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Notes: Abstract. Densitometric measurements are prone to imprecision in elderly subjects and the present study was primarily designed to dissect out the effects of age and bone mineral density on proximal femur dual energy x-ray absorptiometry (DXA) reproducibility. The study comprised 17 elderly women (mean age 74.6 years, range 65–84 years), 13 early postmenopausal women with osteopenia (mean age 56.2 years, range 50-63 years), and 17 elderly men (mean age 73.8 years, range 65-86 years). Each subject was given triplicate proximal femur scans by a QDR 2000 Densitometer (Hologic Inc., Waltham, MA) with repositioning between scans. Because of subject selection in the early postmenopausal women there were no significant differences in bone mineral density (BMD) at any site among the three groups. Despite this, reproducibility errors expressed as either coefficient of variation (CV) % or mean standard deviation (SD) were greater in the elderly subjects, regardless of gender, when compared with the younger female subjects. The variability in measurement errors with age were least marked for the total hip and trochanteric sites. Within the elderly subjects, BMD appeared to exert little influence on measurement errors. We conclude that short-term proximal femur reproducibility is dependent on age-related factors other than BMD. There is no influence of gender on the measurement errors. It is likely that local factors (e.g., hip osteoarthritis) or general frailty may influence repositioning but this needs further exploration. In the meantime, the total hip and trochanteric sites should be used as they provide the most reproducible measurements in the elderly.

Notes: Abstract: Vertebral fractures may be minor or lead to pain, decreased physical function, immobility, social isolation and depression, which together contribute to quality of life. A Working Party of the European Foundation for Osteoporosis has developed a specfic questionnaire for patients with vertebral fractures. This questionnaire, QUALEFFO, includes questions in the domains pain, physical function, social function, general health perception and mental function. QUALEFFO was validated in a multicenter study in seven countries. The study was done in 159 patients aged 55–80 years with clinical osteoporosis, i.e., back pain and other complaints with at least one vertebral fracture and lumbar bone mineral density T-score 〈−1. Patients with a recent vertebral fracture were excluded because of unstable disease. Controls were age- and sex-matched, and did not have chronic back pain or vertebral fractures. Subjects with conditions exerting a major influence on quality of life were excluded. The QUALEFFO was administered twice within 4 weeks and compared with a generic questionnaire, the Short Form 36 of the Medical Outcomes Study (SF-36). Standard spinal radiographs were made for assessment of vertebral height. Seven questions were removed from the analysis because of low response rate, linguistic ambiguities or redundancy. The 41 remaining questions were analyzed for repeatability, internal consistency and the capacity to discriminate between patients with vertebral fractures and controls. Comparison with the SF-36 was performed within similar domains by conditional logistic regression and by receiver operating characteristic (ROC) curves. The repeatability of QUALEFFO was good (kappa statistics 0.54–0.90) and 26 of 41 questions had a kappa score ≥0.70. The internal consistency of the five domains was adequate, with Crohnbach α around 0.80. All except five questions discriminated significantly between patients and controls. The median scores of QUALEFFO were significantly higher in patients with vertebral fractures than in controls in all five domain (p〈0.001), which is consistent with decreased quality of life in patients with osteoporosis. Spinal radiographs were assessed using the McCloskey–Kanis algorithm. According to this, 124 patients (78%) had vertebral fractures of ≥3 SD severity, in contrast with 7 controls (4%). Significant correlations existed between scores of similar domains of QUALEFFO and the SF-36, especially for pain, physical function and mental function. All five domains within each questionnaire discriminated significantly between fracture cases and controls. The odds ratios for pain and social function were greater for QUALEFFO, while general health perception was more discriminating using the SF-36. The ROC curve analysis of QUALEFFO indicated that all five domains were significantly predictive of vertebral fractures. When comparing similar domains of the two questionnaires, QUALEFFO domains demonstrated significantly better performance for pain, physical function and social function. The QUALEFFO total score and SF-36 physical composite score showed similar performance. In conclusion, QUALEFFO is repeatable, coherent and discriminates well between patients with vertebral fractures and control subjects. The results of this study confirm the decreased quality of life in patients with vertebral fractures.

Notes: Abstract: The diagnosis of osteoporosis is based on bone mass measurement. To avoid the errors associated with the measurement of spinal bone density the total hip has been accepted as the standard measurement site. This information is not available for many early measurements. We have assessed whether it is possible to derive clinically useful information about total hip bone mineral density (BMD) from measurements at other hip sites. The bone mass measurements of 46 patients participating in a current trial of therapy for osteoporosis were reviewed. The total hip BMD as directly measured was compared with that obtained from the formula: Total hip BMD = 0.48×Neck BMD + 0.62×Trochanteric BMD + 0.03. In 30 patients with follow-up data the rate of change in hip BMD over a year was also determined by both methods. In the pretreatment state there was good agreement between the two measures (r 2 = 0.96, SEE 0.012 g/cm2). If the formula was used to compute a change in total hip BMD, the agreement between both methods remained good. However, the standard error of the estimate of the change represented 59% of the observed change. This indicates that the error associated with this estimate is too great to allow clinically meaningful conclusions to be drawn from calculated total hip BMD. We conclude that, whilst it may be possible to obtain reasonable point estimates of total hip BMD from other measures in the hip, these estimates are too imprecise to allow conclusions about change in BMD to be made.

Notes: Abstract We assessed a method for the measurement of ultrasound velocity in cortical bone of the human tibia using a probe designed to minimize the effects of surrounding soft tissues. Of four different measurement values, the maximum velocity (average of the five highest readings) gave the lowest errors of reproducibility in relation to the population variance (standardized coefficient of variation=1.8%). The maximum velocity varied according to the tibial site measured and for practical reasons the mid-tibial site was chosen for further study. The short-term intra- and inter-observer reproducibilities (coefficients of variation) were 0.35% (n=22) and 0.50% (n=27) respectively. Long-term reproducibility over 4 months in 31 subjects was 0.68%. There was no significant difference in maximum ultrasound velocity between the dominant and non-dominant tibia in 78 women (3764±209 vs 3763±199 m/s). Tibial ultrasound velocity was significantly higher in 73 premenopausal women (3999±102 m/s) than in 129 women referred for assessment of postmenopausal osteoporosis (3780±168 m/s), 26 women with steroid-induced osteoporosis (3790±188 m/s) and 4 women with hyperparathyroidism (3575±261 m/s). In premenopausal women, ultrasound velocity did not correlate significantly with age, height, weight or body mass index. In women with postmenopausal osteoporosis, ultrasound velocity decreased with age after the menopause (r=−0.47,p〈0.0001) and body weight exerted a weaker protective effect. The apparent annual decrease in velocity with age in postmenopausal osteoporosis (8.5 m/s) was comparable to the error of reproducibility. We conclude that the technique for measuring tibial ultrasound velocity is highly reproducible in relation to the distribution of values in the population and is sensitive to age- and osteoporosis-induced changes in bone. Further studies are required to examine its relationship to other indices of skeletal status to determine the biological and clinical relevance of the technique.

Notes: Abstract The absence of specific criteria for the definition of vertebral fracture has major implications for assessing the apparent prevalence and incidence of vertebral deformity. Also, little is known of the effect of using different criteria for new vertebral fractures in clinical studies. We therefore developed radiological criteria for vertebral fracture in women for assessing both the prevalence and the incidence of vertebral osteoporosis in population and in prospective studies and compared these with several other published methods. Normal ranges for vertebral shape were obtained from radiographs in 100 women aged 45–50 years. These included ranges for the ratios of anterior/posterior, central/posterior and posterior/predicted posterior vertebral heights from T4 to L5. The predicted posterior height was calculated from adjacent vertebrae. In contrast to other methods, our definition of fracture required the fulfilment of two criteria at each vertebral site, and was associated with a lower apparent prevalence of fracture in the control women due to a lower false positive rate. The prevalence and incidence of vertebral deformity using different criteria were then compared in a series of women with skeletal metastases from breast cancer in whom radiographs were obtained 6 months apart. The prevalence of vertebral deformity and the specificity for deformity varied markedly with differing criteria. Using a cut-off of 3 standard deviations the prevalence of vertebral deformity in the women with breast cancer was 46%. Using other methods, the prevalences of deformity ranged from 33% to 74%. Over a 6-month interval 25% of patients with breast cancer sustained 61 deformities using our method, of which only 8% resulted from errors in reproducibility. The number of patients sustaining new deformities was increased twofold when assessed by other methods (45%–53%), but errors of reproducibility may have accounted for 21% of the new deformities. The magnitude and distribution of these errors have important implications for the apparent therapeutic efficacy of agents in clinical trials of osteoporosis. The rapid semi-automated technique for assessing vertebral deformities on lateral spine radiographs that we have developed has a high specificity, and reduces the impact of errors of reproducibility on estimates of prevalence and incidence. The method should prove a value in assessing vertebral deformity both in population studies and in prospective clinical trials.

Notes: Abstract: Metacarpal morphometry represents a potentially cheap and widely available non-invasive assessment of skeletal status. In two cross-sectional studies, we compared the performance characteristics of a semi-automated technique (the Teijin Bonalyzer) with an in-house manual measurement, and with measures of skeletal strength at other sites. The metacarpal cortical index (mCI) was measured on hand radiographs of 178 osteoporotic women using both the Teijin Bonalyzer and a digitizing tablet. Measurements on the latter were consistently lower than with the Bonalyzer except for mCI (0.443 ± 0.080 vs 0.364 ± 0.060, p〈0.001), although correlation coefficients between these two methods were highly significant (r= 0.62–0.83, p〈0.001). The reproducibility errors of metacarpal bone mineral density (mBMD) were constant (1.1–1.2%) whilst those for mCI showed a marked operator-dependency (2.0–7.9%). In 379 elderly community-dwelling women, Bonalyzer mCI and mBMD showed a significant decline with age (r=−0.30 and −0.27 respectively, p〈0.05). Both mCI and mBMD correlated significantly with forearm BMD (r= 0.50 and 0.57 respectively, p〈0.001) and hip BMD (r= 0.48 and 0.53 respectively, p〈0.001). After adjustment for age and weight, hip BMD demonstrated the best discrimination for prevalent vertebral fractures as judged by the gradient of risk for a 1 SD decrease in measurement (odds ratio (OR) 2.17, 95% CI 1.56–3.01). Similar but smaller gradients of risk were shown by Bonalyzer mCI (OR 1.32, 95% CI 1.00–1.75), mBMD (OR 1.35, 95% CI 1.02–1.78) and forearm BMD (OR 1.39, 95% CI 1.08–1.80). MCI, and in particular mBMD, may be useful assessments of bone mass and fracture risk. In our study, it is comparable to peripheral assessment of skeletal status by forearm densitometry.

Notes: Abstract Bisphosphonates are widely used in disorders associated with increased resorption of bone, particularly in Paget's disease of bone and in the hypercalcemia of malignancy. Because of their undoubted efficacy and relatively low toxicity, bisphosphonates are attractive candidates for the management of osteoporosis. Clodronate, one of the many bisphosphonates being tested in osteoporosis, may be given intravenously or by mouth. In contrast to etidronate, even high doses of clodronate do not impair the mineralization of bone, making it suitable for long-term use in osteoporosis. As do all the bisphosphonates tested thus far, clodronate appears to delay the rate of bone loss in osteoporosis. Long-term studies are relatively few, so that its steady-state effects on bone mass are not yet known. Most data suggest clodronate is capable at least of delaying the rate of bone loss, but several pilot studies with this agent suggest that increments of bone mass might be sustainable for several years. Clodronate is likely to decrease the frequency of osteoporotic fractures, but there is no evidence for this at present. Well-controlled, long-term prospective studies are needed.