胰岛素、胰岛素原对胰岛素抵抗状态下HepG2细胞PAI-1分泌的影响

目的研究胰岛素、胰岛素原对胰岛素抵抗状态下ＨｅｐＧ２细胞ＰＡＩ１分泌的影响。方法选择在合成ＰＡＩ１方面与肝细胞相似的ＨｅｐＧ２细胞，以高浓度胰岛素诱导胰岛素抵抗后，分别用生理浓度的胰岛素、胰岛素原刺激２４小时，以观察胰岛素抵抗状态下ＰＡＩ１活性的变化。结果基础状态下胰岛素抵抗ＨｅｐＧ２细胞与非胰岛素抵抗ＨｅｐＧ２细胞相比，ＰＡＩ１活性差异不明显；胰岛素、胰岛素原刺激后，胰岛素抵抗ＨｅｐＧ２细胞ＰＡＩ１活性明显高于非胰岛素抵抗ＨｅｐＧ２细胞。当培液中同时加入１０－４Ｍ二甲双胍后，胰岛素、胰岛素原介导的ＰＡＩ１过量分泌得到明显抑制。结论在胰岛素抵抗状态下，胰岛素、胰岛素原刺激后ＨｅｐＧ２细胞ＰＡＩ１活性明显增加，而二甲双胍可明显抑制此现象。     

Critical years and stages of puberty for spinal and femoral bone mass accumulation during adolescence

Maximizing peak bone mass is advocated as a way to prevent osteoporosis. As a prerequisite to the elaboration of any preventive program aimed at maximizing peak bone mass, it is important to determine how the rate of skeletal growth at clinically relevant sites, such as lumbar spine and femoral neck, proceeds in relation to age and pubertal stages in both sexes. Bone mass was assessed in 207 healthy caucasian boys and girls, aged 9-18 yr. Bone mineral density (BMD; grams per cm2) and content (BMC; grams) were determined in lumbar spine (L2-L4), femoral neck (FN), and midfemoral shaft (FS), using dual energy x-ray absorptiometry. Bone variables were correlated with both chronological age and pubertal stage, and compared with young adult (20-35 yr) reference values. The main results are: 1) in males, compared to females, there was a marked age-related delay in L2-L4 BMD or BMC increase, but no delay was observed in relation to pubertal stages; 2) at the end of the rapid growth spurt, trends for higher mean values in males were observed for L2-L4 BMC, FN BMD, and particularly FS BMD, but no sex difference was observed for L2-L4 BMD; 3) in females, but not in males, a dramatic reduction in bone mass growth was observed after 15 yr of age, particularly for L2-L4 BMD/BMC and FN BMD. This sharp reduction occurred between the second and fourth years after menarche. In the 14- to 15-yr-old female group, BMD in L2-L4, FN, and FS corresponded to 99.2%, 105.1%, and 94.1%, respectively, and BMC in L2-L4 to 97.6% of the mean values recorded in 20- to 35-yr-old women. In conclusion, this cross-sectional study indicates that during pubertal development, major differences are observed in bone mass growth according to sex and skeletal site. Whereas in males bone mass at different skeletal sites continues to increase substantially between 15-18 yr, skeletal mass growth appears to dramatically slow down at the levels of both lumbar spine and FN at 15-16 yr of age in female adolescents. This suggests that the generally accepted notion that in both males and females bone mass continues to substantially accumulate at all skeletal sites until the fourth decade may not be a constant in human physiology.     

Effect of cyclosporine A on bone density in female rheumatoid arthritis patients: results from a multicenter, cross-sectional study

OBJECTIVE: To analyze the influence of cyclosporine A (CYA) on bone using data from a large multicenter, cross-sectional study on bone mineral density (BMD) in rheumatoid arthritis (RA). METHODS: We selected 558 female patients with RA and divided them into two groups on the basis of CYA use: those who had never used CYA (n = 467) and CYA users (n = 91; users for < 24 months n = 50; users for > 24 months n = 41). Demographic, disease and treatment-related variables were collected for each patient. BMD was measured at the lumbar spine and proximal femur using dual x-ray absorptiometry. Data was analyzed by means of a univariate and multivariate statistical procedure. Osteoporosis (OP) was defined as BMD < -2.5 T score. RESULTS: The frequency of OP among non-CYA users and CYA users was 28.2% and 33.3% (p=NS) for the lumbar spine, and 34.2% and 31.3% (p=NS) for the femoral neck, respectively. The prevalence of fragility fractures was not significantly different between the two groups. Mean values for the T-score at either the lumbar spine or the femoral neck were comparable in the two groups, even after adjustment for age, menopausal status, body mass index (BMI), Health Assessment Questionnaire (HAQ) score and steroid use. The generalized linear model showed that age, BMI and the HAQ score were significant independent predictors of BMD at the lumbar and femoral levels, whereas CYA use was not. Logistic analysis showed that only age, the HAQ score and BMI were significantly associated with the risk of OP. However, the duration of CYA therapy > 24 months was associated with an adjusted decreased lumbar BMD and a significantly decreased femoral neck BMD (p = 0.01). The frequency of femoral neck OP in patients on CYA for > 24 months was significantly higher than in patients on CYA for < 24 months: 46.4% vs. 19.44% (p=0.03), while the prevalence of fragility fractures did not differ significantly: 23.1% vs. 16.6%, respectively (p=NS). Logistic analysis showed that CYA use was an independent predictor of osteoporosis at the femoral site. CONCLUSION: Long-term CYA therapy may have negative effects on BMD in female RA patients.     

The use of parenteral clodronate in elderly women with postmenopausal osteoporosis: compliance,effects on bone mineral density and on bone turnover

The aim of the study was to evaluate parenteral clodronate (CLD) compliance in patients with postmenopausal osteoporosis and intolerance to aminobisphosphonates. Moreover, we have also assessed the effects of CLD on bone mineral density (BMD) and bone turnover. Eighty-four consecutive postmenopausal women with osteoporosis (range 62-74 years) were enrolled and randomly allocated to three groups: group A included 26 women who received CLD i.v., 300 mg/2 weeks and oral supplemental calcium carbonate (500 mg x 2/day) and vitamin D3 (400 IU x 2/day); group B included 28 women who received CLD i.m., 100 mg/week, and the same dose of calcium and vitamin D3 administered to group A; group C, the control group, included 30 women receiving only calcium and vitamin D3 at the same doses as the other two groups. The lumbar spine (L1-L4) and femoral neck (FN) BMD were measured by dual energy X-ray absorbiometry at time 0 (T0) and after 6 (T6), 12 (T12), 18 (T18) and 24 (T24) months. At the same time, the serum bone specific alkaline phosphatase and amino-terminal telopeptide of type I collagen normalized by creatinine (NTx/cr) were determined at T0, T6, T12, T18, and T24. Eighty (95.2%) women completed the study, 24 in group A, 27 in group B and 29 in group C. In groups A and B, after 6 months of treatment we found a significantly greater (p < 0.05) increase in the L1-L4 BMD with respect to group C. After 12 months of therapy, in group A the L1-L4 BMD (1.8 +/- 0.5%) was significantly higher (p < 0.05) than that in group B (0.9 +/- 0.3%). At the end of the study, in groups A (1.2 +/- 0.5%) and B (1.1 +/- 0.4%) the percentage increase in the FN BMD was significantly greater (p < 0.05) than in group C (0.6 +/- 0.5%). After 24 months of therapy, there was no difference in the FN BMD between groups A and B. Since the sixth month, both the bone specific alkaline phosphatase and NTx/cr were found to be more markedly and significantly decreased (p < 0.05) in groups A and B with respect to group C. After 18 months, in group A (NTx/cr -16.7 +/- 0.8%) we observed a significantly reduced (p < 0.05) bone resorption with respect to group B (NTx/cr -11.0 +/- 0.5%). In group B, only 3 patients (11.2%) referred pain at the site of drug administration. Our data demonstrate that compliance to parenteral CLD is satisfactory and that this drug reduces bone turnover, increases the L1-L4 BMD and decreases the FN BMD loss. Parenteral CLD administration can represent an effective alternative treatment for postmenopausal women with osteoporosis, especially those who do not tolerate oral aminobisphosphonates.     

Bone mineral density in nonsteroid treated early rheumatoid arthritis.

OBJECTIVES--To determine whether significant reduction in bone mass is detectable in early disease in patients with rheumatoid arthritis (RA) and to examine the possible influences of disease activity and physical disability on bone mineral density (BMD) of the lumbar spine (LS) and femoral neck (FN). METHODS--LS and FN BMD values were measured and Z scores determined in a cross-sectional study of 104 patients with RA of less than five years duration. BMD values were also compared between a subgroup of 64 patients and a normal control group matched for age, sex, menopausal status and body mass. BMD values and Z scores were correlated with disease activity, measured by the Stoke Index, disability, measured by HAQ score, and disease duration. RESULTS--Premenopausal female patients with RA had significantly reduced mean FN Z scores (-0.62, 95% CI -0.30 to -0.94) which correlated with HAQ scores (Rs 0.358, p = 0.05) and age (Rs 0.397, p = 0.03). There were no significant changes of BMD in males or postmenopausal females. Disease duration and disease activity did not correlate with BMD changes. CONCLUSION--BMD is reduced in premenopausal female patients with early RA possibly related to the attainment of peak bone mass. No significant reduction of BMD was found in males or postmenopausal females with early disease. Physical disability but not disease activity appears to play a role in the reduction of FN bone mass.     

Effect of low dose methotrexate on bone density in women with rheumatoid arthritis: results from a multicenter cross-sectional study

OBJECTIVE: To analyze the influence of low dose methotrexate (MTX) on bone using data from a large multicenter, cross-sectional study on bone mineral density (BMD) in women with rheumatoid arthritis (RA). METHODS: We selected 731 female patients with RA divided into 2 groups on the basis of MTX use: never MTX users (n = 485) and MTX users for at least 6 months (n = 246). Demographic, disease, and treatment related variables were collected for each patient. BMD was measured at lumbar spine and proximal femur by dual energy x-ray absorptiometry. Osteoporosis was defined as BMD < -2.5 T-score. RESULTS: The frequency of osteoporosis among never MTX users and MTX users was 29.1% and 28.3% (p = NS) for lumbar spine, and 34.8% and 37.8% (p = NS) for femoral neck, respectively. Mean T-score values at lumbar spine and femoral neck were comparable in the 2 groups, even after adjusting for age, menopausal status, body mass index (BMI), Health Assessment Questionnaire (HAQ) score, and steroid use. The generalized linear model showed that age, menopause, BMI, HAQ score, and steroid use were significant independent predictors of BMD at lumbar or at femoral level, whereas MTX use was not. Logistic procedure showed that only age, HAQ score, and BMI were significantly associated with the risk of osteoporosis. CONCLUSION: We found no negative effect of low dose MTX on BMD in women with RA.     

Bone mineral density in Crohn's disease: a longitudinal study of budesonide,prednisone, and nonsteroid therapy

OBJECTIVE: Corticosteroids may contribute to the bone loss associated with Crohn's disease (CD). We investigated the effect on bone mineral density (BMD) of treatment with budesonide, a steroid with low systemic activity, and compared the outcome with prednisone and nonsteroid therapy in patients with CD. METHODS: Prospective annual BMDs of the lumbar spine (LS) and femoral neck (FN) were measured for 2 yr in 138 patients with quiescent CD treated with mean daily doses of 8.5 mg of budesonide (n = 48), 10.5 mg of prednisone (n = 45), or nonsteroid drugs (n = 45). RESULTS: Between baseline and 1 yr, the mean LS BMD decreased 2.36% in the budesonide group (p < 0.001), 0.61% in the prednisone group (ns), and 0.09% in the nonsteroid group (ns). The difference between budesonide and nonsteroid groups was significant (p = 0.003). In the 2nd yr, LS BMD did not change in the three groups. After 2 yr, FN BMD decreased 2.94% in the budesonide group (p < 0.01), 0.36% in the prednisone group (ns), and 1.05% in the nonsteroid group (ns); the differences among groups were not significant. The proportion of patients with bone loss of >2% per annum at the LS and FN was higher in the budesonide group than in the nonsteroid group (p < 0.001) and prednisone group (p < 0.05). CONCLUSIONS: Patients with CD receiving maintenance treatment for 2 yr with prednisone show little change in BMD, whereas treatment with budesonide may be associated with LS and FN bone loss. Budesonide does not confer an advantage over low-dose prednisone for the preservation of BMD.     

The association of syndesmophytes with vertebral bone mineral density in patients with ankylosing spondylitis

OBJECTIVE: To determine bone mineral density (BMD) using the posteroanterior L2-L4 (PA) and lateral L3 (LAT-L3) projections of dual energy x-ray absorptiometry (DEXA) in patients with ankylosing spondylitis (AS), and to evaluate the relationship between BMD and the presence of syndesmophytes. METHODS: Twenty men with AS were studied. BMD was measured by femoral neck DEXA, PA DEXA, and LAT-L3 DEXA scans. Radiographs of lumbar spine were evaluated to obtain a lumbar spine score (LSS) for the presence of syndesmophytes. Twenty-three age matched healthy men served as controls. RESULTS: While there was no significant difference in BMD from PA DEXA results between AS patients and controls, BMD from the LAT-L3 DEXA was significantly reduced in AS patients (p = 0.009). LSS correlated significantly with BMD from PA DEXA (r = 0.55, p = 0.013), but not with BMD of LAT-L3 DEXA. CONCLUSION: LAT-L3 DEXA was superior to PA DEXA in detecting a decrease of BMD in patients with AS. The presence of syndesmophytes had no distorting effect on BMD measured by LAT-L3 DEXA.     

Reduced bone mineral density in male rheumatoid arthritis patients: frequencies and associations with demographic and disease variables in ninety-four patients in the Oslo County Rheumatoid Arthritis Register

OBJECTIVE: To examine reductions in bone mineral density (BMD) and factors associated with reduced BMD in 94 male rheumatoid arthritis (RA) registry patients ages 20-70 years. METHODS: Dual-energy x-ray absorptiometry was used to measure BMD in the anteroposterior lumbar spine at L2-LA, the femoral neck, and the total hip, and clinical data were collected. The patients were recruited from a validated county RA registry (completeness 85%) comprising 192 men ages 20-70 years. Age-specific BMD values were compared with a pooled healthy European/United States population. Bivariate and multivariate analyses were performed to determine demographic and disease-related associations with BMD and reduced bone mass (Z score of < or =1 SD below the mean value in controls). RESULTS: A statistically significant BMD reduction was found only for the oldest age group (60-70 years): 5.2% reduction in the femoral neck and 6.9% in the total hip. No BMD reduction was found at L2-L4. The proportions (95% confidence intervals) of RA patients with Z scores of < or =1 SD below control (16% expected) were 30.9% (21.6-40.2) for L2-L4, 30.8% (95% CI 21.3-40.3) for the femoral neck, and 33.0% (95% CI 23.3-42.7) for the total hip. Disease activity and severity measures were, in general, not associated with BMD or reduced bone mass. CONCLUSION: A 2-fold statistically significant increased frequency of patients with reduced bone mass (Z score of < or =1 SD below control; 16% expected) was found for both the spine and the hip. The only significant reduction in BMD by age group was for the hip in patients who were ages 60-70 years, with no reduction in L2-LA BMD. Multivariate analyses did not reveal consistent associations between reduced BMD and demographic or disease variables.     

RANKL:osteoprotegerin ratio and bone mineral density in children with untreated juvenile dermatomyositis

OBJECTIVE: To determine bone mineral density (BMD) in patients at the time of diagnosis of juvenile dermatomyositis (DM), to compare the RANKL:osteoprotegerin (OPG) ratio in patients with juvenile DM with that in healthy control subjects, and to evaluate whether BMD is associated with the RANKL:OPG ratio and the duration of untreated disease. METHODS: Thirty-seven children with juvenile DM were enrolled. Dual x-ray absorptiometry (DXA) was performed before treatment, and Z scores for the lumbar spine (L1-L4) were determined. The duration of untreated disease was defined as the period of time from the onset of rash or weakness to the time at which DXA was performed. Serum specimens obtained at the time of DXA were analyzed for concentrations of RANKL and OPG, using enzyme-linked immunosorbent assay. The RANKL:OPG ratio was also determined in 44 age-matched healthy control subjects. RESULTS: At the time of diagnosis of juvenile DM, patients had a significantly increased RANKL:OPG ratio compared with that in healthy children (mean +/- SD 2.19 +/- 3.03 and 0.13 +/- 0.17, respectively; P < 0.0001). In patients with a lumbar spine BMD Z score of -1.5 or lower, the RANKL:OPG ratio was significantly higher than that in patients with a lumbar spine BMD Z score higher than -1.5 (P = 0.038). Lumbar spine BMD Z scores (mean +/- SD -0.13 +/- 1.19 [range -2.10 to 2.85]) were inversely associated with the duration of untreated disease (R = -0.50, P = 0.003). CONCLUSION: Children with juvenile DM have an elevated RANKL:OPG ratio at the time of diagnosis, resulting in expansion of the number of osteoclasts and activation of the bone resorptive function. This may lead to a lack of normal bone mineral accretion and a subsequent reduction in the lumbar spine BMD Z score. Patients with a longer duration of untreated juvenile DM have reduced lumbar spine BMD Z scores. These data suggest that early diagnosis could reduce the likelihood of reduced lumbar spine BMD in these patients by prompting intervention strategies at an early stage.     

Bone mineral density in patients with Parkinson's Disease

BACKGROUND AND AIMS: This study assesses bone mineral density (BMD) in the lumbar spine, proximal femur and hand, and examines the relationship between BMD and disease duration, Hoehn and Yahr staging in Turkish elderly patients with Parkinson's disease (PD). DESIGN: Twenty-four PD patients and 31 age- and sex-matched controls took part in the study. The BMD in the lumbar spine (L2-L4), femoral neck, Ward's triangle, trochanter and bilateral hands were evaluated by dual X-ray absorptiometry (DXA). RESULTS: There was no significant difference in right hand BMD (rHBMD), L2-L4 spinal BMD, and right proximal femur BMD between patients and controls. However, in female patients hand BMD and right femoral neck BMD were significantly lower than in female controls (p<0.05). Male patients had no significant difference in BMD measurements in any sites compared with controls. Patients' Hoehn and Yahr index and disease duration were negatively correlated with BMD in all sites except L2-L4. CONCLUSIONS: We emphasize the increased risk for osteoporosis in elderly female patients with PD, which is more prominent in proximal femur and hand measurements. Elderly female patients should be carefully examined and screened for osteoporosis to prevent bone loss and associated disability.     

Bone metabolism in dialysis patient assessed by biochemical markers and densitometry

A decrease in bone mineral density is common in patients with chronic renal failure. It is also a risk factor for fractures in this population. The aim of the study was to evaluate bone mineral density-BMD and some biochemical markers of bone metabolism in regard to the method of renal replacement therapy: hemodialysis or peritoneal dialysis. The studies were performed in two groups of patients: 2 patients maintained on chronic hemodialyses (HD) and 21 patients treated with chronic ambulatory peritoneal dialysis (CAPD). Bone mineral density was measured using dual energy X-ray absorptiometry (DEXA) in L2-L4 segments of lumbar spine and femoral neck. Concentrations of parathormon, osteocalcin, bone-specific alkaline phosphatase, serum CrossLaps (degradation products of C-terminal telopeptides of type I collagen) vitamin D3 were studied using commercially available kits. In femoral neck bone mineral density was significantly higher in CAPD patients when compared to HD, without significant differences in bone mineral density in lumbar spine. There was statistically significant correlation between BMD of the lumbar spine and time of hemodialysis (r = 0.39, p < 0.05). In CAPD patients BMD of lumbar spine correlated negatively with vitamin D3 (r = -0.54, p < 0.05), osteocalcin (r = -0.54, p < 0.05), and positively with body mass index-BMI (r = 0.63, p < 0.01). BMD of femoral neck correlated positively with BMI (r = 0.59, p < 0.01), and negatively with osteocalcin (r = -0.63, p < 0.05) and time on CAPD (r = -0.52, p < 0.05). On the basis of our finding we conclude that BMD depends on time of renal replacement therapy. Biochemical markers of bone metabolism poorly correlate with bone mineral density in dialyzed patients.     

Serum insulin-like growth factor-I, insulin-like growth factor binding proteins, and bone mineral content in hyperthyroidism.

The mechanism by which thyroid hormones promote bone growth has not yet been elucidated. In vitro, thyroid hormones stimulate insulin-like growth factor-I (IGF-I) production by osteoblasts, which is important for the anabolic effects of the hormone on bone. To determine whether the IGF-I/IGF binding protein (IGFBP) profile is affected when thyroid hormone production is altered in vivo, we studied 36 women who had recently been diagnosed with hyperthyroidism (age: 29-67 years; 19 with Graves' disease, 17 with toxic nodular goiter) and 36 age-matched healthy women as controls. Serum IGF-I, and its binding proteins (IGFBP-3, IGFBP-4, and IGFBP-5), as well as bone mineral density (BMD) at the lumbar spine, femoral neck, and radius midshaft were measured before and 1 year after antithyroid (methimazole) treatment. Serum IGF-I levels were significantly increased in the hyperthyroid patients before treatment (214 +/- 18.2 ng/mL vs. 145 +/- 21.3 ng/mL; p < 0.05). There was no difference in IGF-I levels of patients with Graves' disease and toxic nodular goiter. Serum IGF-I concentrations returned to normal after treatment with methimazole. Serum IGFBP-3 and IGFBP-4 values were significantly elevated in the hyperthyroid group before treatment (3960 +/- 220 ng/mL and 749.7 +/- 53.1 ng/mL vs. 2701 +/- 180 ng/mL and 489.9 +/- 32.4 ng/mL; p < 0.05 and p < 0.01, respectively) and were reduced to those of controls after treatment. Serum IGFBP-5 of hyperthyroid subjects was not different from that of controls either before or after therapy. Serum free thyroxine showed a positive correlation with serum levels of IGF-I (r = 0.73, p < 0.05), IGFBP-3 (r = 0.59, p < 0.05), and IGFBP-4 (r = 0.67, p < 0.05) but not IGFBP-5. BMD at the radius midshaft was significantly lower in hyperthyroid patients at the start of the study and showed a positive correlation with serum IGF-I (r = 0.58; p < 0.001) and a negative correlation with IGFBP-4 (r = -0.61; p < 0.05). Radius BMD showed a 7.2% increase in the hyperthyroid group after 1 year of methimazole treatment, and the correlation between BMD and serum IGF-I disappeared. Our data indicate that thyroid hormones may influence the IGF-I/IGFBP system in vivo in hyperthyroidism. The anabolic effects of increased levels of IGF-I may be limited in hyperthyroidism due to the increases of inhibitory IGFBPs that can counteract the anabolic effects and contribute to the observed net bone loss.     

Femoral bone mineral density is associated with vertebral fractures in patients with ankylosing spondylitis: a cross-sectional study

OBJECTIVE: To determine the association between vertebral fractures and clinical, laboratory, and radiological variables in patients with ankylosing spondylitis (AS). METHODS: Sixty-eight men with AS and 91 sex- and age-matched controls were consecutively enrolled. Vertebral fractures were assessed according to a visual semiquantitative grading system using plain radiographs of the lumbar spine obtained from patients with AS. Disease activity variables including C-reactive protein, erythrocyte sedimentation rate, finger-to-ground distance score, Schober's Index score, Bath Ankylosing Spondylitis Radiology Index for the spine (BASRI-s) score, and syndesmophyte score were identified. Assessments of bone mineral density (BMD) of the lumbar spine and the femur in patients and controls were performed using an anteroposterior dual energy x-ray absorptiometry technique. RESULTS: Eleven patients (16.2%) out of the total of 68 patients with AS had vertebral fractures; these were identified as wedge deformities (n = 5) or biconcave (n = 6) deformities. BMD levels of the lumbar spine and femur in patients were significantly reduced compared with those of age-matched controls. There were significant differences in the Schober's Index scores, finger-to-ground distance scores, BASRI scores of the lumbar spine, syndesmophyte scores, and intertrochanter values of BMD among AS patients both with and without vertebral fractures. Multiple logistic regression analyses revealed that intertrochanteric BMD values also were independently associated with vertebral fractures in AS (p = 0.041). CONCLUSION: We demonstrated evidence of a correlation between low femoral BMD levels and risk of vertebral fractures in patients with AS, especially at the intertrochanteric area. Longitudinal studies in a large population are required to determine the diagnostic implications of femur BMD for increased risk of vertebral fractures in AS.     

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.     

Positive effect of parathyroidectomy on bone mineral density in mild asymptomatic primary hyperparathyroidism

OBJECTIVES: Patients with mild primary hyperparathyroidism (pHPT) often appear asymptomatic, and have previously been regarded as not requiring treatment. However, increased cardiovascular morbidity and dyslipidaemia have also been recognized in mild pHPT, which also seem to be normalized after parathyroidectomy. The present study explores whether postmenopausal women with mild pHPT have decreased bone mineral density (BMD) compared with age-matched healthy controls, and the effects on BMD of parathyroidectomy. DESIGN, SUBJECTS AND INTERVENTION: A population-based health screening of 5202 postmenopausal women identified 87 overtly asymptomatic patients with mild pHPT as well as age-matched healthy controls. A 5-year follow-up included 49 cases who had undergone parathyroidectomy. BMD was measured with DXA at the femoral neck, the lumbar spine and the total body. RESULTS: At study entry, BMD was 5-6% lower in the lumbar spine (L2-L4) and femoral neck in cases compared with matched controls. After the 5-year follow-up, BMD increased in L2-L4 by 2.9% (P = 0.002) in the parathyroidectomized cases and remained stable in the femoral neck. However, femoral neck BMD increased 4.1% (P = 0.013) for cases <67 years old (50% of the cohort). CONCLUSION: In accordance with recent NIH guidelines for pHPT treatment, the level of BMD per se in the investigated group of patients justifies parathyroidectomy in almost half of the cases with mild pHPT. Surgery could be expected to increase BMD in L2-L4 to the level of the controls, to increase femoral neck BMD in patients <67 years of age and to preserve femoral neck BMD in the elderly population.     

Maintenance infliximab treatment is associated with improved bone mineral density in Crohn's disease

OBJECTIVES: Diminished bone mineral density (BMD) is a recognized complication of Crohn's disease (CD). The mechanisms underlying bone loss are unclear but may include a direct effect of inflammatory cytokines related to disease activity. Because tumor necrosis factor alpha (TNF-alpha) plays a central role in the pathogenesis of CD inflammation, we evaluated the effect on BMD of maintenance treatment with infliximab in patients with CD. METHODS: BMD of the lumbar spine (L2-L4) and proximal left femur (neck and trochanter) were measured at baseline and 1 yr in 46 CD patients treated with infliximab (5 mg/kg) at 6-8 wk intervals for 1 yr. Thirteen patients received concurrent prednisone at a mean dose of 10 mg/day (range: 5-15). RESULTS: At baseline, reduced BMD (T-score 相似文献   

Regional bone mineral density after orthotopic liver transplantation

OBJECTIVES: Although there is a fall in lumbar spine bone mineral density (BMD) after liver transplantation, little is known about femoral neck or total body BMD. Therefore we determined: (a) the proportion of patients with preexisting hepatic osteopenia before transplantation and (b) the effects of transplantation on global and regional BMD. DESIGN: Retrospective analysis of BMD measurements of patients before and up to 2 years after liver transplantation. METHODS: BMD was assessed by dual energy X-ray absorptiometry in 56 patients, before and at regular intervals after liver transplantation, for up to 24 months, to measure total body, lumbar spine (L2-L4) and femoral neck BMDs. RESULTS: Pre-transplant, 23% of patients had osteoporosis (a negative Z score > 2). Paired data before and after transplantation revealed no change in total body BMD. However, there was a fall in lumbar spine BMD (1.04+/-0.03 to 1.02+/-0.03 g/cm2; P < 0.04) at 1 month after transplantation. The reduction in lumbar spine BMD was seen up to 12 months, BMD at 18-24 months being similar to pre-transplant values. Femoral neck BMD also fell (0.96+/-0.06 to 0.83+/-0.04 g/cm2; P < 0.03), but only after 6-9 months, thereafter remaining below pre-transplant values until the end of the follow-up period. CONCLUSIONS: Although osteopenia is common in patients with liver disease, total bone density does not fall after transplantation. Nonetheless regional lumbar spine and femoral neck bone density does fall after transplantation with a risk period for femoral neck fracture which may extend for up to 2 years.     

Osteoporosis and lung transplantation: a prospective study

STUDY OBJECTIVE: Osteoporosis is a well-recognized complication of lung transplantation that may significantly impair the quality of life of transplant recipients. We performed a prospective study of bone mineral density (BMD) before and after transplantation to determine the degree of bone mass loss associated with lung transplantation Patients and design: We conducted a prospective study of BMD in 28 patients with various end-stage respiratory diseases pretransplantation and 6 to 12 months posttransplantation. The BMD of the lumbar spine (LS) and femoral neck (FN) were measured. All 28 patients were treated only with vitamin D and calcium supplementation posttransplant. The primary endpoint was the percentage change in BMD. The secondary endpoint was the incidence of fractures posttransplant. A univariate analysis was conducted to determine the various risk factors associated with bone mass loss pretransplant and posttransplant. RESULTS: Prior to transplantation, moderate to severe bone disease was evident. The mean (+/- SD) pretransplant T score (the number of SDs from the peak bone mass) and Z score (the number of SDs from the age-matched mean) for the LS were -1.72 +/- 1.37 and -1.44 +/- 1.31, respectively. The mean pretransplant T score and Z score for the FN were -2.65 +/- 1.01 and -1.5 +/- 1.43, respectively. Within 6 to 12 months posttransplant, the mean BMD for the LS decreased by 4.76% (p < 0.001), while the mean BMD for the FN decreased by 5.3% (p < 0.001). Five of the 28 patients (18%) suffered osteoporotic fractures posttransplant, while no fractures were documented pretransplant. The cumulative steroid dose posttransplant was associated with a drop in BMD for the LS and FN (r = 0.39, p = 0.039 and r = 0.63, p < 0.001, respectively), while a negative association was found between cumulative steroid use pretransplant and baseline LS and FN T scores (r = -0.4, p = 0. 02 and r = -0.43, p = 0.023, respectively). CONCLUSION: Within 6 to 12 months after lung transplantation, there is a significant decrease in BMD at both the LS and FN levels (approximately 5%) despite vitamin D and calcium supplementation. This drop in BMD is associated with a relatively high incidence of osteoporotic fractures posttransplant.     

Pattern of bone mineral density in patients with sporadic idiopathic hypoparathyroidism

OBJECTIVE: Measurement of bone mineral density (BMD) in patients with hypoparathyroidism directly addresses the effect of chronic under-exposure of bone to PTH. Because post-thyroidectomy hypoparathyroidism is potentially complicated by the pre-existence of thyrotoxicosis and the need for postoperative thyroxine replacement, we have studied a large group of patients with sporadic hypoparathyroidism who have been followed up in our endocrine clinic. Studies conducted in limited number of patients with sporadic idiopathic hypoparathyroidism (SIH) have suggested an increase in BMD in such patients. In this current study, we have measured BMD in a large cohort of patients with SIH and have assessed the relationship of BMD with duration of disease and with the adequacy of treatment, as indicated by follow-up serum calcium, phosphate and alkaline phosphatase levels. DESIGN: Case control study and intra-group comparison. SUBJECTS: Forty-seven patients (M : F ratio 23 : 24) with SIH who had been reviewed during 2003-2004 in our endocrine clinic were recruited for this study. Their mean age (+/- SD) was 34.6 +/- 13.6 years and the duration from the time of initial diagnosis was 9.6 +/- 8.5 years. Forty-eight match healthy volunteers were recruited from hospital staff and from normocalcaemic relatives. METHODS: Bone mineral density was measured at total lumbar spine (L1-L4), hip and forearm by dual energy X-ray absorptiometry (DXA). The relationship of BMD was analysed with duration of disease symptoms (group I, < or = 1 year, group II, > 1 and < 5 years and group III, > or = 5 years) and mean serum total calcium observed during follow-up (group A, calcium < or = 1.79 mmol/l and group B, > or = 1.80 mmol/l). RESULTS: Patients with SIH showed significantly higher BMD at total lumbar spine and hip when compared to controls (1.098 +/- 0.187 vs. 0.936 +/- 0.131 g/cm2 and 0.967 +/- 0.141 vs. 0.882 +/- 0.149 g/cm2, P < 0.001 for both). BMD in the forearm was not significantly different in patients and controls. The age- and BMI-adjusted lumbar spine BMD showed correlation with duration of disease (r = 0.348 and P = 0.019). Patients with longer duration of hypoparathyroidism had higher BMD at lumbar spine (group I vs. group III, 0.951 +/- 0.132 vs. 1.156 +/- 0.180 g/cm2, P < 0.05). There was no significant correlation between BMD values in patients with SIH and their mean serum total calcium levels during the period of follow-up (r = 0.192, P = 0.206). Neither was the mean BMD significantly different between group A and B. Serum total alkaline phosphatase showed a significant negative correlation with BMD at lumbar spine (r = -0.445, P = 0.012). CONCLUSIONS: Patients with sporadic idiopathic hypoparathyroidism have increased mean BMD in the lumbar spine and hip but not in the forearm, compared to normal matched healthy controls. The increase in BMD is related to the duration of the disease rather than the serum calcium levels.