Genetic and environmental factors affect bone density variances of families of men and women with osteoporosis

Our aim was to assess the relative impacts of genetics and environment in the families of osteoporotic patients and identify the best subgroup of patients to investigate the genes associated with osteoporosis. We recruited 36 men and 47 women with osteoporosis (probands), median age of 52 and 68 yr, and all their siblings (90) and offspring (83). The families were classified as young or old on the basis of the median age of the probands. We measured the bone mineral density at the femoral neck (FN) and lumbar spine (LS) adjusted for age and weight and standardized (Z-score). Physical activity, nutritional calcium, and alcohol and tobacco consumption were investigated. We compared the mean Z-score using linear mixed model and assessed the familial resemblance using intraclass correlation. The mean Z-scores of the families of osteoporotic patients were significantly negative at FN and LS, with no intergeneration or intergender differences. At FN, but not at LS, the mean Z-score was independently lower in the families of male probands (mean +/- SD: -0.57 +/- 0.96, female: -0.18 +/- 0.85, P = 0.012) and in young families (-0.58 +/- 0.94, old families: -0.11 +/- 0.83, P = 0.006). This suggested that the lower Z-score in the families of men with osteoporosis was related to their younger age. There was significant phenotypic resemblance among members in the families. In the families of female probands, the correlation between the probands and her siblings was weak and disappeared after adjustment on environment, and a resemblance appeared within their children (FN: r = 0.61) suggesting that different environment had masked the resemblance in this subgroup. In the families of male probands, a strong resemblance persisted after adjusting for environment, (proband-offspring at FN: r = 0.46 and within offspring at FN: r = 0.66, at LS: r = 0.61). This showed that resemblance was independent of a common measurable environment in these families of men with osteoporosis. In conclusion, mainly young osteoporotic patients, most of whom were male in our study, are affected by the genetic component.     

Bone assessment in elderly women: what does a low bone ultrasound result tell us about bone mineral density?

Access to dual energy X-ray absorptiometry (DXA) can prove difficult for frail or elderly patients, and bone ultrasound may offer a practical alternative. Even after adjustment for bone mineral density (BMD), ultrasound readings are able to predict hip fracture in elderly women. We consider how bone ultrasound might contribute to bone assessment in a clinical setting. DXA remains the gold standard for bone assessment, with osteoporosis defined as a BMD result more than 2.5 S.D. below the young adult mean. Using an equivalent approach we defined an osteoporotic ultrasound result as broadband ultrasound attenuation (BUA)<54 dB/MHz. In 73 women aged 29-86 (mean 65) years DXA was used to measure BMD at lumbar spine and hip, and ultrasound to measure BUA at the heel. Correlation of BUA with BMD at femoral neck (r=0.64, P<0.001), and lumbar spine (r=0.55, P<0.001) was consistent with previously reported figures for this ultrasound system. All subjects with BUA below the 54 dB/MHz threshold value were shown to have low femoral neck BMD. Women (42%) aged over 65, but only 18% of younger women had low BUA results. In women over 65 years of age measurements of BUA achieved a sensitivity of 61% and specificity of 100% in prediction of low femoral neck BMD. Although a normal BUA did not exclude an osteoporotic BMD result at hip or lumbar spine, a low BUA appeared a highly specific predictor of low BMD at these sites. Since all those women identified as having a low BUA at the heel also had low BMD results, ultrasound appeared to identify a subgroup of elderly patients at a very high risk of fracture.     

Men suffer vertebral fractures with similar spinal T-scores to women

OBJECTIVE: To evaluate the applicability of the WHO densitometric criteria for the diagnosis of spinal osteoporosis in men and to compare it with women with vertebral fractures, as well as to analyze the role of vertebral dimensions in the development of spinal fractures. METHODS: For these purposes we analyzed, using DXA, vertebral projected area and lumbar bone mineral density (BMD), as well as T and Z-scores in lumbar spine in a cohort of 66946 individuals; 2556 of these subjects had one or more atraumatic vertebral fracture (396 men and 2160 postmenopausal women). RESULTS: Men and women with fractures showed significantly lower mean BMD, T-score and Z-score values than individuals without fractures while vertebral dimensions were similar in both groups of patients. When comparing men and women with vertebral fractures, the former showed a significantly greater projected area (46.89+/-5.5 vs. 39.13+/-4.6 cm(2) p<0.001) and lumbar BMD (0.991+/- 0.21 vs. 0.938+/- t0.19 g/cm(2) p<0.001). However, the median lumbar T-score values were similar for both sexes (-2.3 in women vs. -2.2 in men; p: NS). In addition, a similar percentage of men and women with vertebral fractures showed T-score values <-2.5 in the lumbar spine (44% vs. 46%, p=NS). CONCLUSION: We conclude that although men with vertebral fractures have greater vertebral dimensions and BMD than women, the lumbar T-scores are similar. Therefore, it seems reasonable to adopt the same T-score values for the diagnosis of osteoporosis in men and women.     

Osteoporosis in pulmonary clinic patients: does point-of-care screening predict central dual-energy X-ray absorptiometry?

STUDY OBJECTIVES: Patients in a pulmonary clinic have disorders that predispose them to osteoporosis and may use glucocorticoid therapy, which has been associated with low bone mineral density (BMD) and increased fracture risk. Ideally, all patients at risk for osteoporosis would be screened using the best test available, which is central BMD by dual-energy x-ray absorptiometry (DXA). We proposed to stratify the risk for osteoporosis by the use of a simple questionnaire and point-of-care heel ultrasound BMD measurements. DESIGN: Cross-sectional screening study. SETTING: Pulmonary clinic in a single Veterans Affairs Medical Center. PATIENTS: Approximately 200 male and female patients who had not had previous BMD testing were eligible for the study, and 107 gave consent. INTERVENTIONS: One hundred seven men (white, 71 men; black, 35 men; and Asian, 1 man) underwent heel BMD testing and filled out a questionnaire. Ninety-eight men underwent a central DXA. RESULTS: Of 98 subjects, 24.5% had a spine, total hip, or femoral neck (FN) T-score of or= 7 days, and race, which accounted for 52 to 57% of the variance. When a heel ultrasound T-score of -1.0 was tested to predict a central DXA T-score of -2.0, the sensitivity was 61% and the specificity 64%. Adding the questionnaire score and body mass index (BMI) to the heel T-score improved sensitivity but not specificity. Moreover, BMI and age predicted central BMD with similar sensitivity and specificity. Importantly, of 24 patients with a central DXA T-score of 相似文献   

The contribution of IGF-I to skeletal integrity in postmenopausal women

OBJECTIVES: The pathogenic role of the decline in serum concentrations of IGF-I in postmenopausal osteoporosis is not fully elucidated. We investigated the associations among IGF-I, bone mineral density (BMD), ultrasound parameters and prevalence of vertebral fractures in postmenopausal women. DESIGN: A cross-sectional study. PATIENTS: One hundred and fifty-four ambulatory postmenopausal women (61 +/- 7 years) referred for osteoporosis screening. MEASUREMENTS: IGF-I was measured by radioimmunoassay and BMD using dual-energy X-ray absorptiometry. Broadband ultrasound attenuation (BUA) and speed of sound (SOS) at calcaneus were measured by a quantitative ultrasound system. RESULTS: IGF-I was significantly lower in osteoporotic subjects and correlated positively with BMD, BUA and SOS. After adjusting for age, years since menopause and body mass index, IGF-I accounted for 8.5% of the variance at lumbar spine BMD, 4.6% at femoral neck and 7.1% at calcaneal BUA. BUA was associated with IGF-I independently of BMD. IGF-I was lower in women with vertebral fractures (91 +/- 39 microg/l vs. 114 +/- 44 microg/l; P = 0.003). The osteoporosis densitometric criteria (t-score < or = -2.5 SD) was the most strongly independent associated variable with prevalent vertebral fractures [odds ratio (OR): 3.3 (1.4-7.6)], followed by IGF-I levels below 75th percentile [OR: 3 (1-8.8)]. CONCLUSIONS: Our study shows that IGF-I is strongly associated with bone mineral density and reflects aspects of bone quality. The contribution of IGF-I to skeletal integrity in postmenopausal women is clinically relevant.     

Postmenopausal women with Colles' fracture have bone mineral density values similar to those of controls when measured with calcaneus quantitative ultrasound

BACKGROUND: It is a matter of controversy whether or not Colles' fracture is an osteoporotic fracture. Indeed, the usefulness of quantitative ultrasound in distinguishing Colles' fracture from normal fractures is also unclear. METHODS: A cross-sectional case-control study was done on 469 postmenopausal Spanish women, 121 with Colles' fracture and 348 controls. Assessment of risk factors for osteoporosis and measurement of calcaneus quantitative ultrasound were carried out using a Sahara, Hologic device. RESULTS: Patients with Colles' fracture had BUA, SOS, and QUI values that were similar to those of controls, and no statistically significant differences were found. We estimated ROC curves for SOS and a score based on a linear combination of height and SOS (SH-Score). The areas under both curves were 0.56 and 0.61, respectively, which was statistically significant. To obtain 5% false-negative and 10% false-positive figures, the T-score cut-off for SOS was -2.45 and -0.045, respectively. Of these, only 9.2% were classified as high risk and 11% as low risk with 79.8% undetermined. CONCLUSIONS: Patients with Colles' fracture had BUA, SOS, and QUI values that were similar to those of controls. Nevertheless, ROC curves calculated by a combination of height and SOS showed that quantitative calcaneus ultrasound may be a useful tool for identifying postmenopausal women with Colles' fracture. These results indicate that measuring bone mineral density with ultrasound only captures limited aspects of the pathophysiology of Colles' fractures.     

Distal forearm fracture history in an older community-dwelling population: the Nottingham Community Osteoporosis (NOCOS) study.

OBJECTIVES: to assess the prevalence of a history of Colles' fracture (occurring after the age of 40 years) and to ascertain the extent of investigation and treatment of osteoporosis in this population. METHODS: we studied subjects aged > or =60 years from the age-sex register of three general practices. We recorded a history of fractures and details of any previous investigation for osteoporosis and treatment with bone-protective drugs. Bone mineral density was performed at the heel using dual-energy x-ray absorptiometry (Lunar PIXI machine). We classified subjects into normal, osteopaenic or osteoporotic according to the machine manufacturer's recommended World Health Organisation 'equivalent T-score thresholds' (0.6 for osteopaenia and 1.6 for osteoporosis). RESULTS: of the 605 subjects invited, we recruited 259 women and 194 men (response rate=74.8%). Twenty-eight (10.8%) of the women and five (2.6%) of the men had a history of Colles' fracture. Of women with a prevalent Colles' fracture, 39% were osteoporotic and 36% were osteopaenic. These rates were significantly greater than in women without a Colles' fracture (19.9% osteoporotic, 29.4% osteopaenic; P=0.018). Assuming the same PIXI thresholds for men, two (40%) of the five men with a history of Colles' fractures were osteoporotic and the rest were osteopaenic, compared with 20.6 and 31.2% of men without a history of Colles' fractures. None of the subjects in the Colles' fracture group had previously been investigated with bone densitometry. Women with and without a history of Colles' fracture did not differ significantly in ever having (32.1% vs 27.2%; P=0.4) or currently having (14.3% vs 10.4%; P=0.4) hormone replacement treatment. None of the men and only one woman with a previous Colles' fracture had ever taken a non-hormone replacement treatment for osteoporosis. CONCLUSIONS: older community-dwelling subjects with previous Colles' fracture have a high prevalence of osteoporosis and are under-investigated and under-treated. Methods for identifying subjects with a previous Colles' fracture need to be developed in primary and secondary care.     

Ultrasound measurements of calcaneus for estimation of skeletal status in patients with inflammatory bowel disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at risk of developing metabolic bone disease. In diagnosing osteoporosis, bone mineral density (BMD) measurements play a key role. Our aims in this study were to assess the skeletal status with quantitative ultrasound (QUS) and to evaluate the ability of this method to predict BMD as measured by dual-energy X-ray absorptiometry (DXA) in IBD patients. METHODS: Altogether 53 patients with Crohn disease (CD) and 57 with ulcerative colitis (UC) were studied by using a Lunar Achilles ultrasound bone densitometer. The ultrasound variables are broadband ultrasound attenuation (BUA) and speed of sound (SOS). The lumbar spine, femoral neck, and total body BMD were measured with DXA. The age- and sex-adjusted values (Z-scores) were obtained by comparison with age- and sex-matched normal values. RESULTS: In CD patients Z-scores for both BUA and SOS were significantly less than zero, and Z-score for SOS was significantly lower than that for UC patients. Z-scores for BMD measured with DXA were significantly lower at all measurements in patients with CD. QUS and DXA measurements were significantly correlated. However, the agreement between the measurements in each individual patient was poor. Body mass index (BMI) was a major determinant for both BUA and SOS. In CD patients low QUS variables were associated with corticosteroid therapy, and both CD and UC patients with previous fractures had low SOS values. CONCLUSIONS: Our study indicates that QUS and DXA are not interchangeable methods for estimation of bone status. QUS variables are insufficient to provide accurate prediction of BMD values and should therefore not be recommended as a screening test for osteoporosis in IBD patients.     

The effect of long-term, non-suppressive levothyroxine treatment on quantitative ultrasonometry of bone in women

OBJECTIVE: To evaluate the impact of long-term, non-suppressive levothyroxine (L-T(4)) treatment on quantitative ultrasonometry in women. DESIGN: This was a case-control study. SUBJECTS AND METHODS: Altogether 667 women (mean age+/-s.d., 49.5+/-13.1 years) were studied. Of these, 156 (23%) had non-toxic goitre or hypothyroidism and had been taking L-T(4) (75-100 microg/day) for at least 5 years (mean+/-s.d., 12.5+/-7.5 years); the remaining 511 (77%) women were not receiving L-T(4). All women had completed a questionnaire on risk factors for thyroid dysfunction and osteoporosis, and those with diseases or treatments known to effect bone metabolism - other than thyroxine or hormone replacement therapy (HRT) - were excluded. Women underwent quantitative ultrasonometry (QUS) at the heel. Speed of sound (SOS), broadband ultrasound attenuation (BUA) and the stiffness index (SI) were compared, first, in all women taking L-T(4) and controls and, secondly, in women taking L-T(4) and controls pair-matched for age, weight, body mass index (BMI), menopausal status and HRT use. RESULTS: Even after matching for age, weight, BMI, menopausal and HRT status, women taking L-T(4) had significantly lower values for SOS and SI (P<0.05), but not for BUA. However, absolute T- and Z-scores for SI were not low in either the study or control groups. Lower values were associated, but not significantly so, with years since the menopause and duration of L-T(4) treatment. CONCLUSIONS: Long-term, non-suppressive L-T(4) treatment in women with goitre or hypothyroidism was associated with a slight reduction in QUS values, which was more pronounced in postmenopausal women. This group could be at higher risk for osteoporotic fracture.     

骨定量超声测量及OSTA指数与绝经后妇女非椎骨骨折的关系

目的横断面社区研究分析绝经后妇女OSTA指数及多部位定量骨超声（quantitative ultasound,QUS）[超声速率（speed of sound,SOS）],探讨该两个指标预测非椎骨骨折的价值。方法采用以色列Sunlisht Omnisense7000P型QUS仪测量513例女性受试者非优势侧桡骨远端1／3、中指近节指骨及胫骨中段SOS。测量受检者身高、体重,计算OSTA指数,上门问卷形式询问骨折史。结果（1）271例绝经后妇女桡骨、指骨、胫骨SOS显著低于242例绝经前妇女,P〈0．001。（2）绝经后妇女非椎骨骨折组桡骨SOS低于无骨折组（P=0．044）,发生于绝经后的非椎骨骨折妇女,指骨SOS低于无骨折组（P=0．003）。（3）以OSTA〈-4、-4- -1、〉-1将绝经后妇女分为骨质疏松高、中、低风险3组。随骨质疏松风险增加,发生于绝经后的非椎骨骨折率明显升高（χ^2=6．370,P=0．041）,且桡骨、指骨、胫骨SOS显著下降。（4）OSTA取-1及指骨SOSt值取-1．95反映绝经后非椎骨骨折的敏感性分别为75％和81％,特异性分别为48％和40％,受试者工作特征曲线下面积（AUC）分别为0．64和0．66。两者结合敏感性为83％,特异性提高至84％,AUC为0．64。结论OSTA和QUS尤其是指骨SOS具有反映绝经后妇女非椎骨骨折的能力。这两种非常简单、廉价、无创伤性的检查方法有助于筛查高危骨折风险的绝经后妇女。     

The role of quantitative ultrasound in predicting osteoporosis defined by dual X-ray absorptiometry

The aim of this study was to establish whether quantitative ultrasound (QUS) parameters could identify patients classified as osteoporotic and osteopenic on the basis of dual energy X-ray absorptiometry (DEXA). One hundred and twenty-three patients (39 male, 84 female) with osteoporosis and suspected of having osteoporosis were included in this study. Broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured and bone mineral densities (BMD) of the lumbar spine and left hip was measured by DEXA. Subjects were classified into three groups (normal, osteopenic and osteoporotic) on the basis of BMD T-scores measured by DEXA. QUS parameters of the osteoporotic group were significantly lower than those of osteopenic and normal groups; there was no difference in QUS parameters between the normal and osteopenic groups. Correlations of both right and left SOS and BUA with the spine and femoral neck BMD were moderate (r = 0.343-0.539, P < 0.001). There was also reasonable correlation between DEXA and QUS T-scores (r = 0.364-0.510, P < 0.001). QUS had a sensitivity of 21% and a specificity of 95% for diagnosing osteoporosis. We concluded that, although DEXA and QUS parameters were significantly correlated, QUS parameters can not predict osteopenia as defined by DEXA, and sensitivities and specificities of QUS parameters were not sufficiently high for QUS to be used as an alternative to DEXA.     

Self-reported fractures and associated factors in women with systemic lupus erythematosus

OBJECTIVE: To determine the frequency of fractures and associated factors in women with systemic lupus erythematosus (SLE). METHODS: Women with SLE (n = 304) completed this cross-sectional study conducted from 1996 to 2002. Self-reported fractures occurring after the diagnosis of SLE were evaluated. Hip and/or lumbar spine bone mineral density (BMD) was measured using dual-energy x-ray absorptiometry, and the results were expressed as BMD Z-scores. Multiple logistic regression analyses were performed to identify factors associated with fractures. RESULTS: Of the 304 women with SLE, 12.5% experienced fractures. Those with fractures had significantly lower BMD Z-scores at the hip (Fracture group -0.55 vs No Fracture group -0.14, group difference 0.41; 95% CI 0.04 to 0.78), but not at the lumbar spine (Fracture group -0.25 vs No Fracture group -0.18, group difference 0.07; 95% CI -0.43 to 0.57). Among women with fractures, 60.5% and 63.2% had normal BMD Z-scores (BMD Z-score > -1.0) at the hip and lumbar spine, respectively, and 50.0% had normal BMD Z-scores at both anatomical sites. In multiple logistic regression analysis, each year of disease duration (adjusted OR 1.11; 95% CI 1.05 to 1.17) and use of osteoporosis medications (adjusted OR 4.75; 95% CI 1.62 to 13.94) were significantly associated with fractures. CONCLUSION:. Longer duration of SLE and use of osteoporosis medications were significantly associated with fractures. Although women with fractures had significantly lower BMD Z-scores at the hip, an unexpectedly high proportion of women with SLE having normal BMD Z-score experienced fractures following SLE diagnosis.     

Assessment of non-vertebral fracture risk in postmenopausal women

BACKGROUND: Non-vertebral (NV) fractures are responsible for a great amount of morbidity, mortality and cost attributable to osteoporosis. OBJECTIVES: To identify risk factors for NV fractures in postmenopausal women with osteoporosis, and to design an assessment tool for prediction of these fractures. METHODS: 2546 postmenopausal women with osteoporosis included in the placebo groups of three risedronate controlled trials were included (mean age 72 years, mean femoral T-score -2.5; 60% and 53% of patients with prevalent vertebral and NV fractures, respectively). Over 3 years, 222 NV fractures were observed. Baseline data on 14 risk factors were included in a logistic regression analysis. RESULTS: 6 risk factors were associated with NV fracture risk: prevalent NV fracture (p = 0.004), number of prevalent vertebral fractures (p<0.001), femoral T-score (p = 0.031), serum level of 25-hydroxyvitamin D (p<0.001), age (p = 0.012) and height (p = 0.037). An NV risk index was developed by converting the multivariate logistic equation into an additive score. In the group of women with a score > or =2.1, the incidence of NV fracture was 13.2% (95% CI 11.1 to 15.3), 1.5 times higher than that of the general population. CONCLUSIONS: The NV risk index is a convenient tool for selection of patients with osteoporosis with a high risk for NV fractures, and may help to choose from available treatments those with a proven efficacy for reduction of NV fracture risk.     

The development of bone mineral density and the occurrence of osteoporosis from 15 to 20 years of disease onset in patients with rheumatoid arthritis

OBJECTIVE: To ascertain the occurrence of osteoporosis and the development of central bone mineral density (BMD) in long-term rheumatoid arthritis (RA) METHODS: BMD of the lumbar spine (L2-L4) and the femoral neck were measured by dual-energy X-ray absorptiometry in a cohort of 59 patients (49 women and 10 men) with rheumatoid factor-positive RA followed up for 20 years. BMD measurements were obtained at the 15- and 20-year follow-up visits. RESULTS: At the 15-year check-up the mean age was 61 (SD 13)for men and 54 (SD 11) years for women. Bone densitometry of these patients revealed decreased BMD at both lumbar spine and femoral neck, the mean T-scores being -1.1 [95%CI: -1.6 to -0.6] and -1.3 [95%CI: -1.6 to -1], respectively). Eighteen (31 %) patients thus had osteoporosis (BMD T -score < or = -2.5) and 32 (54%) patients were osteopenic (BMD T-score -1.0 to -2.5). However, when compared with reference values, the decreases in central bone mineral in this patient group were of low degree; the mean Z-score -0.2 [95%CI: -0.7 to 0.2] at the lumbar spine and -0.5 [95%CI: -0.8 to -0.3] at the femoral neck, respectively. After the subsequent five years the mean Z-score increased 0.45 [95%CI: 0.32 to 0.58] at the lumbar spine and the mean T-score decreased -0.20 [95%CI: -0.32 to -0.08] at the femoral neck. ESR, Larsen score, gender and cumulative dose of prednisolone during the 5 year follow-up and HAQ-index were used as explanatory parameters of BMD change between the 15- and 20-year follow-ups. None of these parameters explained the BMD change. CONCLUSION: We conclude that in long-term RA central bone densities seemed to be only moderately decreased after 15 years from eruption of RA. No essential change in central BMD was found after the consecutive 5 years.     

Hip fracture in women without osteoporosis

The proportion of fractures that occur in women without osteoporosis has not been fully described, and the characteristics of nonosteoporotic women who fracture are not well understood. We measured total hip bone mineral density (BMD) and baseline characteristics including physical activity, falls, and strength for 8065 women aged 65 yr or older participating in the Study of Osteoporotic Fractures and then followed these women for hip fracture for up to 5 yr after BMD measurement. Among all participants, 17% had osteoporosis (total hip BMD T-score < or = -2.5). Of the 243 women with incident hip fracture, 54% were not osteoporotic at start of follow-up. Nonosteoporotic women who fractured were less likely than osteoporotic women with fracture to have baseline characteristics associated with frailty. Nevertheless, among nonosteoporotic participants, several characteristics increased fracture risk, including advancing age, lack of exercise in the last year, reduced visual contrast sensitivity, falls in the last year, prevalent vertebral fracture, and lower total hip BMD. These findings call attention to the many older women who suffer hip fracture but do not have particularly low antecedent BMD measures and help begin to identify risk factors associated with higher bone density levels.     

A risk assessment tool (OsteoRisk) for identifying latin American women with osteoporosis

OBJECTIVE: To develop a simple and easy-to-use tool for identifying osteoporotic women (femoral neck bone mineral density [BMD] T-scoresor=50 in Latin America who had femoral neck BMD measurements. MEASUREMENTS AND MAIN RESULTS: A risk index was developed from 1,547 patients based on least square regression using age, weight, history of fractures, and other variables as predictors for BMD T-score. The final model was simplified by reducing the number of predictors; sensitivity and specificity were evaluated before and after reducing the number of predictors to assess performance of the index. The final model included age, weight, country, estrogen use, and history of fractures as significant predictors for T-score. The resulting scoring index achieved 91% sensitivity and 47% specificity. Simplifying the index by using only age and weight yielded similar performance (sensitivity, 92%; specificity, 45%). Three risk categories were identified based on OsteoRisk, the index using only age and body weight: high-risk patients (index <=-2; 65.6% were osteoporotic), moderate-risk patients (-2< index <=1; 26.7% were osteoporotic), and low-risk patients (index>1; 8% were osteoporotic). Similar results were seen in a validation sample of 279 women in Brazil. CONCLUSION: Age and weight alone performed well for predicting the risk of osteoporosis among postmenopausal women. The OsteoRisk is an easy-to-use tool that effectively targets the vast majority of osteoporotic patients in Latin America for evaluation with BMD.     

Clinical characteristics and etiologic factors of premenopausal osteoporosis in a group of Spanish women

OBJECTIVES: To analyze the clinical characteristics and the principal causes of osteoporosis in premenopausal women. METHODS: This study included 52 osteoporotic premenopausal women ages 20-51 years (mean 36.2 +/- 7) who were referred to an outpatient rheumatology department for osteoporosis evaluation. Bone mass assessment, automated biochemical profile, urinary calcium excretion, and bone marker assays were performed on all patients. Hormonal measurements were made when a specific etiology was not readily apparent. The diagnosis of osteoporosis was defined by the presence of atraumatic vertebral fractures and/or by densitometric criteria. Previous skeletal fractures, weight, height, body mass index (BMI), age at menarche, and family history of osteoporosis also were recorded. RESULTS: Twenty-nine patients (56%) had idiopathic osteoporosis and 23 (44%) had secondary osteoporosis. Fifteen patients (29%) had vertebral fractures and 12 had previous peripheral fractures. Patients with secondary osteoporosis showed higher BMI (23.2 +/- 3 v 21.2 +/- 2, P =.02) and lower femoral Z-scores of bone mineral density (BMD) (-2.1 +/- 0.6 v -1.5 +/- 0.9, P =.02) than those with idiopathic disease. The most frequent causes of secondary osteoporosis included Cushing syndrome, pregnancy osteoporosis, and osteogenesis imperfecta. Nearly half of the patients (48%) with idiopathic osteoporosis had a family history of osteoporosis. In addition, 11 patients (38%) with idiopathic osteoporosis had associated hypercalciuria. Except for an increase in urinary calcium excretion (248 +/- 53 v 143 +/- 47 mg/24 h, P <.0001), no other significant differences in the remaining variables analyzed were found between hypercalciuric and normocalciuric patients with idiopathic osteoporosis. CONCLUSIONS: Idiopathic osteoporosis was the most frequent diagnosis of pre-menopausal osteoporosis in our unit. These patients showed lower BMI and higher femoral neck Z-scores than patients with secondary causes. A family history of osteoporosis and hypercalciuria were factors frequently associated with this disorder.     

Osteoporosis in men

Male osteoporosis is an increasingly important public health problem: from age 50 onward, one in three osteoporotic fractures occurs in men and fracture-related morbidity and mortality are even higher than in women. In 50% of osteoporotic men, an underlying cause can be identified (secondary osteoporosis). In the absence of an identifiable etiology, male osteoporosis is referred to as 'idiopathic osteoporosis' in men aged 30-70 years and as 'age-related osteoporosis' in older men. As in women, estrogen, not testosterone, appears the most important sex steroid regulating male skeletal status. Diagnosis and treatment recommendations are still largely based on bone mineral density (BMD), with osteoporosis defined as a T-score of 2.5 standard deviations below young adult values. However, there is ongoing discussion as to whether male or female reference ranges should be used and, like in women, treatment decisions are increasingly based on absolute fracture risk estimations rather than on BMD alone. In men, evidence-based data on the efficacy of pharmacologic interventions in reducing fracture risk are convincing but not conclusive. In particular, bisphosphonates and teriparatide seem to be as effective in men as in women.     

Osteoporosis in beta-thalassaemia major patients: analysis of the genetic background

Regular blood transfusions from infancy until adulthood in beta-thalassaemia major patients have substituted severe bone deformities with less marked skeletal lesions as osteoporosis. Osteoporosis is characterized by low bone mass and disruption of bone architecture, resulting in reduced bone strength and increased risk of fractures. Genetic factors have an important role in determining bone mineral density (BMD). We have investigated the possible association between BMD and two polymorphisms in 135 beta-thalassaemic patients: (i) a substitution G-->Tau in a regulatory region of the COLIA1 gene encoding for the major protein of bone (type 1 collagen), and (ii) a one-base deletion in intron 4 (713-8del C) of transforming growth factor beta 1 (TGF-beta1) gene. We have found a remarkable incidence (90%) of osteopenia and osteoporosis among regularly transfused patients. Bone mass was lower in men than in women (P = 0.0023), with a more prevalent osteopenia/osteoporosis of the spine in men than in women (P = 0. 001). The sample was stratified on the basis of BMD expressed as Z-score, i.e. normal, osteopenic and osteoporotic patients, and genotype frequencies of each group were evaluated. TGF-beta1 polymorphism failed to demonstrate a statistical difference in BMD groups. However, subjects with heterozygous or homozygous polymorphism of the COLIA1 gene showed a lower BMD than subjects without the sequence variation (P = 0.012). The differences among genotypes were still present when the BMD was analysed as adjusted Z-score and when men and women were analysed separately (P = 0.022 and 0.004 respectively), with men more severely affected. Analysis of COLIA1 polymorphism could help to identify those thalassaemic patients at risk of osteoporosis and fractures.     

Lumbar osteoarthritis, bone mineral density, and quantitative ultrasound

Low bone mass is a major risk factor for osteoporotic fractures. Thus, bone density evaluation, performed by Dual Energy X-ray Absorptiometry (DXA) is important for diagnosis and monitoring treatment of osteoporosis. The accuracy of DXA, particularly at the lumbar spine, can be affected by several factors such as degenerative diseases. To evaluate the effects of vertebral osteophytosis on densitometric measurements, we examined 198 women, aged 32-81 years, who had undergone lateral X-ray of the lumbar spine. We classified patients according to different grades of osteophytosis, and evaluated bone density at the lumbar spine and the proximal femur by DXA. We also performed quantitative ultrasound at the heel (QUS). Patients with severe osteophytosis were significantly older (p < 0.0005), and values were adjusted for this parameter. We observed a significant increase in lumbar bone density with worsening osteophytosis (p < 0.02). On the contrary, no significant differences were found at the femur and QUS. According to bone density at the femoral neck, we subdivided patients into two groups: osteoporotic (group A) and non-osteoporotic (group B). Both groups showed increasingly high bone density at the spine with worsening osteophytosis (A: p < 0.01; B: p < 0.02). No differences were found in all the other evaluations. In conclusion, lumbar spine measurement is dramatically influenced by osteophytosis, particularly in the elderly. Consequently, other strategies should be performed such as evaluation of the hip and also measurement of the heel by ultrasound, which could be an interesting approach in these cases.