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     

Vertebral Wedge Angle Measured by Morphometric X-ray Absorptiometry

Vertebral wedge angle is greater in older men than in women of similar age, and increases with age in men. Wedge angle may depend less on bone size than other methods (for example, height ratios), and thus could be more effective at identifying wedge deformities. We aimed to compare mean wedge angle measured by morphometric X-ray absorptiometry (MXA) in young men and women, to assess the effect of age on wedge angle in women, and to compare wedge angle and anterior–posterior (ha/hp) height ratios for the identification of vertebral deformities. Mean wedge angle was similar in normal men (n= 46) and women (n= 106) ages 22–50 years, and did not change significantly with age in normal women ages 22–83 years (n= 222). MXA reference intervals for ha/hp ratios (trimmed mean minus 3.0 SD) and wedge angle (trimmed mean + 3.0, 2.5 and 2.0 SD) were used to identify vertebral wedge deformities in 83 women with osteoporosis, ages 49– 87 years. For agreement with semiquantitative assessment of radiographs (SQ), kappa (κ) = 0.76 for wedge angle mean plus 2.0 SD, and 0.74 for ha/hp height ratio mean minus 3.0 SD. Sensitivity was marginally better for wedge angle plus 2.0 SD than for ha/hp when all SQ grades of deformity were included, but there was no difference between methods for detection of moderate to severe deformities (grades 2 to 3). Diagnostic values for the two approaches were broadly similar. The results of this analysis do not provide strong evidence for the preferential use of the wedge angle approach. Received: 2 August 2000 / Accepted: 23 May 2001     

The Health Consequences of Vertebral Deformity in Elderly Chinese Men and Women

The following health consequences of vertebral deformity in Hong Kong elderly Chinese men and women were studied: the prevalence of back pain, disability due to back pain, and low morale. Lateral X-ray films were taken of the thoracic and lumbar spine of 796 community-dwelling Chinese subjects (396 men, 400 women) (aged 70–79). Subjects with one or more definitely deformed vertebra (reduction in vertebral height 3 SD or more below the mean) were classified as definite cases, those with one or more mildly deformed vertebra (reduction in vertebral height 2–2.99 SD below the mean) as mild cases, and the rest as controls. The prevalence and consequences of back pain were measured by a standardized questionnaire, and morale was measured by the Geriatric Morale Score. The relative risk (RR) and 95% confidence interval (CI) of having back pain and being depressed were calculated by logistic regression. Classifications included 16% of men and 30% of women as definite cases, 37% of men and 35% of women as mild cases, and 47% of men and 35% of women as controls. The relative risk (RR) of back pain was 2.3 (95% CI 1.4–3.9) (P < 0.05) in women with definite deformity and 1.5 (95% CI 0.9–2.5) (P > 0.05) in women with mild deformity, as compared with controls. Sixty-four percent of all men had back pain. This prevalence was much higher than figures obtained in a previous survey on low back pain. The prevalence of back pain did not differ by deformity status, but more men with vertebral deformity were on analgesic. There was no significant association between disability due to back pain and vertebral deformity in women. The RR for having a low morale score (of 5 and below) was 2.3 (95% CI 1.3–4.1) (P < 0.05) in women with mild deformity; men with vertebral deformity did not have a low morale. It was concluded that vertebral deformity was associated with significant back pain and psychological morbidity in elderly Chinese women. Although men with vertebral deformity did not report more back pain, more were on analgesics than controls. Received: 2 July 1997 / Accepted: 8 January 1998     

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     

Prevalence of Vertebral Deformity and its Associations with Physical Impairment among Japanese Women: The Hizen-Oshima Study

Vertebral fractures are a hallmark of postmenopausal osteoporosis and an important end point in trials of osteoporosis treatment, but the clinical significance of vertebral deformities remains uncertain. We examined the prevalence of vertebral deformity and associations of vertebral deformities and other characteristics with physical functioning among 584 Japanese women ages 40 to 89 years. Lateral spine radiographs were obtained and radiographic vertebral deformities were assessed by quantitative morphometry, defined as vertebral heights more than 3 SD below the normal mean. A self-administered questionnaire was used to survey participants about difficulty in performing selected basic and instrumental activities of daily living (ADL). Overall, 15% of women had at least one vertebral deformity, and 8% had 2 or more. The prevalence of vertebral deformities increased progressively with age. Half of women ages 80 and over had vertebral deformities. Impaired function was defined as difficulty performing 3 or more ADLs. After adjusting for age, the odds of impaired function were increased by 1.4 times (95% CI: 0.7, 2.9) in women with a single vertebral deformity, and 3.1 times (1.4, 6.8) in those with two or more deformities. Additional adjustment for number of painful joints, number of comorbidities, body mass index, and back pain did not materially alter these findings. In conclusion, women with multiple vertebral deformities had significantly greater impaired function. The association was independent of age, back pain and the number of painful joints, suggesting that deformities may impair function even when back pain is not present. Received: 29 October 2001 / Accepted: 11 April 2002     

Case-Control Study of the Pathogenesis and Sequelae of Symptomatic Vertebral Fractures in Men

To investigate the pathogenesis and sequelae of symptomatic vertebral fractures (VF) in men, we have performed a case–control study, comparing 91 men with VF (median age 64 years, range 27–79 years) with 91 age-matched control subjects. Medical history, clinical examination and investigations were performed in all patients and control subjects, to identify potential causes of secondary osteoporosis, together with bone mineral density (BMD) measurements. BMD was lower at the lumbar spine and all sites in the hip in patients with VF than in control subjects (p<0.001). Potential underlying causes of secondary osteoporosis were found in 41% of men with VF, compared with 9% of control subjects (OR 7.1; 95% CI 3.1–16.4). Oral corticosteroid and anticonvulsant treatment were both associated with a significantly increased risk of VF (OR 6.1; 95% CI 1.3–28.4). Although hypogonadism was not associated with an increased risk of fracture, the level of sex hormone binding globulin was higher (p<0.001) and the free androgen index lower (p<0.001) in men with VF than control subjects. Other factors associated with a significantly increased risk of VF were family history of bone disease (OR 6.1; 95% CI 1.3–28.4), current smoking (OR 2.8; 95% CI 1.2–6.7) and alcohol consumption of more than 250 g/week (OR 3.8; 95% CI 1.7–8.7). Men with VF were more likely to complain of back pain (p<0.001) and greater loss of height (p<0.001) than control subjects, and had poorer (p<0.001) scores for the energy, pain, emotion, sleep and physical mobility domains of the Nottingham Health Profile. We conclude that symptomatic VF in men are associated with reduced BMD, underlying causes of secondary osteoporosis such as corticosteroid and anticonvulsant treatment, family history of bone disease, current smoking and high alcohol consumption, and that they impair the perceived health of the individual. Received: 23 February 1998 / Accepted: 13 May 1998     

Effects of Gender and Age on the Association of Apolipoprotein E ε4 with Bone Mineral Density,Bone Turnover and the Risk of Fractures in Older People*

The aim of this study was to examine whether the presence of apolipoprotein E ε4 (ApoE ε4) is associated with a lower bone mineral density (BMD), lower quantitative ultrasound (QUS) measurements, higher bone turnover and fracture risk, and whether these relations are modified by gender and age. A total of 1406 elderly men and women (≥65 years) of the Longitudinal Aging Study Amsterdam (LASA) participated in this study. In all participants, QUS measurements were assessed, as well as serum osteocalcin (OC) and urine deoxypyridinolin (DPD/Cr urine). Follow-up of fractures was done each three months. In a subsample (n = 604), total body bone mineral content (BMC) and BMD of the hip and lumbar spine were measured. In addition, prevalent vertebral deformities were identified on radiographs. In women, the presence of ApoE ε4 was associated with significantly lower femoral neck BMD (g/cm²; mean ± SEM; ε4+, 0.64 ± 0.01 vs. ε4−, 0.67 ± 0.01; p= 0.04), lower trochanter BMD (g/cm²; mean ± SEM; ε4+, 0.58 ± 0.01 vs. ε4–, 0.61 ± 0.01; p= 0.01) and lower total body BMC (g; mean ± SEM; ε4+, 1787 ± 40.0 vs. ε4–, 1863 ± 23.8; p= 0.04). Women with ApoE ε4 also had a higher risk of severe vertebral deformities (OR=2.78; 95%CI: 1.21–6.34). In men, the associations between ApoE status and both hip BMD and QUS depended on age. Only among the younger men (65–69 years) was the presence of ApoE ε4 associated with lower BMD values. Bone markers and fractures were not associated with ApoE ε4 in either women, or men. In conclusion, this large community-based study confirms the importance of ApoE ε4 as a possible genetic risk factor related to BMD and vertebral deformities and demonstrates that its effect is gender related, and depends on age in men only. Received: 6 July 2001 / Accepted: 2 April 2002     

Bone Mineral Density and Vertebral Fractures in Men

In women, many studies indicate that the risk of vertebral fragility fractures increases as bone mineral density (BMD) declines. In contrast, few studies are available for BMD and vertebral fractures in men. It is uncertain that the strength of the relationship between BMD and fractures is similar in magnitude in middle-aged men and in postmenopausal women. In the present study, 200 men (mean age 54.7 years) with lumbar osteopenia (T-score <−1.5) were recruited to examine the relationships between spine BMD and hip BMD and the associations of BMD with vertebral fractures. Lumbar BMD was assessed from L2 to L4, in the anteroposterior view, using dual-energy X-ray densitometry. At the upper left femur, hip BMD was measured at five regions of interest: femoral neck, trochanter, intertrochanter, Ward’s triangle and total hip. Spinal radiographs were analyzed independently by two trained investigators and vertebral fracture was defined as a reduction of at least 20% in the anterior, middle or posterior vertebral height. Spinal radiographs evidenced at least one vertebral crush fracture in 119 patients (59.5%). The results of logistic regression showed that age, femoral and spine BMDs were significant predictors of the presence of a vertebral fracture. Odds ratios for a decrease of 1 standard deviation ranged from 1.8 (1.3–2.8) for spine BMD to 2.3 (1.5–3.6) for total hip BMD. For multiple fractures odds ratios ranged from 1.7 (1.1–2.5) for spine BMD to 2.6 (1.7–4.3) for total hip BMD. In all models, odds ratios were higher for hip BMD than for spine BMD, particularly in younger men, under 50 years. A T-score <−2.5 in the femur (total femoral site) was associated with a 2.7-fold increase in the risk of vertebral fracture while a T-score <−2.5 in the spine was associated with only a 2-fold increase in risk. This study confirms the strong association of age and BMD with vertebral fractures in middle-aged men, shows that the femoral area is the best site of BMD measurement and suggests that a low femoral BMD could be considered as an index of severity in young men with lumbar osteopenia. Received: 27 October 1998 / Accepted: 22 February 1999     

Identification of Vertebral Deformities in Men: Comparison of Morphometric Radiography and Morphometric X-ray Absorptiometry

Osteoporotic vertebral deformities may be detected by morphometric radiography (MR) using spinal radiographs, and by morphometric X-ray absorptiometry (MXA) using dual-energy X-ray absorptiometry. Reference values for MR may not be appropriate for MXA, and reference values may be affected by gender and age. The aims of this study were to (1) compare mean deformity of vertebral height ratios for MR and MXA in men, (2) compare mean deformity for MXA in men and women, (3) compare mean wedge angle measured by MXA in men and women and (4) assess the effect of aging on MXA values in men. We studied a general practitioner sample of 115 men aged 22–81 years (mean 53 years) and 124 women aged 55–89 years (mean 68 years). Subjects had MXA of T4 to L4 using the Hologic QDR 4500A. Women and men over age 50 years had radiographs of the thoraco-lumbar spine. Scans and radiographs were marked in the same way by one operator and vertebral height ratios and mean deformity were calculated for MR and MXA. The mean wedge angle, θ, was calculated for MXA in all subjects. Mean wedge and biconcavity deformity and standard deviation (SD) in men were greater for MXA than for MR. The mean wedge and biconcavity deformity measured by MXA tended to be greater for men than for women. Vertebral deformity in men increased with age, and was associated with degenerative change seen on spinal radiographs. The mean wedge angle was greater for men than for women, and it increased with age in men. We conclude that sex- and age-specific reference ranges should be established separately for MXA. Received: 14 September 1998 / Accepted: 28 January 1999     

Impact of Hip and Vertebral Fractures on Quality-Adjusted Life Years

The objective of the study was to estimate the impact of hip and vertebral fractures on quality of life in postmenopausal women using a preference-based health measure that is appropriate for economic evaluations and to investigate correlates of health outcome. Interviews to assess health-related quality of life, which also documented other health conditions and characteristics, were undertaken in women age 50 years and older without osteoporotic fractures compared with women with hip and/or vertebral fracture(s). Health status was characterized by self-reported physical limitations and the mental and physical component summary scores of the SF-36. Quality-adjusted life years (QALYs), which reflect each individual’s assessment of her overall health utility, were estimated with time tradeoff values. Regression methods were used to examine QALY correlates (e.g. time since fracture) for each fracture group and to estimate differences in QALYs between fracture and non-fracture subjects after accounting for other patient characteristics. Among 382 women ages 50–96 years, fracture subjects were significantly older, less likely to use hormone replacement therapy and more likely to report physical limitations than non-fracture subjects. On the QALY scale, where 1 represents perfect health and 0 represents death, mean QALY values were 0.82 (95% CI: 0.76, 0.87) among 114 women with one or more vertebral fractures and 0.63 (95% CI: 0.52, 0.74) among 67 with hip fracture compared with 0.91 (95% CI: 0.88, 0.94) among 201 women without fracture. No significant correlates of QALYs were identified among women with vertebral fracture alone. Among hip fracture subjects, time since hip fracture and presence of a vertebral fracture were significant correlates of QALYs. In multiple regression analyses, estimated QALY differences (fracture minus non-fracture subjects) ranged from –0.05 to –0.55 and were equivalent to losses of 20–58 days, 23–65 days and 115–202 days per year for vertebral fracture (p= 0.001), hip fracture (p= 0.009) and hip plus vertebral fracture (p<0.001) subjects, respectively, depending on age. Thus to adequately assess the cost-effectiveness of osteoporosis treatment, the negative impact of vertebral fractures on QALYs, even among women who have survived a hip fracture, must be considered. Received: 2 February 2001 / Accepted: 23 July 2001     

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     

Vertebral Fractures Predict Subsequent Fractures

This population-based study documents an increase in most types of fractures following the occurrence of a clinically recognized vertebral fracture among 820 Rochester, Minnesota, residents. During 4349 person-years of follow-up, 896 new fractures were observed. Relative to incidence rates in the community, there was a 2.8-fold increase in the risk of any fracture, which was greater in men (standardized incidence ratio (SIR), 4.2; 95% CI, 3.2–5.3) than women (SIR, 2.7; 95% CI, 2.4–3.0). The estimated cumulative incidence of any fracture after 10 years was 70%. The greatest increase in risk was for subsequent fractures of the axial skeleton, in particular a 12.6-fold increase (95% CI, 11–14) in additional vertebral fractures. There was a lesser increase in most limb fractures, including a 2.3-fold increase (95% CI, 1.8–2.9) in hip fractures and a 1.6-fold increase (95% CI, 1.01–2.4) in distal forearm fractures. There was a slightly greater association with distal forearm fractures among those whose first vertebral fracture occurred before age 70 years but a similar relationship with hip fractures, including cervical and intertrochanteric hip fractures separately, regardless of age at the initial vertebral fracture. There was also an equivalent increase in subsequent fracture risk whether the initial vertebral fracture was attributed to severe or moderate trauma. These data show that vertebral fractures represent an important risk factor for fractures in general, not just those of the spine and hip. Received: 2 September 1998 / Accepted: 9 February 1999     

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. Received: 29 June 2000 / Accepted: 5 January 2001     

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     

Visual Assessment of Vertebral Deformity by X-ray Absorptiometry: A Highly Predictive Method to Exclude Vertebral Deformity

The accurate identification of prevalent vertebral fractures is important in both the clinical and research setting as they are associated with increased risk of further fracture and irreversible clinical consequences. This study reports a direct comparison of prevalent vertebral deformity identification using X-ray absorptiometry (XA) scans, acquired on a dual-energy X-ray absorptiometry (DXA) machine, and conventional radiographs in a diverse group of 161 postmenopausal women, ranging from healthy subjects with normal bone mineral density (BMD) to osteoporotic subjects with multiple vertebral deformities. Deformities were identified by a trained operator by visual assessment of the XA scans (VXA) and semiquantitatively by an experienced radiologist on the conventional radiographs (XSQ). Subjects were recruited prospectively and were triaged according to their VXA results into normal, equivocal and definite deformity groups. VXA and XSQ demonstrated good agreement (96.3%, κ= 0.79) in classifying vertebrae as normal or deformed in the 1978 of 2093 vertebrae deemed analyzable on both the XA scans and conventional radiographs. VXA showed good sensitivity (91.9%) in the identification of moderate/severe XSQ deformities and an excellent negative predictive value (98.0%) was produced when VXA was used to distinguish subjects without vertebral deformities from those with possible or definite deformities on a per subject basis. The majority of disagreement between the two methods resulted from different classification of mild wedge and endplate deformities and the poor visualization of upper thoracic vertebrae on the XA scans. Agreement improved, particularly on a per subject basis, when analysis was restricted to the vertebral levels from L4 to T7. Visual triage of XA scans by a trained operator would seem to be swift, convenient and cost-effective method, with excellent negative predictive value, to distinguish subjects with very low risk of vertebral deformities from those with possible deformities. These ‘normal’ subjects can then be excluded prior to performing conventional radiographs and further time-consuming and costly methods of vertebral deformity assessment such as XSQ by an experienced radiologist and/or quantitative morphometry. VXA may prove useful in the clinical evaluation of patients at risk of osteoporosis as an adjunct to BMD scans or in the selection of subjects for osteoporosis-related clinical trials. Received: 27 July 1999 / Accepted: 4 February 2000     

Longitudinal Evaluation of Morphometric X-ray Absorptiometry for the Identification of Vertebral Deformities

Morphometric X-ray absorptiometry (MXA) has not been evaluated for the identification of incident vertebral deformities. The reliability of longitudinal measurements in quantitative vertebral morphometry is influenced by the precision of the technique. Long-term precision in vitro (weekly MXA phantom scans) assessed by retrospective cumulative sum (Cusum) analysis, detected one event during a 6-month period when the measurement process was “out of control”. Inspection of service records revealed that repair work was performed around this timepoint. The coefficient of variation (CV) for long-term precision (vertebral heights) in a population-based sample of postmenopausal women ages 56 to 83, mean 65 ± 6 years (n= 48), was 4.0% for morphometric radiography (MRX), 2.9% for MXA using the compare facility for analysis of serial scans, and 3.2% when “compare” was not used. In women with osteoporosis ages 49 to 87, mean 67 ± 9 years (n= 50), the CV was 5.0% for MRX, 4.1% for MXA using “compare” and 8.5% without “compare”. Precision errors for height ratios (MRX and MXA) were greater than for vertebral heights. Incident deformities were identified by MRX and MXA in the women with osteoporosis, using point prevalence, 20% minimum reduction in vertebral height, and percent least significant change (LSC) in vertebral heights and height ratios. Semiquantitative analysis of radiographs by a radiologist (Genant method) was used as the gold standard. The results were similar for MRX and MXA, and all morphometric criteria identified a similar proportion of true incident deformities, although the false positive rate was generally greater for the height ratio approaches. MXA has good long-term precision and is comparable to MRX for the identification of incident deformities when scans are analyzed with the compare facility. Received: 31 July 2000 / Accepted: 6 February 2001     

Performance of COLIA1 Polymorphism and Bone Turnover Markers to Identify Postmenopausal Women with Prevalent Vertebral Fractures

Some studies have suggested that bone turnover markers (BTM) and collagen type I alpha 1 gene (COLIA1) may be useful in the prediction of rates of future bone loss, and may therefore provide information about fracture risk. Our study aimed to examine the association of the COLIA1 genotype with the risk of vertebral fracture and to investigate the predictive value of this genetic factor in comparison with bone mineral density (BMD) and BTM, in ambulatory postmenopausal Spanish women. We determined the COLIA1 polymorphism by polymerase chain reaction, BMD by dual-energy X-ray absorptiometry and BTM in 43 postmenopausal women with prevalent vertebral fracture and a control group of 101 postmenopausal women without fracture. There was a significant overrepresentation of the ‘T’ allele in fractured women (p= 0.029). BTM exhibited no differences between women with or without fractures or COLIA1 genotype groups. After adjusting for all other variables, the osteoporosis densitometric criteria variable was the most strongly associated with fracture (OR = 5 [1.8–13.3]) followed by COLIA1 (OR = 2.1 [1–4.3] per copy of the ‘T’ allele). Our study shows that COLIA1 is associated with prevalent vertebral fracture independently of bone mass, and the performance of this genetic factor to assess prevalent vertebral fracture is better than bone turnover markers. Received: 29 June 2001 / Accepted: 11 December 2001     

Vertebral Fracture Definition from Population-Based Data: Preliminary Results from the Canadian Multicenter Osteoporosis Study (CaMos)

The Canadian Multicenter Osteoporosis Study is a large population-based prospective study of osteoporosis in the Canadian population. The study involves 9424 subjects, both male and female, from nine centers and seven regions of Canada. Each subject completed an extensive interview to obtain medical, demographic and lifestyle information, and was examined by dual-energy X-ray absorptiometry of the spine and hip, ultrasound of the heel and, for subjects over 50 years of age, lateral spine radiographs. Spinal morphometry of the initial radiographs was performed to determine the prevalence of vertebral deformity. A method is utilized to extract reference norms for vertebral shape from a subset of the population data, which is then used to categorize any deformity within the whole data set. Using 3 standard deviations (SD) as a limit of normality, the male prevalence of 21.5% was similar to the female prevalence of 23.5%. Using 4 SD this reduced to 7.3% and 9.3% respectively. The younger men (50–59 years) showed a higher prevalence of deformity than the women and a lower increase of prevalence with age. In the older age group (over 80 years) the female prevalence of 45% compared with 36% for the men using 3 SD (grade 1) to define the limit of normality. The female group presented with more severe deformities on average than the male group. This continuing study will provide longitudinal information regarding the development of osteoporosis and associated risk factors which will eventually be of use to develop public health policies. Received: 27 September 1999 / Accepted: 4 February 2000