Effects of low dose corticosteroids on bone mass in rheumatoid arthritis: a longitudinal study.

Low dose corticosteroids are effective in suppressing synovitis in rheumatoid arthritis (RA), but there remains concern about their side effects, particularly osteoporosis. To examine the effects of low dose corticosteroids on bone loss in RA bone mineral density (BMD) was measured in the lumbar spine and hip for up to two years in 15 patients treated with these agents (mean dose prednis(ol)one 6.6 mg/day). 15 patients not receiving them, and 15 age matched controls. The initial BMD at both skeletal sites was significantly reduced in both patient groups compared with controls. The mean change in bone density was 0.2, 0.1, and -0.1% a year in the spine and -2.0, -1.9, and -1.0% a year in the hip respectively for the three groups. These rates of bone loss were not significantly different between groups at either site. These findings suggest that low dose corticosteroid treatment in RA is not associated with an increased risk of 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.     

The effect of low dose methotrexate on bone density.

OBJECTIVE: High dose methotrexate (MTX) has been linked with bone loss in oncology patients. However, it is unclear whether longterm low dose MTX used in the treatment of inflammatory arthritis is associated with bone loss. We compared the effect of low dose MTX on bone density in prospectively recruited patients with rheumatoid arthritis (RA) and psoriasis/psoriatic arthritis (Ps/PsA). METHODS: Thirty RA patients and 30 Ps/PsA patients taking MTX were compared to controls not taking MTX (30 with RA, 27 Ps/PsA). Bone mineral density (BMD) of the radius, lumbar spine, trochanter, and femoral neck was measured using Lunar dual energy x-ray absorptiometry. Student t tests were used to detect differences in bone density (using Z scores) of the MTX group versus controls for both the RA and Ps/PsA groups. Analysis of covariance was used to examine for confounders including disease duration, disease activity, age, and sex. RESULTS: BMD of the radius/femoral neck/trochanter did not differ significantly between the MTX treated groups and controls when analyzed by Z scores. The mean difference between the MTX group and controls of the femoral neck was 0.040 (95% CI -0.40, 0.12) and 0.060 (95% CI -0.30, 0.15) for the RA and Ps/PsA groups, respectively. The absolute BMD of the lumbar spine (L2-L4) was higher in the RA MTX group than in controls. Analysis of covariance did not reveal an effect of study group on bone density. CONCLUSION: This study suggests that low dose MTX does not have a negative effect on bone density, at either cortical or trabecular sites.     

Decreased axial bone mineral density in perimenopausal women with rheumatoid arthritis--a population based study.

OBJECTIVES--Although periarticular osteoporosis is a well-recognised phenomenon in rheumatoid arthritis (RA), there is considerable controversy over whether RA is associated with more generalised osteoporosis. The aetiology of this bone loss is probably multifactorial, including both life-style risk factors and disease-related determinants. Population-based studies on bone mineral density (BMD) in RA have not previously been conducted, and the purpose of the present cross-sectional population-based study was to determine whether patients with RA are at an increased risk of having osteoporosis. Furthermore, the determinants of BMD in RA patients were investigated. METHODS--BMD at the spine and femoral neck was measured in 143 women with RA. The control group consisted of 1611 women with no disease or taking any drugs known to affect bone metabolism. The study population was a random stratified sample from the Kuopio Osteoporosis Study, which included all perimenopausal women aged 47-56 years residing in Kuopio Province, Eastern Finland in 1989 (n = 14,220). The mean age of the patients at the time of densitometry was 53.7 years. RESULTS--The mean (SD) spinal and femoral neck BMD was significantly lower in patients with RA compared with controls [spine: 1.067 (0.161) v 1.129 (0.157) g/cm2, p < 0.001; femoral neck: 0.851 (0.136) v 0.932 (0.123) g/cm2, p < 0.001]. Analysis of variance showed that at the spine the difference was significant only in patients having corticosteroid treatment, whereas at the femoral neck patients with non-steroid treatment also had significantly lower BMD. When confounding factors were corrected, no significant difference could be found between non-steroid and corticosteroid treated patients with RA, suggesting that the independent effect of corticosteroids on BMD is only minimal. Multiple regression analysis found age, weight and functional grade to be significant predictors of spinal BMD (R2 = 0.403, p < 0.001). In the femoral neck weight, cumulative corticosteroid dose and functional grade were significant predictors of BMD (R2 = 0.410, p < 0.001). CONCLUSIONS--RA is associated with generalised osteoporosis. The physical impairment and body weight are the major determinants of both spinal and femoral bone mass in RA patients. The cumulative corticosteroid dose was also a significant determinant of femoral neck BMD. However, the independent effect of corticosteroids is questionable because the use of corticosteroids may be an indicator of more severe disease.     

Sex hormone status and osteoporosis in postmenopausal women with rheumatoid arthritis

Sex hormones have important effects on bone, especially in postmenopausal women. These hormones may be of particular significance in patients with rheumatoid arthritis (RA), who have a high frequency of osteoporosis. To examine this, we measured estrogen and androgen concentrations and bone mineral density (BMD) in 49 postmenopausal women with RA and 49 normal postmenopausal women. Compared with the controls, postmenopausal RA patients had significantly reduced levels of estrone (median 18 pmoles/liter versus 49; P < 0.001), dehydroepiandosterone sulfate (DHEAS) (median 0.3 μmoles/liter versus 2.0; P < 0.001), testosterone (median 0.6 nmoles/liter versus 0.95; P < 0.001), and femoral BMD (mean 0.72 gm/cm² versus 0.80; P < 0.002). Prednisolone therapy in 22 patients (mean dosage 8 mg/day) was associated with reductions in estrone and testosterone levels; however, DHEAS and femoral BMD were also decreased in RA patients who were not receiving corticosteroids. Reduced DHEAS levels in postmenopausal women with RA may increase their risk of osteoporosis.     

Preferential reduction of bone mineral density at the femur reflects impairment of physical activity in patients with low-activity rheumatoid arthritis

Bone mineral density (BMD) and factors influencing BMD in rheumatoid arthritis (RA) under good or moderate control were examined to assess management of osteoporosis in RA. BMD of the lumbar spine, femur, and distal radius was measured in 105 female patients with well-controlled RA. Laboratory and clinical variables associated with disease activity were measured in the same subjects, and correlations between these variables and BMD were evaluated. The RA patients showed a greater decrease in BMD of the femoral neck than of the lumbar spine. Age, Health Assessment Questionnaire (HAQ) score, and Larsen damage score had negative correlations with BMD of the femoral neck. In multiple regression analysis of the parameters associated with BMD of the femoral neck in simple regression analysis, an increase in HAQ score showed a negative correlation with BMD of the femoral neck. After initiation of treatment with alendronate (ALN), BMD of the femoral neck increased and correlated with improvement in HAQ score. A decrease in BMD of the femoral neck is a characteristic of RA. This suggests that muscle tonus has more effect than weight-bearing activity on BMD in patients with RA. BMD of the femoral neck is a useful index for general evaluation of RA patients.     

Bone mineral density in patients with recent onset rheumatoid arthritis: influence of disease activity and functional capacity.

BACKGROUND. Generalised osteoporosis is often described in patients with rheumatoid arthritis (RA). The aim of this study was to evaluate disease related determinants of bone mineral density (BMD) in patients with RA. METHODS. Subjects were selected from a group of 147 patients with recent onset RA. Disease activity and functional capacity were studied prospectively in this cohort. Activity of the disease was assessed once every three months by various parameters, and functional capacity was measured with a health assessment questionnaire once every six months. Ninety seven patients consented to participate in the study. Bone mineral density was assessed with dual energy x ray absorptiometry in the lumbar spine, in a combined region of interest in the hips, and in Ward's triangle. Multiple linear regression procedures were used to analyse the data. RESULTS. Duration of RA was negatively associated with BMD at all three sites of measurement. The mean erythrocyte sedimentation rate in the six months before BMD measurement was negatively associated with BMD in the hip and in Ward's triangle. Other parameters of disease activity were not related to BMD. The mean health assessment questionnaire score in the 18 months before BMD measurement was negatively associated with BMD in the combined hip region only. Bone mineral density tended to be decreased when patients were compared with a normal reference group, especially in the femoral regions of interest. CONCLUSIONS. It is concluded that BMD may be affected in patients with recent onset RA by disease dependent mechanisms. Several factors have been suggested elsewhere as determinants of BMD in RA. The results of this study show that disease duration, disease activity, and functional impairment may, independently of each other, contribute to bone loss, especially in the proximal femur.     

Bone mineral density evolution in young premenopausal women with idiopathic osteoporosis

Idiopathic osteoporosis is a frequent cause of osteoporosis in young premenopausal women. However, there are no data about the treatment of these patients. The aim of this study was to analyse the evolution of bone mineral density (BMD) in premenopausal women with idiopathic osteoporosis treated with a conservative approach. Retrospective study of 16 premenopausal women with idiopathic osteoporosis (aged 35.7±7 years) with a mean follow-up period of 3 years (1–6 years). BMD measurements at the lumbar spine and femoral neck were obtained in all patients at baseline and yearly (patients had one or more fragility fractures and/or a Z score <−2 in the lumbar spine or femur). Secondary causes of osteoporosis were excluded in all patients. Patients were treated with calcium and vitamin D to achieve a calcium intake of up to 1,500 mg/day and were advised to increase physical activity. A significant increase in lumbar and femoral BMD was observed after 2 and 3 years of follow-up, respectively (1.9±1.9% mean increase in lumbar spine, p= 0.021, at 2 years) (5.6±4.5% mean increase in femur, p=0.04, at 3 years). The serum total alkaline phosphatase (TAP) values increased at 2 years (122±46 vs 140±36 U/l, p=0.054). In addition, a negative correlation between baseline TAP serum values and lumbar BMD evolution at 2 years was observed (r=−0.748, p=0.013). No patient developed new skeletal fractures during the follow-up period. In young premenopausal women with idiopathic osteoporosis the conservative treatment with supplements of calcium and vitamin D associated with an increase of physical activity is associated with an increase in BMD without evidence of further skeletal fractures after more than 3 years of follow-up.     

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.     

Osteoporosis in rheumatoid arthritis: safety of low dose corticosteroids.

Fear of inducing generalised osteoporosis is one reason why corticosteroids are withheld in patients with rheumatoid arthritis (RA). No studies, however, have directly measured bone density in such patients at clinically relevant sites. To assess this risk we measured bone mineral density in the lumbar spine and femoral neck by dual photon absorptiometry in 84 patients with RA, 44 of whom had been treated with low dose prednis(ol)one (mean dose +/- SE 8.0 +/- 0.5 mg/day; mean duration of treatment 89.6 +/- 12.0 months). There were significant reductions in bone mineral density in patients treated with corticosteroids (lumbar 9.6%, p less than 0.001; femoral 12.2%, p less than 0.001) and in those who had not received corticosteroids (lumbar 6.9%, p less than 0.01; femoral 8.9%, p less than 0.001), but the differences between the two groups were not significant. We conclude on the basis of these studies that low dose oral corticosteroids do not increase the risk of generalised osteoporosis in patients with rheumatoid arthritis.     

Bone mineral density and frequency of osteoporosis among Vietnamese women with early rheumatoid arthritis

Generalised bone mineral density (BMD) reduction often occurs in established rheumatoid arthritis (RA); however, in early RA, there is a disagreement with regard to BMD in the femoral neck and lumbar spine, and there is no available information for the whole body. Therefore, the aims of this study were to investigate the BMD, frequency of osteoporosis and the risk factors for BMD reduction in Vietnamese women with early RA. BMD in the femoral neck, lumbar spine L1–4 and whole body was measured in 105 women with early RA (disease duration ≤3 years) and 105 age-matched healthy women (26–73 years) using a dual energy X-ray absorptiometry. Femoral neck and whole body BMD in women with RA were lower (p < 0.05) than controls, while lumbar spine BMD was similar between two groups. The frequency of osteoporosis in the femoral neck, lumbar spine and whole body in women with RA aged ≥50 were higher (p < 0.05) than controls: 41.8% versus 29.5%, 42.2% versus 37.7% and 37.1% versus 28%, respectively. There were associations between the frequencies of osteoporosis at all sites with postmenopausal status, glucocorticoid use, rheumatoid factor positivity and disease activity with lumbar spine BMD and disease disability with femoral neck and whole body BMD. In conclusion, women with early RA had significantly lower femoral neck and whole body BMD, but had similar lumbar spine BMD compared with controls. The frequency of osteoporosis at all sites was significantly higher in women with RA than controls, suggesting that assessment of BMD should be considered in women with early RA.     

Osteoporosis in treated adult coeliac disease.

Forty five women and 10 men with coeliac disease diagnosed in adult life, who were already on a gluten free diet, had serial bone mineral density measurements at the lumbar spine and femoral neck over 12 months. Osteoporosis, defined as a bone mineral density (BMD) < or = 2 SD below the normal peak bone mass was found in 50% of male and 47% of female coeliac patients. Patients with a BMD < or = 2 SD below age and sex matched normal subjects, had a significantly lower body mass index (21.3 kg.m-2 compared with 25.2 kg.m-2, p < 0.02 Wilcoxon rank sum test) and lower average daily calcium intake (860 mg/day compared with 1054 mg/day, p < 0.05 Wilcoxon rank sum test) than patients with normal bone mineral density. In postmenopausal women with coeliac disease there was a strong correlation between the age at menopause and BMD at both the lumbar spine (r = 0.681, p < 0.01, Spearman's rank correlation) and femoral neck (r = 0.632, p < 0.01). No overall loss of bone was shown over the 12 months of follow up, and relative to the reference population there was a significant improvement in BMD at the lumbar spine in women (p < 0.025, paired t test) and at the femoral neck in men (p < 0.05, paired t test). There was a significant negative correlation between the annual percentage change in BMD at the lumbar spine and the duration of gluten free diet (r = -0.429, p<0.01, Spearman's rank correlation), with the largest gain in BMD in patients with most recently diagnosed coeliac disease. Osteoporosis was shown in 47% of patients with treated adult coeliac disease. Recognised risk factors for osteoporosis in the general population including low body mass index, dietary calcium intake, and early menopause are particularly important in coeliac disease. Treatment of coeliac disease with a gluten free diet probably protects against further bone loss, and in the early stages is associated with a gain in bone mineral density.     

The effect of circulating nitric oxide level on axial bone mineral density in postmenopausal Turkish women with rheumatoid arthritis: a preliminary report

The aim is to investigate the differences in the circulating nitric oxide (NO) levels of rheumatoid arthritis (RA) patients, healthy controls and osteoporotic (OP) patients. We also examined whether the circulating NO levels may be correlated with bone mineral density (BMD) in RA patients. Forty-five patients with RA, 30 healthy women and 30 osteoporotic patients were recruited from the outpatient clinic. All the subjects were female and postmenopausal. Serum NO levels were measured (Nitrite/Nitrate, calorimetric method 1746081, Roche diagnostics, Mannheim, Germany) and BMD was measured at the spine and hip using dual energy X-Ray absorbtiometry (DEXA, Norland XR-46). Height and weight were measured and body mass index was calculated. Circulating NO levels were significantly higher in RA patients than other groups. Moreover, the RA group showed significantly higher BMD at lumbar spine and femoral neck regions compared to osteoporotic patients. However, the RA group showed significantly lower BMD at all sites than the controls. There was no correlation between circulating NO levels and BMD in all groups. We suggest that, unlike postmenopausal osteoporosis, inflammation induced osteoporosis is associated with RA is characterised by relatively preserved bone mass at the axial bone regions, and circulating NO levels as a parameter or determinant of inflammation are not correlated with axial BMD in RA patients.     

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   

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.     

Cross-sectional and longitudinal study of osteoporosis in patients with rheumatoid arthritis

To elucidate the pathology of osteoporosis associated with rheumatoid arthritis (RA), bone mass measurements were performed in 146 female patients with RA and compared with those in 150 age-matched female patients with osteoarthritis (OA) and postmenopausal osteoporosis (OP). Bone mineral density (BMD) was measured at the lumbar spine (L-BMD), the mid-radius (MR-BMD) and the calcaneus (C-BMD) by dual-energy X-ray absorptiometry (DXA), and at the distal radius by peripheral quantitative computed tomography (pQCT). The RA group showed significantly lower BMD at all sites, except L-BMD, than the OA group. Compared with the OP group, the RA group showed a significantly higher L-BMD but no difference at other sites. BMD in RA decreased with disease severity at all sites and lean body mass was highly correlated with L-BMD and C-BMD. Cross-sectional analysis revealed early bone loss at the distal radius and a decrease of L-BMD, MR-BMD, and C-BMD with disease duration. Longitudinal analysis showed that the annual loss of L-BMD, MR-BMD and C-BMD tended to be lower with increasing disease duration. Glucocorticoid administration had no influence on L-BMD, MR-BMD or C-BMD. We concluded that, unlike postmenopausal osteoporosis, osteoporosis associated with RA is characterised by relatively preserved bone mass in the axial bone and marked loss in the peripheral bone. The risk factors for generalised osteoporosis are a long disease duration, severity of disease, and decreased lean body mass. Received: 8 May 2001 / Accepted: 18 September 2001     

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.     

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.     

Impact of circulating bone-resorbing cytokines on the subsequent bone loss following bone marrow transplantation

Cytokines including IL-6 and TNF-alpha play an important role in the pathogenesis of postmenopausal osteoporosis. However, the relationship between changes in the cytokine levels and subsequent bone loss in patients undergoing a bone marrow transplantation (BMT) is unclear. A total of 46 patients undergoing an allogeneic BMT were prospectively investigated. The bone turnover markers and the serum cytokines were measured before BMT and serially after BMT. Bone mineral density (BMD) was measured before and 1 year after BMT. At 1 year after BMT, the lumbar spine BMD had decreased by 4.8%, and the total proximal femoral BMD had decreased by 12.3%. The serum IL-6 and TNF-alpha levels increased until 2 and 3 weeks after BMT, respectively. The lumbar BMD was significantly decreased as the serum IL-6 and TNF-alpha levels increased by post-BMT 3 weeks. The lumbar BMD decreased significantly as the cumulative prednisolone and cyclosporine dose increased. Patients with GVHD > or =grade II had higher lumbar bone loss than patients with GVHD 相似文献   

Effects of various antireabsorptive treatments on bone mineral density in hypogonadal young women after allogeneic stem cell transplantation

Ovarian failure after allogeneic stem cell transplant (allo-SCT) is an important risk factor for development of osteoporosis. We investigated the effects of various antiresorptive treatments in long-term surviving females with ovarian failure after allo-SCT. A total of 60 women with osteoporosis or osteopenia were divided randomly into four groups of 15 women each. Group 1 was treated with calcium and vitamin D alone, group 2 received the same treatment in combination with hormone replacement therapy (HRT), group 3 received risedronate (35 mg weekly, orally for 1 year) and group 4 zoledronic acid (3 monthly doses of 4 mg (intravenous)). All groups were similar for age, body mass index, underlying disease and time elapsed from transplant. Lumbar and femoral bone mineral density (BMD) were measured at baseline and after 12 months, together with serum osteocalcin and urinary hydroxyproline. At 12 months, a significant decrease in lumbar and femoral BMD was observed in group 1 and a milder decrease in group 2. Risedronate treatment increased significantly lumbar BMD and prevented bone loss at the femoral neck. Zoledronic acid increased significantly both lumbar and femoral BMD. In groups 3 and 4 the hydroxyproline excretion was significantly reduced, while osteocalcin mildly increased only in group 4. In conclusion, bisphosphonate administration is useful to prevent and treat bone demineralization in young adult women after allo-SCT.