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     

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     

Survival after Hip Fracture: Short- and Long-Term Excess Mortality According to Age and Gender

The purpose of this study was to analyze the excess mortality after hip fracture and to reveal whether, and eventually when, the excess mortality vanished in different groups of age and gender. A population-based, prospective, matched-pair, cohort study among persons 50 years of age and older was conducted involving 1338 female and 487 male hip fracture patients with 11 086 and 8141 controls respectively. Occurrence of hip fracture and mortality were recorded from 1986 until 1995. We studied the excess mortality of the hip fracture patients versus controls by using Kaplan–Meier curves and extended Cox regression with hip fracture (yes/no) as time-dependent covariate. The male hip fracture patients had higher mortality than the women the first year after the injury, irrespective of age, both in absolute terms (31% and 17% respectively) and relative to their age-matched controls. The relative risk (RR) of dying within 1 year for hip fracture patients versus controls was 3.3 (95% confidence interval (CI) 2.1–5.2) for women and 4.2 (95% CI 2.8–6.4) for men below 75 years of age. The corresponding figures for persons 85 years and older were 1.6 (95% CI 1.2–2.0) for women and 3.1 (95% CI 2.2–4.2) for men. All groups of age and gender, except women 85 years and older, had a large and significant excess mortality lasting for many years after the hip fracture – at least 5–6 years for women below 75 years of age (RR = 3.2, 95% CI 1.9–5.6). The excess mortality after hip fracture for women 85 years and older had vanished after 3 months (RR = 1.0, 95% CI 0.8–1.1). When referring to the excess mortality after hip fracture it is therefore necessary to specify sex, age and time since injury. Received: 15 September 1998 / Accepted: 23 December 1998     

A Population-Based Study of Fracture Incidence in Southern Tasmania: Lifetime Fracture Risk and Evidence for Geographic Variations within the Same Country

Symptomatic fractures are a significant problem in terms of both morbidity and financial cost. Marked variation in both total and site-specific fracture incidence has been documented internationally but there is limited within-country data. This prospective population-based study documented the incidence of all symptomatic fractures occurring from July 1, 1997 to June 30, 1999 in adults ≥50 years of age resident in Southern Tasmania (total population ≥50 years: 64 688). Fractures were ascertained by reviewing reports from all the radiology providers within the area. There were 701 fractures in men and 1309 fractures in women. The corresponding fracture incidence in men and women was 1248 and 1916 per 100 000 person-years, respectively. Residual lifetime fracture risk in a person aged 50 years was 27% for men and 44% for women with fractures other than hip fractures constituting the majority of symptomatic fracture events. These fracture risk estimates remained remarkably constant with increasing age. In comparison to Geelong, there were significantly lower hip fracture rates (males: RR 0.59, 95% CI 0.45–0.76; females: RR 0.61, 95% CI 0.53–0.71) but significantly higher distal forearm fractures (males: RR 1.87, 95% CI 1.10–3.78; females: RR 1.31, 95% CI 1.11–1.55) and total fractures in men (RR 1.31, 95% CI 1.17–1.46) but not women (RR 1.05, 95% CI 0.98–1.13). In contrast, Southern Tasmania had lower age-standardized rates of all fractures compared with Dubbo (RR 0.28–0.79). In conclusion, this study provides compelling evidence that fracture incidence varies between different geographic sites within the same country, which has important implications for health planning. In addition, the combination of high residual fracture risk and short life expectancy in elderly subjects suggests fracture prevention will be most cost-effective in later life. Received: 27 April 2000 / Accepted: 16 August 2000     

Prevalent vertebral deformities predict increased mortality and increased fracture rate in both men and women: A 10-year population-based study of 598 individuals from the Swedish cohort in the European Vertebral Osteoporosis Study

The aim of this study was to evaluate whether a prevalent vertebral deformity predicts mortality and fractures in both men and women. In the city of Malmö, 598 individuals (298 men, 300 women; age 50–80 years) were selected from the city's population and were included in the Swedish part of the European Vertebral Osteoporosis Study (EVOS). At baseline the participants answered a questionnaire and lateral spine radiographs were performed. The prevalence of subjects with vertebral deformity was assessed using a morphometric method. The mortality during a 10-year follow-up period was determined through the register of the National Swedish Board of Health and Welfare. Eighty-five men and 43 women died during the study period. The subsequent fracture incidence during the follow-up period was ascertained by postal questionnaires, telephone interviews and by a survey of the archives of the Department of Radiology in the city hospital. Thirty-seven men and 69 women sustained a fracture during the study period. Data are presented as hazard ratios (HR) with 95% confidence interval (95% CI) within brackets. Prevalent vertebral deformity, defined as a reduction by more than 3 standard deviations (SD) in vertebral height ratio, predicted mortality during the forthcoming decade in both men [age-adjusted HR 2.4 (95% CI 1.6–3.9)] and women [age-adjusted HR 2.3 (95% CI 1.3–4.3)]. In men there was an increased mortality due to cardiovascular and pulmonary diseases and in women due to cancer. Prevalent vertebral deformity predicted an increased risk of any fracture during the forthcoming decade in both men [age-adjusted HR 2.7 (95% CI 1.4–5.3)] and women [age-adjusted HR 1.8 (95% CI 1.1–2.9)]. Prevalent vertebral deformity predicted an increased risk of any subsequent fragility fracture in women [age-adjusted HR 2.0 (95% CI 1.1–3.5)]; however, in men the increased risk was nonsignificant [age-adjusted HR 1.9 (95% CI 0.7–5.1)]. In summary, a prevalent vertebral deformity can predict both increased mortality and increased fracture incidence during the following decade in both men and women. We conclude that prevalent vertebral deformity could be used as a risk factor in both genders for mortality and future fracture.     

Asymptomatic vertebral deformity as a major risk factor for subsequent fractures and mortality: a long-term prospective study.

In elderly men and women, asymptomatic vertebral deformity was found to be associated with subsequent risk of symptomatic fractures, particularly vertebral fracture, and increased risk of mortality after a fracture. INTRODUCTION: Vertebral deformity is associated with an increased risk of fracture and mortality. However, it is unclear whether the three events of vertebral deformity, fracture, and mortality are linked with each other and what role BMD plays in these linkages. MATERIALS AND METHODS: Vertebral deformity was determined from quantitative analysis of thoracolumbar spine X-rays in 300 randomly individuals (114 men and 186 women) 60 years of age (as of mid-1989), who were randomly selected from the prospective Dubbo Osteoporosis Epidemiology Study. Incidence of atraumatic fractures and subsequent mortality were ascertained from 1989 to 2003. Cox's proportional hazards model was used to determine the association between asymptomatic vertebral deformities, osteoporotic fractures, and risk of mortality. RESULTS: The prevalence of asymptomatic vertebral deformity was 31% in men and 17% in women. During the follow-up period, subjects with vertebral deformity had a significantly higher risk of any fracture than those without vertebral deformity (44% versus 29%; hazards ratio [HR], 2.2; 95% CI, 1.4-3.7), particularly symptomatic vertebral fracture (relative risk [RR], 7.4; 95% CI, 3.2-17.0). Mortality rate was highest after a symptomatic fracture among those with vertebral deformity (HR, 9.0; 95% CI, 3.1-26.0). These associations were independent of age, sex, and BMD. CONCLUSION: Vertebral deformity was a strong predictor of subsequent risk of fractures, particularly symptomatic vertebral fracture, and may modify fracture-associated mortality in both elderly men and women.     

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     

Factors Associated with Mortality after Hip Fracture

There is a well-known excess mortality subsequent to hip fracture, which is probably restricted to subgroups of hip fracture patients with reduced health status. We studied the association between risk factors and death in 248 hip fracture patients and 248 controls originally enrolled in a population-based case–control study. This cohort was followed for 3 1/2 years with respect to total mortality. A markedly increased mortality was found in hip fracture patients passing a mental status test at a low score [relative risk (RR) = 2.3, 95% confidence interval (CI) 1.4-3.7], in hip fracture patients reporting two or more selected chronic diseases (RR = 3.3, 95% CI 1.8–6.1), in hip fracture patients not walking outdoors before the fracture (RR = 3.2, 95% CI 2.0–5.1) and in hip fracture patients in the lower half of handgrip strength distribution (RR = 2.3, 95% CI 1.6–3.4), all compared with the control group. In contrast, hip fracture patients without these risk factors did not have increased mortality compared with the control group. This study suggests that otherwise healthy and fit patients do not have increased mortality subsequent to hip fracture. The excess mortality is restricted to persons with reduced mental status, reduced somatic health and low physical ability. Special attention should be paid to patients with such risk factors in the treatment and rehabilitation period. Received: 2 March 1999 / Accepted: 17 August 1999     

Fluoride for the Treatment of Postmenopausal Osteoporotic Fractures: A Meta-Analysis

We conducted an efectiveness meta-analysis to determine the efficacy of fluoride therapy on bone loss, vertebral and nonvertebral fractures and side effects in postmenopausal women. A literature search was conducted on MEDLINE, Current Contents and the Cochrane Controlled Trial Registry. Two independent reviewers selected randomized controlled trials which met predetermined inclusion criteria. They independently extracted data using predetermined forms and assessed the methodologic quality of the trials using a validated scale. For dichotomous outcomes, the relative risk (RR) was calculated, and for continuous outcomes, the weighted mean difference (WMD) of percentage change from baseline was calculated. Where heterogeneity existed (determined by a chi-square test) a random effects model was used. Eleven studies (1429 subjects) met the inclusion criteria. The increase in lumbar spine bone mineral density (BMD) was found to be higher in the treatment group than in the control group with a WMD 8.1% (95% CI: 7.15, 9.09) after 2 years of treatment and 16.1% (95% CI: 14.65, 17.5) after 4 years. The RR for new vertebral fractures was not significant at 2 years [0.87 (95% CI: 0.51, 1.46)] or at 4 years [0.9 (95% CI: 0.71, 1.14)]. The RR for new nonvertebral fractures was not significant at 2 years [1.2 (95% CI: 0.68, 2.10)] but was increased at 4 years in the treated group [1.85 (95% CI: 1.36, 2.50)], especially if used at high doses and in a non-slow-release form. The RR for gastrointestinal side effects was not significant at 2 years [2.18 (95% CI: 0.86, 1.21)] but was increased at 4 years in the treated group [2.18 (95% CI: 1.69, 4.57)], especially if fluoride was used at high doses and in a non-slow-release form. The number of withdrawals and dropouts was not different between treated and control groups at 2 and 4 years. Thus, although fluoride has an ability to increase bone mineral density at the lumbar spine, it does not result in a reduction in vertebral fractures. Increasing the dose of fluoride increases the risk of nonvertebral fractures and gastrointestinal side effects without any effect on the vertebral fracture rate. Received: 23 February 2000 / Accepted: 23 February 2000     

Survival and Potential Years of Life Lost After Hip Fracture in Men and Age-matched Women

Hip fracture is associated with a higher mortality rate in men than in women. However, mean age of men and women with hip fracture differs markedly. Thus, some of the differences in the clinical pattern and outcome between genders could be related to different ages. To avoid the influence of age on gender-specific outcome, we analyzed prefracture conditions and hip fracture outcome in a cohort of men and of age-matched women. Risk factors for low bone mass were recorded in 106 men (mean age ± SD, 80.3 ± 9.3 years) and 264 age-matched women (mean age 81.4 ± 8.0) with hip fracture. We compared mortality rate, survival, years of potential life lost and modification of housing conditions. These outcomes were prospectively assessed during an average 3.6 years follow-up (up to 7 years). Men with hip fracture differed from age-matched hip-fractured women by a higher alcohol and tobacco consumption, a greater frequency of living in couple, and by less prevalent fractures. Mortality rate after hip fracture was significantly higher in men (RR = 1.74, 95% CI 1.34–2.24). Since mortality is higher in the general male population, we compared reduction in life expectancy taking into account the gender-specific mortality rate. The excess mortality in each age-group of hip-fractured patients, which was measured during the whole follow-up period, and is an estimate of death attributable to fracture, did not differ between genders. Reduction in life expectancy due to hip fracture was similar in both genders (5.9 ± 4.5 and 5.8 ± 4.8 years, in men and women, respectively; NS), but the proportion of the years of life lost was higher in men (70 ± 33%) than in women (59 ± 42%, p < 0.01). It was concluded that for the same age, mortality rate after hip fracture was higher in men than in women. Although the reduction in life expectancy was similar in both genders, the proportion of the years of life lost was higher in men, suggesting a worse impact of hip fracture on survival in men, even after consideration of the higher mortality rate in the general male population. Received: 9 October 2001 / Accepted: 22 April 2002     

Risk Factors for Fractures of the Wrist,Shoulder and Ankle: The Blue Mountains Eye Study

Few studies have examined risk factors for fractures of the wrist, shoulder or ankle. The Blue Mountains Eye Study is a population-based longitudinal study in 3654 people aged 49 years or older resident in an area west of Sydney, Australia. Detailed eye examinations and interviews were carried out at baseline (1992–3) and after 5 years (1997–9). Information about fractures sustained during follow-up were collected by a combination of self-report and a search of hospital radiology records. After 4.7 years follow-up subjects had sustained 53 fractures of the distal forearm, 20 fractures of the proximal humerus and 33 ankle fractures. In multivariate models factors independently associated with wrist fractures in women were no vigorous exercise in the past 2 weeks (relative risk RR 0.4, 95% CI 0.2–0.9) and ever use of HRT (RR 0.4, 95% CI 0.1–1.0). Factors independently associated with ankle fractures were male sex (RR 0.3, 95% CI 0.1–0.8) and visual field loss (RR 2.8, 95% CI 1.2–6.6). These findings are in keeping with other studies, and suggest that different types of osteoporotic fracture have different, if overlapping, sets of risk factors. Received: 28 December 2000 / Accepted: 21 June 2001     

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     

Weight Variability, Weight Change and the Incidence of Hip Fracture: A Prospective Study of 39000 Middle-aged Norwegians

There is an increased risk of hip fracture and low bone mass in thin individuals. An association between weight loss and hip fracture has also been reported. In addition, it has been suggested that weight cycling might lead to bone loss. We studied weight variability and change in 19938 women and 19151 men who all attended three consecutive health examinations during an average period of 12 years, and assessed the effect of these on the incidence of hip fracture during a subsequent follow-up. Mean age at start of follow-up was 48.6 years in women and 48.5 years in men. For each subject weight variability and linear trend in weight change between the three examinations were assessed by linear regression of weight versus time. The cohort was followed on average 11.6 years from the third examination with respect to hip fracture. During follow-up, 148 hip fractures were identified in women and 59 in men. In both sexes, those with most weight variability had increased risk of fracture (relative risk (RR) = 2.07, 95% confidence interval (CI) 1.24–3.46 in women, and RR = 2.70, 95% CI 1.25–5.86 in men, high vs low quarter of weight variability). Overall, the effect of weight variability was not affected by adjustment for body mass index and linear trend in weight change. In men, there was also an association between weight loss and hip fracture. In summary, high weight variability defined a group with increased risk of hip fracture in this middle-aged cohort. The effect was independent of body mass index and linear trend in weight change. Whether weight variability leads to increased risk of fracture per se or whether it defines a group with otherwise increased risk of fracture is not known, and needs further investigation. Received: 14 October 1997 / Accepted: 8 January 1998     

Risedronate Reduces the Risk of First Vertebral Fracture in Osteoporotic Women

Risedronate treatment reduces the risk of vertebral fracture in women with existing vertebral fractures, but its efficacy in prevention of the first vertebral fracture in women with osteoporosis but without vertebral fractures has not been determined. We examined the risk of first vertebral fracture in postmenopausal women who were enrolled in four placebo-controlled clinical trials of risedronate and who had low lumbar spine bone mineral density (BMD) (mean T-score =–3.3) and no vertebral fractures at baseline. Subjects received risedronate 5 mg (n= 328) or placebo (n= 312) daily for up to 3 years; all subjects were given calcium (1000 mg daily), as well as vitamin D supplementation (up to 500 IU daily) if baseline serum 25-hydroxyvitamin D levels were low. The incidence of first vertebral fracture was 9.4% in the women treated with placebo and 2.6% in those treated with risedronate 5 mg (risk reduction of 75%, 95% confidence interval 37% to 90%; P= 0.002). The number of patients who would need to be treated to prevent one new vertebral fracture is 15. When subjects were stratified by age, similar significant reductions were observed in patients with a mean age of 64 years (risk reduction of 70%, 95% CI 8% to 90%; P= 0.030) and in those with a mean age of 76 years (risk reduction of 80%, 95% CI 7% to 96%; P= 0.024). Risedronate treatment therefore significantly reduces the risk of first vertebral fracture in postmenopausal women with osteoporosis, with a similar magnitude of effect early and late after the menopause. Received: 12 September 2001 / Accepted: 11 December 2001     

Risk Factors for Perimenopausal Fractures: A Prospective Study

This prospective study was aimed at determining the risk factors for the development of fractures in perimenopausal women. The study group (n= 3068) was comprised of a stratified population sample of women aged between 47 and 56 years. During the follow-up period of 3.6 years, 257 (8.4%) of the women sustained a total of 295 fractures. After adjustment for covariates, the relative risk (RR) of sustaining a fracture was found to be 1.4 [95% confidence interval (CI) 1.2–1.6] for a 1 standard deviation (SD) decrease in the spinal and femoral neck bone mineral density (BMD). Women with a previous fracture history were found to have an increased risk of fracture [RR 1.7 (95% CI 1.3–2.2)] and those reporting three or more chronic illnesses exhibited a RR of 1.4 (95% CI 1.0–1.9). Women not using hormone replacement therapy (HRT) had a RR of 1.5 (95% CI 1.1–2.2) for all fracture types. When osteoporotic fractures (vertebral, hip, proximal humerus and wrist fractures; n= 98) were used as an endpoint, the independent risk factors were found to be a low BMD (RR for a 1 SD decrease in both spinal and femoral neck BMD was 1.6, 95% CI 1.3–2.0), a previous fracture history (RR 1.9, 95% CI 1.3–2.9) and nonuse of HRT (RR 2.2, 95% CI 1.3–4.0). The independent risk factors for all other fractures (n = 158) were a low BMD (RR for a 1 SD decrease in the spinal BMD was 1.4, 95% CI 1.2–1.6 and in the femoral neck BMD was 1.3, 95% CI 1.1–1.5), a previous fracture history (RR 1.6, 95% CI 1.1–2.2), smoking (RR 1.8, 95% CI 1.1–2.7) and having had three or more chronic illnesses (RR 1.6, 95% CI 1.1–2.2). Weight, height, age, menopausal status, maternal hip fracture, use of alcohol, coffee consumption or dietary calcium intake were not independently associated with the development of any particular type of fracture. We conclude that the independent risk factors for perimenopausal fractures are a low bone density, previous fracture history, nonuse of HRT, having had three or more chronic illnesses and smoking, the gradient of risk being similar for spinal and femoral neck BMD measurements in the perimenopausal population. The risk factors are slightly different for perimenopausal osteoporotic than for other types of fractures. Received: 6 April 1999 / Accepted: 18 August 1999     

Health Impact Associated with Vertebral Deformities: Results from the European Vertebral Osteoporosis Study (EVOS)

To study the association between vertebral deformities and subjective health outcome indicators, including back pain and disability, a cross-sectional survey with spinal radiographs and personal interviews was carried out in 36 study centres in 19 European countries on a total of 15570 men and women aged 50–79 years (population-based stratified random samples). No interventions were done. The main outcome measures were the presence and intensity of current and previous back pain, functional capacity (ADL questionnaire) and overall subjective health. The presence and intensity of back pain and functional and health impairments varied within wide ranges with no obvious regional pattern. However, the associations between negative health outcomes and vertebral deformity were homogeneous between countries and between centres within countries. In logistic regression analyses weak but significant associations between the presence of vertebral deformities and various health indicators were demonstrated. The magnitude of the associations increased with severity and number of deformities. Compared with subjects without deformities those with low-grade deformities had no or only a weakly elevated risk for back pain, disability and impaired subjective health (odds ratios (OR) 1.2–1.3). The odds ratios increased for individuals with single severe deformities (OR 1.3–2.1) and were highest in those with multiple severe deformities (OR 1.7–4.2). The associations between vertebral deformities and negative health outcomes were stronger in men than in women. In this cross-sectional study radiologically assessed vertebral deformities were therefore weakly associated with both current and previous back pain as well as with functional and health impairments in both women and men. Multiple severe deformities were associated with severe and disabling back pain with stronger effects in men. Received: 27 December1997 / Accepted: 31 December 1997     

The Influence of Osteoporotic Fractures on Health-Related Quality of Life in Community-Dwelling Men and Women across Canada

Health-related quality of life (HRQL) was examined in relation to prevalent fractures in 4816 community-dwelling Canadian men and women 50 years and older participating in the Canadian Multicentre Osteoporosis Study (CaMos). Fractures were of three categories: clinically recognized main fractures, subclinical vertebral fractures and fractures at other sites. Main fractures were divided and analyzed at the hip, spine, wrist/forearm, pelvis and rib sites. Baseline assessments of anthropometric data, medical history, therapeutic drug use, spinal radiographs and prevalent fractures were obtained from all participants. The SF-36 instrument was used as a tool to measure HRQL. A total of 652 (13.5%) main fractures were reported. Results indicated that hip, spine, wrist/forearm, pelvis and rib fractures had occurred in 78 (1.6%), 40 (0.8%), 390 (8.1%), 19 (0.4%) and 125 (2.6%) individuals, respectively (subjects may have had more than one main fracture). Subjects who had experienced a main prevalent fracture had lower HRQL scores compared with non-fractured participants. The largest differences were observed in the physical functioning (−4.0; 95% confidence intervals (CI): −6.0, −2.0) and role-physical functioning domains (−5.8; 95% CI: −9.5, −2.2). In women, the physical functioning domain was most influenced by hip (−14.9%; 95% CI: −20.9, −9.0) and pelvis (−18.1; 95% CI: −27.6, −8.6) fractures. In men, the role-physical domain was most affected by hip fractures (−35.7; 95% CI: −60.4, −11.1). Subjects who experienced subclinical vertebral fractures had lower HRQL scores than those without prevalent fractures. In conclusion, HRQL was lower in the physical functioning domain in women and the role-physical domain in men who sustained main fractures at the hip. Subclinical vertebral fractures exerted a moderate effect on HRQL. Received: 1 November 2000 / Accepted: 23 March 2001     

Characteristics of Falls and Risk of Hip Fracture in Elderly Men

The steep rise in hip fracture incidence rates with age is not fully explained by an increase in the frequency of falls or by reduction in bone mineral density, suggesting that circumstances of falls may also affect the risk of hip fracture. Previous studies conducted mainly among women have identified the importance of the orientation of a fall in the etiology of hip fracture. In this case–control study among men of 45 years and older, we evaluated how the circumstances of falls affect the risk of hip fracture. We compared 214 cases with hip fracture due to a fall with 86 controls who had fallen within the past year but did not sustain a hip fracture. As expected, in multivariable age-adjusted analyses men who reported hitting the hip/thigh in a fall had a markedly elevated risk of hip fracture (OR = 97.8; 95% CI = 31.7–302). Hitting the knee in a fall was associated with reduced risk (OR = 0.24; 95% CI = 0.09–0.67). Other factors that were associated with reduced risk of hip fracture among men who fell were more hours of physical activity in the past year (OR = 0.84; 95% CI = 0.73–0.97, for each additional 4 h per week), a greater body mass index (OR = 0.60; 95% CI = 0.40–0.90, for each additional 4 kg/m²), and a history of a fracture when age 45 years or older (OR = 0.26; 95% CI = 0.10–0.69). Reported lower limb dysfunction was associated with increased risk of hip fracture (OR = 6.41; 95% CI = 2.09–19.6) among fallers. The increased risk associated with hitting the hip/thigh in a fall and the reduced risk associated with high body mass index suggest that preventive efforts for older men at high risk might include protective hip pads to reduce the force on the hip in a fall. Exercise and strength training programs may also reduce the risk of hip fracture among men who fall. Received: 12 May 1997 / Accepted: 14 October 1997     

Influence of Age and Sex on Vertebral Shape Indices Assessed by Radiographic Morphometry

Vertebral shape indices (VSI) assessed by radiographic morphometry are currently used to define vertebral fractures in clinical trials and epidemiologic studies on osteoporosis. However, there is little information concerning the influence of sex or age on VSI. Furthermore, previous reports on the variation of VSI with age showed conflicting results. The aim of this study was to assess the influence of sex and age on VSI in order to better define reference values for the clinical and epidemiologic evaluation of vertebral osteoporotic fractures. Measurements were performed on thoracic and lumbar spine radiographs from 50 men and 50 women (age range 25–75 years) without evidence of osteoporotic, degenerative or other disease-related vertebral deformity. The anterior (AH), middle (MH) and posterior (PH) heights of each vertebral body from T4 to L5 were measured and VSI were calculated as follows: wedging = (AH minus PH) divided by PH; concavity = (MH minus PH) divided by PH. Wedging and concavity, especially at the mid and lower thoracic spine, increased significantly with age in both sexes. We also demonstrated that VSI at the lumbar spine were significantly dependent on gender, with greater values of wedging and concavity in men than in women. Consequently, reference values used for the definition of vertebral osteoporotic fractures assessed by radiographic morphometry should take into account both sex and age effects. Received: 15 October 1998 / Accepted: 18 May 1999     

Effects of Raloxifene on Fracture Severity in Postmenopausal Women with Osteoporosis: Results from the MORE Study

Raloxifene reduces the risk of new vertebral fractures, but its effect on the severity of these new fractures has not been determined. The MORE (Multiple Outcomes of Raloxifene Evaluation) trial studied the effects of placebo, raloxifene 60 or 120 mg/day in 7705 postmenopausal women with osteoporosis. Radiologists assessed new vertebral fractures from radiographs and graded the fracture severity as normal (no fracture) or mild, moderate or severe. New clinical vertebral fractures were defined as new vertebral fractures associated with symptoms, such as back pain, and confirmed in radiographs. In the total study population, the majority (76.4%) of the women who experienced clinical vertebral fractures were diagnosed with new moderate/severe vertebral fractures. In turn, women with moderate/severe vertebral fractures in the overall population were more likely to experience clinical symptoms suggestive of fracture than were women who had new mild-only vertebral fractures. The incidence of new mild-only and moderate/severe fractures was the same in women without prevalent vertebral fractures, but the incidence of new moderate/severe fractures was 2 to 3 times higher than that for new mild-only fractures in women with prevalent vertebral fractures. Raloxifene 60 mg/day decreased the risk of at least 1 new moderate/severe vertebral fracture by 61% in women without prevalent vertebral fractures [RR 0.39 (95% CI 0.17, 0.69)], and by 37% in women with prevalent vertebral fractures [RR 0.63 (95% CI 0.49, 0.83)] at 3 years. The risk reductions for at least 1 new moderate/severe vertebral fracture were not significantly different between the raloxifene doses, in women with and without prevalent vertebral fractures. The effects of raloxifene on significantly decreasing the risk of new moderate/severe vertebral fractures may explain the risk reduction for new painful clinical vertebral fractures observed with raloxifene, and is particularly important in postmenopausal women with severe osteoporosis who are at higher risk for moderate or severe fractures. Received: 11 April 2002 / Accepted: 19 June 2002 Correspondence and offprint requests to: Ethel Siris, MD, Toni Stabile Osteoporosis Center, Department of Medicine, College of Physicians and Surgeons, Columbia University, 180 Fort Washington Ave, New York, NY 10032, USA. Tel: +1 (212) 305 2529. Fax: +1 (212) 305 6482. e-mail: es27@columbia.edu