| 1. |
- Elkan, Ann-Charlotte, et al.
(författare)
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Rheumatoid cachexia, central obesity and malnutrition in patients with low-active rheumatoid arthritis : Feasibility of anthropometry, Mini Nutritional Assessment and body composition techniques
- 2009
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Ingår i: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6207 .- 1436-6215. ; 48:5, s. 315-322
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: The concurrent decrease in fat free mass (FFM) and increase in fat mass (FM), including central obesity, in patients with rheumatoid arthritis (RA) may be related to increased cardiovascular morbidity as well as to functional decline. The objectives of this study were to evaluate body composition and nutritional status in patients with RA and the feasibility of bioelectrical impedance (BIA) to detect rheumatoid cachexia. METHODS: Eighty RA outpatients (76% women), mean age 61 (range 22-80) years and with mean disease duration of 6 (range 1-52) years, were assessed by body mass index (BMI), waist circumference (WC), whole-body dual-energy X-ray absorptiometry (DXA), BIA and the Mini Nutritional Assessment (MNA). RESULTS: Fat free mass index (FFMI; kg/m(2)) was low in 26% of the women and in 21% of the men. About every fifth patient displayed concomitant low FFMI and elevated fat mass index (FMI; kg/m(2)), i.e. rheumatoid cachexia. BMI and MNA were not able to detect this condition. Sixty-seven percent had increased WC. Reduced FFM was independently related to age (p = 0.022), disease duration (p = 0.027), ESR (p = 0.011) and function trendwise (p = 0.058). There was a good relative agreement between DXA and BIA (FM r (2) = 0.94, FFM r (2) = 0.92; both p < 0.001), but the limits of agreement were wide for each variable, i.e. for FM -3.3 to 7.8 kg; and for FFM -7.9 to 3.7 kg. CONCLUSION: Rheumatoid cachexia and central obesity were common in patients with RA. Neither BMI nor MNA could detect this properly. There was a good relative agreement between DXA and BIA, but the limits of agreement were wide, which may restrict the utility of BIA in clinical practice.
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| 2. |
- Engvall, Inga-Lill
(författare)
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Body composition and bone mineral density in rheumatoid arthritis : influence of inflammation and treatment with glucocorticoids and TNF-blocking agents
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Rheumatoid arthritis (RA) is a chronic inflammatory disease. Besides symptoms from the joints, changes in body composition and reduced bone mineral are common. Increased fat mass (FM) and loss of muscle mass contribute to increased morbidity and mortality. The aim of this thesis was to study the impact of inflammation and medical treatment on body composition and bone mineral density (BMD) in patients with RA. The work is based on two cross-sectional studies in established RA and two prospective, randomized studies in early RA, analysing the effects of glucocorticoids (GCs) and anti-TNF therapy, respectively. The patients were assessed clinically and by assays, such as markers of bone remodelling, insulin-like growth factor-1 (IGF-1), apolipoproteins, leptin and adiponectin. Dual X-ray energy absorptiometry (DXA) was performed and fat free mass index (FFMI, kg/m2) and fat mass index (FMI, kg/m2) were calculated. Low fat free mass (FFM), below the 10th percentile of a reference material, was frequent. The highest frequency, 50%, was found in RA inpatients and was associated with high disease activity, physical disability and low bioavailable IGF-1. The proportion of outpatients with established disease that had low FFM was 38% and in patients with early RA 19%. Between 34 and 45% of the patients had high FM, above the 90th percentile of the reference population, and 80% had FM% corresponding to overweight or obesity. The frequency of osteoporosis was 26-28% in established RA and 9% in early RA. In established RA, patients with long-term GC therapy had higher FM than those without, whereas BMD in lumbar spine and femoral neck did not differ between patients treated with GC and those not. Further, there was no significant difference between the treatment groups in the markers of bone formation. In contrast, in the prospective study in early RA, GC treatment was associated with a rapid decrease in the marker of bone synthesis during the first 3 months in contrast to patients not treated with GC. Also the markers of bone resorption decreased and it seemed that GC treatment could counteract the negative impact of inflammation on bone tissue, as BMD in femoral neck was preserved after 2 years treatment. However, GC treatment could not prevent bone loss in spine in postmenopausal women, where BMD decreased significantly more than in those not treated with GC. Treatment with TNF antagonists was associated with a significant increase in FM after 2 years, an increase that was not found in patients treated with a combination of disease modifying anti-rheumatic drugs (DMARDs), despite similar reduction of disease activity. The increase of FM seemed thus to be a specific effect of anti-TNF blockade and was not associated with an atherogenic lipid profile. Further, levels of leptin and adiponectin increased, of which adiponectin normally is associated with improved insulin sensitivity and endothelial function. This may at least partially explain the reduced frequency of CVD found when disease activity is reduced in RA, also when anti-TNF therapy is used. In conclusion, a large proportion of RA patients have changes in body composition, which contribute to increased morbidity and mortality. GC treatment is associated with increased FM and can counteract the negative impact of inflammation on bone but need special attention to postmenopausal women. Anti-TNF therapy also increases FM but at the same time increases adiponectin, which have favourable effects on CVD risk factors.
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| 3. |
- Engvall, Inga-Lill, et al.
(författare)
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Impact of low-dose prednisolone on bone synthesis and resorption in early rheumatoid arthritis: experiences from a two-year randomized study
- 2008
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Patients with rheumatoid arthritis (RA) have an increased frequency of osteoporosis, mainly because of increased bone resorption. Reduction of disease activity is suggested to reduce bone remodelling. It might also be possible that prednisolone treatment could cause this effect because prednisolone has been shown to arrest the development of joint destruction in early RA. Therefore, we examined the effects of low-dose prednisolone on serum concentrations of bone remodelling markers and insulin-like growth factor-1 (IGF-1) in RA patients in relation to bone mineral density. Methods One hundred and fifty patients, 67% women, with early RA, mean disease duration of six months (95% confidence interval (CI) = three to eight months), who had participated in the BARFOT (Better Anti-Rheumatic FarmacOTherapy) low-dose prednisolone study were included. They had been randomised to either the P-group, who were treated with 7.5 mg prednisolone daily (n = 70, mean age = 51 years, 95% CI 48 to 54 years), or the NoP-group, who received no prednisolone (n = 80, mean age 58 years, 95% CI 56 to 61 years), when they started their first disease-modifying anti-rheumatic drug (DMARD). Serum samples were analysed at baseline, 3 and 12 months for procollagen type I N-terminal propeptide (P1NP), a marker of bone formation, and the C-telopeptide crosslaps of type I collagen (CTX-1) and C-terminal telopeptide of type I collagen (1CTP), markers of bone degradation. IGF-1 was analysed at baseline and after 12 months. Bone mineral density at the lumbar spine and femoral neck was assessed by dual-energy X-ray absorptiometry at baseline and after 24 months. Results Levels of P1NP decreased rapidly in the P-group (p < 0.001). Levels of CTX-1 and 1CTP decreased in both treatment groups, but significantly more in the P-group (differences between groups p < 0.019 and p < 0.001, respectively). IGF-1 increased in the P-group (p < 0.001) but remained stable in the NoP-group. Bone mineral density decreased in the spine in both groups, significantly more in postmenopausal women from the P-group. Femur bone mineral density only decreased in the NoP-group. Conclusions Low-dose prednisolone in early RA counteracts the negative impact of rheumatoid inflammation on bone tissue in the hip, a juxta-articular localisation. Thus bone mineral density was preserved in the femur in the P-group and 1CTP decreased rapidly. However, the systemic inflammatory consequences on bone could not be prevented in the lumbar spine, especially not in postmenopausal women, probably because of the combined effect of suppression of bone synthesis by prednisolone and the postmenopausal status.
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| 4. |
- Engvall, Inga-Lill, et al.
(författare)
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Low-dose prednisolone in early rheumatoid arthritis inhibits collagen type I degradation by matrix metalloproteinases as assessed by serum 1CTP--a possible mechanism for specific inhibition of radiological destruction
- 2013
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 52:4, s. 733-742
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study the effects of low-dose prednisolone on the osteoclast-regulating proteins osteoprotegerin (OPG) and RANK ligand (RANKL) and on markers of bone resorption, 1CTP generated by MMPs and CTX-1 generated by cathepsin K, in patients with early RA in relation to inflammation and joint destruction.METHODS: In 225 patients, who at the start of the first DMARD had been randomized to 7.5 mg prednisolone daily for 2 years, the P-group, or no prednisolone, the NoP-group, OPG and RANKL were analysed at 0-24 months and 1CTP and CTX-1 at 0-12 months. Radiographs of hands and feet were assessed at 0, 1 and 2 years using the modified Sharp-van der Heijde score and radiological progression defined as increase in total Sharp score above 5.8. Data were analysed with a mixed linear model and by the GENMOD procedure.RESULTS: In the P-group, RANKL and the ratio OPG/RANKL were stable between baseline and 24 months, whereas in the NoP-group, RANKL increased and the ratio OPG/RANKL decreased. CTX-1 decreased significantly more in the P-group. 1CTP decreased over time in both groups, but more in the P-group, P < 0.001, a difference also present in the subgroups of patients in remission. The decrease in 1CTP was associated with less radiological progression after 2 years and displayed a significant interaction with treatment. CONCLUSION: Low-dose prednisolone may inhibit progression of joint destruction by interfering with MMP activity, seen as a marked decrease in 1CTP, as well as by impairing osteoclast activation, shown by a stable OPG/RANKL ratio.
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