation (BUA) of the calcaneus and bone mineral density (BMD) of the radius measured once in 1997–1998. The women with BMI ≤ 25.1 kg m² had lower BUA (p < 0.0001) and radial BMD values (p < 0.0001) than women with higher BMI. Lifestyle factors associated with BUA in the leanest women were: low physical activity at work (RR 0.4; 95% confidence interval 0.2 to 0.8), low habitual exercise at the ages 30 years , 50 years and currently (RR 1.5; 1.0 to 2.4; RR 1.5; 1.1 to 2.6; RR 1.7; 1.1 to 2.7), poor mobility (RR 1.9; 1.2 to 3.0), coffee intake ≥ 5 cups/day (RR 1.7; 1.1 to 2.7), type 2 diabetes (RR 0.3; 0.1 to 0.9) and hypertension (RR 0.5; 0.3 to 0.8). Type 2 diabetes protected lean women from lower distal and ultradistal radial bone density (RR 0.3; 0.1 to 0.8; RR 0.1; 0.1 to 0.5). The selected lifestyle factors were not associated with lowered calcaneal or radial bone density in the higher categories of BMI. In conclusion, risk factors for lower calcaneal and radial bone density appear to be different among lean and normal/obese women. Lifelong recreational physical activity, low physical activity at work, type 2 diabetes and hypertension seem to be associated with increased bone density, while high coffee intake may increase the risk of lower bone density in lean elderly women. These factors are potentially modifiable, and intervention studies targeted at this risk category of women are needed.     

Development and Validation of the Mini-Osteoporosis Quality of Life Questionnaire (OQLQ) in Osteoporotic Women with Back Pain due to Vertebral Fractures. Osteoporosis Quality of Life Study Group

The objective of the study was to evaluate a shortened osteoporosis quality of life questionnaire (OQLQ) in osteoporotic women with back pain due to vertebral fractures. From the longer 30-item OQLQ (four to nine items per domain) we created the mini-OQLQ by choosing the two items with the highest impact in each of five domains (symptoms, physical function, activities of daily living, emotional function, leisure). We administered the OQLQ, the Sickness Impact Profile, the SF-36 and the Brief Pain Index to patients at baseline, after 2 weeks and after 6 months. The intraclass correlations between baseline and the 2-week follow-up for the five mini-OQLQ domains ranged from 0.72 to 0.86. Cross-sectional correlations between the domains of the mini-OQLQ and other health instruments were moderate to large (0.35–0.80) and greater than predicted. The mini-OQLQ items showed moderate to large correlations with items omitted from the shortened questionnaire (0.44–0.88). Correlations between the OQLQ domains and the other three instruments were greater than those of the mini-OQLQ, and partial correlations between OQLQ items omitted from the mini-OQLQ and the other three instruments after considering mini-OQLQ items were substantial (0.19–0.71) and statistically significant. Sample sizes of less than 200 per group should be required to detect minimally important differences in parallel-group clinical trials. Longitudinal correlations between the mini-OQLQ and the other measures were often significant but generally lower than predicted (0.10–0.49). The partial correlations revealed that the omitted items explained a significant portion of the longitudinal variance in each domain. We conclude that in a selected group of patients with back pain caused by vertebral fractures, the mini-OQLQ demonstrated good discriminative and adequate evaluative properties. The mini-questionnaire should be useful in clinical settings. Received: 14 September 1998 / Accepted: 8 February 1999     

Broadband ultrasound attenuation (BUA) of the heel bone and its correlates in men and women in the EPIC-Norfolk cohort: a cross-sectional population-based study

Osteoporotic fractures have substantial clinical and public health impact. Bone quality is an important determinant of fracture risk. Quantitative ultrasound (QUS) of bone measured as broadband ultrasound attenuation (BUA) has been shown to predict fracture risk. However, there have been very few large population studies, particularly in men. We investigated the correlates of calcaneal BUA using a CUBA clinical machine in 15,668 middle and older aged men and women (42–82 years) from the UK, EPIC-Norfolk cohort. At all ages mean BUA was significantly greater in men than women (men, 90.1±17.6; women 72.1±16.5). The age-related decline in BUA was five times greater in women than men (–0.77 vs. –0.15 dB/MHz per year). Pre- and post-menopausal bone loss was 0.39 and 0.85 dB/MHz per year, respectively. In univariate regression BUA increased with weight and height by 0.45 dB/MHz per kg and 0.68 per cm in women and 0.24 dB/MHz per kg and 0.33 per cm in men. BUA increased with body mass index (BMI) by 0.84 dB/MHz per kg/m² in women and 0.55 in men. However, weight was twice as influential as height in men and seven times as great in women. Age, weight and height explained 27% of the variance of BUA in women, but only 3% in men. Adjusted BUA was significantly lower in men and women with an existing history of any hip, wrist or spinal fracture both overall and when analysed for specific site. Figures were: all fractures 66.8 vs. 72.5 dB/MHz (P<0.001), women; 84.1 vs. 90.5 (P<0.001), men; hip fractures 61.9 vs. 72.2 dB/MHz (P<0.001), women; 81.5 vs. 90.2 (P<0.001), men; wrist fractures 66.6 vs. 72.5 dB/MHz (P<0.001), women; 81.5 vs. 90.2 (P<0.001), men; spinal fractures 68.1 vs. 72.1 dB/MHz (P<0.01), women; 85.1 vs. 90.2 (P<0.01), men. These differences equate to reductions of 14, 9 and 6% and 10, 7 and 6% for fractures of the hip, wrist and spine in the BUA of women and men, respectively. Thus, despite the overall gender difference in BUA the relative magnitude of a previous history of fracture was equally important in both men and women. Adjusted BUA was also lower in those with previous history of osteoporosis. In women currently taking hormone replacement therapy (HRT) the adjusted BUA was 5 dB/MHz or one-third of an SD greater than in those who did not. The BUA of those with a current smoking habit was 1.7% lower in women and 3.2% lower in men. Overall, there are substantial sex differences in the relationship of the physical and osteoporotic risk factors associated with BUA. A better understanding of these determinants of heel ultrasound may provide insights into how some of the sex differences in bone health can be explained and bone loss in later life minimised.