Bone mineral density and its correlation with clinical and laboratory factors in chronic peritoneal dialysis patients

The aim of this study was to assess the clinical and laboratory correlations of bone mineral density (BMD) measurements among a large population of patients on chronic peritoneal dialysis (PD). This cross-sectional, multicenter study was carried out in 292 PD patients with a mean age of 56 ± 16 years and mean duration of PD 3.1 ± 2.1 years. Altogether, 129 female and 163 male patients from 24 centers in Canada, Greece, and Turkey were included in the study. BMD findings, obtained by dual-energy X-ray absorptiometry (DEXA) and some other major clinical and laboratory indices of bone mineral deposition as well as uremic osteodystrophy were investigated. In the 292 patients included in the study, the mean lumbar spine T-score was −1.04 ± 1.68, the lumbar spine Z-score was −0.31 ± 1.68, the femoral neck T-score was −1.38 ± 1.39, and the femoral neck Z score was −0.66 ± 1.23. According to the WHO criteria based on lumbar spine T-scores, 19.2% of 292 patients were osteoporotic, 36.3% had osteopenia, and 44.4% had lumbar spine T-scores within the normal range. In the femoral neck area, the prevalence of osteoporosis was slightly higher (26%). The prevalence of osteoporosis was 23.3% in female patients and 16.6% in male patients with no statistically significant difference between the sexes. Agreements of lumbar spine and femoral neck T-scores for the diagnosis of osteoporosis were 66.7% and 27.3% and 83.3% for osteopenia and normal BMD values, respectively. Among the clinical and laboratory parameters we investigated in this study, the body mass index (BMI) (P < 0.001), daily urine output, and urea clearance time × dialysis time/volume (Kt/V) (P < 0.05) were statistically significantly positive and Ca × PO₄ had a negative correlation (P < 0.05) with the lumbar spine T scores. Femoral neck T scores were also positively correlated with BMI, daily urine output, and KT/V; and they were negatively correlated with age. Intact parathyroid hormone levels did not correlate with any of the BMD parameters. Femoral neck Z scores were correlated with BMI (P < 0.001), and ionized calcium (P < 0.05) positively and negatively with age, total alkaline phosphatase (P < 0.05), and Ca × P (P < 0.01). The overall prevalence of fractures since the initiation of PD was 10%. Our results indicated that, considering their DEXA-based BMD values, 55% of chronic PD patients have subnormal bone mass—19% within the osteoporotic range and 36% within the osteopenic range. Our findings also indicate that low body weight is the most important risk factor for osteoporosis in chronic PD patients. An insufficient dialysis dose (expressed as KT/V) and older age may also be important risk factors for osteoporosis of PD patients.     

Ultrasound Velocity Through the Phalanges in Normal and Osteoporotic Patients

Quantitative ultrasound (US) measurements have been shown to be a new technique assessing bone status. This study aimed to assess a new US instrument, the DBM Sonic 1200? (IGEA) which permits the measurement of the speed of sound in the proximal phalanges (SOSp) of the hand. The results obtained were compared with DXA (SOPHOS) and US measurements at the calcaneus (Achilles? LUNAR). The in vivo precision expressed by coefficient of variation was 0.91%. Ultrasound measurements of phalanges were significantly correlated with BMD in the entire group of 90 subjects: osteoporotic patients (n = 47) and controls (n = 43) (r = 0.44, femoral neck and 0.45, lumbar spine, P < 0.01). A significant correlation was also found in the control group (r = 0.33, lumbar spine and 0.38, femoral neck, P < 0.05) but not in the osteoporotic group (r = 0.3, lumbar spine and 0.17, femoral neck, P > 0.05). Mean values for 31 postmenopausal, osteoporotic women and age-matched controls showed a significant decrease in US measurements at the phalanges (P < 0.05) and the calcaneus (P < 0.01) as well as bone mineral density (BMD) at the spine and femoral neck (P < 0.01) in the osteoporotic group. A decision threshold for a sensitivity of 80% for osteoporotic fractures resulted in a specificity value of only 37% for SOSp, between 53 to 65% for calcaneus US measurements and 45 to 56% for BMD. The Z score, the odds ratio, the ROC curves, and areas under the curves plotted for the subgroup of 31 fractures and their healthy controls showed poorer values for SOSp than BMD and calcaneus US measurements. In conclusion, US measurements of phalanges seem to be less efficient than calcaneus US and BMD measurements to distinguish osteoporotic from healthy women. Other studies and also prospective studies are required to assess the interest in fracture risk assessment. Received: 23 September 1996 / Accepted: 25 November 1997     

绝经后妇女骨质疏松性椎体骨折与腰椎骨密度的关系

目的探讨绝经后妇女骨质疏松性椎体骨折与腰椎骨密度的关系。方法选择骨质疏松性椎体骨折的绝经后妇女23例为骨折组,无椎体骨折的25例绝经后骨质疏松妇女为对照组。两组的年龄、绝经年限、身高、体重、体重指数差异无显著性,均行胸腰椎正侧位X线摄片。用双能X线吸收仪（DXA）测量的腰椎（L2-4）前后位骨密度（BMD）、骨矿含量（BMC）和T值。结果骨折组BMD、BMC和T值均低于对照组（P〈0.01）。结论腰椎BMD降低与绝经后妇女的骨质疏松性椎体骨折相关。绝经后骨质疏松妇女应重视BMD变化,预防椎体骨折的发生。     

Determination of serum 25-hydroxyvitamin D(3) levels in early postmenopausal Iranian women: relationship with bone mineral density.

Serum levels of 25-hydroxyvitamin D(3) (25-OHD(3)) and bone mineral density (BMD) were determined in 73 selected, early postmenopausal women referred to the Bone Densitometry Center, Loghman-Hakim Hospital, Tehran, Iran. The relationship between them was also assessed. 25-OHD(3) levels were measured using high-performance liquid chromatography. BMD was measured with dual-energy X-ray absorptiometry of the lumbar spine and proximal femur regions. 25-OHD(3) levels ranged from 3.8 to 64.0 ng/mL (mean +/- SD: 17.1 +/- 11.3). Twenty-six subjects (36%) were vitamin D-deficient (<12 ng/mL). In the lumbar spine (L2-4) BMD measurements, 28 subjects (38%) were normal (T score > -1), 26 (36%) were osteopenic (T < or = -1 to >-2.5), and 19 (26%) were osteoporotic (T < -2.5). In the hip (total) BMD measurements, 41 subjects (56.1%) were normal, 31 (42.5%) were osteopenic, and 1 (1.4%) was osteoporotic. There was a significant correlation between spine BMD (Z score) and 25-OHD(3) (r = 0.23, p < 0.05), but the correlation was not significant for hip BMD. It was concluded that vitamin D deficiency was evident in early postmenopausal Iranian women, and serum 25-OHD(3) was weakly correlated with spine BMD, which may have physiological significance.     

Risk for developing osteoporosis in untreated premature menopause

Summary The bone mineral density (BMD) of the lumbar spine and proximal femur was determined by dual photon absorptiometry in 32 women with untreated premature menopause (cessation of menses before 45 years of age). The BMD of the spine and proximal femur in four obese patients was not different from the BMD of the age-matched controls. On the contrary, the BMD of the nonobese females with premature menopause was significantly lower with respect to the average values found in healthy young women, in age-matched and menopause-matched controls. The BMD deficit was greater over the lumbar spine than in the proximal femur. Forty three percent of nonobese patients were already under the vertebral fracture threshold and 25% of nonobese patients were below the hip fracture threshold. The BMD deficit in the lumbar spine was correlated to the loss observed in the femoral neck (r=0.59, P<0.001), in the trochanter (r=0.65, P<0.001) and in the Ward's triangle (r=0.73, P<0.001). A negative correlation was observed between years of menopause and the BMD of the lumbar spine (r=-0.39, P<0.05). The results indicate the high individual risk for osteoporotic fractures in nonobese females with untreated premature menopause. The BMD loss was greater over the skeletal areas that are predominantly composed of trabecular bone compared with cortical bone.     

Bone mineral density and body composition in men with systemic lupus erythematosus: a case control study

OBJECTIVE: To study the bone mineral density (BMD) and body composition in men with systemic lupus erythematosus (SLE). METHODS: Consecutive male patients who fulfilled > or =4 ACR criteria for SLE and age-matched healthy men were recruited for measurement of BMD and body composition by DXA scan. Risk factors for low BMD in SLE patients were evaluated. RESULTS: 40 male SLE patients were studied (age 42.6+/-12 years; disease duration 84.7+/-79 months). 34 (85%) patients were treated with long-term glucocorticoids. Compared with 40 controls, SLE patients had a significantly lower BMD at the lumbar spine (0.96+/-0.16 vs 1.03+/-0.11 g/cm2; p=0.02) and the hip (0.87+/-0.14 vs 0.94+/-0.12 g/cm2; p=0.04). At the spine, 12 (30%) SLE patients had Z scores< - 2.0 and 2 (5%) had osteoporotic fractures. At the hip, 3 (7.5%) patients had Z scores< - 2.0 but none had hip fractures. The BMD Z scores at the femoral neck and spine were significantly lower in SLE patients than controls. The total lean body mass was also lower in patients than control subjects (46.4+/-7.3 vs 50.5+/-5.9 kg; p=0.01). Multiple regression revealed increasing age, habitual drinking, lower BMI and use of high-dose prednisolone were unfavorably associated with lower BMD at the spine in SLE patients. CONCLUSIONS: Reduced BMD and lean body mass are prevalent in men with SLE. Appropriate measures against osteoporosis should be undertaken, especially in older patients with low BMI who receive high-dose glucocorticoids.     

Bone microarchitecture assessed by TBS predicts osteoporotic fractures independent of bone density: the Manitoba study

The measurement of BMD by dual‐energy X‐ray absorptiometry (DXA) is the “gold standard” for diagnosing osteoporosis but does not directly reflect deterioration in bone microarchitecture. The trabecular bone score (TBS), a novel gray‐level texture measurement that can be extracted from DXA images, correlates with 3D parameters of bone microarchitecture. Our aim was to evaluate the ability of lumbar spine TBS to predict future clinical osteoporotic fractures. A total of 29,407 women 50 years of age or older at the time of baseline hip and spine DXA were identified from a database containing all clinical results for the Province of Manitoba, Canada. Health service records were assessed for the incidence of nontraumatic osteoporotic fracture codes subsequent to BMD testing (mean follow‐up 4.7 years). Lumbar spine TBS was derived for each spine DXA examination blinded to clinical parameters and outcomes. Osteoporotic fractures were identified in 1668 (5.7%) women, including 439 (1.5%) spine and 293 (1.0%) hip fractures. Significantly lower spine TBS and BMD were identified in women with major osteoporotic, spine, and hip fractures (all p < 0.0001). Spine TBS and BMD predicted fractures equally well, and the combination was superior to either measurement alone (p < 0.001). Spine TBS predicts osteoporotic fractures and provides information that is independent of spine and hip BMD. Combining the TBS trabecular texture index with BMD incrementally improves fracture prediction in postmenopausal women. © 2011 American Society for Bone and Mineral Research     

Analysis of factors affecting increase in bone mineral density at lumbar spine by bisphosphonate treatment in postmenopausal osteoporosis

Bisphosphonate is an effective drug to reduce fracture risk in osteoporotic patients; however, factors affecting the efficacy of bisphosphonate treatment are not fully known, especially in Japanese patients. In the present study, we examined the relationships between an increase in lumbar spine bone mineral density (BMD) by bisphosphonates and several pretreatment parameters, including biochemical, bone/mineral, and body composition indices, in 85 postmenopausal osteoporotic patients treated with alendronate or risedronate. BMD increase was measured by dual-energy X-ray absorptiometry at the lumbar spine before and 2 years after treatment. BMD increase at the lumbar spine was observed as independent of age, height, weight, body mass index, and fat mass, although lean body mass seemed slightly related. On the other hand, fasting plasma glucose (FPG) levels were significantly and positively related to BMD increase at the lumbar spine. In multiple regression analysis, FPG levels were not significantly related to BMD increase at the lumbar spine when lean body mass was considered. As for bone/mineral parameters, BMD increase at the lumbar spine was not significantly related to serum levels of calcium, parathyroid hormone (PTH), and alkaline phosphatase or urinary levels of deoxypiridinoline and calcium excretion. As for BMD parameters, Z-scores of BMD at any site and bone geometry parameters obtained by forearm peripheral quantitative computed tomography were not significantly related to BMD increase at the lumbar spine. BMD increases at the lumbar spine were similar between groups with or without vertebral fractures. In conclusion, BMD increase at the lumbar spine by bisphosphonate treatment was not related to any pretreatment parameters, including body size, body composition, and bone/mineral metabolism in postmenopausal Japanese women with primary osteoporosis, although FPG correlated partly to BMD through lean body mass.     

The Beneficial Effect of Leisure-Time Physical Activity on Bone Mineral Density in Pre- and Postmenopausal Women

Regular exercise and physical activity (PA) are known to be protective factors for maintaining bone mineral density (BMD) and preventing osteoporotic fracture. We investigated the associations between leisure-time PA and BMD in 2,903 premenopausal and 2,267 postmenopausal women in Korea. BMDs of the lumbar spine and femur were measured using dual-energy X-ray absorptiometry. Leisure-time PA levels were assessed by a self-administrated questionnaire, and a total metabolic equivalent (MET) score was obtained. Regardless of menopausal status, performing more than moderate levels of leisure-time PA or total MET score had a significant positive association with BMD at both the lumbar spine and femur. In the premenopausal group, women whose total MET score was 1,050-1,500 (MET-min/week) appeared to have the highest lumbar spine and femoral BMD (p?相似文献   

Not All Postmenopausal Women on Chronic Steroid and Estrogen Treatment are Osteoporotic: Predictors of Bone Mineral Density

Chronic steroid use results in osteoporosis, and postmenopausal women are believed to be at a high risk for steroid-induced bone loss. The purpose of this study was to determine predictors of bone mineral density (BMD) in postmenopausal women on both chronic steroid and hormone replacement therapy. Seventy-six postmenopausal women (≥3 years postmenopausal, ≥2 years of steroid treatment of ≥5 mg/day of prednisone, and ≥1 year of hormone replacement therapy) were recruited into this study. Measurements of BMD of the lumbar spine and femoral neck were obtained in all subjects. Risk factors for osteoporosis were obtained by questionnaire. Discriminant analysis was performed to determine predictors of BMD. Osteoporosis, defined by a T score of <−2.5, was present in the lumbar spine or femoral neck in 34 of the 76 subjects. Based on these criteria, women with osteoporosis were significantly older, were more years postmenopausal, and had a lower body mass index (BMI) than women who did not have osteoporosis. Predictors of osteoporosis for both the femoral neck and spine included a low BMI (P < 0.05), more years postmenopausal (P < 0.01), and more years on steroids (P < 0.01). Low BMI was the only significant predictor of osteoporosis in the lumbar spine (P < 0.05), whereas for the femoral neck both years on steroids (P < 0.05) and BMI (P < 0.05) were significant predictors of low BMD. In summary, not all postmenopausal women on chronic steroid and hormone replacement therapy are osteoporotic but a low BMI, more years on steroids, and more years postmenopausal were significant predictors of osteoporosis in these subjects. Received: 8 November 1997 / Accepted: 21 May 1997     

Lateral Spine Densitometry in Obese Women

The lateral (LAT) spine scan has been suggested as a more sensitive measure than posterior-anterior (PA) scanning for assessing age-related bone loss in normal-weight postmenopausal women. The measurement error of PA and LAT bone mineral density (BMD) using dual energy X-ray absorptiometry (DXA) has also been shown to rise with incremental increases in fat and from large variance in fat thickness, respectively. The purpose of this cross-sectional study was to determine specific affects of obesity on paired PA and LAT lumbar (L₂–L₄) BMD and Z score (BMD of patient versus age-matched reference database) correlation in 30 obese postmenopausal women (mean BMI ± SD = 33.3 ± 4.06). The mean PA and LAT BMD ± SD were 0.946 ± 0.123 and 0.749 ± 0.134, respectively. The mean PA and LAT Z scores were −0.17 ± 1.15 and 0.80 ± 1.7. The correlation between PA and LAT BMD was significantly lower (r = 0.55; P < 0.05) than previously reported, and PA and LAT Z score correlation was (r = 0.57; P= 0.0016). After adjusting for body mass index (BMI), percent body fat, fat mass, and truncal fat by DXA, waist:hip ratio (WHR) and visceral and subcutaneous abdominal fat by computerized axial tomography (CT), PA and LAT Z score correlation increased to r = 0.62; P= 0.0065. In our subjects, the mean LAT Z score was 4.6 times higher than the mean AP Z, contrary to previous observations in normal-weight postmenopausal women. Our findings may be due to increased soft tissue composition and fat inhomogeneity in the LAT scanning field resulting in increased X-ray attenuation in obesity. Received: 22 July 1997 / Accepted: 26 January 1998     

Osteoporosis assessment by whole body region vs. site-specific DXA

The ability of regional data from whole body scans to provide an accurate assessment of site-specific BMD, osteoporosis prevalence and fracture risk has not been fully explored. To address these issues, we measured total body (TBBD) and site-specific BMD in an age-stratified population sample of 351 women (21–93 years) and 348 men (22–90 years). We found an excellent correlation between AP lumbar spine and total body lumbar spine subregion BMD (r ²=0.92), but weaker ones for total hip compared to pelvis region (r ²=0.72) or between total wrist and left arm subregion from the whole body scan (r ²=0.83). The error in estimating site-specific BMD from total body regions ranged from 4.3% (lumbar spine) to 11.2% (femoral neck) in women and from 4.9 to 11.1%, respectively, in men. Site-specific versus regional measurements at the lumbar spine and total hip/pelvis provided comparable overall estimates of osteoporosis prevalence, but disagreed on the status of individuals; measurements at whole body regions underestimated osteoporosis as assessed at the femoral neck or total wrist. All measurements were associated with a history of various fractures [age adjusted odds ratios (OR), 1.3 to 2.1 in women and 1.2 to 1.5 in men] and were generally interchangeable, but femoral neck BMD provided the best estimate of osteoporotic fracture risk in women (OR, 2.9; 95% CI, 1.7–5.0). Although there are strong correlations between BMD from dedicated scans of the hip, spine and distal forearm and corresponding regions on the whole body scan, the measurements provide somewhat different estimates of osteoporosis prevalence and fracture risk.     

Vitamin D receptor start codon polymorphism (<Emphasis Type="Italic">Fok</Emphasis>I) is related to bone mineral density in healthy adolescent boys

 Peak bone mass is considered a major determinant in the emergence of osteoporosis and is mainly genetically regulated. Several genes have been investigated, among them the vitamin D receptor (VDR) gene. A single-nucleotide polymorphism (defined by the endonuclease FokI) located in the start codon of the VDR creates the alleles F and f, resulting in different proteins. A number of previous studies have proved the F allele to be more advantageous as concerns bone mineral density (BMD). In this longitudinal study of 88 adolescent boys, we have investigated whether the different genotypes are associated with BMD, bone mineral content (BMC), or bone area. BMD, BMC, and bone area of the right femoral neck, lumbar spine, and total body were measured using dual-energy X-ray absorptiometry. Differences in phenotypes in relation to the FokI polymorphism were calculated by means of an analysis of variance (ANOVA), with Bonferroni's correction for multiple comparisons. At the first examination, the FokI genotypes were significantly related to lumbar spine BMC and total body bone area in boys aged 16.9 ± 0.3 years (mean ± SD). There was a strong tendency towards significance as regards pubertal stage, total body and femoral neck BMC, weight, lean body mass, lumbar spine bone area, and lumbar spine BMD. There were no significant differences in height, fat mass, birth height and weight, total body and femoral neck BMD, and femoral neck bone area. Regression analysis proved the FokI genotypes to be independently related to lumbar spine BMD (FF > ff; P < 0.01), and possibly total body BMD (P = 0.06), but not femoral neck BMD. At the second examination, approximately 2 years later, our ANOVA results showed significance as regards femoral neck BMC and weight. Using multiple regression, the FokI genotypes were independently related to lumbar spine BMD (FF > ff; P = 0.03), and total body BMD (P < 0.05), but not femoral neck BMD. This study proves the FokI polymorphism to be an independent predictor of lumbar spine BMD are probably total body BMD, but not femoral neck BMD. Received: December 25, 2001 / Accepted: October 7, 2002 Offprint requests to: M. Lorentzon     

Associations between osteoprotegerin and femoral neck BMD in hemodialysis patients

Numerous humoral factors are involved in the development of renal osteodystrophy, causing perturbations in bone mineral density (BMD) in patients with end-stage renal disease (ESRD). The RANKL/OPG cytokine system appears to mediate the effects of many of these factors on bone turnover, contributing to the pathogenesis of renal bone disease. The aim of this study was to evaluate the clinical and biochemical correlations of BMD measurements in patients on chronic hemodialysis. Fifty-four hemodialysis patients underwent measurement of BMD at the proximal femur and the lumbar spine (L2–L4). Intact parathyroid hormone (PTH), osteoprotegerin (OPG), sRANKL, and main bone biochemical markers were also measured in serum samples of all patients. BMD of the femoral neck was negatively correlated with OPG levels (r = 0.333, P = 0.014). OPG levels were significantly different among normal, osteopenic, and osteoporotic tertiles defined according to BMD of the femoral neck. The highest OPG levels were measured in the lowest T-score (osteoporotic) tertile and were higher than in the osteopenic and normal tertiles (P < 0.05). A threshold level for OPG at 21.5 pmol/l enabled the detection of osteoporotic patients with 76.5% sensitivity and 62.2% specificity. BMD values of trabecular bone-rich sites of the skeleton such as lumbar spine (L2–L4), trochanter, and Ward’ s triangle were inversely correlated with total ALP levels (P < 0.05). Hemodialysis patients with low BMD of the femoral neck demonstrated higher OPG levels than patients with normal BMD. Those with lumbar spine (L2–L4), trochanteric, and Ward's triangle BMDs below the normal range presented higher total ALP levels. These results suggest that OPG and total ALP may be clinically useful markers in the detection of significant femoral neck and trabecular bone mineral deficit in hemodialysis patients, warranting further investigations.     

Association of a single-nucleotide polymorphism in low-density lipoprotein receptor-related protein 5 gene with bone mineral density

Low-density lipoprotein receptor-related protein 5 (LRP5) is an important regulator of osteoblast growth and differentiation, affecting peak bone mass in vertebrates. Here, we analyzed whether the LRP5 gene was involved in the etiology of postmenopausal osteoporosis, using association analysis between bone mineral density (BMD) and an LRP5 gene single-nucleotide polymorphism (SNP). Association of an SNP in the LRP5 gene at IVS17-1677C > A (intron 17) with BMD was examined in 308 postmenopausal Japanese women (65.2 ± 9.6 years; mean ± SD). The subjects bearing at least one variant A allele (CA + AA; n = 142) had significantly lower Z scores for total body and lumbar BMD than the subjects with no A allele (CC; n = 166) (total body, 0.08 ± 1.09 versus 0.50 ± 1.03; P = 0.0022; lumbar spine, –0.42 ± 1.43 versus –0.02 ± 1.42; P = 0.013). These findings suggest that the LRP5 gene is a candidate for the genetic determinants of BMD in postmenopausal women, and this SNP could be useful as a genetic marker for predicting the risk of osteoporosis.     

Spine and femur BMD by DXA in patients with varying severity spinal osteoporosis

Summary Bone mineral density (BMD) at the lumbar spine, femoral neck, trochanteric region, and Ward's triangle was measured using dual-energy X-ray absorptiometry (DXA) in 118 women with osteoporotic vertebral collapse (average age 65 years), divided into four groups according to numbers and SD of vertebral deformation below norms: group 1:-3SD deformations only; group 2: one-4SD deformation; group 3: two-four-4SD deformations; and group 4: 5 or more-4SD deformations. There were no significant differences between the groups. Results were compared with those from 80 premenopausal (average age 32 years, range 20–40 years) and 109 postmenopausal normal women (average age 64, range 60–70 years). Mean BMD in osteoporotic group 1 was lower than premenopausal normal women by 32% at the lumbar spine, 31% femoral neck, 30% trochanteric region, and 44% at Ward's triangle, and postmenopausal controls by 17% lumbar spine, 16% femoral neck, 17% trochanter, and 14% Ward's triangle. There was a clear trend to reduction in mean BMD between osteoporotic groups 1 and 4 at all four measured sites with significant differences at the spine of 0.102 g/cm² (P<0.01) and Ward's triangle 0.059 g/cm² (P<0.01). When compared with premenopausal controls, there was a reduction in mean BMD between osteoporotic groups 1 and 4 of 10% at the lumbar spine, 7% femoral neck, 8% trochanteric region, and 13% Ward's triangle. Receiver operating characteristic analysis showed no significant differences in diagnostic sensitivities among the four measured sites for vertebral fractures. We conclude from this crosssectional data that the majority of bone loss in spinal osteoporosis occurs before the onset of fractures.     

A Randomized, Double-Blind, Placebo-Controlled Trial of Intravenous Zoledronic Acid in the Treatment of Thalassemia-Associated Osteopenia

Beta-thalassaemia major is associated with low bone mass and fractures. We conducted a 2 year randomized controlled trial of zoledronic acid 4 mg administered intravenously every 3 months or placebo in the treatment of β-thalassaemia-associated osteopenla. We recruited 23 subjects from 2 university hospitals with a T score of less than −1.0 at either the lumbar spine or hip, and 23 subjects completed the study (17 M, 6 F). Treatment groups did not differ significantly with respect to bone mineral density (BMD), age, height, weight and body mass index (BMI) at baseline. BMD was assessed at baseline, 12 months and 24 months by dual-energy X-ray absorptiometry (DXA) at the lumbar spine, femoral reek, total hip and total body. After two years average lumbar spine BMD was 8.9% greater (95%CI 2.3–15.5%, P = 0.011), average femoral neck BMD was 9.1% greater (95%CI 5.5–12.7%, P < 0.0001), average total hip BMD was 9.6% greater (95%CI 6.5–12.6%, P < 0.0001) and average total body BMD was 4.7% greater (95%CI 2.7–6.8%, P < 0.0001) in the treated group compared to placebo. The absolute change in BMD from baseline to 2 years and the annualized rate of change of BMD was significantly greater in treated patients at all four sites. Age, gender, height, weight and BMI did not interact with the effect of treatment and so unadjusted data was used. The serum total ALP decreased 45% by 12 months (P = 0.004) and urinary deoxypyridinoline/creatinine ratio decreased 47% by 3 months (NS). We conclude that zoledronic acid (4 mg i.v. 3 monthly) suppresses bone turnover and increases BMD in β-thalassaemia-associated osteopenia.     

The role of estrogen receptor-α gene TA polymorphism and aromatase gene TTTA polymorphism on peak bone mass attainment in males: is there an additive negative effect of certain allele combinations?

Idiopathic osteoporosis in males is influenced predominantly by low peak bone mass as a feature under a strong genetic control. Among a number of candidate genes, α-estrogen receptor (ERα) and CYP19 genes are of particular interest due to important role of estrogen in pathophysiology of osteoporosis. In the present study we examined the association of certain allelic combinations of ERα gene thymine–adenine (TA) polymorphism and aromatase gene TTTA polymorphism on bone mineral density (BMD) in young men. The study sample consisted of 92 unrelated healthy male volunteers, aged 21–35. In each subject, lumbar spine and proximal femur BMD, parameters of bone turnover and 25-OHD level were measured. Two ERα (TA) _n alleles, allele 19 and allele 21, were found to be associated with lower BMD. The presence of allele 19 was associated with significantly lower lumbar spine (P = 0.006) and trochanter (P = 0.02) BMD while the subjects positive for allele 21 had significantly lower lumbar spine (P = 0.04), trochanter (P = 0.02) and total hip (P = 0.03) BMD. Men with CYP19 (TTTA)_7-3/ERα (TA)₁₉ allele combination had significantly lower lumbar spine BMD (P = 0.02) and those with CYP19 (TTTA)_7-3/ERα (TA)₂₁ allele combination had significantly lower BMD for all three measurements, i.e. lumbar spine (P = 0.02), femoral neck (P = 0.02) and total hip (P = 0.008). These particular combinations of high-risk alleles were associated with lower median lumbar spine, femoral neck and total hip BMD than either of the allele alone suggesting that negative effect of two risk alleles on peak bone mass add up.     

Is there a role for a random measurement of 24-hour urine calcium excretion and serum total alkaline phosphatase in the determination of fracture risk in osteoporotic postmenopausal women?

Our objective was to explore whether a casual determination of 24-hour urinary calcium excretion and serum total alkaline phosphatase (TAP), in osteoporotic postmenopausal women are independent predictors for osteoporotic fracture. Subjects were 121 women with postmenopausal osteoporosis (mean age 62.8 +/- 9.9) segregated in two study groups based on prevalence of osteoporotic fractures (51 women with prevalent fractures and 70 without fractures), similar in terms of age and BMI. We measured bone mineral density (BMD) by DXA at lumbar spine and femoral neck. Vertebral fracture assessment was done by plain X ray evaluation. Routine blood tests and extensive endocrine evaluation were performed in all patients to exclude secondary causes of osteoporosis. Serum TAP, calcium, phosphate and urinary calcium excretion was measured to evaluate bone metabolism. We did not find any significant differences between groups regarding lumbar T score (-3.1/-2.9 SD), femoral neck T score (-2.2/-1.8 SD), lumbar Z score (-1.5/-1.9 SD) or femoral neck Z score (-1.5/-1.8 SD). Serum TAP was higher in fracture group (211.5 UI) comparing to non-fracture osteoporotic women (208.3 UI) without statistical significance. We were not able to find any significant difference between groups in terms of urinary calcium excretion (9.13/5.4 mEq/24h) or serum total calcium (4.8/4.9 mmol/l). CONCLUSION: in spite of a mean TAP near the upper limit of normal range which could be related to low bone mass, there is no significant relationship to fracture risk in osteoporotic postmenopausal women. Based on our data, a casual measurement of urinary calcium excretion seems irrelevant for BMD independent fracture risk assessment in this clinical setup.     

Characteristics of regional bone mineral density and soft tissue composition in patients with atraumatic vertebral fractures

To clarify the characteristics of total body and regional bone mineral density (BMD) and soft tissue composition in patients with atraumatic vertebral fractures (AVF), we measured total body and regional BMD, lean mass, and fat mass using dual-energy X-ray absorptiometry. Sixty-four women, aged 55–75 years, were divided into two groups: women with AVF (fracture group, n = 30) and women without AVF (nonfracture group, n = 34). Mean BMD of the second to fourth lumbar vertebrae (L2–4BMD), regional BMD, and soft tissue mass were measured. Regional BMD was measured in the head, arms, legs, ribs, thoracic vertebrae, lumbar vertebrae, and pelvis. Lean mass and fat mass of head, arms, legs, and trunk were measured. L2–4BMD, total body BMD, and BMD of the lumbar spine, thoracic spine, and pelvis of the fracture group were significantly lower than those of the nonfracture group (P < 0.001). Total lean and fat mass of the fracture group tended to be lower than that of the nonfracture group. The results suggest that BMD of weight-bearing bones, except for that of the bones of the legs of the fracture group, is significantly lower than that of the nonfracture group, and that total body lean and fat mass may be a predictor for AVF. Received: September 27, 1999 / Accepted: January 7, 2000