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     

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     

FDG-PET Findings of Vertebral Compression Fractures in Osteoporosis: Preliminary Results

The aim of this study was to evaluate FDG-PET findings in patients with osteoporosis or preclinical osteoporosis and acute vertebral compression fractures in order to determine whether FDG-PET has a value for distinction of pathological from osteoporotic vertebral fractures. 17 patients with a spontaneous compression fracture of the spine were evaluated by bone scanning with Tc-99m HDP, positron emission tomography with fluorine-18 deoxyglucose (FDG-PET) and magnetic resonance imaging (MRI). Osteoporosis had been established in all cases by X-ray and osteodensitometry. PET and bone scan images were scored independently from 0 (no pathological uptake) to 4 (definitive pathological uptake) by two blinded nuclear medicine physicians. The results of the blinded scoring were compared to MRI findings which served as gold standard. In 13 out of 17 patients, MRI demonstrated a vertebral fracture generating from osteoporosis. In 12 of these 13 cases, PET scans were scored with 0 or 1 and categorized as true negative. Standard uptake values (SUV) ranged between 1.1 and 2.4. In one of the 13 patients, PET was interpreted false positive with an uptake score of 3 (SUV = 2.9). Of the 17 patients, MRI revealed a pathological fracture caused by spondylodiscitis in three patients and by plasmacytoma in one patient. In these patients, all PET scans were highly positive with a score of 3 and 4 and SUV values between 3.8 to 9.8. The bone scans of all 17 patients were positive with scores of 3 or 4 but a differentiation between osteoporotic and pathological fractures was not possible. Our preliminary results indicate that acute vertebral fractures that originated from osteoporosis or preclinical osteoporosis tend to have no pathologically increased FDG uptake. Since a high FDG uptake is characteristic for malignant and inflammatory processes, use of FDG-PET may have potential value for differentiation between osteoporotic and pathological vertebral fractures. Received: 18 October 2001 / Accepted: 25 April 2002     

Acute and Long-Term Increase in Fracture Risk after Hospitalization for Vertebral Fracture

The aims of this study were to determine the magnitude of the increase in risk of further fracture following hospitalization for vertebral fracture, and in particular to determine the time course of this risk. The records of the Swedish Patient Register were examined from 1987 to 1994 to identify all patients who were admitted to hospital for thoracic or lumbar vertebral fractures. Vertebral fractures were characterized as due to high- or low-energy trauma. Patients were followed for subsequent hospitalizations for hip fracture, and for all fractures combined. A Poisson model was used to determine the absolute risk of subsequent nonvertebral fracture and compared with that of the general population. We analyzed 13.4 million hospital admissions from which 28.869 individuals with vertebral fracture were identified, of which 60% were associated with low-energy trauma. There was a marked increase in subsequent incidence of hip and all fractures within the first year following hospitalization for vertebral fracture in both men and women. Thereafter, fracture incidence declined toward, but did not attain, baseline risk. Increased risks were particularly marked in the young. The increase in fracture risk was more marked following low-energy vertebral fracture than in the case of high-eneergy trauma. We conclude that the high incidence of new fractures within a year of hospitalization for vertebral fractures, irrespective of the degree of trauma involved, indicates that such patients should be preferentially targeted for treatment. It is speculated that short courses of treatment at the time of first vertebral fracture could provide important therapeutic dividends. Received: 6 June 2000 / Accepted: 28 September 2000     

Comparison of Four Morphometric Definitions and a Semiquantitative Consensus Reading for Assessing Prevalent Vertebral Fractures

The assessment of vertebral fracture in patients with osteoporosis by conventional radiography has been improved over the past 10 years using either the semiquantitative (SQ) method devised by Genant et al. or quantitative morphometry. However, there is still no internationally agreed definition for vertebral fracture and there have been few comparative studies between these different approaches. Our study assessed the reproducibility of the SQ method and of four commonly used morphometric algorithms (Melton’s, Eastell’s, Minne’s and McCloskey’s methods) for assessing prevalent vertebral fractures, and examined the agreement of each morphometric algorithm with a SQ consensus reading performed by three experts. With this consensus reading in place of a gold standard, we determined relative measures of sensitivity, specificity and optimal cutoff threshold for each morphometric algorithm. The study was conducted in 39 postmenopausal women who had at least one osteoporotic vertebral fracture. Normal values were derived from 84 healthy postmenopausal women with apparently normal vertebral bodies. Our results indicate that the concordance of SQ method was excellent (intraobserver agreement on serial radiographs = 96.4%, κ= 0.91; agreement between individual readings and the consensus reading = 98%, κ= 0.95). Three morphometric approaches demonstrated good intra- and interobserver concordance (Melton: intraobserver agreement on serial radiographs = 92.7%, κ= 0.82, interobserver agreement = 91.1%, κ= 0.79; Eastell: intraobserver agreement on serial radiographs = 87.6%, κ= 0.66, interobserver agreement = 88.6%, κ= 0.68; McCloskey: intraobserver agreement on serial radiographs = 91.5%, κ= 0.72, interobserver agreement = 93.9%, κ= 0.78). Except for McCloskey’s method, the optimal cutoff thresholds defined in our study by highest κ score or Youden index in comparison with the SQ consensus reading were near the cutoff thresholds that were arbitrarily fixed. The four morphometric algorithms provided a good agreement with the results of the SQ consensus reading, but the more complex algorithm did not provide better results and even if we adjusted the cutoff threshold, no morphometric algorithm agreed perfectly with the SQ consensus reading. We conclude that morphometric approaches currently used should not be employed alone to detect prevalent vertebral fractures in studies on osteoporosis, but should rather be used in combination with a visual assessment. The SQ approach that allows differential diagnosis of vertebral deformities and has demonstrated a better reproducibility can be employed alone when it is performed by experienced and well-trained readers. Received: 3 July 2000 / Accepted: 26 March 2001     

Stiffness in Discrimination of Patients with Vertebral Fractures

We measured the ultrasound parameters of the heels of 49 women with vertebral fractures and 87 age-matched controls using an Achilles ultrasound device. Average broadband ultrasound attenuation (BUA), speed of sound (SOS) and Stiffness were significantly lower in fracture patients (p<0.0001). We also estimated the ultrasound parameters of patients compared with age-matched non-fracture controls and found the mean BUA to be −1.02 SD below control values. The mean SOS was −0.97 SD and the mean Stiffness was −1.12 SD below control values.  Femoral bone mineral density (BMD) at the neck, Ward’s triangle and the trochanter, the total-body BMD and L2–4 BMD were measured with dual-energy X-ray absorptiometry (DXA) and found to be significantly lower in fracture patients (p<0.0001). All correlation coefficients between ultrasound parameters and DXA measurements were >0.5 and statistically significant (p<0.0001). A stepwise logistic regression with presence or absence of vertebral fracture as the response variable and all ultrasound – DXA parameters as the explanatory variables indicated that the best predictor of fracture was Stiffness, with additional predictive ability provided by spine BMD. Sensitivity and specificity of all measures were determined by the areas under the receiver operating characteristic (ROC) curve, which were 0.76 ± 0.04 for BUA, 0.77 ± 0.04 for SOS, 0.78 ± 0.04 for Stiffness and 0.78 ± 0.03 for spine BMD. The areas under the ROC curves of BUA, SOS, Stiffness and spine BMD were compared and it was found that Stiffness and spine BMD were significantly better predictors of fracture than BUA and SOS. These results support many recent studies showing that ultrasound measurements of the os-calcis have diagnostic sensitivity comparable to DXA, and also demonstrated that Stiffness was a better predictor of fracture than spine BMD. Received: 23 September 1997 / Accepted: 10 April 1998     

Digital X-ray Radiogrammetry Predicts Hip,Wrist and Vertebral Fracture Risk in Elderly Women: A Prospective Analysis from the Study of Osteoporotic Fractures

Digital X-ray radiogrammetry (DXR) is a technique that uses automated image analysis of standard hand radiographs to estimate bone mineral density (DXR-BMD). Previous studies have shown that DXR-BMD measurements have high precision, are strongly correlated with forearm BMD and are lower in individuals with prevalent fractures. To determine whether DXR-BMD measurements predict wrist, hip and vertebral fracture risk we conducted a case–cohort study within a prospective study of 9704 community-dwelling elderly women (the Study of Osteoporotic Fractures). We compared DXR-BMD, and BMD of the radius (proximal and distal), calcaneus, femoral neck and posteroanterior lumbar spine in women who subsequently suffered a wrist (n= 192), hip (n= 195), or vertebral fracture (n= 193) with randomly selected controls from the same cohort (n= 392–398). DXR-BMD was estimated from hand radiographs acquired at the baseline visit. The radiographs were digitized and the Pronosco X-posure System was used to compute DXR-BMD from the second through fourth metacarpals. Wrist fractures were confirmed by radiographic reports and hip fractures were confirmed by radiographs. Vertebral fractures were defined using morphometric analysis of lateral spine radiographs acquired at baseline and an average of 3.7 years later. Age-adjusted odds ratio (OR, vertebral fracture) or relative hazard (RH, wrist and hip fracture) for a 1 SD decrease in BMD were computed. All BMD measurements were similar for prediction of wrist (RH = 1.5–2.1) and vertebral fracture (OR = 1.8–2.5). Femoral neck BMD best predicted hip fracture (RH = 3.0), while the relative hazards for all other BMD measurements were similar (RH = 1.5–1.9). These prospective data indicate that DXR-BMD performs as well as other peripheral BMD measurements for prediction of wrist, hip and vertebral fractures. Therefore, DXR-BMD may be useful for prediction of fracture risk in clinical settings where hip BMD is not available. Received: 27 April 2001 / Accepted: 10 October 2001     

Treatment of Painful Osteoporotic Vertebral Fractures with Percutaneous Vertebroplasty or Kyphoplasty

Vertebral fracture is the most common complication of osteoporosis. It results in significant mortality and morbidity, including prolonged and intractable pain in a minority of patients. Vertebroplasty and kyphoplasty, procedures that involve percutaneous injection of bone cement into a collapsed vertebra, have recently been introduced for treatment of osteoporotic patients who have prolonged pain (several weeks or longer) following vertebral fracture. To determine the details of the procedures and to gather information on their safety and efficacy, we performed a MEDLINE search using the terms “vertebroplasty” and “kyphoplasty.” We reviewed reports of these procedures in patients with osteoporosis. We supplemented the articles found with other papers known to the authors and with presentations at national meetings. Randomized trials of vertebroplasty and kyphoplasty have not been reported. Case reports suggest that these procedures are associated with pain relief in 67% to 100% of cases. Short-term complications, mainly the result of extravasation of cement, include increased pain and damage from heat or pressure to the spinal cord or nerve roots. Proper patient selection and good technique should minimize complications, but rarely, decompressive surgery is needed. Long-term benefits have not yet been shown, but potentially include prevention of recurrent pain at the treated level(s) with both procedures, and, with kyphoplasty, reversal of height loss and spinal deformity, an improved level of function, and avoidance of chronic pain and restriction of internal organs. Possible long-term complications, again not fully evaluated, include local acceleration of bone resorption caused by the treatment itself or by foreign-body reaction at the cement–bone interface, and increased risk of fracture in treated or adjacent vertebrae through changes in mechanical forces. Controlled trials are needed to determine both short-term and long-term safety and efficacy of vertebroplasty and kyphoplasty. Both procedures may be useful for osteoporotic patients who have prolonged pain following acute vertebral fracture. Until there is conclusive evidence for efficacy and long-term safety, these procedures should be done only in carefully selected patients, only by experienced operators with appropriate high-quality imaging equipment, and ideally at centers that are participating in controlled trials. Received: 26 January 2001 / Accepted: 21 February 2001     

Lengthy Hospitalization Associated with Vertebral Fractures Despite Control for Comorbid Conditions

This study established whether length of hospital stay (LOS) in Canadians 50 years and older is attributable to their vertebral fractures versus comorbid conditions. The study used a case–control design and data in the Canadian Institute for Health Information (CIHI) database on hospital discharges in Ontario, Alberta, and British Columbia between April 1, 1996 and March 31, 1997. Patients with vertebral fractures were identified by International Classification of Diseases (ICD-9) codes. LOS constituted the dependent measure in a multivariate linear regression that calculated the independent contributions to LOS by vertebral fractures while controlling for: age, gender, province, discharged deceased, hip fractures, all other fractures, motor vehicle accidents, all other injuries, and the major disorder classifications in ICD-9. Mean LOS for all patients admitted for vertebral fractures was 10.1 days. LOS attributed solely to vertebral fractures was 4.8 days based on a 50-year-old woman with no comorbid conditions, and 6.1 days based on a 75-year-old woman. Of 18 health conditions, vertebral fractures were among the top 3 in accounting for LOS, along with hip fractures and mental disorders which accounted for 5.9 days and 6.1 days in a 50-year-old woman. Among patients admitted for other problems, comorbid vertebral fractures added 2.1 days. These findings indicate that hospital stays for vertebral fractures are lengthy despite control for comorbidity. Received: 12 December 2000 / Accepted: 23 April 2001     

Recognition of Vertebral Fracture in a Clinical Setting

Osteoporosis-related vertebral fractures have important health consequences for older individuals, including disability and increased mortality. Because these fractures can be prevented with appropriate medications, recognition and treatment of high-risk patients is warranted. A cross-sectional survey was carried out in a large, regional hospital in New England to examine the frequency with which vertebral fractures are identified and treated by clinicians in a population of hospitalized older women who have radiographic evidence of fractures. The study population consisted of 934 women aged 60 years and older who were hospitalized between October 1, 1995 and March 31, 1997, and who had a chest radiograph obtained. Vertebral fractures in the thoracic region were identified by two radiologists. Discharge diagnoses, medical record notes and radiology reports were compared with the results of the radiologists’ readings to determine the frequency with which fractures were identified and appropriate, osteoporosis-preventing medications prescribed. Moderate or severe vertebral fractures were identified for 132 (14.1%) study subjects, but only 17 (1.8%) of the 934 participants had a discharge diagnosis of vertebral fracture. Of these 132, only 17% had fracture noted in the medical record or discharge summary; 50% of contemporaneous radiology reports identified a fracture as present; and 23% of the time it was found in the radiologist’s summary impression. Only 18% of medical records indicated that fracture patients had been prescribed calcium, vitamin D, estrogen replacement or an antiresorptive agent. Relatively few hospitalized older women with radiographically demonstrated vertebral fractures were thus identified or treated by clinicians, suggesting a need for improved recognition. Received: 15 November 1999 / Accepted: 23 December 1999     

Costs Induced by Hip Fractures: A Prospective Controlled Study in Belgium

The economic burden of hip fractures is thought to be important, but the excess medical costs they induce remain largely unknown. We assessed the direct medical costs induced by hip fractures during and after hospitalization. Hospital costs of 170 consecutive Belgian women with hip fracture were gathered. During the year following discharge, all medical costs were collected for the 159 hip fracture women who survived the acute hospitalization stay. A similar collection of data was performed on a comparison group of 159 age-and residence-matched women without a history of hip fracture. The mean cost of the acute hospital stay was C8667, and the mean 1-year hip-fracture-related extra costs after hospitalization was C6636. During the year following the acute hospital stay, 19% of the hip fracture women and 4% of the comparison women were newly admitted to nursing homes (p<0.001). Although health care costs increased with age, hip-fracture-related extra costs after hospitalization seemed similar in those below or above 81 years old. These extra costs amounted to C7710 in women not living in nursing homes at the time of fracture, and to C3479 in women who lived in nursing homes. Health or mental status before hip fracture seemed not to affect extra costs. Taking into account the higher mortality of women with hip fracture, the extra costs during the acute hospital stay and during the 1-year follow-up amounted to a mean C 15151. In conclusion, both acute hospital stays and subsequent medical care contribute significantly to medical costs induced by hip fractures. Received: 12 April 1999 / Accepted: 9 November 1999     

Randomized Trial of the Effects of Risedronate on Vertebral Fractures in Women with Established Postmenopausal Osteoporosis

The purpose of this randomized, double-masked, placebo-controlled study was to determine the efficacy and safety of risedronate in the prevention of vertebral fractures in postmenopausal women with established osteoporosis. The study was conducted at 80 study centers in Europe and Australia. Postmenopausal women (n= 1226) with two or more prevalent vertebral fractures received risedronate 2.5 or 5 mg/day or placebo; all subjects also received elemental calcium 1000 mg/day, and up to 500 IU/day vitamin D if baseline levels were low. The study duration was 3 years; however, the 2.5 mg group was discontinued by protocol amendment after 2 years. Lateral spinal radiographs were taken annually for assessment of vertebral fractures, and bone mineral density was measured by dual-energy X-ray absorptiometry at 6-month intervals. Risedronate 5 mg reduced the risk of new vertebral fractures by 49% over 3 years compared with control (p<0.001). A significant reduction of 61% was seen within the first year (p= 0.001). The fracture reduction with risedronate 2.5 mg was similar to that in the 5 mg group over 2 years. The risk of nonvertebral fractures was reduced by 33% compared with control over 3 years (p= 0.06). Risedronate significantly increased bone mineral density at the spine and hip within 6 months. The adverse-event profile of risedronate, including gastrointestinal adverse events, was similar to that of control. Risedronate 5 mg provides effective and well-tolerated therapy for severe postmenopausal osteoporosis, reducing the incidence of vertebral fractures and improving bone density in women with established disease. Received: 29 September 1999 / Accepted: 10 November 1999     

Ten Year Probabilities of Osteoporotic Fractures According to BMD and Diagnostic Thresholds

The objectives of the present study were to estimate 10 year probabilities of osteoporotic fractures in men and women according to age and bone mineral density (BMD) at the femoral neck. Risks were computed from the incidence of a first hip, distal forearm, proximal humerus and symptomatic vertebral fracture from patient records in Malmo¨, Sweden and future mortality rates for each year of age from Poisson models using the Swedish patient register and statistical year book. Fracture probability was computed using the Swedish population and cut-off values for T-scores based on the NHANES III female population. We assumed that the risk of fracture increased with decreasing BMD as assessed by meta-analysis in independent studies. The 10-year probability of any fracture was determined from the proportion of individuals fracture-free from the age of 45 years. With the exception of forearm fractures in men, 10 year probabilities increased with age and T-score. In the case of hip and spine fractures, fracture probabilities for any age with low BMD were similar between men and women. The effect of age on risk independently of BMD suggests that intervention thresholds should not be at a fixed T-score but vary according to absolute probabilities. Intervention thresholds based on hip BMD T-scores are similar between sexes. Received: 14 December 2000 / Accepted: 2 July 2001     

Physical Activity and Risk Factors for Hip Fractures in Thai Women

Hip fractures are among the most important causes of ill health and death among elderly people. Several potentially modifiable risk factors have been reported. Most claimed physical activity as a promising, inexpensive preventive measure for hip fracture. However, knowledge about risk factors for hip fracture in Asian populations is very limited. We therefore conducted a case–control study to assess the relationships between physical activity and risk of hip fractures in Thai women. From 14 hospitals in Thailand, 229 cases with a radiologically confirmed first hip fracture were enrolled. Two hundred and twenty-four controls were randomly recruited from the same neighborhood and were matched to the cases by age within a 5 year range. Information on physical activity as well as other potential confounders was obtained through personal interviews. Multivariate logistic regression revealed that past physical activity was protective in both very active and active women (OR = 0.67, 95% CI = 0.40–1.12 for moderately active women and OR = 0.20, 95% CI = 0.10–0.38 for very active women; p value for trend <0.01). Recent physical activity reduced the risk to about two-thirds (OR = 0.33, 95% CI = 0.19–0.60 and OR = 0.35, 95% CI = 0.18–0.69 for moderately and very active women respectively). In addition, breastfeeding was identified to be a protective factor (OR = 0.87, 95% CI = 0.80–0.94). In contrast, the following risk factors were identified: current use of antihistamine (OR = 13.96, 95% CI = 1.38–141.13) or traditional medicine (OR = 7.66, 95% CI = 2.71–21.63), underlying cerebrovascular diseases (OR = 6.53, 95% CI = 2.10–20.34), history of fracture (OR = 4.04, 95% CI = 1.26–12.99), parental Chinese racial background (OR = 2.52, 95% CI = 1.49–4.23), alcohol consumption (OR = 2.30, 95% CI = 1.04–5.09). Received: 14 April 2000 / Accepted: 17 October 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     

Semiquantitative Evaluation of Prevalent Vertebral Deformities in Men and their Relationship with Osteoporosis: The MINOS Study

Epidemiologic studies have shown a high prevalence of vertebral deformities in men without a steep increase with aging, suggesting that a substantial number of these deformities are not related to osteoporosis. To determine which vertebral deformities are likely to be osteoporotic fractures, we compared vertebral deformities and bone mineral density (BMD) in a cohort of 786 men aged 51-85 years (the MINOS study). Normal vertebral height ratios were defined in a group of 120 healthy men aged 21-50 years. We classified vertebral deformities by using the semiquantitative method described by Genant et al., which was slightly modified at the level of thoracic kyphosis (T6-T9). At that level, grade 1 wedge deformities were defined as a 25-30% decrease in anterior vertebral height and grade 2 by a 30-40% decrease. The same cutoff of 40% was used for grade 3 for all vertebrae from T4 to L4. BMD was measured with a Hologic 1500 device at the lumbar spine, hip and whole body and with an Osteometer DTX 100 device at the forearm. Z-scores were calculated in 10-year age groups. The prevalence of vertebral deformities increased significantly with age. After adjustment for age and body weight, BMD did not differ between those with and without vertebral deformities. In patients having grade 2 and 3 deformities, BMD was lower than in men having no deformities or only grade 1 deformities when adjusted for age and body weight. Using the age- and body-weight-adjusted test of linear trend for sextiles of BMD, prevalence of grade 2 and 3 vertebral deformities increased with a decrease in BMD at all the sites of measurement. Grade 1 deformities were not correlated with BMD at any site. Among 126 patients who had only grade 1 vertebral deformities, 32 deformities in 30 men were confirmed as vertebral fractures according to their morphology but their BMD did not differ from the nonfractured men. These findings were confirmed when vertebral deformities were measured by the conventional morphometric method in a subgroup of 131 men. Our data suggest that a cutoff of 30% for wedge deformities from T6 to T9 and of 25% for other deformities has a high specificity and a moderate sensitivity for identifying vertebral deformities related to low BMD in men. Grade 1 deformities are often either false positive or deformities related to nonosteoporotic disease of the spine.     

Quantitative Ultrasound and Symptomatic Vertebral Fracture Risk in Chinese Women

Quantitative ultrasound (QUS) is emerging as a simple, inexpensive and noninvasive method for assessing bone quality and assessing fracture risk. We assessed the usefulness of a contact calcaneal ultrasonometer by studying normal premenopausal women (group I, n= 53), normal postmenopausal women (group II, n= 198), and osteoporotic women without (group III, n= 141) and with vertebral fractures (group IV, n= 53). The osteoporotic subjects had a T-score of the spine or hip neck bone mineral density (BMD) <−2.5 based on the local Chinese peak young mean values. When compared with postmenopausal controls, mean broadband ultrasound attenuation (BUA), speed of sound (SOS), and quantitative ultrasound index (QUI) were 26%, 2.1% and 25% lower in women with vertebral fractures (p all <0.005). The correlation coefficients between QUS parameters and BMD of the spine and hip ranged between 0.4 and 0.5. The ability of the QUS to discriminate between patients groups was determined based on the mean value of normal premenopausal women in group I. The mean T-score for women with fractures was −2.87 ± 1.02 for BUA, −2.54 ± 0.79 for SOS, −3.17 ± 0.70 for QUI, −2.65 ± 0.86 for L2–4 BMD and −2.53 ± 0.66 for hip neck BMD. After adjustment for age and body mass index, the odds ratio of vertebral fracture was 1.71 (95% CI 1.2–2.6) for each 1 SD reduction in BUA, 2.72 (1.3–5.3) for SOS, 2.58 (1.4–4.6) for QUI, 2.33 (1.6–3.3) for L2–4 BMD, 2.09 (1.37–3.20) for femoral neck BMD and 1.88 (1.34–2.92) for total hip BMD. The association between the QUS parameters and vertebral fracture risk persisted even adjustment for BMD. The area under the receiver operating characteristic curve for BUA for vertebral fracture was 0.92, for SOS, QUI, L2–4 BMD and femoral neck BMD was 0.95, and for total hip was 0.91. Received: 7 January 1999 / Accepted: 18 May 1999     

A Statistical Method to Minimize Magnification Errors in Serial Vertebral Radiographs

Incident vertebral deformities are commonly defined by observed changes in height between measurements on two consecutive radiographs. However, conventional radiographs are subject to magnification, and this magnification may differ between films, leading to artifactual changes in height. In order to minimize this effect, it is common practice to record the spine–film and film–focus distances, and from this to calculate a magnification factor for each film. We present a simple statistical method for correcting for differences in magnification between two films if the spine–film and film–focus distances are unknown. This method is shown to reduce the variance of the magnification differences in vertebral heights by 14%, considerably more than is possible using the spine–film distance. Using the statistical method, the number of vertebrae that showed not only a reduction in one or more height of 15%, but were also judged clinically to be free from any incident deformity by an expert radiologist, was reduced from 100 to 46. The number showing a reduction of 20% that were judged fracture-free was reduced from 15 to 9. In the subset of subjects for whom the spine–film distance was known, the reduction in false positives was similar, whichever method was used to correct for magnification. There was no difference in the number of confirmed incident fractures detected when magnification correction by either method was employed. It is concluded that correcting for magnification differences using the statistical method outlined here reduces the number of false positive deformities very substantially and by a similar extent as correcting the magnification using reliable, measured spine–film and film–focus distances. A further advantage of this method is that it can be used retrospectively. Received: 26 May 1999 / Accepted: 9 May 2001     

Measurement of Vertebral Body Heights: Ex Vivo Comparisons Between Morphometric X-ray Absorptiometry, Morphometric Radiography and Direct Measurements

Morphometric X-ray absorptiometry (MXA) offers some potential advantages over spinal radiography for the quantitative evaluation of vertebral fractures in individuals with spinal osteoporosis. This ex vivo study examined the accuracy of MXA and quantitative morphometry (QM) for the evaluation of vertebral height, in relation to direct measurements from cadaveric vertebral columns. Spinal radiographs and MXA scans were obtained from nine cadaveric vertebral columns (mean age at death 64 years). Anterior, middle and posterior vertebral body heights of all segments from T4 to L4 were measured interactively using MXA software and QM (from the spinal radiographs), and compared with direct measurements derived using digital callipers following cadaveric dissection. Coefficients of variation for repeat QM and MXA scan analysis were less than 2%. The QM and MXA measurements were both strongly correlated (r ²= 0.99) with the direct measurements, with accuracy errors of between 2.6% and 4.3%, and 4.5% and 4.8%, for QM and MXA respectively. At the three measurement sites, analysis of measurement differences showed that QM tended to overestimate the true height and MXA tended towards under-estimation. The mean difference between the direct measurements and QM measurements ranged from 2.7% to 8.7%, and the mean difference between direct and MXA measurements ranged from –2.9% to 4.1%. There was strong linear association between the MXA and QM measurements (r ²= 0.99) with mean differences at the three measurement sites ranging from –4.1% to –5.9%. Under the optimal (ex vivo) scanning conditions used in this study, MXA is comparable to spinal radiography for the assessment of vertebral height. Further studies are required to determine the conditions under which satisfactory MXA image resolution and measurement accuracy can be achieved in a clinical population. Received: 12 May 1998 / Accepted: 13 October 1998