The study of bone mineral density and bone turnover markers in postmenopausal women with active rheumatoid arthritis

Abstract

The aim of this study was to investigate determinants of reduced bone mineral density (BMD) in postmenopausal women with active rheumatoid arthritis (RA) and to evaluate whether there are common markers of bone loss. We evaluated BMD of the femoral neck using dual-energy X-ray absorptiometry, and the measured biochemical markers included serum bone-specific alkaline phosphatase (BALP), serum osteocalcin (OC), and serum cross-linked N-telopeptidases of type I collagen (NTx). Serum BALP and NTx concentrations were measured by enzyme-linked immunsorbent assay, and OC was measured using an immunoradiometric assay. One hundred and forty postmenopausal Japanese women who had not received treatment with bisphosphonates or hormone replacement therapy were entered into the study. Thirty-four patients (41.0%) had femoral osteopenia (T score ?1 to ?2.5) and 23 patients (27.7%) had osteoporosis (T < ?2.5). The body mass index of patients with normal BMD (T score ≥ ?1.0) was significantly higher (P < 0.01) than in patients with osteoporosis at the femoral neck. The T score exhibited a significant negative correlation with age and the duration of RA disease. Serum BALP and serum OC, markers of osteoblast function, were negatively related to erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and matrix metalloproteinase-3 (MMP-3). However, serum NTx, a marker of resorptive function, exhibited a positive correlation with ESR, CRP, and MMP-3. From these results, this study suggests that generalized bone loss occurs in active RA and is characterized by evidence of bone resorption that is correlated with the high levels of inflammation. Body mass index, disease duration, and high serum NTx level were common risk factors in osteoporosis of postmenopausal women with RA.     

The study of bone mineral density and bone turnover markers in postmenopausal women with active rheumatoid arthritis

The aim of this study was to investigate determinants of reduced bone mineral density (BMD) in postmenopausal women with active rheumatoid arthritis (RA) and to evaluate whether there are common markers of bone loss. We evaluated BMD of the femoral neck using dual-energy X-ray absorptiometry, and the measured biochemical markers included serum bone-specific alkaline phosphatase (BALP), serum osteocalcin (OC), and serum cross-linked N-telopeptidases of type I collagen (NTx). Serum BALP and NTx concentrations were measured by enzyme-linked immunsorbent assay, and OC was measured using an immunoradiometric assay. One hundred and forty postmenopausal Japanese women who had not received treatment with bisphosphonates or hormone replacement therapy were entered into the study. Thirty-four patients (41.0%) had femoral osteopenia (T score −1 to −2.5) and 23 patients (27.7%) had osteoporosis (T < −2.5). The body mass index of patients with normal BMD (T score ≥ −1.0) was significantly higher (P < 0.01) than in patients with osteoporosis at the femoral neck. The T score exhibited a significant negative correlation with age and the duration of RA disease. Serum BALP and serum OC, markers of osteoblast function, were negatively related to erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and matrix metalloproteinase-3 (MMP-3). However, serum NTx, a marker of resorptive function, exhibited a positive correlation with ESR, CRP, and MMP-3. From these results, this study suggests that generalized bone loss occurs in active RA and is characterized by evidence of bone resorption that is correlated with the high levels of inflammation. Body mass index, disease duration, and high serum NTx level were common risk factors in osteoporosis of postmenopausal women with RA.     

Association of bone mineral density and vertebral deformity in patients with rheumatoid arthritis

The aim of this study was to investigate the association of vertebral deformities developed as a result of osteoporosis in female patients with rheumatoid arthritis (RA) with bone mineral density (BMD) and disease activity parameters. In the study, 100 female patients with the diagnosis of RA and 56 healthy subjects were recruited. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and rheumatoid factor (RF) tests were performed and the number of swollen and tender joints, level of pain and health assessment questionnaire (HAQ) were recorded in order to evaluate disease activity. Anteroposterior and lateral thoracic and lumbosacral roentgenograms of all patients were taken for radiological examination and deformities of vertebrae were assessed. BMD measurements of patients were performed on vertebrae L1–4 of lumbar region and on total hip, femur neck, trochanter and Ward’s triangle of the right side. Vertebral deformity was established in 30% of RA patient group and 7.1% of control group and this was statistically significant. In the statistical analysis, no statistically significant difference was found between BMD measurements of RA and control groups. Patients with RA were divided into two subgroups with regard to using corticosteroids (CS) or not. Vertebral deformity was 32.4% in the subgroup using CS and 24.1% in the subgroup not using CS, and the difference was not statistically significant. There was a correlation between number of deformed joint and age and vertebral deformity incidence. RA is a risk factor on its own for the development of osteoporosis and vertebral deformity and this risk increases by age, excess number of deformed joints and severe course of disease. We think that precautions should be taken immediately to suppress the disease activity as well as to protect the quality and density of bone and to prevent the development of vertebral deformity and fracture while planning the treatment of patients with RA.     

Predictors of bone density testing in patients with rheumatoid arthritis

Patients with rheumatoid arthritis (RA) are at increased risk of low bone density and fractures. This study identifies predictors of initiation of dual energy X-ray absorptiometry (DXA) testing in RA. We identified RA patients from the CORRONA registry with ≥1 year follow-up without reported DXA at study entry. The primary outcome was report of DXA in the first year of follow-up (DXA initiation). Variables associated with DXA initiation were considered for the multivariate model. Stepwise logistic regression identified independent predictors. Of the 2,717 RA patients without DXA documented at enrollment, 297 (11%) reported DXA initiation. Independent predictors of DXA initiation included age, female sex, history of fracture, steroid use, and physician’s assessment of RA activity. In conclusion, DXA initiation in RA patients in the CORRONA cohort is low despite increased risk of osteoporosis. Predictors of DXA initiation include fracture, common risk factors for osteoporosis, and RA-associated factors. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

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 evaluation and treatment recommendations in rheumatoid arthritis

In this chapter, we emphasize among rheumatoid arthritis (RA) patients, whom and how to screen for osteoporosis. We highlight certain modalities, advancements in technology, secondary osteoporosis workup, and laboratory testing as well as their caveats. Finally, we discuss current guidance on how to direct the laboratory and radiology testing in the context of the individual patient with RA to guide and select from the osteoporosis treatment options currently available.     

Serum leptin in rheumatoid arthritis

Leptin is a peptide hormone that has an essential role in the regulation of body weight by inhibiting food intake and stimulating energy expenditure. The role of leptin in the modulation of the immune response and inflammation has been regarded as important. In rheumatoid arthritis (RA) patients it was reported that fasting leads to an improvement of clinical and biological measures of disease activity, which was associated with a marked decrease in serum leptin. These features suggest that leptin may also influence the inflammatory mechanisms of arthritis in humans. In this study we assessed serum leptin levels in RA and osteoarthritis (OA) patients and found a correlation between serum leptin level and other markers as well as bone mass density changes, activity of disease, disease duration and the age of the patients. The blood was collected from 30 RA and 30 OA patients who constituted the control group. Serum leptin level was determined using the DRG Leptin ELISA Kit—a solid phase enzyme—linked immunosorbent assay based on the sandwich principle. The serum level of leptin in RA patients ranged from 1.8 to 81.1 ng/ml and median value was 11.2. There was a positive correlation between body mass index (BMI) of RA patients and serum level of leptin (correlation coefficients Spearman’s r = 0.81). According to correlation coefficients, serum leptin level is independent of age of RA patients, stage of disease, number of painful and swollen joints, duration of morning stiffness, disease duration as well as value of titre of the Waaler–Rose, disease activity score (DAS 28) value and presence of rheumatoid nodules. There was a negative correlation between serum leptin level and glomerular filtration rate (GFR). No correlation between the serum leptin level and T-score was found. An influence of steroid treatment on the serum leptin level was not shown. The median serum leptin level in OA patients was 9.2 ng/ml. There was a positive correlation between body mass index of OA patients and serum level of leptin (correlation coefficients Spearman’s r = 0.57). No correlation was found between serum leptin level and patient’s age, duration of disease and value of laboratory data. There were no correlations between serum leptin level and visual analogue pain scale (VAS) for the lower-limb afflicted patients as well as stage of disease according to Kellgren and Lawrence’s score in OA patients. There was a negative correlation between serum leptin level and T-score value in OA patients (r = −0.58, P < 0.05). No statistically significant differences were found between serum leptin levels for RA and OA patients.     

Telopeptides as markers of bone turnover in rheumatoid arthritis and osteoarthritis

AIMS: The aim of the present study was to determine if urinary excretion of type I collagen N-terminal telopeptides (UrNTx) and deoxypyridinoline (UrDPD) and serum levels of type I collagen C-terminal telopeptides (SeCTx) differed in patients with rheumatoid arthritis (RA) compared with populations matched for age and gender with and without osteoarthritis (OA). The correlation of markers of bone turnover with disease activity in patients with RA or radiographic severity in patients with OA was also examined. METHODS: Patients with RA aged >50 years (men) and >60 years (women) were identified from computer databases at two tertiary referral centres for rheumatology. Strict exclusion criteria were applied to avoid the effects of factors known to influence markers of bone turnover. Patients with RA and OA were matched for age and sex with a control population free of known arthritic disease and a population with OA. Bone markers were assayed in serum and urine. Urine markers were measured on three consecutive days and mean values used to minimize day-to-day variability of these analytes. RESULTS: The level of UrNTx was elevated in patients with RA compared with normal controls and patients with OA. UrNTx and UrDPD correlated with markers of disease activity in patients with RA (erythrocyte -sedimentation rate and C-reactive protein), but not with -clinical signs of inflammation (swollen and tender joint counts). Patients with OA failed to show any correlation between markers of bone turnover and radiographic severity. CONCLUSIONS: These data support a role for the use of UrNTx and UrDPD in further studies of the patho-physiology of RA and in longitudinal studies designed to modify the course of clinical disease.     

Serum sclerostin levels in rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) is an autoimmune disease that may lead to joint destruction and disability. Wingless (Wnt) pathway is involved in bone formation and has been found to contribute to bone loss in RA. Sclerostin is a key molecule in Wnt pathway.ObjectiveTo study the serum levels of sclerostin in rheumatoid arthritis patients and to study its association with radiological changes.MethodsForty-five patients with RA and 45 age and gender matched healthy controls were enrolled. Serum sclerostin was measured by ELISA. Modified version of Larsen score was used to assess joint damage in radiographs and Magnetic resonance imaging (MRI) of wrist and hand was assessed for synovitis and bone erosion.ResultsSerum sclerostin levels were higher in patients with RA as compared to controls (p < 0.01). Serum sclerostin levels correlated with ESR (r = 0.655), CRP(r = 0.623), modified DAS 28 (r = 0.711), MRI synovitis (r = 0.802) and MRI erosion score (r = 0.832).ConclusionIncreased serum levels of sclerostin may play a role in joint damage and bone erosion in RA.     

Serum and synovial fluid leptin levels and markers of inflammation in rheumatoid arthritis

This study was designed to investigate the serum and synovial fluid leptin levels, and inflammatory markers in rheumatoid arthritis (RA) patients. Serum and synovial fluid leptin levels were significantly higher (P > 0.05) in RA patients than control group; RA patients with moderate disease activity (DAS < 2.7) having significantly higher leptin levels (P > 0.05) than those with low disease activity (DAS < 2.7). Leukocytes and erythrocyte sedimentation rate (ESR) were found to be significantly higher in moderate disease activity RA group compared to low activity group (P > 0.05, P < 0.001, respectively). Serum leptin level is found to be independent of age and inflammatory markers. ESR is positively correlated with DAS activity and CRP values. Our finding of no correlation between leptin and BMI shows that regulation of leptinemia is complex, and leptin levels cannot be used to assess RA activity.     

Generalized osteoporosis in non-steroid treated rheumatoid arthritis

Summary To investigate the presence of reduced bone mineral density (BMD) and to assess determinants of bone loss in rheumatoid arthritis, 45 female patients suffering from non-steroid treated rheumatoid arthritis were submitted to dual photon absorptiometry of the lumbar spine and to laboratory tests for calcium metabolism. The rheumatoid arthritis patients were divided into two groups according to anatomic grade and functional class; no abnormalities in calcium metabolism were defected whereas BMD was significantly lower in the third and fourth grade and in the third and fourth class patients (P<0.005 versus controls, versus grades I and II and versus classes 1 and 2). BMD was significantly correlated with age (P<0.001) and years postmenopausal (P<0.01), but not with duration of disease. By multiple inear regression we derived an equation predictive of BMD. Osteoporosis in rheumatoid arthritis is observed even in non-corticosteroid treated patients; articular lesions with subsequent reduction in physical activity appear to play an important role in axial bone loss in rheumatoid arthritis.     

Physical activity prevents bone loss in premenopausal women with rheumatoid arthritis: a cohort study

The aim of the study was to compare the bone loss and the influence of physical activity between premenopausal women with rheumatoid arthritis (RA) and healthy women. A total of 71 patients with RA and 29 healthy premenopausal women with the criteria of the American College of Rheumatology for RA were followed for 2 years. Of these 85% were Caucasian, aged 38 +/- 6.6 years and with a duration of disease of 88 +/- 50 months and 48 (71.8%) used GC, mean daily dose, 7.3 +/- 3.5 mg. There was a reduction in the T-score of the femoral neck (P = 0.04) and in the Ward region (P = 0.05) in RA. Through logistic regression, it was found that sedentarism was a risk factor for osteopenia in RA, with relative risk of 1.6 (IC = 1.238-1.734). Moderate physical activity reduced the risk of osteopenia by 50%. Sedentarism and low weight are the main factors associated with bone loss. Physical activity reduces bone loss. Early preventive and therapeutic measures must be encouraged.     

Risk factors associated with bone loss and occurrence of fragility fractures in rheumatoid arthritis patients

Aim of the work

To investigate the bone mineral density (BMD) in rheumatoid arthritis (RA) Tunisian patients, to identify the risk factors associated with its decrease and to assess the fracture risk.

Structural mechanisms of bone loss in iliac biopsies: comparison between rheumatoid arthritis and postmenopausal osteoporosis

To assess the mechanisms that cause generalized osteoporosis in rheumatoid arthritis (RA), 40 postmenopausal women with RA (46–74 years) and 40 age-matched controls with osteopenia underwent iliac bone biopsies. A structural analysis of histomorphometry and two-dimensional strut analysis were performed As compared to those with primary osteoporosis, there were a few unique characteristics in those with RA. Trabecular thickness and wall thickness declined with age, and this decline was especially accelerated by glucocorticoids. Decreased connectivity of the trabecular (Nd.Nd) was more prominent than the disappearance of the nodes. The connectivity of cortical bone to the nodes (Ct.Nd) and cortical thickness significantly decreased with age. With glucocorticoid therapy, the disappearance of the nodes was accelerated. In the case of vertebral compression fractures, the parameters of Nd.Nd and Ct.Nd significantly decreased. Although a bone biopsy is needed to analyze strut, this method is useful to evaluate the quality or intensity of the bone. Received: 19 October 1998 / Accepted: 17 December 1998     

The effect of methotrexate on bone metabolism markers in patients with rheumatoid arthritis

The aim of the present study was to evaluate the influence on urinary excretion levels of N-telopeptide of type I collagen (NTX) and deoxypyridinoline (DPD) as a useful marker for bone resorption, and on serum-bone alkaline phosphate (BAP) levels as a useful marker for bone formation and an early marker of osteoblast differentiation in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX). Thirty patients with RA, diagnosed according to the criteria of the American College of Rheumatology, were involved in this study between March 2003 and January 2005. None of the patients had a history of hormone (estrogen) replacement therapy. All patients were treated with MTX. Methotrexate was administered perorally at a dosage of 4–10 mg/week. All patients underwent general and physical examinations and routine blood and urinary analysis at the baseline, 3 months and 6 months after the initial treatment. Then the levels of NTX and DPD in urine and BAP in serum were measured in all patients. For comparison with the effect of other DMARDs on bone metabolism markers in RA patients, we measured the levels of NTX and DPD in urine and BAP in serum of RA patients, 13 patients treated with salazosulfapyridine (SASP), and 14 patients treated with actarit (ACT). In patients treated with MTX, NTX levels decreased significantly at 3 months after the initial treatment and remained low at 6 months after the initial treatment, and DPD levels significantly decreased at 6 months after the initial treatment. The mean serum BAP levels changed without significant differences from the baseline at 3 months and 6 months. In patients treated with SASP and ACT, all bone metabolism markers had not changed significantly at the three time points. On disease activity erythrocyte sedimentation rate, C-reactive protein, the number of swollen joints and tender joints, and mHAQ score decreased significantly at 3 months after the initial treatment, and remained at low levels at 6 months after the initial treatment with MTX. Methotrexate therapy looks promising in inhibiting generalized bone loss in patients with RA. In addition, NTX is a more sensitive marker than DPD.     

The effect of methotrexate on bone metabolism markers in patients with rheumatoid arthritis

Abstract

The aim of the present study was to evaluate the influence on urinary excretion levels of N-telopeptide of type I collagen (NTX) and deoxypyridinoline (DPD) as a useful marker for bone resorption, and on serum-bone alkaline phosphate (BAP) levels as a useful marker for bone formation and an early marker of osteoblast differentiation in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX). Thirty patients with RA, diagnosed according to the criteria of the American College of Rheumatology, were involved in this study between March 2003 and January 2005. None of the patients had a history of hormone (estrogen) replacement therapy. All patients were treated with MTX. Methotrexate was administered perorally at a dosage of 4–10?mg/week. All patients underwent general and physical examinations and routine blood and urinary analysis at the baseline, 3 months and 6 months after the initial treatment. Then the levels of NTX and DPD in urine and BAP in serum were measured in all patients. For comparison with the effect of other DMARDs on bone metabolism markers in RA patients, we measured the levels of NTX and DPD in urine and BAP in serum of RA patients, 13 patients treated with salazosulfapyridine (SASP), and 14 patients treated with actarit (ACT). In patients treated with MTX, NTX levels decreased significantly at 3 months after the initial treatment and remained low at 6 months after the initial treatment, and DPD levels significantly decreased at 6 months after the initial treatment. The mean serum BAP levels changed without significant differences from the baseline at 3 months and 6 months. In patients treated with SASP and ACT, all bone metabolism markers had not changed significantly at the three time points. On disease activity erythrocyte sedimentation rate, C-reactive protein, the number of swollen joints and tender joints, and mHAQ score decreased significantly at 3 months after the initial treatment, and remained at low levels at 6 months after the initial treatment with MTX. Methotrexate therapy looks promising in inhibiting generalized bone loss in patients with RA. In addition, NTX is a more sensitive marker than DPD.     

Knee deformity in rheumatoid arthritis is closely correlated with generalized osteoporosis

To examine the relationship between knee deformity and osteoporosis in women with rheumatoid arthritis (RA), bone mineral density (BMD) in the lumbar spine and distal radius was measured using dual X-ray absorptiometry, and knee deformity (valgus or varus deformity) was measured using plain radiograms in 55 women with RA. Associations between knee deformity and BMD, disease related variables, including RA stage, RA duration, age, cumulative doses of administered glucocorticosteroids, body mass index, or postmenopausal period were evaluated. Cut-off values of the BMD defining RA patients with knee deformity were very close to the BMD value corresponding to 70% of young adult mean in the lumbar spine and distal radius. The femorotibial alignment was significantly correlated with age and deformity of the proximal tibia. Deformity of the proximal tibia was negatively correlated with the radial BMD and lumbar BMD. Deformity of the proximal tibia showed a significant difference between the groups of less than 5 years after menopause and the group of 5–10 years after menopause. We concluded that knee deformity in RA derived from deformity of the proximal tibia, and it was closely correlated with generalized osteoporosis.     

The effect of low-dose prednisone on bone mineral density in Peruvian rheumatoid arthritis patients

Objective The aim of this study was to determine the difference between bone mineral density (BMD) of rheumatoid arthritis (RA) patients on low-dose prednisone and matched RA patients without prior systemic corticosteroid therapy.Methods Ninety patients attending our clinics and receiving 10 mg/day of prednisone or less for at least the previous 3 consecutive months were studied. The control group comprised 90 selected RA patients without corticosteroid therapy matched for age, race, gender, disease duration, use of methotrexate, postmenopause, and Health Assessment Questionnaire score. The BMD was measured using dual X-ray absorptiometry.Results Patients on prednisone had lower BMD than controls (0.94±0.17 vs 0.96±0.17 for L2–4 and 0.73±0.14 vs 0.76±0.16 for femoral neck), but these differences were not statistically significant (P>0.05). In post hoc analysis, postmenopausal women on prednisone had more bone loss in femoral neck than controls (0.68±0.13 vs 0.74±0.15).Conclusion Bone mineral density was not significantly reduced by low-dose prednisone in this diverse group of RA patients. A reduction in hip BMD was seen in postmenopausal women on prednisone.     

Serum osteocalcin as an index of bone turnover in active rheumatoid arthritis and in active psoriatic arthritis

Summary Juxtaarticular osteoporosis is a recognized clinical feature in both rheumatoid arthritis (RA) and psoriatic arthritis (PA), while generalised osteopenia seems to be characteristic of RA only. To assess differences in bone turnover in the two forms of disease, we measured serum osteocalcin levels and other parameters of bone metabolism in two groups of female, ambulant, age-matched patients suffering from active RA or active PA and never treated with steroid therapy. Serum osteocalcin levels were significantly higher in RA patients than in PA patients (13.05±1.27 ng/ml vs 4.83±0.88 ng/ml;p<0.001), with a significant positive correlation between osteocalcin and serum alkaline phosphatase in both groups. These data suggest that bone turnover is higher in active RA than in active PA. Juxtaarticular osteoporosis could be mediated by local disease mechanisms both in RA and in PA, while factors specifically related to active RA seem to determine a more generalized impairment of bone turnover.