Influence of handedness on calcaneal ultrasound: Implications for assessment of osteoporosis and study design

Calcaneal ultrasound has been increasingly studied for its potential in the assessment of osteoporotic fracture risk. The accuracy of such an assessment is, in part, dependent on the reproducibility of the measurement. This study examines the impact of handedness on ultrasound measurements [broadband ultrasound attenuation (BUA) and velocity of sound (VOS)] in the calcaneus. Two hundred and sixty-four subjects (57 men and 297 women) aged 51.1+13.6 years (mean ± SD) were studied. For each subject, calcaneal ultrasound measurements were performed on both heels with a McCue CUBA ultrasound densitometer. Right-handed dominance (94.7%) was determined by structured interview. In men, BUA measurements were significantly higher on the dominant side: mean difference 4.1±1.5 dB/MHz (mean ± SD;p=0.009), equivalent to 4.2+1.5% and more than 4 times the average rate of annual change in BUA. The difference between sides was greater in young (<50 years) than old men (>50 years). Among the women, the difference was not statistically significant (0.7±0.9 dB/MHz;p=0.4); however, it was significant in younger women (20–30 years) (99±4 vs 90±4 dB/MHz,p=0.01). By contrast VOS did not differ between sides in either men or women irrespective of age. Within-subject standard deviation of BUA was 9.8 dB/MHz for men and 8.6 dB/ MHz for women and the component due to right and left difference was 8.4 dB/MHz for men and 6.9 dB/MHz for women. This variability of BUA between right and left heels could increase the false-positive rate by up to 28% for a cut-off of 2 SD below the mean. These data indicate that variation between left and right heel measurements of BUA is higher than that of random error measurements, particularly in men and younger, presumably more physically active subjects. Although VOS measurements were not side dependent, in the smaller number of studies examining VOS and fracture risk, VOS appears to have a weaker predictive power than BUA. Clinical and epidemiological studies involving calcaneal BUA measurements should standardize the side measured to either the dominant or non-dominant heel, to reduce within-subject variation and increase their power.     

原发性骨质疏松患病率调查

目的：了解原发性骨质疏松症(primary osteoporosis.POP)的患病率。方法：选取235名志愿者，男性97名，女性138名，年龄19—79岁，平均53．22岁。运用Scanner SN 3314对跟骨的骨质密度(BMD)进行测量。结果：男性BMD高于女性，有统计学意义(P＜0．01)；男女的BMD随着年龄的增长均降低。POP患病率女性高于男性，女性急病率在60岁以后明显增加。     

Ex vivo estimation of thoracolumbar vertebral body compressive strength: The relative contributions of bone densitometry and vertebral morphometry

The estimation of vertebral fracture risk in individuals with suspected osteopenia is commonly based on measurements of lumbar spine bone density. The efficacy of vertebral size and deformity, as assessed by vertebral morphometry, in the prediction of fractures has been less studied. In an ex vivo investigation the regional relationships between vertebral size, vertebral deformity, bone density and compressive strength throughout the thoracolumbar spine were examined. In 16 vertebral columns (T1–L5) the bone mineral content (BMC) and bone mineral density (BMD) of each segment were measured using lateral projection dual-energy X-ray absorptiometry, and the vertebral cancellous density (VCD) and mid-vertebral cross-sectional area (CSA) measured using quantitative computed tomography. Vertebral body heights were determined from mid-sagittal CT scans, and vertical height ratios calculated for each segment. The failure load and failure stress of the isolated vertebral bodies were determined using a material testing device. Separate analyses were performed for the upper (T1–4), middle (T5–8) and lower (T9–12) thoracic, and lumbar (L1–5) segments. In all regions, failure load was strongly correlated with BMD (r=0.82–0.86), moderately correlated with VCD (r=0.60–0.71) and vertebral height (r=0.22–0.49), and poorly correlated with the height ratios (r=0.04–0.33). Failure stress was best predicted by BMD (r=0.73–0.78) and VCD (r=0.70–0.78) but was poorly correlated with all morphometric variables (r=0.01–0.33). The segmental correlations between BMD and VCD ranged fromr=0.49 tor=0.79. For all regions, BMD and VCD were included in the stepwise regression models for predicting failure load and failure stress. Either the mid-vertebral height or CSA were included in all the failure load models, while mid-vertebral height was included in only one of the failure stress models. The results suggest that vertebral deformity and size (as assessed by vertebral morphometry) make only a minor contribution to the prediction of vertebral strength additional to that provided by bone densitometry alone. The consistent regional relationships between variables appear to support the practice of global fracture risk assessment based on lumbar spine densitometry.     

骨质疏松股骨颈经CCPC强化后螺钉固定的生物力学研究

目的　评价不同直径螺钉固定时添加复合磷酸钙骨水泥 (CCPC)对骨质疏松股骨颈生物力学变化的影响。方法　采用 2 4个股骨上段标本 ,随机分为三组 :深螺纹强化组、中等螺纹强化组和浅螺纹强化组。结果　三组均灌注CCPC ,深螺纹组、中螺纹组和浅螺纹组的螺钉初始松动加载力分别为(32 8 9± 34 9)N、(335 7± 2 6 6 )N、(2 84 8± 2 5 9)N ;最大轴向拔出力分别为 (36 9 5± 2 1 9)N、(36 4 0± 17 5 )N、(30 5 6± 2 4 5 )N ,深螺纹组、中螺纹组均和浅螺纹组差异有显著性意义 (P <0 0 5 )。结论　螺钉直径与骨质疏松股骨颈强化后的稳定性有关。     

骨质疏松防治药物研究（8）：喹啉酮类新衍生物的合成

作者合成了９个喹啉酮类新衍生物，其结构经红外光谱，核磁共振氢谱，质谱及元素分析证实，对合成的化合物ＴＭ－９进行抗骨质疏松活性测定，初步结果表明，目标化合物ＴＭ－９促进骨形成活性高于日本已上市的异丙氧基异黄酮。     

The use of etidronate and calcium versus calcium alone in the treatment of postmenopausal osteopenia: Results of three years of treatment

The purpose of this open, prospective, controlled, randomized trial was to study the effect of intermittent, cyclic etidronate on the bone mass of osteoporotic postmenopausal women with or without fractures. Eligible subjects were asymptomatic women less than 75 years old who had been amenorrhoeic for at least 1 year. Those with secondary osteoporosis were excluded. Subjects also had to be ambulant with a bone mineral density (BMD) of the lumbar spine >1 SD below that of age matched controls (Z-score < –1 SD). Eighty patients were enrolled, of whom 65 were recruited through a screening programme conducted in the practices of two general practitioners. The remaining patients were from other referrals. The subjects were randomized to two groups of 40 women. Treatment regimens were as follows. The etidronate group was treated with etidronate 400 mg once daily for 14 days followed by 76 days of 500 mg of elementary calcium once daily; this cycle was repeated every 3 months. The calcium group took 500 mg of elementary calcium once daily. The groups were not different in age, height, weight, time since menopause, BMD at baseline and prevalent vertebral fractures. In 50 patients (28 in the etidronate group and 22 in the calcium group) no vertebral fractures were present (67%). Sixty-four patients (35 in the etidronate group and 29 in the calcium group) completed the 3 years of the study. In the etidronate group the mean BMD of the lumbar spine, femoral neck, trochanter and Ward's triangle increased by 5.7%, 1.4%, 7.1% and 10.9% from baseline values respectively (p<0.05 at all sites except for the femoral neck). In the calcium group no significant changes from baseline were found at any time point at any site after 3 years, except for the femoral neck, where BMD at 156 weeks decreased significantly by 3% (p<0.003). In 3 patients, all in the calcium group, six new fractures were found. There were no serious adverse effects. We conclude that intermittent, cyclic treatment with etidronate causes a significant increase in the BMD of the lumbar spine and the proximal femur in osteopenic postmenopausal women, and that treatment is safe and has no serious adverse effects.     

福善美对绝经后妇女骨密度的影响

目的　评价福善美 (Fosamax)治疗绝经后骨质疏松症妇女的近期及中期疗效 ,以及改善骨量作用。方法　绝经 1年以上女性 80名 ,分成 4组 ,A组 :14例 ,年龄 5 4 . 97± 5. 5 1(47～ 6 2 )岁 ,绝经年限≤10年 ,疗程 6个月～ 1年 ;B组 :2 3例 ,年龄 5 5 . 5 5± 3. 6 6 (5 0～ 6 2岁 ) ,绝经年限≤ 10年 ,疗程 1年以上 ;C组 :18例 ,年龄 6 8. 18± 5 . 5 9(5 9～ 78岁 ) ,绝经年限 >10年 ,疗程 6个月～ 1年 ;D组 :2 5例 ,年龄6 7. 2 5± 6 .19(5 2～ 80岁 ,绝经年限 >10年 ,疗程 1年以上。患者每天接受口服福善美 10mg和元素钙5 0 0mg,疗程 6个月～ 2 8年。治疗前、后应用双能X线吸收仪 (HologicQDR 2 0 0 0型 )进行骨密度(BMD)测定。结果　 4组不论绝经年限长短 ,通过 6个月～ 2年以上福善美治疗 ,腰椎BMD平均增加百分率 3 74 %～ 5 4 5 % ,较基础值均有明显增加 (P <0 . 0 0 1) ,4组间差异无统计学意义 (P >0 . 0 5 )。股骨颈部位治疗后BMD平均增加百分率为 0 84 %～ 4 2 1% ,其中绝经年限相同时 ,疗程长者高于短者 ,即B组高于A组 ,D组高于C组 ;疗程相同时 ,绝经年限长者高于短者 ,即C组高于A组 ,D组高于B组 ,但 4组间差异无显著性 (P >0 . 0 5 )。大转子部位治疗后BMD增加平均变化百分率 1 4. 2 %～     

Does Follow-up of Osteoporotic Women Treated with Antiresorptive Therapies Improve Effectiveness?

The use of biochemical markers of bone turnover has been advocated to improve follow-up of women receiving antiresorptive therapies for osteoporosis, but this strategy is not yet supported by trials showing it improves effectiveness of treatments. To explore the potential value of markers of bone turnover to monitor antiresorptive treatments of osteoporosis, we conducted a decision analysis using a decision tree and Markov modeling. We have compared two strategies: treatment of a woman without specific monitoring; and treatment of this woman with measurement of a serum marker of bone resorption after 3 months of treatment, with change of treatment if response to treatment assessed by this marker was not satisfactory. The base case is the treatment of a 60-year-old osteoporotic woman with a total hip T-score of −3, using a second generation bisphosphonate during 5 years. We found that follow-up produced slightly greater quality adjusted life years (QALYs) than no follow-up (8.1560 vs 8.1532, i.e. a one day difference). In a two-way sensitivity analysis, the follow-up option produced higher QALYs so long as adherence rate with follow-up was equal or superior to the proportion of women who adhered without follow-up. For example, if the proportion of women adherent to treatment was increased from 50% to 60% by follow-up, then the expected value of the follow-up branch was increased from 8.1560 QALYs to 8.1800 QALYs (i.e. a difference of 9 days). In addition, the higher the non-response rate, the greater the benefit from monitoring with a biochemical marker. In conclusion, our decision analysis model suggests that follow-up of osteoporotic women treated with a second generation bisphosphonate during a 5-year period using an early measurement of a serum marker of bone resorption may increase effectiveness of the treatment on quality of life, but the effect is very small. So, the use of follow-up measures of bone turnover may be based on patient and physician preferences. Received: 6 July 2001 / Accepted: 1 April 2002     

Aromatization of androgens is important for skeletal maintenance of aged male rats

A nonsteroidal aromatase inhibitor vorozole (VOR) was administered to aged (12 months old) male Wistar rats and its effect was compared with the effect of androgen deficiency. The rats were either sham-operated (SHAM) or orchidectomized (ORCH) and treated with or without VOR. Thus, four experimental groups were created (SHAM, ORCH, SHAM + VOR, ORCH + VOR). The follow-up period was 4 months. At the end of the experimental period, bone mineral density (BMD) of the first four lumbar vertebrae and right femur was measured ex vivo with dual-energy X-ray absorptiometry, bone formation was evaluated by serum osteocalcin, and bone resorption by urinary excretion of (deoxy)pyridinoline. Orchidectomy increased bone resorption 2- to 3-fold whereas bone formation was only slightly increased. Treatment of intact male rats with VOR also increased bone resorption (+30% increase) whereas bone formation was not increased in this SHAM + VOR group. Their BMD was 7% lower in the femur (P < 0.01) and 6% lower in the lumbar vertebrae (P < 0.01) compared with the SHAM group that had not received VOR. Moreover, this decrease of bone mineral density was not significantly different from the expected decrease of bone density observed in the ORCH groups (6–10%). This was also reflected by a decrease of calcium content of the first four lumbar vertebrae of 15% (P < 0.001) in the SHAM + VOR group and 9–14% (P < 0.05) in the ORCH groups compared with the SHAM group, respectively. These data therefore suggest that inhibition of aromatization of androgens into estrogens increases bone resorption and bone loss similar to that observed after complete removal of androgens. Aromatization of androgens into estrogens may therefore, at least partly, explain the effects of androgens on skeletal maintenance. Received: 13 October 1995 / Accepted: 23 February 1996     

Prevalent vertebral deformities: Relationship to bone mineral density and spinal osteophytosis in elderly men and women

The aims of this study were to ascertain vertebral deformity prevalence in elderly men and women and to describe the association between bone mineral density (BMD) at the lumbar spine and femoral neck, severity of spinal degenerative disease and vertebral deformity prevalence. We performed standardized spinal radiographs in a random sample of 300 elderly men and women participating in the Dubbo Osteoporosis Epidemiology Study, a population-based study of fracture risk factors. Radiographs were read independently by masked observers for the prevalence of vertebral deformity and severity of osteophytosis. BMD was measured by dual-energy X-ray absorptiometry. The prevalence of vertebral deformities was critically dependent on the criterion used. The less strict criteria seemed to overestimate deformities at either end of the spine region analysed. However, irrespective of the criterion used, prevalence of deformity was higher in men than in women (25% vs 20% for the 3 SD criterion, 17% vs 12% for the 4 SD criterion and 27% vs 25% for the 25% criterion). Femoral neck BMD was more strongly associated with vertebral deformities than spinal BMD for the 25% criterion (OR/SD change in BMD 1.39 (p=0.02) vs 1.20 (p=0.19)), 3 SD criterion (OR/SD change in BMD 1.45 (p=0.01) vs 1.10 (p=0.34)) and 4 SD criterion (OR/SD change in BMD 1.98 (p=0.0002) vs 1.68 (p=0.008)). BMD was also more strongly associated with biconcave deformities than either wedge or crush deformities and more so in men than in women. Severity of spinal osteophytosis was not associated with vertebral deformity. In conclusion, femoral neck BMD is at least equivalent to the lumbar spine BMD in strength of association with prevalent vertebral fractures. Spinal osteophytosis falsely elevates BMD without a concomitant decrease in fracture risk, indicating that any interpretation of spinal BMD needs to be adjusted for osteophytosis. These findings support the use of femoral neck bone densitometry in older men and women. Moreover, these data indicate that current criteria for radiological assessment of vertebral deformity are sufficiently loose to include a substantial proportion of non-fractures in the elderly, with important implications for the design of clinical trials. However, irrespective of the criterion used, vertebral deformities in men are at least as common, if not more so, than in women, suggesting that vertebral osteoporotic fractures are overlooked in men.