Predictors of Osteoporosis and Vertebral Fractures in Patients Presenting with Moderate-to-Severe Chronic Obstructive Lung Disease

Abstract

Bone mineral density (BMD) alone does not reliably predict osteoporotic fractures. The Fracture Risk Assessment Tool (FRAX) was developed to estimate the risk of fracture in the general population. This study was designed to identify predictors of osteoporosis and vertebral fractures in patients presenting with chronic obstructive pulmonary disease (COPD). We studied 85 patients (mean age = 75 years; 92% men) with moderate to very severe COPD. Osteoporosis and vertebral fractures were diagnosed with dual energy X-ray absorptiometric scan and vertebral X-rays, respectively. Patient characteristics, including age, gender, body mass index (BMI), and results of pulmonary function tests, chest computed tomography scan, blood and urinary biomarkers of bone turnover were recorded, and a FRAX score was calculated by a computer-based algorithm. Osteoporosis, defined as a T score < –2.5, found in 20 patients (24%), was associated with female gender, BMI, dyspnea scale, long-term oxygen therapy (LTOT), vital capacity (VC), emphysema score on computed tomography, measurements of serum and urinary biomarkers of bone turnover. Vertebral fractures, diagnosed in 29 patients (35%), were strongly correlated with age, LTOT, VC, and forced expiratory volume in 1 sec, treatment with oral corticosteroid or warfarin, and weakly associated with the presence of osteoporosis. There was no correlation between FRAX score and prevalence of vertebral fractures, suggesting that neither BMD alone nor FRAX score would predict the presence of vertebral fractures in COPD patients. A disease-specific algorithm to predict osteoporotic fractures is needed to improve the management of patients suffering from COPD.     

What community measurements can be used to predict bone disease in patients with COPD?

BACKGROUND: Osteoporosis is common in patients with COPD. Previously we have reported that loss of fat-free mass (FFM), measured by dual X-ray absorptiometry (DXA) is associated with loss of bone mineral density (BMD). In addition, in patients with a low body mass index (BMI) and a low FFM, all had evidence of bone thinning, 50% having osteopenia and 50% osteoporosis. We explored the utility of different anthropometric measures in detecting osteoporosis in a community-based COPD population. METHODS: Patients with confirmed COPD and not on long-term oral corticosteroids (n=58) performed spirometry. They underwent nutritional assessment by skinfold anthropometry, midarm circumference, calculation of both % ideal body weight (IBW) and BMI. All had DXA assessment of BMD. RESULTS: A total of 58 COPD patients had anthropometric measurements taken, with a mean age of 66.8 (SD 8.7) years, 31 (58%) were male, with a forced expiratory volume in 1s (FEV(1)) of 54.17 (20.18)% predicted. Osteoporosis was present at either the hip or lumbar region in 14 patients (24%). The useful anthropometric measurements identifying those with osteoporosis were both % IBW and BMI. The adjusted odds ratio for %IBW was 0.93 (95% confidence interval (CI) 0.87, 0.99), p=0.016 and for BMI: 0.79 (0.64-0.98), p=0.03. The receiver operating characteristics (ROC) score for both was 0.88, indicating a good fit. CONCLUSION: Osteoporosis is common, even in patients with mild airways obstruction. Nutritional assessment, incorporating a calculation of their BMI or %IBW may confer an additional benefit in detecting those at risk of osteoporosis and guide referral for BMD measurement.     

Predictors of osteoporosis and vertebral fractures in patients presenting with moderate-to-severe chronic obstructive lung disease

Bone mineral density (BMD) alone does not reliably predict osteoporotic fractures. The Fracture Risk Assessment Tool (FRAX) was developed to estimate the risk of fracture in the general population. This study was designed to identify predictors of osteoporosis and vertebral fractures in patients presenting with chronic obstructive pulmonary disease (COPD). We studied 85 patients (mean age = 75 years; 92% men) with moderate to very severe COPD. Osteoporosis and vertebral fractures were diagnosed with dual energy X-ray absorptiometric scan and vertebral X-rays, respectively. Patient characteristics, including age, gender, body mass index (BMI), and results of pulmonary function tests, chest computed tomography scan, blood and urinary biomarkers of bone turnover were recorded, and a FRAX score was calculated by a computer-based algorithm. Osteoporosis, defined as a T score < -2.5, found in 20 patients (24%), was associated with female gender, BMI, dyspnea scale, long-term oxygen therapy (LTOT), vital capacity (VC), emphysema score on computed tomography, measurements of serum and urinary biomarkers of bone turnover. Vertebral fractures, diagnosed in 29 patients (35%), were strongly correlated with age, LTOT, VC, and forced expiratory volume in 1 sec, treatment with oral corticosteroid or warfarin, and weakly associated with the presence of osteoporosis. There was no correlation between FRAX score and prevalence of vertebral fractures, suggesting that neither BMD alone nor FRAX score would predict the presence of vertebral fractures in COPD patients. A disease-specific algorithm to predict osteoporotic fractures is needed to improve the management of patients suffering from COPD.     

A comparison of bone mineral density in elderly female patients with COPD and bronchial asthma

BACKGROUND: A recent study has shown that osteoporosis and vertebral fractures are quite common in patients with advanced COPD and showed a significant relationship to the mortality of these patients. These results suggested that management of osteoporosis in advanced COPD is an important intervention. But whether patients with COPD who had never received chronic systemic corticosteroids have a high incidence of osteoporosis and whether these patients require treatment strategies to decrease osteoporotic fracture is not yet known. Furthermore, it is unclear whether there are differences in terms of the degree of osteoporosis between patients with COPD and patients with bronchial asthma. OBJECTIVES: To compare the degree of osteoporosis and bone metabolism markers between elderly women with COPD and those with bronchial asthma who had never received chronic systemic corticosteroids, and to determine the factors influencing bone metabolism in these patients. DESIGN: Cross-sectional medical survey. PATIENTS: A total of 44 elderly female patients with COPD (n = 20) or bronchial asthma (n = 24) who had not received chronic systemic corticosteroids were enrolled (mean +/- SEM age, 74.6 +/- 1.0 years). MEASUREMENTS: Total body and lumbar bone mineral density (BMD) were measured by dual-energy x-ray absorptiometry, and the data were compared between the two groups. In addition, the association between bone mass and clinical variables was determined. RESULTS: When lumbar BMD was expressed as a Z score, the Z scores of patients with COPD were significantly lower than those of patients with bronchial asthma (p < 0.01). The prevalence of osteoporosis was also significantly higher in patients with COPD (50% vs 21%, p < 0.05). In patients with COPD, body mass index was positively correlated with BMD in the lumbar spine (r = 0.55, p = 0.02) and total body (r = 0.49, p = 0.03). Other clinical, biochemical, and anthropometric variables were not correlated with BMD. CONCLUSIONS: In elderly female patients, osteoporosis is more common in cases of COPD than in bronchial asthma, even if these patients had not received long-term systemic corticosteroids. The explanation for the higher prevalence of osteoporosis in COPD is still not known, but preventive strategies to decrease osteoporotic fractures should be added to the management of elderly patients with COPD.     

Progression of osteoporosis in patients with COPD: a 3-year follow up study

Currently, our knowledge on the progression of osteoporosis and its determinants is limited in patients with chronic obstructive pulmonary disease (COPD). Bone mineral density generally remains stable in patients with COPD over a period of 3 years. Nevertheless, the progression of vertebral fractures was not assessed, while an increase of vertebral fractures over time may be reasonable. Aims of the current study were to determine the percentage of newly diagnosed osteoporotic patients after a follow up of 3 years and to identify baseline risk factors for the progression of osteoporosis in COPD. Clinically stable COPD outpatients were included. Lung function parameters, body composition measures, six minute walk distance, DXA-scan and X-spine were assessed at baseline and repeated after 3 years. Prevalence of osteoporosis in COPD patients increased from 47% to 61% in 3 years mostly due to an increase of vertebral fractures. Lower baseline T-score at the trochanter independently increased the risk for the development of osteoporosis. Additionally, baseline vitamin D deficiency increased this risk 7.5-fold. In conclusion, the prevalence of osteoporosis increased over a 3-year period in patients with COPD. Baseline risk factors for the development of osteoporosis are osteopenia at the trochanter and vitamin D deficiency.     

36 month intermittent cyclical etidronate treatment in patients with established corticosteroid induced osteoporosis.

OBJECTIVE: To determine the longterm safety and efficacy of etidronate therapy in patients in whom corticosteroid induced bone loss has already occurred. METHODS: We performed a 36 month observational cohort study in which all data were obtained from Canadian Database of Osteoporosis and Osteopenia (CANDOO) patients. The etidronate group consisted of 24 patients who received 400 mg of etidronate disodium for 14 days, followed by 76 days of calcium carbonate (500 mg of elemental calcium), repeated every 3 mo; the control group included 37 patients who received calcium carbonate 500 to 1000 mg daily. Outcome measurements included changes within groups from baseline and differences between groups in the bone mineral density (BMD) of the lumbar spine, femoral neck, and trochanter at 12, 24, and 36 months. The incidence of vertebral fractures was also determined. RESULTS: Etidronate therapy resulted in a meaningful percentage increase from baseline in lumbar spine BMD, primarily during the first 24 months of treatment, and this increase was sustained for the remainder of the 36 month study period (5.2%; p = 0.016). Analysis of covariance revealed a significant percentage difference (SD) between groups in lumbar spine BMD at 12 [5.5 (13.5) percent; p = 0.003] and 24 months [6.0 (17.4) percent; p = 0.011] in favor of the etidronate group. After 3 years of therapy, one patient (4%) experienced one vertebral fracture in the etidronate group, whereas 3 patients (8%) experienced 5 vertebral fractures in the control group. CONCLUSION: Etidronate treatment administered for 36 months reversed lumbar spine bone loss, and appeared to be safe in patients with established corticosteroid induced osteoporosis.     

Disease activity and disability but probably not glucocorticoid treatment predicts loss in bone mineral density in women with early rheumatoid arthritis

OBJECTIVES: Osteoporosis is a known complication of rheumatoid arthritis (RA). This prospective study aimed to evaluate whether disease activity, disability, and glucocorticoid (GC) treatment in early RA were risk factors for loss of bone mineral density (BMD). METHODS: We followed 97 women (mean age 58 years), for 24 months, with a history of RA of less than 12 months. At baseline, 77 women were receiving standard treatment with disease-modifying antirheumatic drugs (DMARDs) and 20 were receiving no treatment. Risk factors for osteoporosis were recorded. Disease activity score (DAS28), Health Assessment Questionnaire (HAQ) score, and medications were registered at baseline and every 6 months and calculated as areas under the curve (AUCs). Femoral neck and lumbar spine BMD were measured at baseline and after 2 years and compared to BMD in age- and gender-matched controls. Risk factors were analysed by linear regression models. RESULTS: BMD loss was comparable to that of age-matched women in both the lumbar spine and the femoral neck, although neither was significantly different from baseline. In multivariate analyses the AUC for DAS28 was an independent predictor of changes in lumbar spine BMD (p = 0.003) and that for HAQ of changes in femoral neck BMD (p = 0.018). GC use was not an overall predictor of BMD loss. CONCLUSION: BMD loss was predicted by high disease activity and disability but not by GC treatment. With the DMARD, GC, hormone replacement therapy (HRT), and bisphosphonate treatment strategies used during the study period, the general outcome seems favourable concerning loss of BMD in patients with early RA.     

Prevalence of and risk factors for low bone mineral density and vertebral fractures in patients with systemic lupus erythematosus

OBJECTIVE: To examine the prevalence of and risk factors for low bone mineral density (BMD) and vertebral fractures in patients with systemic lupus erythematosus (SLE). METHODS: We studied 107 SLE patients. Demographic and clinical data were collected, and radiographs of the thoracic and lumbar spine and BMD measurements by dual x-ray absorptiometry were performed. Vertebral deformities were scored according to the method of Genant et al: fractures were defined as a reduction of > or = 20% of the vertebral body height. Osteoporosis was defined as a T score less than -2.5 SD and osteopenia as a T score less than -1.0 SD in at least 1 region of measurement. RESULTS: Osteopenia was present in 39% of the patients and osteoporosis in 4% (93% female; mean age 41.1 years). In multiple regression analysis, low BMD in the spine was associated with a low body mass index (BMI), postmenopausal status, and 25-hydroxyvitamin D deficiency. Low BMD in the hip was associated with low BMI and postmenopausal status. At least 1 vertebral fracture was detected in 20% of the patients. Vertebral fractures were associated with ever use of intravenous methylprednisolone and male sex. CONCLUSION: Risk factors for low BMD in SLE patients are low BMI, postmenopausal status, and vitamin D deficiency. While osteoporosis defined as a low T score was found in only 4% of the patients, osteoporotic vertebral fractures were detected in 20%. The high prevalence of low BMD and vertebral fractures implies that more attention must be paid to the prevention and treatment of osteoporosis and fractures in SLE.     

Osteoporosis in chronic obstructive pulmonary disease

Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of osteoporosis because of their age, limited physical activity, low body mass index, smoking, hypogonadism, malnutrition, and use of corticosteroids. Systemic inflammation represents an additional pathomechanism contributing to the development of osteoporosis in COPD patients. Males in their mid to late 60s with a smoking history of greater than 60 pack-years have a prevalence rate of vertebral fractures similar to, and possibly greater than, postmenopausal women greater than or equal to 65 years old: in patients with severe COPD, up to 50-70% have osteoporosis or osteopenia, and up to 24-30% have compression vertebral fractures. Correlates of osteoporosis in COPD are mainly measures of body composition, disease severity and the use of corticosteroids, although causality has not been proven. Systemic corticosteroids remain the most common cause of drug-related osteoporosis, and a meta-analysis concluded that the use of more than 6.25 mg prednisone daily led to decreased bone mineral density (BMD) and increased fracture risk. In contrast, the effects of the long-term use of inhaled corticosteroids on BMD remain debatable. Effects of treatment of osteoporosis have not been investigated in samples consisting of COPD patients only but the recommendations follow the general recommendations for the diagnosis and treatment of osteoporosis. Early recognition of BMD loss is essential, and assumes close interdisciplinary cooperation between respirologists and reumatologists. Longitudinal follow-up to assess determinants of osteoporosis in COPD and randomised placebo-controlled trials on the effects of treatment of osteoporosis in patients with COPD only are warranted. In the future, novel therapeutical strategies such as monoclonal antibodies against osteoclasts activators may prove their beneficial effects in the treatment of COPD-related osteoporosis.     

Longterm effect of intermittent cyclical etidronate therapy on corticosteroid-induced osteoporosis in Japanese patients with connective tissue disease: 7-year followup

OBJECTIVE: To determine the efficacy and safety of intermittent cyclical etidronate therapy of up to 7 years for corticosteroid-induced osteoporosis. METHODS: One hundred two Japanese patients who originally participated in a 3-year prospective randomized study were enrolled into an open-label followup study. All patients had received > 7.5 mg of prednisolone daily for at least 90 days before entry into the original study and were randomly assigned to 2 treatment arms: E, those receiving etidronate disodium (200 mg per day) for 2 weeks together with 3.0 g of calcium lactate and 0.75 microg of alphacalcidol daily; and C, controls receiving only the latter. Endpoints included changes from baseline in bone mineral density (BMD) of the lumbar spine and the rate of new vertebral fractures. RESULTS: The mean (+/- SD) lumbar spine BMD had increased by 5.9% +/- 8.8% (p = 0.00007) and 2.2% +/- 5.8% (p = 0.013) from baseline after 7 years in groups E and C, respectively. This improvement in BMD in group E was significantly better than in group C (p = 0.02). The frequency of new vertebral fractures was lower in group E, resulting in reduction of the risk of such new fractures by 67% at year 7 (odds ratio 3.000; 95% confidence interval, 0.604 14.90; p = 0.18). There were no severe adverse events in group E during our study. CONCLUSION: Our results indicate that longterm (up to 7 years) intermittent cyclical etidronate therapy is safe and effective for prevention and treatment of corticosteroid-induced osteoporosis in patients with connective tissue diseases.     

Vertebral fractures and bone mineral density in idiopathic, secondary and corticosteroid associated osteoporosis in men

OBJECTIVE: To investigate bone mineral density (BMD) in men with symptomatic osteoporosis and compare BMD in patients with idiopathic, secondary and corticosteroid associated osteoporosis. METHODS: Age, number of vertebral fractures at presentation and BMD were investigated in men presenting to a bone metabolism clinic with idiopathic (n=105; group 1), secondary (n=67; group 2) and corticosteroid osteoporosis (n=48; group 3). BMD was measured in 176 healthy men (controls). Osteoporosis was diagnosed if there was >/=20% vertebral deformity. RESULTS: Age at peak BMD in controls was 20-29 years at spine (LS-BMD) and femoral neck (FN-BMD). LS-BMD did not change with age but FN-BMD decreased in controls and groups 1 and 2. Mean (SD) age was similar in groups 1 (62.8 (11.5) years, 2 (60.2 (11.0)) years and 3 (62.7 (10.4) years with 45%, 51% and 40% of patients respectively presenting before 60 years. Back pain, present for up to 12 months, was the commonest cause of referral. Vertebral fractures at presentation averaged mean (SD) 2.51 (1.9) in group 1, 2.76 (2.2) in group 2 and 2.48 (1.8) in group 3. LS-BMD Z scores and T scores were more negative in group 1 patients with /= 1 fracture.     

A multicenter cross sectional study on bone mineral density in rheumatoid arthritis. Italian Study Group on Bone Mass in Rheumatoid Arthritis

OBJECTIVE: To determine the frequency of osteoporosis in a large cohort of women with rheumatoid arthritis (RA) and to investigate the main determinants of bone mineral density (BMD) and risk factors for vertebral fractures in this population. METHODS: We recruited 925 consecutive female patients with RA at 21 Rheumatology Centers in Italy. For each patient pre-registered demographic, disease, and treatment-related variables were collected. BMD was measured at lumbar spine and proximal femur by dual x-ray absorptiometry technique. Collected variables underwent a univariate and multivariate statistical procedure. Osteoporosis was defined as BMD > -2.5 T score. RESULTS: The frequency of osteoporosis in the whole sample was 28.8% at lumbar spine and 36.2% at femoral neck and increased linearly from Steinbrocker's functional stage I to IV (p = 0.0001). Patients with spinal or femoral osteoporosis were significantly older (p = 0.0001), had a lower body mass index (BMI) (p < 0.02), a significantly longer disease duration (p < 0.02) and a significantly higher Health Assessment Questionnaire (HAQ) score (p = 0.0001). These differences were significant, even after adjusting for age. Steroid use was associated with significantly lower lumbar and femoral BMD (p = 0.0001) even after adjusting for the main confounding covariates. Analysis of lateral spine radiographs revealed 74 women with at least one vertebral fracture. These women had a significantly lower lumbar and femoral BMD (p = 0.0001). The generalized linear model showed that steroid use, menopause, BMI, age, and HAQ were all significant independent predictors of lumbar and femoral BMD. The logistic procedure showed that age (OR 1.05, 95% CI 1.03-1.07), HAQ (OR 1.3, 95% CI 1.07-1.7), menopause (OR 1.9, 95% CI 1.1-3.2), use of steroids (OR 1.5, 95% CI 1.07-2.1), and BMI (OR 0.8, 95% CI 0.8-0.9) were significantly associated with the risk for osteoporosis. The only variables associated with an increased risk for vertebral fracture were age (OR 1.04, 95% CI 1.01-1.08), HAQ (OR 1.7, 95% CI 1.08-2.09), and cumulative steroid intake (OR for 1 g of prednisone 1.03, 95% CI 1.006-1.07). CONCLUSION: To prevent osteoporosis and its dramatic complications in RA the therapeutic challenge is to preserve functional capacity using the lowest possible dosage of corticosteroids.     

Effect of twelve-months therapy with oral ambroxol in preventing exacerbations in patients with COPD. Double-blind, randomized, multicenter, placebo-controlled study (the AMETHIST Trial)

The objective of this prospective, randomized, double-blind, placebo-controlled, multicenter parallel-group study was to evaluate the effect of long-term ambroxol treatment in preventing exacerbations of chronic obstructive pulmonary disease (COPD). Two hundred and forty-two outpatients with COPD defined by ATS criteria with value of FEV1 between > or =60 and 80% of predicted and history of one or more exacerbations in the previous year were recruited by 26 Respiratory Medicine Centers in Italy and treated for 1 year with one ambroxol retard capsule of 75 mg twice daily or placebo. The percentage of patients free from exacerbation at 6 months was 63% with ambroxol and 60% with placebo (p=0.366) and at 12 months 56% with ambroxol and 53% with placebo (p=0.363). In a subset of 45 patients with more severe baseline symptoms, ambroxol therapy was associated with a significant higher percentage of patients free from exacerbation compared to placebo: 63 vs. 38% (p=0.038). In conclusion, we did not find a significant difference between long-term ambroxol therapy and placebo, in preventing exacerbations in patients with COPD. In patients with more severe respiratory symptoms at baseline, however, we observed a significant difference in the cumulative exacerbation-free persistence between ambroxol and placebo, suggesting that long-term muco-regulatory therapy with ambroxol could be useful in highly symptomatic patients with COPD.     

Prevalence of depressive symptoms in postmenopausal women with low bone mineral density and/or prevalent vertebral fracture: results from the Multiple Outcomes of Raloxifene Evaluation (MORE) study

OBJECTIVE: To examine the prevalence of depressive symptoms in a cross-sectional study of postmenopausal women with osteoporosis with and without prevalent vertebral fracture. METHODS: Participants were a subset of English-speaking women (n = 3798, mean age 66.7 yrs) from the Multiple Outcomes of Raloxifene Evaluation trial, who had low bone mineral density (BMD) and/or prevalent vertebral fractures. Vertebral fractures were measured at baseline by radiography using a semiquantitative technique. Depressive symptoms were assessed at baseline using the Geriatric Depression Scale (GDS), a valid and reliable scale for depression screening in elderly patients. Women were considered as probably depressed if > or = 6 symptoms of depression were reported. RESULTS: Postmenopausal women with prevalent vertebral fracture reported more depressive symptoms as assessed by the GDS than women without prevalent vertebral fracture (1.54 vs 1.26; p = 0.001). There was an absolute increase of 2.5% (p = 0.008) in the prevalence of probable depression (GDS score > or = 6) in women with prevalent fracture compared to those without prevalent fracture. The prevalence of probable depression was 4.1% among women without prevalent vertebral fracture and 6.6% in women with a prevalent vertebral fracture. The prevalence of probable depression was 3-fold higher in women with at least 3 prevalent vertebral fractures compared to women without prevalent fracture (12.8% vs 4.1%; p < 0.001). CONCLUSION: Postmenopausal women with prevalent vertebral fractures had greater prevalence of depressive symptoms and probable depression as assessed by the GDS than women without vertebral fracture with low BMD. The dual diagnosis of depression and osteoporosis may mean worse health outcomes. Patients with prevalent vertebral fractures may be considered not only for interventions that address fracture risk reduction, but also for psychosocial interventions that address depressive symptoms.     

Bone mineral density in patients with recently diagnosed, active rheumatoid arthritis

OBJECTIVES: Osteoporosis is a well-known extra-articular phenomenon in patients with uncontrolled, long-standing rheumatoid arthritis (RA). In the present study, the extent of osteoporosis and reduced bone mineral density (BMD) and the disease-related and demographic factors that are associated with osteoporosis and reduced BMD were examined in patients with recently diagnosed, active RA. METHODS: BMD of the total hip and the lumbar spine was measured using dual-energy x ray absorptiometry in 381 patients with recently diagnosed active RA, who had never been treated with DMARDs or corticosteroids. Osteoporosis was defined as a T score 相似文献   

Determinants of bone mass in systemic lupus erythematosus: a cross sectional study on premenopausal women.

OBJECTIVE: To evaluate bone mineral density (BMD) in young ambulatory female patients with systemic lupus erythematosus (SLE) and to assess the influence of disease related variables and use of corticosteroids. METHODS: Lumbar and femoral BMD were measured by dual x-ray absorptiometry (DXA) in 84 premenopausal patients with SLE (age 30.5+/-7.5 years). All patients were receiving corticosteroids at the time of the study. Variables evaluated were: disease duration, clinical pattern, disease activity (SLEDAI), cumulative damage index (SLICC/ACR), current and cumulative prednisone dose, duration of steroid treatment, and use of immunosuppressive agents. Osteoporosis was defined as a t score below 2.5 SD compared to a reference population of healthy women in at least one region of measurement. RESULTS: Vertebral and femoral BMD were significantly lower in patients with SLE than in age matched controls. Osteoporosis was detected in 22.6% of patients. No significant differences in BMD were detected between patients according to clinical pattern or activity index, whereas patients with damage index > 0 (n = 46) had a significantly lower BMD at both the lumbar (p = 0.008) and the femoral (p = 0.05) level. Compared with non-osteoporotic patients with SLE, women with osteoporosis had similar age, lower body mass index, significantly longer disease duration (p < 0.0001), higher cumulative steroid intake (p < 0.006), and higher SLICC/ACR score (p < 0.01). Stepwise logistic regression analysis showed that disease duration is independently associated with osteoporosis (OR 1.2 for each year of disease, 95% CI 1.07-1.33). Since disease duration and duration of steroid treatment were highly correlated, a new stepwise logistic model was run without disease duration, which revealed that prednisone was associated with an increased risk for osteoporosis (OR 1.16 for each year of treatment, 95% CI 1.05-1.29). CONCLUSION: Osteoporosis is a frequent feature in young patients with SLE. Disease duration is associated with an increased risk for osteoporosis, but the role of glucocorticoid treatment seems to be crucial. Steroid exposure was the only treatment related variable exerting an influence on the development of osteoporosis.     

老年慢性阻塞性肺疾病患者发生骨质疏松的危险因素

目的 探讨老年慢性阻塞性肺疾病(COPD)患者发生骨质疏松的危险因素及与肺功能损害程度的关系.方法 选择COPD急性加重(AECOPD)入院治疗的患者180例(女性82例,男性98例),入院期间采用双能X线骨密度测定仪测定患者腰椎2～4节段和髋关节的骨密度,依据骨密度检测结果将患者分为COPD合并骨质疏松组和单纯COPD组,并记录所有患者吸烟史、骨折发生次数、激素使用情况等.入院期间测定肺功能、6min步行距离(6MWD)、体质指数(BMI)、血浆白蛋白水平等.结果 患者年龄65～79岁,平均(72±7)岁,平均吸烟量(59±27)包/年,第1秒用力呼气容积占预计值百分比(FEV1%)为(36.5±9.8)%,其中30%(54/180)患者近期吸入或口服糖皮质激素大于3个月.骨密度测定结果显示,171例(95%)的患者骨密度低于正常,其中119例(66%)患有骨质疏松,男性61例,发生率62%,女性58例,发生率70%,性别间差异无统计学意义(x2=1.435,P=0.330),52例(29%)骨量减少.骨折发生人数女性15例(18%),略高于男性的12例(12%)(x2=1.281,P=0.258).BMI与骨质疏松相关(r=0.362,P=0.000),6MWD与骨质疏松相关(r=0.635,P=0.048),肺残气占预计值百分比(RV%)与骨质疏松相关(r=0.688,P=0.037),用力肺活量占预计值百分比(FVC%)与骨质疏松明显相关(r=0.973,P=0.006).结论 骨质疏松是老年COPD患者主要的肺外表现之一,中、重度COPD患者骨质疏松发生率明显高于同龄健康人群,应给予足够的重视和积极的干预.     

Impairment of small airways in COPD patients with frequent exacerbations and effects of treatment with tiotropium

Disease exacerbations are an important aspect of COPD, because they affect its course and are associated with higher lung function decline. On the other hand, data obtained by biopsies have demonstrated that the progression of COPD is related to an increasing impairment of small airways. We sought to evaluate the small airway impairment (FEF25–75) in two groups of COPD patients (each group had 37 subjects) in relation to the frequency of exacerbations and the effectiveness of treatment with tiotropium bromide on the small airway impairment. The mean number of exacerbations was 3.6/year and 1.38/year in frequent and in infrequent exacerbators, respectively (p < 0.001). The mean value of FEF25–75 at baseline was 624 mL and 865 mL in frequent and in infrequent exacerbators respectively (p = 0.002). The changes in respiratory parameters versus baseline showed increases in mean FEV₁, FVC, and FEF25–75 in both groups but only the increase in FEF25–75 in frequent exacerbators was statistically significantly (p = 0.013). During the 3-month period of the study the mean number of exacerbations was 0.66 in frequent and 0.12 in infrequent exacerbators. These findings indicate that COPD patients with frequent exacerbations have a higher impairment of small airways. Treatment with tiotropium in COPD subjects with frequent exacerbations proved to be effective in improving small airway impairment.     

African Americans and men with severe COPD have a high prevalence of osteoporosis

Osteoporosis is a non-pulmonary manifestation whose true prevalence is uncertain in severe chronic obstructive pulmonary disease (COPD). We describe the prevalence and risk factors for osteoporosis in a large, well characterized COPD cohort. Dual energy x-ray absorptiometry of the lumbar spine and hip, full pulmonary function testing, cardiopulmonary exercise test, 6 minute walk distance and demographics were performed in 179 non-selected COPD patients. Patients were 59 +/- 7 years old, smoked 53 +/- 32 pack years, FEV(1) 26% +/- 9.8, and 45% were currently taking prednisone. Bone mineral density measurements were abnormal in 97%; 66% had dual energy X-ray absorptiometry defined osteoporosis, while 31% had osteopenia. The prevalence of osteoporosis in males versus females was 70% versus 62% (p = 0.33); both groups had similar fracture rates. The prevalence of osteoporosis in African Americans versus Caucasians was 69% versus 65% (p = 0.78). Caucasians had a significantly lower Ward's Triangle T score than African Americans (-2.52 +/- -0.96 vs. -2.16 +/- -0.91, p = 0.04). Those with bone fractures took higher doses of prednisone than those without fractures. Univariate analysis identified BMI and FVC% as predictors for osteoporosis (p = 0.03 OR 0.934 p = 0.006 OR 0.974). Multivariate analysis revealed only FVC% as a significant predictor (p = 0.006, OR 0.974). Osteoporosis is highly prevalent in severe COPD, and affects males and African Americans to a similar degree as females and Whites. Osteoporosis should be considered in severe COPD regardless of race or gender.     

Dual energy X-ray absorptiometry outcomes in male COPD patients after treatment with different glucocorticoid regimens

STUDY OBJECTIVES: To compare bone mineral density (BMD) outcomes of patients who received continuous oral systemic glucocorticoids (GCs) with BMD outcomes of patients who received multiple GC courses, oral or IV. DESIGN: Cross-sectional study. PARTICIPANTS: Eighty-six white men with COPD selected from the outpatient clinic for pulmonary diseases. INTERVENTION: Data analysis from medical records, bone densitometry, and pulmonary function tests of consecutive selected patients. Inclusion period into the study was exactly 1 year. MEASUREMENTS AND RESULTS: Ten patients received oral prednisolone daily (group 1). Eleven patients were treated for several exacerbations with multiple systemic prednisolone courses, up to a period of 2 weeks per course, with a cumulative dose of > or = 1,000 mg (group 2). Likewise, 28 patients were treated with multiple systemic prednisolone courses, but with a cumulative dose < 1,000 mg (group 3). Thirty-seven patients were never treated with systemic prednisolone, and partly with inhaled corticosteroids (ICS) [group 4]. All groups were balanced for age and pack-years of smoking. In group 2, body mass index (BMI) and FEV(1) were lowest and hyperinflation was highest. The cumulative systemic prednisolone dose was highest in group 1, irrespective of the additional ICS treatments. Dual energy x-ray absorptiometry scanning of the lumbar spine, total hip, and femoral neck regions revealed a T score < or = 2.5 SD in 27 patients (31%), 31 patients (36%), and 34 patients (40%), respectively. BMD outcomes at any site were lower in patients receiving multiple systemic prednisolone courses > 1,000 mg, cumulatively (group 2), compared to the other groups, and these values were (mean +/- 1 SD) 0.759 +/- 0.238 g/cm(2), 0.683 +/- 0.115 g/cm(2), and 0.686 +/- 0.125 g/cm(2), respectively (p < 0.0001). Multivariate regression analysis revealed a correlation between the cumulative dose of prednisolone in group 2 and BMD of the lumbar spine (adjusted r = 0.48; p < 0.01). At the total hip and femoral neck regions, only a correlation between BMI and BMD was observed (adjusted r = 0.65 and 0.58, respectively; p < 0.0001 for both sites). CONCLUSIONS: Despite a far lower cumulative GC dose in comparison with patients treated with systemic corticosteroids continuously, after adjusting for BMI and lung function, osteoporosis of the lumbar spine was most frequent in patients receiving > 1,000 mg of prednisolone cumulatively, administered in multiple courses for the treatment of exacerbations of COPD.