Alendronate in rheumatoid arthritis patients treated with methotrexate and glucocorticoids

Rheumatoid arthritis (RA) is a systemic inflammatory disease. Along with synovial joint inflammation, extra-articular involvement is a common feature of RA. Periarticular and generalized osteoporosis are seen both as an extra-articular feature of the disease itself and due to various medications like glucocorticoids and methotrexate (MTX). In this study, we investigated the effects of oral alendronate in RA patients treated with MTX and prednisolone by comparing the effects of “alendronate+calcium” and “only calcium” on bone mineral density (BMD). Fifty RA patients classified according to American Rheumatism Association (ARA) criteria were included in the study. The control group consisted of 20 postmenopausal osteoporotic patients. The RA patients were divided randomly into two groups. All patients were started on MTX 7.5 mg/week, 2.5-mg daily folic acid, and 7.5-mg daily prednisolone. The first group, consisting of 25 female RA patients, was also given 10-mg daily alendronate and 1000-mg daily calcium. The second group also consisted of 25 female patients and was given only 1000-mg calcium per day. The postmenopausal control group was given daily 10-mg alendronate and 1000-mg calcium. Bone mineral densities were measured by dual-energy x-ray absorptiometry (DEXA) and again at the end of the sixth month. At the end of the study, RA patients given only calcium had reduced mean BMD, and patients treated with alendronate and calcium showed increased mean BMD almost in all regions. This increase was significant in the L2 and L1–4 total regions. In postmenopausal osteoporotic patients, we saw statistically significant increases in BMD in all regions. The increase in BMD values in RA patients treated with alendronate was smaller than in those of the control group of postmenopausal osteoporosis patients. In conclusion, RA itself has a risk factor for osteoporosis in addition to the risks of the medications like corticosteroids and MTX. In the prevention and treatment of RA-associated osteoporosis, alendronate and calcium therapy is effective and well tolerated. Received: 16 June 2000 / Accepted: 20 August 2000     

Peripheral bone density in patients with rheumatoid arthritis

Bone loss in patients with rheumatoid arthritis (RA) varies at different skeletal sites. The aim of the study was to evaluate whether bone mineral density (BMD) of the forearm is significantly different in patients with RA and controls and may correlate to BMD or other parameters of inflammation or bone resorption. We included 421 patients (357 women: mean age 58.4 ± 12.87 years and 64 men: mean age 56.11 ± 12.80 years) with RA in the study. BMD values of the ultradistal forearm (0.381 ± 0.052 g/cm²) and middistal forearm (0.519 ± 0.091 g/cm²) were significantly (p < 0.01) lower in women with RA than controls (0.395 ± 0.043 and 0.535 ± 0.052 g/cm², respectively). In contrast, there was no difference in bone density at the lumbar spine (women 0.921 ± 0.l570 g/cm², men 0.941 ± 0.144 g/cm²) or hip (women 08.11 ± 0.140 g/cm², men 0.895 ± 0.143 g/cm²) in patients with RA in comparison to controls (lumbar spine: women 0.930 ± 0.146 g/cm²; men 0.960 ± 0.146 g/cm²; hip: women 0.820 ± 0.122 g/cm²; men 0.899 ± 0.144/cm²). Patients with increased inflammatory activity (elevated C-reactive protein) presented with significantly lower BMD of the hip (0.7533 ± 0.144 versus 0.825 ± 0.138 g/cm²) and ultradistal forearm (0.366 ± 0.09 versus 0.390 ± 0.07 g/cm²). This was not the case for the lumbar spine. BMD of the forearm is precise and, in contrast to BMD of the lumbar spine, significantly lower in patients with RA. It is related to inflammatory activity, grip strength, and treatment with glucocorticoids in patients with RA.     

降钙素治疗老年骨质疏松症的临床研究

目的　观察鲑鱼降钙素对老年骨质疏松症的治疗效果。　方法　将经双能X线骨密度仪 (DEXA)测定确诊为骨质疏松且有临床症状的老年患者 86例分成两组 ,鲑鱼降钙素组 4 6例 ,予以鲑鱼降钙素肌肉注射 ,每天 1次 10 0IU ,连用 3d后 ,改为 5 0IU隔天 1次 ,连用 1个月 ,间歇 1个月后再重复 ,共半年 ,同时加服钙尔奇D每天 1片 ;对照组 4 0例 ,单纯口服钙尔奇D每天 1片 ,疗程半年 ,两组治疗前后均测定 1～ 4腰椎 (L1-4)及股骨近端骨密度 (BMD) ,治疗后记录临床症状。　结果　鲑鱼降钙素组较对照组骨痛症状缓解 (91 3%和 4 7 5 % )效果明显 (P <0 0 1) ,鲑鱼降钙素组腰椎BMD (0 78± 0 12 ) g/cm2 较治疗前 (0 73± 0 10 ) g/cm2 有所升高 (P <0 0 5 ) ,股骨近端BMD变化不明显 ;对照组BMD无明显改变。　结论　鲑鱼降钙素与钙剂联合对治疗老年骨质疏松患者有缓解临床症状及增加腰椎BMD的作用。     

Increased bone mass with pamidronate treatment in rheumatoid arthritis. Results of a three-year randomized,double-blind trial

Objective. Osteoporosis is a frequent complication of rheumatoid arthritis (RA). We therefore investigated the effect of oral pamidronate therapy as a specific bone-sparing agent in RA. Methods. The study design was a 3-year randomized, double-blind trial of 300 mg oral pamidronate/day compared with placebo in 105 RA patients. Bone mineral density (BMD) measured at 12-month intervals was the primary efficacy parameter. Results. In 3 years, lumbar spine and forearm BMD increased significantly in the pamidronate-treated group (by 8.4 ± 6.9% [mean ± SEM] [P < 0.0001] and 5.2 ± 6.5% [P < 0.005], respectively), compared with nonsignificant changes in the placebo-treated patients (increase of 0.6 ± 5.2% and decrease of 1.2 ± 5.8%, respectively). Femoral neck BMD increased in the pamidronate-treated group (by 2.6 ± 8.6%) and decreased significantly in the placebo-treated group (by 4.0 ± 1.3% [P < 0.005]). The changes in BMD with time at all 3 measurement sites were significantly different between the treatment groups (P < 0.0001). Changes in radiographic signs of joint damage and in disease activity were similar in the 2 groups. Conclusion. The present study provides the first evidence that long-term treatment with an orally administered bisphosphonate overcomes bone loss and increases bone mass when compared with placebo. This finding may have significance with regard to the treatment of patients with RA.     

鲑鱼降钙素鼻喷剂治疗绝经后骨质疏松患者骨密度及骨转换指标的变化

目的 观察鼻喷鲑鱼降钙素(calcitonin)治疗绝经后骨质疏松症(postmenopausal osteoporosis,PMO)患者6个月和12个月后骨密度及骨转换指标的变化.方法 选择PMO患者共67例,给予鼻喷降钙素治疗37例;其余30例PMO患者单纯服用钙剂和维生素D作为对照组.各组分别于用药前和用药后6个月和12个月采用DEXA骨密度仪测定骨密度;定量夹心酶联免疫法(ELISA)测定Ⅰ型胶原N末端肽(NTX)、骨特异性碱性磷酸酶(BALP)、抗酒石酸酸性磷酸酶(TRACP-5b)、25-羟维生素D,化学发光法测定骨钙素(BGP).结果 5例患者因医疗费用、拒绝坚持治疗退出试验,鼻喷降钙素组共32例完成试验.鼻喷降钙素治疗6个月后可见患者股骨颈和腰椎骨密度均较前有所增加,但仅在腰椎差异有统计学意义(P＜0.05),而在股骨颈治疗前后骨密度的差异无统计学意义(P＞0.05).治疗12个月时股骨颈和腰椎骨密度较前均明显升高,差异有统计学意义(P＜0.05).对照组在治疗6个月时的腰椎和治疗12个月时的股骨颈和腰椎部位骨密度均较治疗前降低,差异有统计学意义(P＜0.05).鼻喷降钙素治疗6个月和12个月时,股骨颈和腰椎骨密度均较对照组升高(P＜0.05).鼻喷降钙素治疗6个月后,TRACP-5b、NTX/Cr较治疗前降低,差异有统计学意义(P＜0.05);治疗12个月后,除TRACP-5b、NTX/Cr较前降低更加明显以外(P＜0.01),BALP较治疗前有升高,差异有统计学意义(P＜0.05).对照组在治疗12个月时,BALP较前有降低,差异有统计学意义(P＜0.05).25-羟维生素D在各组经治疗后,均明显升高,差异有统计学意义.结论 本研究结果显示鼻喷降钙素治疗6个月有效,12个月效果显著,可预防骨丢失,增加骨量.

Abstract：

Objective To study the changes of bone mineral density(BMD)and bone turnover in postmenopausal osteoporotic patients treated with salmon calcitonin nasal spray. Methods Sixty-seven postmenopausal osteoporotic patients were enrolled in our trial. All of them received calcium and vitamin D; 37patients were treated with salmon calcitonin nasal spray for 12 months and the other 30 patients received calcium and vitamin D only. Dual-energy X-ray absorptiometry(DEXA)and measurements of a series of bone turnover indices were performed before and after medication for 6 and 12 months. Results After treatment with salmon calcitonin nasal spray for6 months, BMD in lumbar spine 2-4 increased but no change occurred in femoral neck. However, after treatment for 12 months, BMD in both lumbar spine 2-4 and femoral neck increased. In the control group, BMD in lumbar spine 2-4 decreased after treatment for 6 and 12 months, but BMD in femoral neck decreased only after 12months. Comparing with the control group, after treatment with salmon calcitonin nasal spray, BMD in lumbar spine 2-4 and femoral neck were increased obviously. The level of TRACP-5b and NTX/Cr decreased after treatment with salmon calcitonin nasal spray for6 months and 12 months, while BALP increased only after treatment for 12 months. In the control group, BALP decreased after treatment for 12 months. The level of 25-(OH)vitamin D increased after treatment for 6 months and 12 months in both groups. Conclusions Long-term treatment with salmon calcitonin nasal spray prevents bone loss and may increase bone mass.     

VERTEBRAL OSTEOPOROSIS IN RHEUMATOID ARTHRITIS PATIENTS: EFFECT OF LOW DOSE PREDNISONE THERAPY

The effect of low dose prednisone therapy on spinal bone massis controversial. We measured lumbar trabecular and corticalbone mineral density (BMD) in 74 rheumatoid arthritis (RA) patientsby dual energy quantitative computerized tomography in a cross-sectionalstudy. The presence of vertebral deformities was evaluated ona lateral spine radiograph. Patients who had never been treatedwith corticosteroids (n=44) were compared with patients on long-termlow dose ( 10 mg/day) prednisone therapy (n=30). After correctionfor confounding variables the lumbar BMD was highly sig nilicantlyinfluenced by prednisone therapy in postmenopausal patients(estimated influence –31.2% on trabecular BMD and –37.2%on cortical BMD). Vertebral deformities were also significantlymore frequent in prednisone treated postmenopausal patients.No negative effect of prednisone treatment could be demonstratedin male patients. In contradiction to previous reports we concludethat long-term prednisone therapy may be associated with developmentof spinal osteoporosis in postmenopausal RA patients, even whenlow doses are used. KEY WORDS: Corticosteroids, Osteoporosis, Bone densitometry, Dual energy quantitative computerized tomography, Vertebral fractures, Postmenopause     

The relation between joint erosion and generalized osteoporosis and disease activity in patients with rheumatoid arthritis

The aim of this study is to investigate the correlation between joint erosion and osteoporosis in patients with rheumatoid arthritis (RA). Fifty-one patients with RA were included for the study. Hand radiograms of all patients were evaluated by the Larsen modified Sharp and carpometacarpal ratio methods. Bone mineral density (BMD) measurements were performed at the femur, lumbar, and forearm regions. Disease activity was assessed clinically by the health assessment questionnaire (HAQ), visual analog scale, erythrocyte sedimentation rate, C-reactive protein (CRP), and the rheumatoid factor (RF). There was no statistically significant difference in terms of the BMD values at L1-4 between the patients with RA and the control group. The BMD measurements at the right forearm and the right hip were statistically significantly lower in the patient group. For radiological scoring, hand radiograms were evaluated by three different methods. There was a significant correlation between the duration of disease and the radiological evaluation methods. HAQ scores, Larsen and Sharp methods 1/3 distal and mid-distal (MID), and BMD measurements of the forearm were correlated. Moreover, 1/3 distal, MID, and ultra-distal BMD showed significant correlations with CRP levels. Radiogram continues to have an important role in determining and following-up the joint erosion seen in patients with RA. However, we believe that as establishing periarticular osteoporosis in the early term by performing BMD measurements on the forearm is correlated with disease activity, it may be useful in the early diagnosis of RA and its objective results will be efficient in predicting the progression of disease     

The treatment of osteoporosis in patients with rheumatoid arthritis receiving glucocorticoids: a comparison of alendronate and intranasal salmon calcitonin

Objective The purpose of this study was to assess the effects of alendronate and intranasal salmon calcitonin (sCT) treatments on bone mineral density and bone turnover in postmenopausal osteoporotic women with rheumatoid arthritis (RA) receiving low-dose glucocorticoids.Methods Fifty osteoporotic postmenopausal women with RA, who had been treated with low-dose corticosteroids for at least 6 months, were randomized to receive alendronate 10 mg/day or sCT 200 IU/day for a period of 24 months. All patients received calcium supplementation 1,000 mg and vitamin D 400 IU daily. Bone mineral density (BMD) of the lumbar spine, femoral neck, and trochanter was measured annually using dual-energy X-ray absorptiometry. Bone metabolism measurements included urinary deoxypyridinoline (DPD), serum bone alkaline phosphatase (BAP), and serum osteocalcin (OC).Results Over 2 years, the lumbar spine (4.34%, P <0.001), femoral neck (2.52%, P <0.05), and trochanteric (1.29%, P <0.05) BMD in the alendronate group increased significantly. The sCT treatment increased lumbar spine BMD (1.75%, P <0.05), whereas a significant bone loss occurred at the femoral neck at month 24 (–3.76%, P <0.01). A nonsignificant decrease in the trochanteric region was observed in the sCT group (–0.81%). The difference between the groups with respect to the femoral neck and trochanteric BMD was statistically significant ( P <0.001and P <0.05, respectively). The decreases in urinary DPD (–21.87%, P <0.001), serum BAP (–10.60%, P <0.01), and OC (–19.59%, P <0.05) values were statistically significant in the alendronate group, whereas nonsignificant decreases were observed in the sCT group (–5.77%, –1.96%, and –4.31%, respectively). A significant difference was found in the DPD and BAP levels between the two treatment groups in favor of the alendronate group at all time points ( P =0.001 and P <0.05, respectively).Conclusion The results of this study demonstrated that alendronate treatment produced significantly greater increases in the femoral neck BMD and greater decreases in bone turnover than intranasal sCT in RA patients receiving low dose glucocorticoids.     

Increase in bone mineral density of patients with rheumatoid arthritis treated with anti-TNF-alpha antibody: a prospective open-label pilot study

OBJECTIVE: To determine the changes in bone mineral density (BMD) in patients with rheumatoid arthritis (RA; without osteoporosis) treated with infliximab. METHODS: Twenty-six patients (19 women, seven men) aged 54.2 yr (range 27-75), with persistently active RA despite a high dose of non-steroidal anti-inflammatory drugs and/or treatment with methotrexate or leflunomide, were studied. Mean duration of disease was 9.8 yr. Patients receiving or having received bisphosphonates or hormone replacement therapy were excluded. The patients were treated with 3.5 mg/kg infliximab at weeks 0, 2, 6 and then every 6-8 weeks. Lumbar and femoral BMD was measured by dual-energy X-ray absorptiometry at baseline and 12 months later. Serum osteocalcin and serum crosslaps were measured at baseline (week 0) and after 12 months. Twelve patients were taking calcium (1 g/day) and vitamin D (800 IU/day). Twenty patients were receiving methotrexate (mean dose 12.5 mg/day), six patients were receiving leflunomide (mean dose 20 mg/day) and nine patients were concomitantly receiving corticosteroids at a mean daily dose of 10 mg. RESULTS: After 12 months of infliximab therapy, there was a significant increase in BMD in the spine (BMD, P < 0.001; T-score, P < 0.001; Z-score, P < 0.001) and the femoral neck (BMD, P < 0.001; T-score, P < 0.001; Z-score, P < 0.01). With regard to the root mean square average, there was a significant increase in BMD at the left femoral neck (11.6% for a root mean square of 6%) but only a trend towards improvement in the spine (2.7% for a root mean square of 4%) during the study period. There was a significant increase in osteocalcin serum levels between baseline and after 12 months (P < 0.01) and a significant decrease in the marker for bone resorption (P < 0.01) but no change in serum calcium was observed. However, the changes in markers of bone metabolism and BMD were not correlated. CONCLUSION: The data support the hypothesis that anti-TNF therapy may exert beneficial effects on bone metabolism in RA patients.     

Calcitonin therapy in postmenopausal osteoporosis: effects on serum levels of interleukin‐1, interleukin‐6 and tumor necrosis factor‐α

Background: It has been suggested that the effects of calcitonin (CT) therapy for senile and postmenopausal osteoporosis were due to its modulatory effects on bone‐related cytokines. A significantly increased release of IL‐1, IL‐6 and TNF‐α, which have bone resorptive effects, has been reported in osteoporotic patients. Aim: In this study we investigated the effects of CT therapy on the levels of IL‐1, IL‐6 and TNF‐α. Method: Forty postmenopausal osteoporotic women were included to the study. The first group consisting of 20 patients were given 100 IU CT subcutaneously and 1000 mg elemental calcium for 15 consecutive days. The second group or the control group also consisting of 20 patients were only given 1000 mg elemental calcium and both of the groups were not allowed to take any other medication. Results: In the first group the mean serum TNF‐α level significantly decreased from 16.9 ± 24.2 pg/mL to 8.6 ± 13 pg/mL after 1500 IU CT therapy (P < 0.05). The control group's mean serum level of IL‐1, IL‐6 and TNF‐α did not reveal any statistically significant differences (P > 0.05). Conclusion: Our results suggest that CT therapy for osteoporosis may partially be due to its inhibitory effects on TNF‐α, and probably IL‐1. However, further in‐vitro and ex‐vivo studies are needed to clarify this hypothesis.     

特立帕肽和降钙素治疗中国绝经后骨质疏松症患者的效果比较

目的比较特立帕肽[重组人甲状旁腺激素（1—34）;rhPTH（1—34）]与降钙素鼻喷剂对中国绝经后妇女骨质疏松症的治疗效果。方法特立帕肽组患者（N=217）采用特立帕肽20μg／d皮下注射,降钙素组患者（N=110）用鲑鱼降钙素鼻喷剂200IU／d滴鼻,疗程均为24周。2组患者均每天补充≥500mg的钙和200～400Iu的维生素D。主要终点是基线至终点腰椎BMD的变化率。结果特立帕肽组患者腰椎BMD从基线到终点的变化率与降钙素组相比差异有统计学意义（P〈0．0001）。与降钙素组相比,特立帕肽组患者从基线到终点血清骨钙素水平明显升高（P〈0．0001）。2组患者全髋和转子BMD变化率的差异均无统计学意义。2组患者出现不良事件（AE）者均较少,特立帕肽组AE较降钙素组多。结论特立帕肽增加腰椎BMD的效果优于降钙素,2种疗法均安全且耐受性好。     

Influence of long-term low-dose methotrexate therapy on periarticular and generalized osteoporosis in rheumatoid arthritis

Abstract

Our objective was to evaluate the effect of low-dose methotrexate therapy on periarticular and generalized osteopenia in patients of rheumatoid arthritis (RA). Fifty-five women received one of four therapeutic regimens. The periarticular radial bone mineral density (BMD) was analyzed by dual energy X-ray absorptiometry. Generalized osteopenia was assessed by measuring the BMD and height of the lumbar spine (L₂-L₄). Vertebral deformity was also assessed on plain Xray film. Physical activity, age and menopausal status were similar among the four treatment groups. The decrease of lumbar BMD was greatest in the group given steroids plus another disease modifying antirheumatic drug (DMARD), followed by the steroid/methotrexate group, methotrexate group and the other DMARD group. The decreases of lumbar vertebral height was greatest in the steroid/methotrexate group, followed by the steroid/DMARD group, methotrexate group and the other DMARD group. Vertebral compression was found in 22% of the steroid/methotrexate group and 14% of the steroid/DMARD group. Radial periarticular BMD was significantly lower in patients with active wrist joint synovitis than in patients without synovitis, but was increased by methotrexate therapy. We conclude that low-dose methotrexate did not increase lumbar osteopenia or vertebral compression in RA patients and might preven periarticular osteopenia by suppressing synovitis     

Determinants of axial bone loss in rheumatoid arthritis

To assess mechanisms that cause generalized osteoporosis in rheumatoid arthritis (RA), we measured bone mineral density (BMD) by dual photon absorptiometry in the lumbar spine and femoral neck of 111 patients with RA. BMD was significantly reduced at both sites in these patients. Physical activity correlated significantly with BMD in patients with RA, and was found, by multiple regression analysis, to be a significant predictor of femoral bone density in female patients. Multiparity exerted a protective effect on lumbar bone density. Prednisolone (mean dosage 8 mg/day) was not associated with significantly increased bone loss in women, whereas higher dosages in men (mean 10.3 mg/day) were associated with increased lumbar bone loss. Reduced physical activity leading to a form of disuse osteoporosis appears to be an important factor in axial bone loss in RA.     

Influence of long-term low-dose methotrexate therapy on periarticular and generalized osteoporosis in rheumatoid arthritis

Our objective was to evaluate the effect of low-dose methotrexate therapy on periarticular and generalized osteopenia in patients of rheumatoid arthritis (RA). Fifty-five women received one of four therapeutic regimens. The periarticular radial bone mineral density (BMD) was analyzed by dual energy X-ray absorptiometry. Generalized osteopenia was assessed by measuring the BMD and height of the lumbar spine (L₂-L₄). Vertebral deformity was also assessed on plain Xray film. Physical activity, age and menopausal status were similar among the four treatment groups. The decrease of lumbar BMD was greatest in the group given steroids plus another disease modifying antirheumatic drug (DMARD), followed by the steroid/methotrexate group, methotrexate group and the other DMARD group. The decreases of lumbar vertebral height was greatest in the steroid/methotrexate group, followed by the steroid/DMARD group, methotrexate group and the other DMARD group. Vertebral compression was found in 22% of the steroid/methotrexate group and 14% of the steroid/DMARD group. Radial periarticular BMD was significantly lower in patients with active wrist joint synovitis than in patients without synovitis, but was increased by methotrexate therapy. We conclude that low-dose methotrexate did not increase lumbar osteopenia or vertebral compression in RA patients and might preven periarticular osteopenia by suppressing synovitis     

Effect of methotrexate on pulmonary involvement in patients with rheumatoid arthritis

Objective: The aim of this study is to determine the effects of methotrexate (MTX) therapy on pulmonary involvement in patients with rheumatoid arthritis (RA). Method: Fifty‐five non‐smoking RA patients were included in the study. Routine laboratory investigations, pulmonary function tests (PFT), high resolution computed tomography (HRCT) and arterial blood gas analysis were performed in all of the patients. Randomly dividing the patients into two groups, the first group were given 7.5 mg/week MTX and the second group were given 250 mg/day chloroquine phosphate. At the end of the sixth month all the tests and the analysis were repeated and evaluated by using χ² and Student's t‐test; P < 0.05 was considered statistically significant. Results: At the beginning of the study, HRCT examination revealed 92.7% pulmonary involvement in 55 RA patients. At the sixth month although the RA patients in the chloroquine group did not show any difference, RA patients in the MTX group displayed statistically significant increases in their pulmonary involvement (P < 0.05). Patients in the MTX group also displayed significant decreases at FEV₁/FVC and significant increases at FEV₁ in PFT and O₂ saturation (P < 0.05, P < 0.05 and P < 0.01, respectively). In the chloroquine group we observed significant increases in FEV₁ and vital capacity (P < 0.05). Conclusion: Although the MTX therapy increases the risk of pulmonary involvement in patients with RA, it also increases the ventilation which in turn increases the functional capacity of the patient. Considering the beneficial effect on the radiological progression of the disease, we think that MTX therapy should be taken into account as the first choice in the treatment of RA.     

The effect of low-dose methotrexate on bone mineral density in patients with early rheumatoid arthritis

OBJECTIVE: The intent of this study was to assess the effect of low-dose methotrexate treatment on bone mineral density (BMD) in patients with early rheumatoid arthritis (RA). METHODS: Forty-six premenopausal women with early RA not previously treated with disease-modifying antirheumatic drugs or corticosteroid were randomized to 7.5 mg/week of methotrexate or 2 g/day of sulphasalazine for 18 months. Bone mineral density of the lumbar spine, femoral neck, and trochanter was measured using dual-energy X-ray absorptiometry (DEXA). Biochemical studies included serum calcium, phosphorus, total alkaline phosphatase, beta-2 microglobulin, parathyroid hormone and 25-hydroxyvitamin D(3) concentrations, spot urinary calcium, and 24-h urinary calcium excretion. Disease activity was assessed by modified disease activity score (DAS 28), and functional impairment was estimated by the Health Assessment Questionnaire. RESULTS: No significant difference in BMD of the lumbar spine, femur neck, or trochanter was observed at 18 months in either group. There was also no significant change in the biochemical parameters of both groups. CONCLUSION: Our findings suggest that low-dose methotrexate has no negative effect on BMD in premenopausal RA patients.     

吡格列酮对2型糖尿病患者骨钙素、降钙素和骨密度的影响

目的探讨噻唑烷二酮类药物吡格列酮对2型糖尿病（T2DM）患者骨钙素、降钙素和骨密度的影响。方法89例T2DM患者,随机分为T2DM对照组56例和T2DM实验组33例,在口服降糖药治疗的基础上,实验组加服吡格列酮（30mg／日）,疗程3个月;正常对照30例。以双能X线吸收测量法（DXA）测量T2DM实验组、T2DM对照组治疗前后及正常对照组骨密度（BMD）,放射免疫分析法（RIA）测定T2DM实验组、T2DM对照组治疗前后及正常对照血清骨钙素（BGP）和降钙素（CT）水平,并进行比较。结果①T2DM组血清BGP和CT水平均低于正常对照组（P〈0．01）;②T2DM实验组经吡格列酮治疗后BGP和CT水平均降低,与治疗前比较差异有显著性意义（P〈0．01）;③T2DM组骨密度（BMD）低于正常对照组（P〈0．05）;④T2DM实验组经吡格列酮治疗后髋部及腰椎BMD均有所下降;⑤BGP与糖尿病患者年龄及空腹血糖负相关,与髋部及腰椎BMD正相关;CT与糖尿病患者年龄负相关。结论吡格列酮可致2型糖尿病患者血清BGP和CT水平明显降低,骨密度下降,其中对女性的影响尤为显著,提示该药可致骨量丢失加速,对骨代谢有不利影响。     

Relationship between bone mineral density and duration of rheumatoid arthritis

BackgroundLonger disease duration is believed to be associated with more pronounced bone loss in rheumatoid arthritis (RA). This study was designed to assess bone mineral density (BMD) status in RA compared with age-matched control in relation to disease duration.MethodsThis study included 177 RA and 283 age-matched non-RA controls. BMD at the femoral neck and lumbar spine was assessed by Dual Energy X-ray Absorptiometry Osteoporosis was diagnosed according to WHO criteria. We divided patients with RA into groups based on disease duration of <2, 2–5, 5–10, and >10 years and compared them with controls. The relationship between disease duration and BMD was investigated by chi square and Spearman test.ResultsMean age of patients and control subjects was 51.2 ± 12.5 and 52.2 ± 6.7 years, respectively and mean disease duration was 86.5 ± 73.3 months. Osteoporosis at the femoral neck and lumbar spine in patients with RA was significantly higher than in controls. Femoral neck BMD in RA was negatively correlated with disease duration and 4.5% variations of femoral neck BMD was explained by disease duration (r² = 0.045, P = 0.005). Odds Ratio (OR) for osteoporosis in RA patients as compared to controls was increased by prolongation of disease duration from 2.38 (0.38–14.7) in patients with disease duration <2 years to 12.56 (2.24–70.2) in patients with disease duration >10 years. For patients treated with methotrexate compared to those who had never received methotrexate the odds ratio for femoral neck osteoporosis reduced by 64% (OR = 0.36, 95% CI, 0.15–0.91).ConclusionThere is a significant negative relationship between femoral neck BMD and disease duration in RA. The value of OR increases proportionately with lengthening of disease duration which can be reduced significantly by methotrexate therapy.     

The effect of raloxifene after discontinuation of long-term alendronate treatment of postmenopausal osteoporosis

OBJECTIVE: The aim of this study was to compare bone mineral density (BMD) and biochemical markers of bone turnover in patients receiving long-term alendronate therapy who continued alendronate, were switched to raloxifene, or discontinued antiresorptive therapy. DESIGN, PATIENTS, AND INTERVENTIONS: Ninety-nine ambulatory women who were diagnosed with postmenopausal osteoporosis and treated with alendronate (10 mg/d) for a mean period of 43 months were randomized to double-blind raloxifene (60 mg/d; n = 33), placebo (n = 33), or continuation of open-label alendronate (n = 33) for 12 months. Patients continued their assigned treatment in a subsequent 12-month, open-label extension phase. All patients received supplemental calcium (500 mg/d) and vitamin D (800 IU/d). MAIN OUTCOME MEASURES: BMD (lumbar spine, total femur, femoral neck, distal forearm, and total body) and biochemical markers (serum intact amino-terminal propeptide of type I procollagen, type 1 collagen cross-linked C-telopeptide, and osteocalcin) were measured at baseline and follow-up visits. RESULTS: Discontinuation of alendronate therapy resulted in a decrease in lumbar spine BMD at 12 months (-2.66%; P < 0.05), but did not change total femur BMD (+0.35%; nonsignificant). Raloxifene and alendronate, compared with discontinuation, prevented lumbar spine BMD loss (-0.75% and -0.54% at 12 months, respectively; P < 0.05). Raloxifene and alendronate caused a similar increase in total femur BMD at 12 months (1.45% and 1.56%; both P < 0.05 vs. baseline; nonsignificant vs. discontinuation). Patients, who discontinued alendronate therapy experienced an increase in bone turnover. Bone turnover increases were less pronounced in patients taking raloxifene and were absent in those who continued alendronate. Of the three groups, mean bone turnover in raloxifene patients was the closest to premenopausal mean values. CONCLUSIONS: BMD preservation and increase were most pronounced in patients continuing alendronate. Raloxifene treatment, compared with placebo, demonstrated beneficial effects on BMD and bone turnover after discontinuation of long-term alendronate therapy.