Immunoreactive parathyroid hormone, 25-hydroxycalciferol and bone histology in renal osteodystrophy (author's transl)

Immunoreactive parathyroid hormone (iPTH) and 25-hydroxycalciferol (25(OH)D) serum levels were determined in 32 patients with renal osteopathy, they were correlated with the results of bone biopsy and other clinical parameters. iPTH was closely related to bone histology, it did not correspond to serum calcium and alkaline phosphatase, but the correlation to serum phosphate was statistically significant. 25(OH)D levels were not related to the histological findings of osteomalacia or increased bone resorption, while a correlation between the vitamin D metabolite and serum calcium could be observed. Since iPTH and 25(OH)D levels exhibited a significant correlation, an inhibitory effect of 25(OH)D on parathyroid gland function in renal failure was discussed.     

Decreased bone mineral density in premenopausal patients with systemic lupus erythematosus

To study bone mineral density (BMD) in premenopausal adult female patients with systemic lupus erythematosus (SLE) and its relation with clinical parameters, 56 SLE patients (mean age 31 years, mean disease duration 6.3 years) and 15 normal controls were studied. BMD at the lumbar vertebrae (L2-L4) was measured by dual energy X-ray absorptiometry (DEXA). Classification of BMD was made according to the WHO criteria in 1994. Correlation between BMD and clinical parameters was calculated. It was found BMD in the SLE patients (0.942 +/- 0.136 g/cm2) was lower than in the control group (1.055 +/- 0.080 g/cm2) (P < 0.01). According to the WHO criteria, 17 patients (30%) had normal BMD, 22 patients (40%) had osteopenia and 17 patients (30%) had osteoporosis. BMD was inversely correlated with disease duration in SLE patients (p < 0.005). The minimal disease duration for a female SLE patient to develop osteopenia was 3.5 years. In conclusion, SLE patients have lower lumbar BMD than normal controls. SLE patients with longer disease duration have lower BMD. In order to achieve early prevention of osteoporosis, we suggest that female SLE patients with disease duration for more than 3.5 years should take a BMD examination.     

Changes in bone mineral density in patients with Paget''s disease treated with risedronate

Our purpose was to evaluate the impact of intravenous and oral tocolysis on prolongation of gestation for women with preterm uterine contractions and/or labor. Candidates for evaluation and treatment including women with contractions between 24 and 35 weeks. Two hundred women (group I) without cervical changes met the protocol criteria and 175 women (group II) who presented with or developed cervical changes were treated by protocol. A representative sample of both groups received oral terbutaline maintenance therapy until 37 weeks' gestation. Primary outcome variables included the length of gestation obtained following initial treatment and the preterm birth rate. Women in group II were twice as likely to deliver before 35 weeks, 23% versus 9.5%, respectively, and to have a delivery before 37 weeks' gestation, 45% versus 22%, respectively, (p < 0.05). There was no significant difference in days gained in utero for women on oral terbutaline for either group. Women in group II on oral therapy were more likely to be readmitted and retreated with parenteral tocolysis. In conclusion, oral maintenance tocolysis has no significant impact on further prolongation of pregnancy after intravenous tocolysis.     

Association of bone mineral density with vitamin D receptor gene polymorphism--changes in radial bone mineral density with long-term follow-up: longitudinal study

Recent studies have shown that genetic effects on bone mineral density (BMD) and bone turnover are related to vitamin D receptor (VDR) gene polymorphism. However, discordant studies have been published and it is still not clear whether VDR genotypes influence bone mass accretion and/or postmenopausal bone loss. To assess allelic influence of the VDR gene on BMD, we determined changes in 1/6-radial-BMD by several repeat measurements in the same subjects for about ten years and analyzed VDR polymorphism of BsmI restriction enzyme in 53 normal healthy Japanese women (age: 50.3 +/- 4.7 years, mean +/- SD). Twenty-seven (age: 53.2 +/- 4.7 years) of the subjects were post-menopausal (POST group). Among these 53 subjects, the distribution of bb, Bb and BB genotypes was 64.2%, 34% and 1.9%, respectively. The genotype frequencies in this study were very similar to those in previous reports concerning other Japanese women. There was no difference between the b group (women with bb genotype) and B group (women with BB or Bb genotype) in age, body weight, height, body mass index (BMI), years since menopause, serum osteocalcin and serum alkaline phosphatase values. In the POST group, BMD of the B group at menopause was lower than that of the b group (p < 0.05). About ten years after menopause, BMD did not differ significantly between these groups because the decrease in BMD in the b group was larger than that in the B group. Regarding changes in BMD in the POST group for four years after menopause, BMD of the b group was significantly decreased compared with the B group (p < 0.01). Our findings suggest that the differences in BMD by VDR genotype were larger among pre- and pri-menopausal women and seemed to decrease with years after menopause. It is suggested that there are other factors influencing BMD and postmenopausal bone loss in elderly women.     

Comparison of total and bone-specific alkaline phosphatase in patients with nonskeletal disorder or metabolic bone diseases

To evaluate the diagnostic validity of new assays for bone-specific alkaline phosphatase (BAP), we compared measurements of total alkaline phosphatase (TAP) in serum with results for three different assays of serum BAP in healthy adults (n = 119), patients with chronic nonskeletal disorders (n = 123), and patients with metabolic bone diseases (n = 113). Serum TAP was determined by a standard colorimetric assay, BAP by the methods of lectin precipitation (L-BAP), enzyme immunoassay (E-BAP), and immunoradiometric assay (I-BAP). Impairment of liver function resulted in significant increases of all alkaline phosphatase (AP) measurements, with the smallest changes being exhibited by E-BAP. Compared with the results by TAP, diagnostic sensitivity (i.e., of values exceeding the reference interval) was not improved by BAP, but receiver-operating characteristic (ROC) curve analyses revealed improved discrimination for primary hyperparathyroidism by E-BAP. These results indicate that, in the presence of liver disease, the specificity of AP measurements is improved by measuring BAP. In most other clinical situations, serum TAP appears to provide sufficient clinical information; however, the cross-sectional study design used here allows no statement about the usefulness of BAP in serial measurements.     

Osteoporotic fracture rate, bone mineral density, and bone metabolism in Taiwan

Taiwanese people have spinal bone mineral density (BMD) values similar to those of Caucasians, whereas their hip BMD values are 10% to 15% lower. In 1992, the prevalence of vertebral fractures, diagnosed according to the -3 SD morphometric criteria, was 18% for women and 12% for men older than 65 years in the major cities of Taiwan. Despite this high prevalence of vertebral fractures, the incidence of hip fractures in the elderly of both sexes was only 203 per 100,000 in 1996, which was lower than in Caucasians and similar to that in mainland Chinese. Hip and vertebral fractures are both associated with lower BMD values. The risk factors for low BMD in Taiwan include a lighter body weight and aging in both sexes, and menopause for women. An increased bone turnover rate is associated with a lower BMD in both men and postmenopausal women, although the rate seems to increase in women but decrease in men with aging. In Taipei City, daily calcium intake is relatively low (mean intake +/- SD; 640 +/- 240 mg), but the vitamin D stores seem to be generally adequate for middle-aged and elderly women. There was a significant association between a higher daily calcium intake and a higher BMD/lower bone turnover rate for women in this age group. Vitamin D receptor allelic polymorphism was not an important factor in low BMD and rapid bone turnover.     

Suppressive effect of calcium on parathyroid hormone release in adynamic renal osteodystrophy and secondary hyperparathyroidism

Serum parathyroid hormone (PTH) levels are markedly lower in patients with the adynamic lesion (AD) of renal osteodystrophy than in those with secondary hyperparathyroidism (2 degrees HPT), but serum PTH values are often moderately elevated in AD when compared to subjects with normal renal and parathyroid gland function (NL). To study the inhibitory effect of calcium on PTH release in AD and in 2 degrees HPT, the response to two-hour intravenous calcium infusions was examined in 6 patients with AD, in 31 patients with 2 degrees HPT and in 20 NL. Basal serum PTH levels were 88 +/- 51, 536 +/- 395, and 26 +/- 6 pg/ml, respectively, in AD, 2 degrees HPT and NL, whereas basal ionized calcium levels did not differ. When expressed as a percentage of pre-infusion values, PTH levels at the end of two-hour calcium infusions were higher both in AD (23.2 +/- 5.6%) and in 2 degrees HPT (27.8 +/- 12.3%) than in NL, (11.9 +/- 5.8%, P < 0.001). Both the amplitude of suppression (%) and the rate of decline (min-1) in serum PTH were less in AD and 2 degrees HPT than in NL, P < 0.05 for each parameter; corresponding values for each group, with 95% confidence intervals, were 77% (73 to 82) and 0.039 min-1 (0.030 to 0.048) in AD, 72% (68 to 76) and 0.031 min-1 (0.025 to 0.036) in 2 degrees HPT and 87% (84 to 89) and 0.070 min-1 (0.058 to 0.089) in NL. Neither variable differed between AD and 2 degrees HPT. Basal and nadir serum PTH levels were highly correlated: r = 0.95 and P < 0.05 in AD; r = 0.90 and P < 0.01 in 2 degrees HPT; r = 0.75 and P < 0.01 in NL. The slope of this relationship was less, however, both in AD and in 2 degrees HPT than in NL, P < 0.05 by analysis of co-variance. Thus, serum PTH levels fell below 20% of pre-infusion values in fewer subjects with AD (1 of 6) or 2 degrees HPT (9 of 31) than in NL (17 of 20) (chi 2 = 17.81, P < 0.005). The results indicate that the inhibitory effect of calcium on PTH release in vivo does not differ in AD and 2 degrees HPT despite marked differences in basal serum PTH levels. Variations in functional parathyroid gland mass rather than disturbances in calcium-sensing by the parathyroids probably account not only for the lower basal serum PTH levels in patients with AD compared to those with 2 degrees HPT, but also for the moderately elevated serum PTH values commonly seen in patients with AD.     

Loss of regional bone mineral density in the first 12 months following renal transplantation

We performed 2 studies aimed at developing a frozen platelet panel suitable for platelet cross-matching. The stability of the most important platelet membrane glycoproteins and the reactivity of antigens of the human platelet antigen (HPA) and of the human leukocyte antigen (HLA) systems were evaluated with the platelet suspension immunofluorescence test (PSIFT) in a panel of platelets frozen in microplates with 6% dimethylsulfoxide. In study No. 1 we evaluated platelet reaction with a broad-spectrum weak anti-HLA and a potent anti-HPA-1a antiserum and the expression of glycoproteins Ib and IIb/IIIa complex on platelet membrane before freezing and after 0.5, 1, 2, 3, 4, 5, 6 and 12 months of storage at -80 degrees C. In study No. 2 we examined platelet reactivity with anti-HPA-1b, -HPA-2a, -HPA-3a, -HLA-A2, -HLA-A3 of platelets stored frozen for 12 months in parallel with fresh platelets from the same donors. Study No. 1 showed that glycoprotein expression was stable and that the weak anti-HLA and the potent anti-HPA-1a antibodies were clearly detected during 12 months at -80 degrees C. Of the 35 paired PSIFT performed in study No. 2 with fresh and frozen/thawed platelets incubated with anti-HPA-1b, -HPA-2a, -HPA-3a, -HLA-A2, -HLA-A3 antisera and AB serum, concordant reactions were obtained in all cases with the exception of 1 case of HLA-A3-positive platelets incubated with anti-HLA-A3 antiserum, that was reactive with frozen/thawed platelets but nonreactive with fresh platelets from the same donor.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bone ultrasound and diagnosis of osteoporosis: correlation of 2 quantitative ultrasound methods with bone density

In this study, 96 women (mean +/- SD, 65.3 +/- 13.2 years) were investigated by bone mineral densitometry (DXA, Hologic QDR 2000) and quantitative ultrasound (QUS) of the tibia (n = 96; Sound-Scan2000, Myriad) and phalanges (n = 84: DBM Sonic 1200, IGEA). We observed a good correlation of QUS measurement with bone mineral content (BMD) on lumbar spine and both hips (Ward and Neck). Correlation of the two QUS-techniques measuring at different skeletal sites within the same patient was good. QUS instruments measuring at the various skeletal sites and their suitability for screening patients at risk of osteoporosis are discussed. The usefulness of the different QUS methods and the best measuring site for the assessment of fracture risk in osteoporotic patients still have to be established.     

Dietary calcium intake and its relation to bone mineral density in patients with inflammatory bowel disease

OBJECTIVES: To investigate calcium intake and its association with bone mineral density (BMD) and the type and extent of the disease in patients with inflammatory bowel disease (IBD). SETTING: University hospital clinic. SUBJECTS: A total of 152 unselected IBD patients and 73 healthy controls. MEASUREMENTS: Dietary calcium intake was assessed with a food frequency questionnaire and BMD of the lumbar spina and proximal femur was measured. RESULTS: The IBD patients had lower dietary calcium intake (1034 [SD 493] mg) than the controls (1334 [514] mg, P < 0.001). The difference was significant in the males (1047 [552] mg and 1575 [586] mg, respectively, P < 0.001), but not in the females (1020 [422] mg and 1112 [303] mg). The dietary daily calcium intake was below 1000 mg in 53% of the patients and 27% of the controls (P = 0.0004) and below 400 mg in 9.2% of the patients and none of the controls (P = 0.007). The calcium intake was not associated with the severity or the type of IBD. Seventy-one (47%) patients and eight (11%) controls avoided lactose in their diet (P < 0.001). In the IBD patients, no association between the calcium intake and BMD was detected, whereas in the controls a positive correlation between the calcium intake and the BMD of the proximal femur was found. CONCLUSIONS: Calcium intakes below the recommendations are seen more often in the IBD patients than in the healthy controls, but in the IBD patients the calcium intake is not associated with BMD in a cross-sectional study. A low-lactose diet is common among IBD patients. To reduce the risk of inadequate calcium intake, unnecessary dietary restrictions concerning, e.g. milk products, should be avoided for these patients.     

Separation and quantification of corticosteroid-induced, bone and liver alkaline phosphatase isoenzymes in canine serum

Quantifying alkaline phosphatase (ALP) isoenzymes in canine serum would provide a useful index in a clinical laboratory. To achieve this goal, we tested a semi-automatic assay combining wheat germ lectin (WGL) precipitation and chemical inhibition of isoenzymes of the TNS gene with levamisole to quantify bone ALP (BALP) and corticosteroid-induced ALP (CALP), respectively. The liver ALP (LALP) isoenzyme was then calculated from the equation: TALP = BALP + LALP + CALP BALP, LALP and CALP standards from serum of puppies, bile-duct ligated dogs and dogs on 4.4 mg/kg/day prednisolone for 30 days, respectively, were used. The suitability of standard sera was tested by affinity electrophoresis. Levamisole (4.2 mM) inhibits 98% of BALP and LALP but only 42% CALP. Multiplying measured CALP by 1.8 gives the total CALP value in serum. WGL precipitated 92.3% BALP, 23.3% LALP and 26.8% heated CALP standards. These values were used to adjust precipitated ALP to obtain the exact levels of BALP. WGL was then tested on pooled serum standards in which the relative proportions of all the ALPs were known and controlled. BALP was adequately quantified except when LALP and CALP levels were extremely high. The assay was also applicable under conditions resulting in high ALP. Therefore, combining WGL and levamisole inhibition provides an adequate separation and quantification of canine ALP isoenzymes. The method has great potential for diagnostic use and should be tested further for routine implementation.     

Genetic and environmental contributions to the association between quantitative ultrasound and bone mineral density measurements: a twin study

This study was designed to assess the relative contributions of genetic and environmental factors to the variation and covariation of quantitative ultrasound (QUS) measurements and their relationships to bone mineral density (BMD). Forty-nine monozygotic (MZ) and 44 dizygotic (DZ) female twins between 20 and 83 years of age (53 +/- 13 years, mean +/- SD) were studied. Digital (phalangeal) QUS (speed of sound [SOS]) and calcaneal QUS (broadband ultrasound attenuation [BUA] and velocity of sound [VOS]) were measured using a DBM Sonic 1200 ultrasound densitometer and a CUBA ultrasound densitometer, respectively. Femoral neck (FN), lumbar spine (LS), and total body (TB) BMD were measured using dual-energy X-ray absorptiometry. Familial resemblance and hence heritability (proportion of variance of a trait attributable to genetic factors) were assessed by analysis of variance, univariate, and multivariate model-fitting genetic analyses. In both QUS and BMD parameters, MZ twins were more alike than DZ pairs. Estimates of heritability for age- and weight-adjusted BUA, VOS, and SOS were 0.74, 0.55, and 0.82, respectively. Corresponding indices of heritability for LS, FN, and TB BMD were 0.79, 0.77, and 0.82, respectively. In cross-sectional analysis, both BUA and SOS, but not VOS, were independently associated with BMD measurements. However, analysis based on intrapair differences suggested that only BUA was related to BMD. Bivariate genetic analysis indicated that the genetic correlations between BUA and BMD ranged between 0.43 and 0.51 (p < 0.001), whereas the environmental correlations ranged between 0.20 and 0.28 (p < 0.01). While the genetic correlations within QUS and BMD measurements were significant, factor analysis indicates that common genes affect BMD at different sites. Also, individual QUS measurements appear to be influenced by some common sets of genes rather than by environmental factors. Significant environmental correlations were only found for BMD measurements and ranged between 0.50 and 0.65 (p < 0.001). These data suggest that QUS and BMD measurements are highly heritable traits. While it appears that there is a common set of genes influencing both QUS and BMD measurements, specific genes yet to be identified appear to have greater effects than that of shared genes in each trait.     

Assessment of bone density in children with Scheuermann's disease

Twenty four children with Scheuermann's disease (11 girls and 13 boys) aged 9-18 years measured for bone mineral density. The total skeleton (TB BMD) and lumbar spine (L2-L4 BMD) mineral density were investigated by dual energy X-ray absorptiometry (DEXA). In nine patients with Scheuermann's disease and backache we found lower levels of TB BMD and L2-L4 BMD in comparison with reference population of Lunar database. Osteopenia in these children may be caused by decreased physical activity due to vertebral pain.     

Body weight and bone mineral density in postmenopausal women with primary hyperparathyroidism

OBJECTIVE: To assess bone mineral density and body composition in postmenopausal women with primary hyperparathyroidism. DESIGN: Cross-sectional study with an age-matched control group. SETTING: University teaching hospital. PATIENTS: 41 postmenopausal women with mild primary hyperparathyroidism and 43 eucalcemic, age-matched controls. MEASUREMENTS: Total body, lumbar spine, and proximal femoral (femoral neck, Ward's triangle, and trochanter) bone mineral density; body composition; and fat distribution were measured using dual-energy x-ray absorptiometry. RESULTS: Women with primary hyperparathyroidism were heavier (75.5 kg compared with 66.3 kg; difference, 9.2 kg [95% CI, 3.7 to 14.7 kg]; P = 0.002), had a higher fat mass (33.3 kg compared with 26.1 kg; difference, 7.2 kg [CI, 3.0 to 11.4 kg]; P = 0.001), and had a more android pattern of fat distribution (android-to-gynoid fat ratio, 1.05 compared with 0.84; difference, 0.21 [CI, 0.1 to 0.32]; P = 0.0004) than the controls. Unadjusted bone mineral density was similar in patients and controls at all sites: total body, 0.990 compared with 1.023 g/cm2 (difference, 0.033; CI, -0.004 to 0.070); posteroanterior lumbar spine, 1.032 compared with 1.018 g/cm2 (difference, 0.014; CI, -0.031 to 0.059); lateral lumbar spine, 0.569 compared with 0.528 g/cm2 (difference, 0.041; CI, -0.022 to 0.104); femoral neck, 0.799 compared with 0.825 g/cm2 (difference, 0.026; CI, -0.072 to 0.124); Ward's triangle, 0.653 compared with 0.677 g/cm2 (difference, 0.024; CI, -0.035 to 0.089); trochanter, 0.734 compared with 0.733 g/cm2 (difference, 0.001; CI, -0.024 to 0.026); and arms, 0.720 compared with 0.739 g/cm2 (difference, 0.019; CI, -0.015 to 0.053). After adjustment for body weight, bone mineral density in women with primary hyperparathyroidism was lower than that in controls for total body (P = 0.0004), femoral neck (P = 0.001), Ward's triangle (P = 0.01), trochanter (P = 0.02), and arms (P = 0.0006). Spinal bone mineral density did not differ between groups. CONCLUSIONS: Body weight, total body fat mass, and proportion of android fat are increased in postmenopausal women with primary hyperparathyroidism; these unexplained factors may be relevant to the increased incidence of cardiovascular disease in this condition. Unadjusted bone mineral density values are similar in patients with primary hyperparathyroidism and in controls, suggesting that this condition is not associated with an increased risk for fracture.     

Effects of the bisphosphonate tiludronate on bone resorption, calcium balance, and bone mineral density

Bone resorption inhibitors, such as bisphosphonates, are potentially useful in treatments aimed at increasing bone mass. Among bisphosphonates, tiludronate has proven efficacious in preventing bone loss in postmenopausal women. However, it is not clearly established whether bisphosphonates are more potent when given intermittently or continuously. We investigated the effects of tiludronate on (1) retinoid-stimulated bone resorption in thyroparathyroidectomized rats, (2) calcium balance in intact rats, and (3) bone mineral density (BMD) as measured by dual-energy x-ray absorptiometry at the levels of the lumbar spine, tail, and tibia in 6-month-old rats made osteoporotic by ovariectomy (OVX), in which an intermittent cyclic schedule of treatment was compared to continuous administration. Tiludronate induced a dose-dependent decrease in retinoid-stimulated bone resorption. It increased the intestinal absorption and body retention of calcium. In OVX rats it caused a time- and dose-dependent increase in BMD at the level of the three investigated sites, the effects being maintained for at least 8 weeks after the end of therapy. Continuous and intermittent cyclic regimens appeared to induce similar increases in BMD. These results indicate that tiludronate is efficacious in decreasing bone resorption and increasing calcium balance and bone mineral density in rats.     

Femoral and spinal bone mineral density in Japanese osteoporotics with hip fracture

In the present study, bone mineral density (BMD) of femoral neck and lumbar spine was compared between 38 Japanese female patients with hip fracture (age 63-89 years, mean +/- SD 76 +/- 7 years) and 162 age-matched female controls (age 62-90 years, mean +/- SD 75 +/- 7 years). BMD was measured in the femoral neck and lumbar spine (L2-4) using dual-photon absorptiometry (Norland model 2600). BMD values of femoral neck as well as lumbar spine were significantly lower in patients with hip fracture than in controls (0.504 +/- 0.097 v 0.597 +/- 0.101, p < 0.01, for femoral neck; 0.661 +/- 0.146 v 0.720 +/- 0.128, p < 0.05, for lumbar spine). Patients with hip fracture and controls were stratified according to their BMD levels at two measuring sites, and the ratio of the number of patients and controls at each BMD level was calculated as an indicator of fracture rate. This ratio showed an exponential increase as the femoral neck BMD declined, but only a gradual increase as the lumbar spine BMD declined. Specificity-sensitivity analysis revealed that BMD values of 0.59 and 0.54 g/cm2 at the femoral neck provided a specificity of 52% and 68% with a sensitivity of 90% and 75%, respectively. These findings suggest that Japanese patients with hip fracture are more osteoporotic than age-matched controls and that the selective measurement of femoral neck would be useful for predicting the risk of hip fracture.