The Burden of Osteoporotic Fractures: A Method for Setting Intervention Thresholds

The aim of this study was to assess the relationship between morbidity from hip fracture and that from other osteoporotic fractures by age and sex based on the population of Sweden. Osteoporotic fractures were designated as those associated with low bone mineral density (BMD) and those that increased in incidence with age after the age of 50 years. Severity of fractures was weighted according to their morbidity using utility values based on those derived by the National Osteoporosis Foundation. Morbidity from fractures other than hip fracture was converted to hip fracture equivalents according to their disutility weights. Excess morbidity was 3.34 and 4.75 in men and women at the age of 50 years, i.e. the morbidity associated with osteoporotic fractures was 3–5 times that accounted for by hip fracture. Excess moribidity decreased with age to approximately 1.25 between the ages of 85 and 89 years. On the assumption that the age- and sex-specific pattern of fractures due to osteoporosis is similar in different communities, the computation of excess morbidity can be utilized to determine the total morbidity from osteoporotic fractures from knowledge of hip fracture rates alone. Such data can be used to weight probabilities of hip fracture in different countries in order to take into account the morbidity from fractures other than hip fracture, and to modify intervention thresholds based on hip fracture risk alone. If, for example, a 10-year probability of hip fracture of 10% was considered an intervention threshold, this would be exceeded in women with osteoporosis aged 65 years and more, but when weighted for other osteoporotic fractures would be exceeded in all women (and men) with osteoporosis. Received: 1 May 2000 / Accepted: 1 December 2000     

Long-Term Risk of Osteoporotic Fracture in Malmö

The objectives of the present study were to estimate long-term risks of osteoporotic fractures. The incidence of hip, distal forearm, proximal humerus and vertebral fracture were obtained from patient records in Malmo¨, Sweden. Vertebral fractures were confined to those coming to clinical attention, either as an inpatient or an outpatient case. Patient records were examined to exclude individuals with prior fractures at the same site. Future mortality rates were computed for each year of age from Poisson models using the Swedish Patient Register and the Statistical Year Book. The incidence and lifetime risk of any fracture were determined from the proportion of individuals fracture-free from the age of 45 years. Lifetime risk of shoulder, forearm, hip and spine fracture were 13.3%, 21.5%, 23.3% and 15.4% respectively in women at the age of 45 years. Corresponding values for men at the age of 45 years were 4.4%, 5.2%, 11.2% and 8.6%. The risk of any of these fractures was 47.3% and 23.8% in women and men respectively. Remaining lifetime risk was stable with age for hip fracture, but decreased by 20–30% by the age of 70 years in the case of other fractures. Ten and 15 year risks for all types of fractures increased with age until the age of 80 years, when they approached lifetime risks because of the competing probabilities of fracture and death. We conclude that fractures of the hip and spine carry higher risks than fractures at other sites, and that lifetime risks of fracture of the hip in particular have been underestimated. Received: 9 November 1999 / Accepted: 2 February 2000     

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     

Direct Medical Costs Attributable to Osteoporotic Fractures

Osteoporotic fractures are a major cause of morbidity in the elderly, the most rapidly growing segment of our population. We characterized the incremental direct medical costs following such fractures in a population-based cohort of men and women in Olmsted County, Minnesota. Cases included all County residents 50 years of age and older with an incident fracture due to minimal or moderate trauma between January 1, 1989 and January 1, 1992. For each case, a control of the same age (± 1 year) and sex who was attended in the local medical system in the same year was identified. Total incremental costs (cases – controls) in the year after fracture were estimated. Unit costs for each health service/procedure were obtained through the Mayo Cost Data Warehouse, which provides a standardized, inflation-adjusted estimate reflecting the national average cost of providing the service. Regression analysis was used to identify factors associated with incremental costs. There were 1263 case/control pairs; their average age was 73.8 years and 78% were female. Median total direct medical costs were $761 and $625, respectively, for cases and nonfracture controls in the year prior to fracture, and $3884 and $712, respectively, in the year following fracture. The highest median incremental costs were for distal femur ($11 756) and hip fractures ($11 241), whereas the lowest were for rib fractures ($213). Although hip fractures resulted in more incremental cost than any other fracture type, this amounted to only 37% of the total incremental cost of all moderate-trauma fractures combined. Regression analyses revealed that age, prior year costs and type of fracture were significant predictors of incremental costs (p<0.03 for all comparisons). The incremental costs of osteoporotic fractures are therefore substantial. Whereas hip fractures contributed disproportionately, they accounted for only one-third of the total incremental cost of fractures in our cohort. The use of incremental costs in economic analyses will provide a more accurate reflection of the true cost-effectiveness of osteoporosis prevention. Received: 13 November 2001 / Accepted: 6 March 2001     

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     

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 Digitized Images with Original Radiography for Semiquantitative Assessment of Osteoporotic Fractures

We validated a vertebral fracture assessment (VFA) workstation developed by our group for semiquantitative assessment of vertebral fractures in large-scale, multicenter osteoporosis drug trials. Baseline and follow-up spine radiographs (lateral views) of 50 patients who participated in a clinical trial were digitized and were archived on CD-ROM. Both original radiographs and the digitized images were independently assessed by three experienced radiologists. Prevalent fracture scores of vertebrae were rated in increments of 1 on a 4-point scale. Incident fractures were defined as any worsening of grade on follow-up films. Generally good to excellent agreement among the three readers was found between the two methods, with kappa scores (κ) from 0.91 to 0.96 for prevalence of fractures, and from 0.80 to 0.90 for incidence of fractures. Reproducibility (intra-reader variability) of each method was comparable. For assessing prevalent fracture, κ was from 0.87 to 0.96 using radiographs, and from 0.87 to 0.94 using VFA images. For incident fractures, the κ was from 0.78 to 0.89 using radiographs, and from 0.82 to 0.88 using VFA images. Level-specific agreement between the two approaches was consistent. Overall, there is no difference between readings of digital images and readings of conventional radiographs. The quality of the new VFA for visualization of vertebral fracture is excellent. Received: 26 October 1998 / Accepted: 29 March 1999     

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     

Reduced Pulmonary Function in Patients with Spinal Osteoporotic Fractures

Vertebral deformation in spinal osteoporosis results in spinal and thoracic deformation, causing pain, disability and an overall decrease in quality of life. We sought to determine whether thoracic spinal deformation may lead to impaired pulmonary function. We studied expiratory relaxed vital capacity (VC) and forced expiratory volume in 1 s (FEV1) in 34 patients with spinal osteoporotic fractures and 51 patients with chronic low back pain (CLBP) due to reasons other than osteoporosis. Measurements of pulmonary function tests were calculated as a percentage of the normal range adjusting for age, sex, and height using the equations for normal values of the EKGS (Europ?ische Gesellschaft für Kohle und Stahl). Severity of osteoporosis was determined by calculation of the spine deformity index (SDI-total and SDI-anterior) on lateral radiographs of the spine and clinical measures of body stature (height reduction, distance from lowest ribs to iliac crest and distance from the occiput to the wall). Patients with osteoporosis had a lower vital capacity (%VC of the reference value) than patients with CLBP. The differences were more prominent (p<0.05) when the previous body height, at age 25 years, was used as reference for calculation of VC (mean ± SD: 93.6%± 15.3% in patients with osteoporosis v 105.6%± 15.1% in patients with CLBP). FEV1 was significantly (p<0.05) lower in patients with osteoporosis when previous body height was considered, in comparison with patients with CLBP (mean ± SD: 85.0%± 14.2% in patients with osteoporosis v 92.4%± 13.6% in patients with CLBP). In patients with osteoporosis VC (standardized on previous body height) was significantly negatively correlated with SDI-anterior (r=–0.4, p<0.03). Furthermore, VC standardized on previous body height showed a weak but significant negative correlation with some clinical measures of osteoporosis (height reduction vs %VC: r=–0.34, p<0.05; distance from the lowest ribs to iliac crest vs %VC: r= 0.35, p<0.04). In conclusion, we found that pulmonary function is significantly diminished in patients with spinal osteoporotic fractures as compared with CLBP patients without evidence of manifest osteoporosis. Reduction of pulmonary function is correlated significantly with clinical and radiological measures of severity of spinal deformation due to osteoporotic fractures. Received: 17 March 1997 / Accepted: 21 October 1997     

Lifetime Risk of Hip Fractures is Underestimated

Estimates of lifetime risk of osteoporotic fracture have assumed that mortality rates do not change. Since mortality in the elderly is decreasing in all regions of the world we assessed the effect of this on lifetime risks for hip fracture using Sweden as a reference country. Lifetime risks of hip fracture at the age of 50 years were 4.6% and 13.9% in men and women respectively, assuming all survive to current average life expectancy. Estimates increased to 8.1% and 19.5% when based on present mortality and to 11.1% and 22.7% respectively based on predicted mortality. We conclude that lifetime risks of hip fracture have been considerably underestimated. Received: 15 September 1997 / Revised: 17 March 1998     

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     

Risk of Hip Fracture Derived from Relative Risks: An Analysis Applied to the Population of Sweden

Bone mineral density measurements are widely used to estimate the relative risk of hip fracture. In addition, many other risk factors have been identified, some of which are known to add to the risk independently of other risk factors, including bone mineral density measurements. In this paper we develop an algorithm that converts relative risks for hip fracture to absolute (15 years and lifetime) risks, modeled on the population of Sweden. Lifetime risks increased as expected with increments in relative risk. Average lifetime risk in women at the age of 50 years was 22.7%, which increased to 64.9% when the relative risk was 6.0. In men the risk increased from 11.1% to 41.3%. The identification of high-risk groups had little effect on the specificity of assessments but increased the sensitivity over a wide range of assumptions. The increment in lifetime risk was relatively stable across all ages, reducing the complexity of computing lifetime risks from relative risk. The derivation of absolute risk from relative risk permits the optimization of selection of individuals or populations either for further risk assessment or for treatment. Received: 21 December 1999 / Accepted: 2 July 1999     

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     

Urinary Excretion of Type I Collagen Degradation Products in Healthy Women and Osteoporotic Patients with Vertebral and Hip Fractures

We have evaluated both the effect of normal aging and menopause on urinary CrossLaps™ (u-CTx) excretion and the bone resorption status by u-CTx in patients with vertebral fracture and hip fracture. In 246 healthy women, 76 patients with vertebral fracture, and 63 patients with hip fracture, u-CTx excretion was measured by ELISA. The age-related changes of u-CTx in healthy females reflected the marked increase of bone resorption associated with modeling at childhood. The values in the subgroups of postmenopausal women 1–3 years since menopause and ≤10 years since menopause were significantly higher than those in the subgroups of premenopausal adult women. The values in the vertebral fracture group were significantly higher than those in the premenopause group, but not those in the postmenopause groups. The values in the hip fracture group were significantly higher than those in the other groups. Of the 70 postmenopausal subjects aged 45–64 years, 43% had u-CTx values more than 2 SD above premenopausal mean. The corresponding values in the patients with vertebral fracture and those with hip fracture were 58% and 64%, respectively. This marker reflects well the increase of bone resorption associated with bone modeling at childhood and with high bone turnover after menopause. The excretions in the patients with hip fracture were much higher than those in the age-matched subjects and also higher than those in the patients with vertebral fracture. These findings indicate that the abnormality of bone resorption in the patients with hip fracture is more severe than in the patients with vertebral fracture. Received: 30 January 1997 / Accepted: 7 August 1997     

Lifetime and Five-Year Age-Specific Risks of First and Subsequent Osteoporotic Fractures in Postmenopausal Women

We examined the incidence of fragility fractures in Australian women 50 years of age and over using a Markov process with Monte Carlo simulations. The lifetime risks and the risks of sustaining first and subsequent clinically diagnosed fractures at osteoporotic sites were estimated according to age, nursing home entry and mortality rates. Hip and spine fractures were evaluated individually and fractures of humerus, forearm, wrist, ribs, pelvis, upper leg (excluding proximal femur) and tibia/fibula were considered in combination. The model predicted that 42.1% of women aged 50 years will sustain at least one fracture in their remaining lifetime, of whom half are expected to sustain multiple fractures. The lifetime risks of sustaining hip, clinical spine and other fractures were 17.0%, 9.6% and 30.4%, with the risks of multiple fractures at these sites estimated at 19.5%, 39.7% and 35.7% respectively. The proportion of women expected to sustain their first fracture increased from 1.9% of the population under 55 years of age up to 49.1% of women over 89 years of age. The 5-year age-specific risks of sustaining any subsequent fractures increased from 2.8% of women under the age of 55 years to 61.6% for women age 89 years and over. The increased risks of new fractures following a first fracture lead to a considerable burden of multiple fractures. Received: 2 February 2000 / Accepted: 5 June 2000     

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     

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     

The Cost of Treating Osteoporotic Fractures in the United Kingdom Female Population

Osteoporotic fractures represent a significant burden to society. The costs of osteoporotic fractures to the UK health care system have not previously been accurately described. In this paper, we quantify the health care and social care costs of fractures occurring in women aged 50 years and over in the UK. We used a variety of data sources. For acute hospital hip fracture costs existing published estimates were used whilst for social care costs a survey of resource use among fracture patients before and after hip fracture was utilized. We undertook a case–control study using the General Practice Research Database to estimate primary care costs. From these data we estimated that the cost of a hip fracture is about ￡12000, with non-acute hospital costs representing the larger proportion. The other fractures were less expensive, at ￡468, ￡479 and ￡1338 for wrist, vertebral and other fractures, respectively. For all fractures the annual cost to the UK is ￡727 million. Assuming each male hip fracture costs the same as a female fracture, including these would increase the total costs to ￡942 million. Received: 10 November 1997 / Revised: 23 February 1998