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     

Prevalence of Vertebral Fractures in Chinese Men and Women in Urban Taiwanese Communities

Reports on the prevalence (or incidence) rates of vertebral fracture have been available, but they are limited concerning non-white populations and men of all races. This study used the radiomorphometric method to survey the prevalence rate of vertebral fracture for ethnic Chinese women 40 years and older and Chinese men 65 and older who were randomly selected from four major cities in Taiwan. Three sets of reference values of the height ratios were used for middle-aged women, elderly women, and elderly men. The results showed that in Chinese women, the prevalence rate of vertebral fracture was low before age 50 and showed a steady increase thereafter. In men, the increase was small until age 80. The overall adjusted prevalence rate of vertebral fracture for women older than 65 was 20% and that for men, 12.5% (95% confidence interval 18–22% and 11–14%, respectively.) If only severe deformity was counted [height ratio lower than normal mean minus 4 standard deviations (SD), or Grade II deformity], the adjusted prevalence rate was 15.5% for elderly women and 9.5% for elderly men (95% confidence interval 14–17%, and 8–11%, respectively.) The overall adjusted prevalence rate for women aged 40 and over was 6.8% (95% confidence interval 5.7–8%), or 4.5% (95% confidence interval 3.6–5.5%) for Grade II lesions. Moreover, for subjects with fracture, elderly women tended to have more fractured vertebrae per person and more Grade II fractures than elderly men. Thus, Chinese women residing in cities of Taiwan had a relatively high prevalence rate of vertebral fracture, a finding compatible with that for United States or European white women, or for Japanese women residing in America. Elderly Chinese men also have a high prevalence rate of vertebral fracture. The age-specific female-to-male ratio of prevalence rate was about 1.5 to 2.3 between age 65 and 80, and close to unity after age 80. Received: 10 August 1995 / Accepted: 13 February 1996     

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     

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     

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     

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     

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     

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     

The relationship between phalangeal bone density and vertebral deformities

Radiographic absorptiometry (RA) of the phalanges is a convenient and reliable technique for measuring bone mineral density (BMD). It needs only a radiograph of the hand, which can be sent for evaluation to a central facility, whereas other techniques require specialized equipment. We assessed the relationship between RA measurements and the presence of vertebral deformities in a population-based cohort of postmenopausal women, and to compare the results with simultaneously obtained BMD of the hip by dual-energy X-ray absorptiometry (DXA). A total of 389 women aged 55–84 (mean age 67.2 years, SD 8.7) were randomly selected from a large general practice. RA, DXA of the hip, and vertebral deformities in the lateral spine X-rays by vertebral morphometry were assessed. Thirty-eight women (9.8%) had severe (grade II) vertebral deformities, and their BMD at the phalanges and femoral neck was significantly lower than that of women without severe vertebral deformities. Odds ratios for the presence of severe vertebral deformities of 1.5 (95% CI: 1.1–2.1) for RA and 1.3 (95% CI: 0.9–1.9) for DXA, together with similar receiver operating characteristics curves, were found using age-adjusted logistic regression. Phalangeal BMD is related to vertebral deformities at least as closely as BMD of the femoral neck BMD. RA may therefore help to evaluate fracture risk, especially if no DXA equipment is available. Received: 21 July 1998 / Accepted: 1 July 1999     

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     

A Single Bone Density Measurement Can Predict Fractures Over 25 Years

The purpose of the present study was to determine the predictive ability of a single bone mineral density (BMD) measurement on a 25-year perspective. A group of 1076 women (age 20–78 years) had had their forearm BMD measured from 1970 to 1975. In those women that were still alive at the end of 1994 (n = 410), all fragility fractures (distal end of the radius, proximal end of the humerus, hip, and vertebra) that had occurred after the BMD measurement and that were roentgen verified were recorded, after a follow-up time of 20–25 years. Altogether, 213 fractures occurred in the cohort. In the age group ≥40–70 (at time of BMD measurement) the relative risk (RR) associated with a 1 SD decrease of forearm BMD was 1.66 (CI 1.13–2.46) for a hip fracture (n = 43), 1.79 (CI 1.22–2.62) for a vertebral fracture (n = 63), and 1.33 (CI 1.20–1.73) for all fractures. In the age group 30–50, a fracture of the distal end of the radius after 20 years could be predicted; RR 1.90 (CI 1.02–3.55). These are slightly lower predictive values compared with previous studies of the same population with follow-up times of 11 and 13 years, especially with regard to hip fractures. However, the present study demonstrates that a single BMD measurement at the forearm has a predictive ability for fragility fractures—including hip fractures—on a 25-year perspective. Received: 13 March 1996 / Accepted: 19 July 1996     

Forearm Fractures as Predictors of Subsequent Osteoporotic Fractures

To assess the ability of distal forearm fractures to predict future fractures, we conducted a population-based retrospective cohort study among the 1288 residents (243 men, 1045 women) of Rochester, Minnesota age 35 years or older who experienced their first distal forearm fracture in 1975–94. During 9664 person-years of follow-up, 548 patients experienced 1109 subsequent fractures, excluding 195 that occurred on the same day as the index forearm fracture. The cumulative incidence of any subsequent fracture was 55% by 10 years and 80% by 20 years following the initial distal forearm fracture. Compared to expected fracture rates in the community, the risk of a hip fracture following the index forearm fracture was increased 1.4-fold in women (95% CI, 1.1–1.8) and 2.7-fold in men (95% CI, 0.98–5.8). In women, the risk of hip fracture differed by age, as we had found in a previous study. Women over age 70 had a 1.6-fold increase (95% CI, 1.2–2.0) in subsequent hip fracture risk whereas women who sustained their first forearm fracture before age 70 years did not have significantly increased risk. By contrast, vertebral fractures were significantly increased at all ages, with a 5.2-fold increase (95% CI, 4.5–5.9) in risk among women and a 10.7-fold increase (95% CI, 6.7–16.3) among men following a first distal forearm fracture. The increased risk in men suggests that a sentinel forearm fracture should not be ignored. Among the women, we also found a missed opportunity for intervention as hormone replacement therapy was underutilized. Received: 8 May 1998 / Accepted: 16 October 1998     

Public Perceptions and Self-Reported Prevalence of Osteoporosis in South Australia

The self-reported prevalence of, and attitudes to and perceptions of, osteoporosis in the South Australian community were assessed using data collected as part of the 1995 South Australian Health Omnibus Survey (household interviews) – a clustered, self-weighting, multistage sample of households in metropolitan and country centers. The self-reported prevalence was 4.8 (95% CI: 3.7–5.8) and 1.4% (95% CI: 0.8–2.0) for women (n= 1531) and men (n= 1485) respectively. For individuals with osteoporosis, calcium was the favored treatment (52%), while 33% of women were on hormone replacement therapy. An appropriate definition of osteoporosis was given by 62% of women and 37% of men. The main risk factors were reported as lack of calcium and age. There was a significant association between knowledge of the definition of osteoporosis and identification of correct risk factors. A high perceived risk of osteoporosis was reported in 23% of women and 7% of men. Osteoporosis risk was assessed as higher in those who did not adopt recognized prevention measures. Perception of risk was not related to the individual's own risk factors. Self-reported prevalence of osteoporosis significantly underestimates the likely true prevalence and general awareness and knowledge is much lower for men than women. The importance of individual risk factors for osteoporosis are not understood by the general community. Received: 12 August 1997 / Revised: 18 February 1998     

Sodium Fluoride Treatment is a Major Protector Against Vertebral and Nonvertebral Fractures When Compared with Other Common Treatments of Osteoporosis: A Longitudinal,Observational Study

In a 5-year observational study we have compared sodium fluoride (NaF) with different treatments commonly used in the treatment of osteoporosis: calcium, estrogens, androgens, and calcitonin, referred to as non-NaF. We have looked at the incidence of vertebral and nonvertebral fractures. At baseline, the NaF group, consisting of 125 patients (89% females) aged 65 ± 10 (X ± SE) had more crush fractures (P < 0.0001) and more months since menopause (P= 0.004) than the non-NaF group, consisting of 127 patients (90% females) aged 63 ± 10. Fractures were evaluated by X-ray. The entire follow-up of patients treated with NaF accounted for 361 person-years, of whom 43 patients suffered one or more new vertebral fractures (68 vertebral fractures in total) and 18 patients suffered one or more new nonvertebral fractures (22 complete peripheral fractures in total); follow-up of patients treated with non-NaF regimes accounted for 382 person-years, of whom 53 patients suffered one or more new vertebral fractures (69 vertebral fractures in total) and 20 patients suffered one or more new nonvertebral fractures (27 complete peripheral fractures in total). After adjusting for significant covariates at baseline, NaF proved to be a significant protector for vertebral fractures [odds ratio (OR) 0.48, 95% confidence interval (CI) 0.2–0.9], and for peripheral fractures (OR 0.41, 95% CI 0.2–0.9). On the other hand, the probability of suffering undesired effects was much higher with NaF treatment (OR 5.04, 95% CI 2.1–11.9). We conclude that in the treatment of osteoporosis, NaF has a protective effect against vertebral and nonvertebral fractures, does not increase the risk of femoral fractures, but has a higher incidence of untoward symptomatology. Received: 25 September 1995 / Accepted: 23 September 1996     

Timed Loaded Standing: A Measure of Combined Trunk and Arm Endurance Suitable for People with Vertebral Osteoporosis

Chronic back tiredness or fatigue is a common complaint of people who have a history of osteoporotic vertebral fracture. Trunk muscle endurance has not been studied in people with vertebral osteoporosis, partly due to the lack of assessment tools. We developed a measure of combined trunk and arm endurance suitable for people with vertebral osteoporosis, timed loaded standing (TLS). TLS measures the time a person can stand while holding a two-pound dumbbell in each hand with the arms at 90° of shoulder flexion and the elbows extended. Intraclass correlation coefficients (ICCs) for same day inter-trial and six to ten day test-retest reliability were 0.89 (lower bound 95% confidence interval [LB 95% CI] 0.79) and 0.84 (LB 95% CI 0.68), respectively, in a sample of 21 older women with no known osteoporosis. In 127 women with vertebral fractures, the ICC for same day inter-trial reliability was 0.81 (LB 95% CI 0.75). In a sub-sample of 30 of these women with vertebral fractures, the six to ten day test-retest reliability was 0.85 (LB 95% CI 0.75). Moderately strong and statistically significant (p≤0.05) correlations were found between TLS and sixteen of eighteen measures of physical impairment and function. Functional reach distance, gait velocity, MOS-36 Physical Function Subscale, shoulder flexion strength, and six minute walk distance were most strongly associated with TLS time. Women with vertebral fractures who endorsed having back tiredness when standing and working with the arms in front of the body, sitting to rest because of back tiredness or pain, and planning rest periods because of back tiredness or pain had significantly lower TLS times. TLS is a simple, safe physical performance measure of combined trunk and arm endurance that demonstrates acceptable reliability (inter-trial and test- retest) and concurrent validity. Received: 27 October 1999 / Accepted: 4 April 2000     

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     

Symptomatic Fracture Incidence in Southern Tasmania: Does Living in the Country Reduce Your Fracture Risk?

There are limited data describing urban–rural differences in fracture incidence and the overall effect remains controversial. The aim of this study was to compare symptomatic fracture incidence occurring in geographically defined rural (n= 34 619) and urban (n = 194 974) populations of Southern Tasmania from July 1, 1997 to June 30, 1999. Fractures were ascertained by reviewing reports from all the radiology providers within the area. In the 2-year study time frame there were 3644 fractures in males and 2657 fractures in females. Fracture incidence was significantly higher in urban compared with rural populations in both sexes (male: RR 1.60, 95% CI 1.47–1.75; female: RR 1.77, 95% CI 1.58–1.98). This higher urban fracture incidence was present across all age groups and all fracture types with the exception of knee and pelvis fractures in males (although not all were statistically significant). In addition, urban men >50 years old had a higher fracture incidence than rural women >50 years old (RR 1.25, 95% CI 1.05–1.50), suggesting that in later life the factors responsible for the urban–rural difference are able to offset completely the effect of gender. While some of the reduced fracture incidence in the rural population may be explained by urban drift and underreporting of minor fractures such as foot fractures, the overall pattern of higher fracture risk was very consistent, suggesting a real difference in whole-of-life symptomatic fracture incidence. Further research at an individual level is required to determine what factors account for these large urban–rural differences, as they imply a substantial potential for fracture prevention. Received: 28 November 2001 / Accepted: 5 April 2001     

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.     

Vitamin D Binding Protein Gene in Male Osteoporosis: Association of Plasma DBP and Bone Mineral Density with (TAAA)n-Alu Polymorphism in DBP

Vitamin D binding protein (DBP) is a major carrier protein for the vitamin D metabolites, but may also play an important role in osteoclast differentiation. Polymorphisms of the DBP gene have been reported, including (TAAA)_n-Alu repeat polymorphisms downstream of intron 8. We have examined the relationship between polymorphisms of the DBP gene and bone mineral density (BMD) and vertebral fractures in a group of 26 men with vertebral fractures but no underlying secondary cause of osteoporosis (median age 64, ages 27–72 years) and 21 male control subjects (median age 65, ages 40–77 years). There was no apparent effect of DBP phenotype on BMD, but there was a relationship between certain genotypes of (TAAA)_n-Alu repeats and reduced BMD and vertebral fracture. Lumbar spine and femoral neck BMD were significantly lower in men with 10/8 genotype than 10/10 genotype (P < 0.05). Furthermore, the predominant genotype in men with vertebral fractures was 10/8, whereas the most common genotype in control subjects was 10/10 (odds ratio 56; 95% confidence interval 7–445). Plasma DBP was higher in men with 10/8 genotype than those with 10/10 genotype (P < 0.05), and patients with vertebral fractures were found to have higher levels than control subjects (P < 0.0005). Although our study is small because of the relative rarity of idiopathic osteoporosis in men, the results suggest that (TAAA)_n-Alu polymorphism may have an important effect on plasma levels of DBP, bone density and fracture risk in men. Received: 5 May 1998 / Accepted: 10 April 1999