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- Forsblad d'Elia, Helena, 1961, et al.
(författare)
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Hormone replacement therapy, calcium and vitamin D3 versus calcium and vitamin D3 alone decreases markers of cartilage and bone metabolism in rheumatoid arthritis: a randomized controlled trial [ISRCTN46523456]
- 2004
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Ingår i: Arthritis Res Ther. - : Springer Science and Business Media LLC. - 1478-6362 .- 1465-9905. ; 6:5
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to evaluate the effects of hormone replacement therapy (HRT), known to prevent osteoporosis and fractures, on markers of bone and cartilage metabolism. Furthermore, we assessed whether changes in these markers corresponded to alterations in bone mineral density and radiographic joint destructions in postmenopausal women with rheumatoid arthritis. Eighty-eight women were randomized to receive HRT, calcium, and vitamin D3, or calcium and vitamin D3 alone, for 2 years. Bone turnover was studied by analyzing serum levels of C-terminal telopeptide fragments of type I collagen (CTX-I), C-terminal telopeptide of type I collagen (ICTP), bone sialoprotein, and C-terminal propeptide of type I procollagen (PICP) and cartilage turnover by urinary levels of collagen type II C-telopeptide degradation fragments (CTX-II) and cartilage oligomeric matrix protein (COMP) in serum. Treatment with HRT resulted in decrease in CTX-I (P < 0.001), ICTP (P < 0.001), PICP (P < 0.05), COMP (P < 0.01), and CTX-II (P < 0.05) at 2 years. Reductions in CTX-I, ICTP, and PICP were associated with improved bone mineral density. Of the markers tested, CTX-I reflected bone turnover most sensitively; it was reduced by 53 +/- 6% in the patients receiving HRT. Baseline ICTP (P < 0.001), CTX-II (P < 0.01), and COMP (P < 0.05) correlated with the Larsen score. We suggest that biochemical markers of bone and cartilage turnover may provide a useful tool for assessing novel treatment modalities in arthritis, concerning both joint protection and prevention of osteoporosis.
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| 2. |
- Forsblad d'Elia, Helena, 1961
(författare)
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Hormone replacement therapy in rheumatoid arthritis
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Rheumatoid arthritis (RA) is 2-3 times more frequent in women as compared to men. The peak incidence in women coincides with the years around the menopause and the course of RA is also influenced by events associated with hormonal alterations. Animal studies have revealed distinct beneficial effects on arthritis by treatment with estradiol (E2) whereas human studies have been inconclusive. RA is associated with increased prevalence of osteoporosis and fractures related to the reduced bone mineral density (BMD).We have conducted a two-years randomised controlled trial with the aim of evaluating different aspects of HRT in 88 postmenopausal women with RA. All patients received a daily dose of 500 mg calcium and 400 IE vitamin D3 and women in the HRT group were given E2 plus noretisterone acetate. The patients took also part in a cross sectional observational study investigating the frequency of osteoporosis and predictors of reduced BMD and joint destruction.The disease activity, measured by the 28 joint count disease activity score (DAS 28) decreased significantly more in the HRT group as compared to the controls. Erythrocyte sedimentation rate (ESR) and orosomucoid, decreased and hemoglobin (Hb) increased in the HRT group. The improved Hb levels were believed to be secondary to the reduced inflammation as indicated by simultaneously increase in serum iron, total iron binding capacity and saturation of transferrin.The BMD increased significantly in the total hip, lumbar spine and forearm in the HRT group and estimations revealed that the improved BMD in the hip corresponded to a 20 % risk reduction of fractures in the hip in the HRT group. There was no overall difference in the radiographic outcome between the groups but, in the subgroup of patients with increasing joint damage, HRT retarded significantly the progression of destruction.HRT reduced biochemical markers reflecting bone metabolism assessed by decrease in two different fragments of C-terminal telopeptide of type I collagen, CTX-I and ICTP and the C-terminal propeptide of type I procollagen, PICP. The reductions of the markers were associated with improved BMD at two years. CTX-I was the most sensitive of all markers tested. HRT also reduced biochemical markers reflecting cartilage turnover assessed by decrease in urinary levels of collagen type II C-telopeptide degradation fragments, CTX-II and serum levels of cartilage oligomeric matrix protein, COMP.HRT reduced serum levels of soluble interleukin 6 receptor (sIL-6R), an agonist to IL-6, a cytokine involved in both bone remodelling and the inflammatory process in RA. The bone-anabolic factor, insulin-like growth factor 1 (IGF-1) increased significantly in the HRT group. Both of these findings; might be involved in the mechanisms mediating the beneficial effects of HRT in RA. Interestingly, the increase in IGF-1 was modestly connected with decrease in ESR and elevation of serum levels of E2 was associated with reduction of sIL-6R.Fifty-six % of the postmenopausal RA women, not treated with HRT or bisphosphonate, had osteoporosis in at least one measured site. High age, low body weight and severe joint damage were the most important determinants of reduced BMD whereas elevated CRP and long disease duration were the best predictors of high Larsen score found in the multiple stepwise regression analyses.
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| 4. |
- Forsblad d'Elia, Helena, 1961, et al.
(författare)
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Hormone replacement therapy in rheumatoid arthritis is associated with lower serum levels of soluble IL-6 receptor and higher insulin-like growth factor 1.
- 2003
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Ingår i: Arthritis research & therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1465-9905. ; 5:4
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Tidskriftsartikel (refereegranskat)abstract
- Hormone replacement therapy (HRT) modulates the imbalance in bone remodeling, thereby decreasing bone loss. Sex hormones are known to influence rheumatic diseases. The aim of this study was to investigate the effects of HRT on the serum levels of hormones and cytokines regulating bone turnover in 88 postmenopausal women with active rheumatoid arthritis (RA) randomly allocated to receive HRT plus calcium and vitamin D3 or calcium and vitamin D3 alone for 2 years. An increase in estradiol (E2) correlated strongly with improvement of bone mineral density in the hip (P < 0.001) and lumbar spine (P < 0.001). Both baseline levels and changes during the study of IL-6 and erythrocyte sedimentation rate were correlated positively (P < 0.001). HRT for 2 years resulted in an increase of the bone anabolic factor, insulin-like growth factor 1 (IGF-1) (P < 0.05) and a decrease of serum levels of soluble IL-6 receptor (sIL-6R) (P < 0.05), which is known to enhance the biological activity of IL-6, an osteoclast-stimulating and proinflammatory cytokine. Baseline levels of IL-6 and IGF-1 were inversely associated (P < 0.05), and elevation of IGF-1 was connected with decrease in erythrocyte sedimentation rate (P < 0.05) after 2 years. Interestingly, increase in serum levels of E2 was associated with reduction of sIL-6R (P < 0.05) and reduction of sIL-6R was correlated with improved bone mineral density in the lumbar spine (P < 0.05). The latter association was however not significant after adjusting for the effect of E2 (P = 0.075). The influences of IGF-1 and the IL-6/sIL-6R pathways suggest possible mechanisms whereby HRT may exert beneficial effects in RA. However, to confirm this hypothesis future and larger studies are needed.
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| 5. |
- Forsblad d'Elia, Helena, 1961, et al.
(författare)
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Influence of hormone replacement therapy on disease progression and bone mineral density in rheumatoid arthritis.
- 2003
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Ingår i: The Journal of rheumatology. - 0315-162X .- 1499-2752. ; 30:7, s. 1456-63
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Hormone replacement therapy (HRT) is known to exert a positive effect in preventing bone loss and a beneficial effect on the disease activity in rheumatoid arthritis (RA). We evaluated the effects of HRT on bone mineral density (BMD) and on the course of established RA. METHODS: Eighty-eight postmenopausal women with RA were randomly allocated to receive HRT, vitamin D3, and calcium supplementation or vitamin D3 and calcium supplementation alone for 2 years. The effects of additional HRT on laboratory and clinical measures of disease activity, quality of life, and BMD and on radiographic joint damage were investigated. RESULTS: Treatment with HRT suppressed signs of inflammation as shown by reduction in erythrocyte sedimentation rate (ESR) (p = 0.025) and an elevation in hemoglobin concentration (p = 0.007), a better clinical outcome assessed by response on the Disease Activity Score 28 (DAS28) (p = 0.036), increased BMD in the forearm, proximal femur and spine (p < 0.01), and retarded (p = 0.026) progression of joint destruction among patients with radiological progressive disease. No significant effect on quality of life was seen. CONCLUSION: Two years of HRT in women with active RA had significant ameliorating effects on inflammation, DAS28 response, and BMD and was associated with slower progression of radiological joint destruction. The mechanisms by which HRT exerts its effects remain to be elucidated. We suggest HRT can be used in addition to conventional therapy in the management of postmenopausal patients with RA.
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| 6. |
- Forsblad d'Elia, Helena, 1961, et al.
(författare)
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Radiographic joint destruction in postmenopausal rheumatoid arthritis is strongly associated with generalised osteoporosis.
- 2003
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 62:7, s. 617-23
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To investigate determinants of joint destruction and reduced bone mineral density (BMD) in postmenopausal women with active rheumatoid arthritis (RA) not treated with bisphosphonates or hormone replacement therapy and to evaluate if there are common markers of erosive disease and bone loss. METHODS: BMD was measured using dual x ray absorptiometry and joint damage was examined by x ray examination according to the Larsen method in 88 patients with RA. Associations between BMD and Larsen score, and between demographic and disease related variables, including proinflammatory cytokines, HLA-DR4 epitopes, and markers of bone and cartilage turnover, were examined bivariately by simple and multiple linear regression analyses. RESULTS: 49/88 (56%) patients had osteoporosis in at least one site. Reduced BMD and increased joint destruction were associated with: at the forearm and femoral neck, high Larsen score, low weight, and old age (R(2)=0.381, p<0.001; R(2)=0.372, p<0.001, respectively); at the total hip, low weight, high Larsen score, and dose of injected glucocorticosteroids (R(2)=0.435, p<0.001); at the lumbar spine, low weight, reduced cartilage oligomeric matrix protein, and increased carboxyterminal propeptide of type I procollagen (R(2)=0.248, p<0.001). Larsen score was associated with long disease duration and increased C reactive protein (CRP) (R(2)=0.545, p<0.001). CONCLUSIONS: Osteoporosis is common in postmenopausal patients with RA. Low weight and high Larsen score were strongly associated with BMD reduction. Increased CRP and long disease duration were determinants of erosive disease in postmenopausal women with RA. These findings indicate common mechanisms of local and generalised bone loss in RA.
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