| 1. |
- Juhasz, Balazs, et al.
(författare)
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Peripheral quantitative computed tomography in the assessment of bone mineral density in anti-TNF-treated rheumatoid arthritis and ankylosing spondylitis patients
- 2021
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Ingår i: BMC Musculoskeletal Disorders. - : BioMed Central (BMC). - 1471-2474. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are associated with osteoporosis. There have not been many peripheral quantitative computed tomography (QCT) studies in patients receiving biologics. We assessed volumetric and areal bone mineral density (BMD) by forearm QCT and dual-energy X-ray absorptiometry (DXA), respectively in addition to laboratory biomarkers in these arthritides. Methods Forty RA and AS patients treated with either etanercept (ETN) or certolizumab pegol (CZP) were undergoing follow-ups for one year. Volumetric and areal BMD, as well as parathyroid hormone (PTH), osteocalcin, RANKL, 25-hydroxyvitamin D (VITD), P1NP, CTX, sclerostin (SOST), Dickkopf 1 (DKK-1) and cathepsin K (CATHK) were determined. Results We did not observe any further bone loss during the 12-month treatment period. Volumetric and areal BMD showed significant correlations with each other (p<0.017 after Bonferroni's correction). Trabecular QCT BMD at baseline (p=0.015) and cortical QCT BMD after 12 months (p=0.005) were inversely determined by disease activity at baseline in the full cohort. Trabecular QCT BMD at baseline also correlated with CTX (p=0.011). In RA, CRP negatively (p=0.014), while SOST positively (p=0.013) correlated with different QCT parameters. In AS, RANKL at baseline (p=0.014) and after 12 months (p=0.007) correlated with cortical QCT BMD. In the full cohort, 12-month change in QTRABBMD was related to TNF inhibition together with elevated VITD-0 levels (p=0.031). Treatment and lower CATHK correlated with QCORTBMD changes (p=0.006). In RA, TNF inhibition together with VITD-0 (p<0.01) or CATHK-0 (p=0.002), while in AS, treatment and RANKL-0 (p<0.05) determined one-year changes in QCT BMD. Conclusions BMD as determined by QCT did not change over one year of anti-TNF treatment. Disease activity, CATHK, RANKL and VITD may be associated with the effects of anti-TNF treatment on QCT BMD changes. RA and AS may differ in this respect.
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| 2. |
- Karras, Dimitrios, et al.
(författare)
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Effectiveness of Teriparatide in Postmenopausal Women with Osteoporosis and Glucocorticoid Use : 3-Year Results from the EFOS Study
- 2012
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Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 39:3, s. 600-609
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To describe clinical fracture rates, back pain, and health-related quality of life (HROOL) in postmenopausal women with osteoporosis who are receiving glucocorticoids (GC), during a 36-month study of teriparatide treatment for up to 18 months, with an additional 18-month followup period when patients were receiving other osteoporosis medications. Methods. A prospective, multinational, observational study. Data for clinical fractures, back pain (by visual analog scale; VAS) and HRQOL (by EQ-5D) were collected over 36 months. Fracture data were summarized in 6-month segments and analyzed using logistic regression with repeated measures. Changes from baseline in back pain VAS and EQ-VAS were analyzed. Results. Of 1581 enrolled women with followup data, 294 (18.6%) had antecedents of GC use. Of these, 49 (16.7%) patients sustained a total of 69 fractures during the 36-month study period. Adjusted odds of fracture were significantly decreased during the last year of followup compared with the first 6 months of teriparatide treatment: an 81% decrease in the 24 to < 30-month period (p < 0.05), and an 89% decrease in the 30 to < 36-month period (p < 0.05). There were significant reductions in back pain and improvements in HRQOL in both groups of GC users and nonusers. Conclusion. Postmenopausal women with severe osteoporosis receiving GC, who were treated with teriparatide for up to 18 months, showed a reduced incidence of clinical fractures during the third year while receiving sequential osteoporosis treatments compared with the first 6 months, together with reduced back pain and improved HRQOL. Our results should be interpreted in the context of an uncontrolled observational study in a routine clinical setting.
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| 3. |
- Knoop, Jesper, et al.
(författare)
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Association of lower muscle strength with self-reported knee instability in osteoarthritis of the knee: Results from the Amsterdam Osteoarthritis Cohort
- 2012
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Ingår i: Arthritis Care and Research. - : Wiley. - 2151-4658 .- 2151-464X. ; 64:1, s. 38-45
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Tidskriftsartikel (refereegranskat)abstract
- Objective To determine whether muscle strength, proprioceptive accuracy, and laxity are associated with self-reported knee instability in a large cohort of knee osteoarthritis (OA) patients, and to investigate whether muscle strength may compensate for impairment in proprioceptive accuracy or laxity, in order to maintain knee stability. Methods. Data from 283 knee OA patients from the Amsterdam Osteoarthritis cohort were used. Univariable and multivariable logistic regression analyses were performed to assess the association between muscle strength, proprioceptive accuracy (motion sense), frontal plane varus-valgus laxity, and self-reported knee instability. Additionally, effect modification between muscle strength and proprioceptive accuracy and between muscle strength and laxity was determined. Results. Self-reported knee instability was present in 67% of the knee OA patients and mainly occurred during walking. Lower muscle strength was significantly associated with the presence of self-reported knee instability, even after adjusting for relevant confounding. Impaired proprioceptive accuracy and high laxity were not associated with self-reported knee instability. No effect modification between muscle strength and proprioceptive accuracy or laxity was found. Conclusion. Lower muscle strength is strongly associated with self-reported knee instability in knee OA patients, while impairments in proprioceptive accuracy and laxity are not. A compensatory role of muscle strength for impaired proprioceptive accuracy or high laxity, in order to stabilize the knee, could not be demonstrated.
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| 4. |
- Knoop, Jesper, et al.
(författare)
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Identification of Phenotypes With Different Clinical Outcomes in Knee Osteoarthritis: Data From the Osteoarthritis Initiative
- 2011
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Ingår i: Arthritis Care and Research. - : Wiley. - 2151-4658 .- 2151-464X. ; 63:11, s. 1535-1542
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To identify subgroups or phenotypes of knee osteoarthritis (OA) patients based on similarities of clinically relevant patient characteristics, and to compare clinical outcomes of these phenotypes. Methods. Data from 842 knee OA patients of the Osteoarthritis Initiative were used. A cluster analysis method was performed, in which clusters were formed based on similarities in 4 clinically relevant, easily available variables: severity of radiographic OA, lower extremity muscle strength, body mass index, and depression. Univariable and multivariable regression analyses were used to compare phenotypes on clinical outcomes (pain and activity limitations), taking into account possible confounders. Results. Five phenotypes of knee OA patients were identified: "minimal joint disease phenotype," "strong muscle phenotype," "nonobese and weak muscle phenotype," "obese and weak muscle phenotype," and "depressive phenotype." The "depressive phenotype" and "obese and weak muscle phenotype" showed higher pain levels and more severe activity limitations than the other 3 phenotypes. Conclusion. Five phenotypes based on clinically relevant patient characteristics can be identified in the heterogeneous population of knee OA patients. These phenotypes showed different clinical outcomes. Interventions may need to be tailored to these clinical phenotypes.
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| 5. |
- Langdahl, Bente L., et al.
(författare)
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Reduction in fracture rate and back pain and increased quality of life in postmenopausal women treated with teriparatide : 18-month data from the European Forsteo Observational Study (EFOS)
- 2009
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Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 85:6, s. 484-493
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Tidskriftsartikel (refereegranskat)abstract
- The European Forsteo Observational Study was designed to examine the effectiveness of teriparatide in postmenopausal women with osteoporosis treated for up to 18 months in normal clinical practice in eight European countries. The incidence of clinical vertebral and nonvertebral fragility fractures, back pain, and health-related quality of life (HRQoL, EQ-5D) were assessed. Spontaneous reports of adverse events were collected. All 1,648 enrolled women were teriparatide treatment-naive, 91.0% of them had previously received other anti-osteoporosis drugs, and 72.8% completed the 18-month study. A total of 168 incident clinical fractures were sustained by 138 (8.8%) women (821 fractures/10,000 patient-years). A 47% decrease in the odds of fracture in the last 6-month period compared to the first 6-month period was observed (P < 0.005). Mean back pain VAS was reduced by 25.8 mm at end point (P < 0.001). Mean change from baseline in EQ-VAS was 13 mm by 18 months. The largest improvements were reported in the EQ-5D subdomains of usual activities and pain/discomfort. There were 365 adverse events spontaneously reported, of which 48.0% were considered related to teriparatide; adverse events were the reason for discontinuation for 79 (5.8%) patients. In conclusion, postmenopausal women with severe osteoporosis who were prescribed teriparatide in standard clinical practice had a significant reduction in the incidence of fragility fractures and a reduction in back pain over an 18-month treatment period. This was associated with a clinically significant improvement in HRQoL. Safety was consistent with current prescribing information. These results should be interpreted in the context of the open-label, noncontrolled design of the study.
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| 6. |
- Ljunggren, Östen, et al.
(författare)
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Effective osteoporosis treatment with teriparatide is associated with enhanced quality of life in postmenopausal women with osteoporosis : the European Forsteo Observational Study
- 2013
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 14, s. 251-
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Tidskriftsartikel (refereegranskat)abstract
- Background: To describe changes in health-related quality of life (HRQoL) of postmenopausal women with osteoporosis treated with teriparatide for up to 18 months and followed-up for a further 18 months, and to assess the influence of recent prior and incident fractures. Methods: The European Forsteo Observational Study (EFOS) is an observational, prospective, multinational study measuring HRQoL using the EQ-5D. The primary objective was to assess changes in HRQoL during 36 months in the whole study population. A secondary post-hoc analysis examined fracture impact on HRQoL in four subgroups classified based on recent prior fracture 12 months before baseline and incident clinical fractures during the study. Changes from baseline were analysed using a repeated measures model. Results: Of the 1581 patients, 48.4% had a recent prior fracture and 15.6% of these patients had an incident fracture during follow-up. 10.9% of the 816 patients with no recent prior fracture had an incident fracture. Baseline mean EQ-VAS scores were similar across the subgroups. In the total study cohort (n = 1581), HRQoL (EQ-VAS and EQ-5D index scores) improved significantly from baseline to 18 months and this improvement was maintained over the 18-month post-teriparatide period. Improvements were seen across all five EQ-5D domains during teriparatide treatment that were maintained after teriparatide was discontinued. Subjects with incident clinical fractures had significantly less improvement in EQ-VAS than those without incident fractures. Recent prior fracture did not influence the change in EQ-VAS during treatment. Conclusions: EFOS is the first longitudinal study in women with severe postmenopausal osteoporosis in the real world setting to show a substantial improvement in HRQoL during teriparatide treatment that was sustained during subsequent treatment with other medications. The increase in HRQoL was lower in the subgroups with incident fracture but was not influenced by recent prior fracture. The results should be interpreted in the context of the design of an observational study.
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| 7. |
- Pusztai, Anita, et al.
(författare)
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Associations of vascular and bone status in arthritis patients
- 2021
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Cardiovascular (CV) disease and osteoporosis (OP) have been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Bone and vascular biomarkers and parameters along with the effect of 1-year anti-TNF therapy on these markers were assessed in order to determine correlations between vascular pathophysiology and bone metabolism in RA and AS. Thirty-six patients treated with etanercept or certolizumab pegol and 17 AS patients treated with ETN were included in a 12-month follow-up study. Bone and vascular markers were previously assessed by ELISA. Bone density was measured by DXA and quantitative CT (QCT). Flow-mediated vasodilation (FMD), common carotid intima-media thickness (IMT) and pulse-wave velocity (PWV) were assessed by ultrasound. Multiple correlation analyses indicated associations between bone and vascular markers. Osteoprotegerin, sclerostin and cathepsin K were significantly associated with FMD, IMT and PWV, respectively (p < 0.05). Moreover, total and trabecular BMD determined by QCT inversely correlated with IMT (p < 0.05). On the other hand, among vascular parameters, platelet-derived growth factor BB and IMT correlated with DXA femoral and QCT total BMD, respectively (p < 0.05). In the RM-ANOVA analysis, anti-TNF treatment together with baseline osteocalcin, procollagen 1 N-terminal propeptide (P1NP) or vitamin D3 levels determined one-year changes in IMT (p < 0.05). In the MANOVA analysis, baseline disease activity indices (DAS28, BASDAI), the one-year changes in these indices, as well as CRP exerted effects on multiple correlations between bone and vascular markers (p < 0.05). As the pattern of interactions between bone and vascular biomarkers differed between baseline and after 12 months, anti-TNF therapy influenced these associations. We found a great number of correlations in our RA and AS patients undergoing anti-TNF therapy. Some of the bone markers have been associated with vascular pathophysiology, while some vascular markers correlated with bone status. In arthritis, systemic inflammation and disease activity may drive both vascular and bone disease.
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| 8. |
- Soos, Boglarka, et al.
(författare)
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Effects of targeted therapies on bone in rheumatic and musculoskeletal diseases
- 2022
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Ingår i: Nature Reviews Rheumatology. - : Springer Nature. - 1759-4790 .- 1759-4804. ; 18:5, s. 249-257
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Forskningsöversikt (refereegranskat)abstract
- Targeted therapies, including biologic DMARDs and Janus kinase inhibitors, can interfere with the mechanisms of pathological bone metabolism in inflammatory arthritis. In this Review, the authors discuss the effects of these therapies on local and generalized bone changes. Generalized bone loss (osteoporosis) and fragility fractures can occur in rheumatic and musculoskeletal diseases including rheumatoid arthritis and spondyloarthritis (SpA; including ankylosing spondylitis and psoriatic arthritis). In addition, rheumatoid arthritis can involve localized, periarticular bone erosion and, in SpA, local (pathological) bone formation can occur. The RANK-RANKL-osteoprotegerin axis and the Wnt-beta-catenin signalling pathway (along with its inhibitors sclerostin and Dickkopf 1) have been implicated in inflammatory bone loss and formation, respectively. Targeted therapies including biologic DMARDs and Janus kinase (JAK) inhibitors can stabilize bone turnover and inhibit radiographic joint damage, and potentially also prevent generalized bone loss. Targeted therapies interfere at various points in the mechanisms of local and generalized bone changes in systemic rheumatic diseases, and they effect biomarkers of bone resorption and formation, bone mass and risk of fragility fractures. Studies on the effects of targeted therapies on rates of fragility fracture are scarce. The efficacy of biologic DMARDs for arresting bone formation in axial SpA is debated. Improved understanding of the most relevant therapeutic targets and identification of important targeted therapies could lead to the preservation of bone in inflammatory rheumatic and musculoskeletal diseases.
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| 9. |
- Walsh, J. Bernard, et al.
(författare)
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Effectiveness of Teriparatide in Women Over 75 Years of Age with Severe Osteoporosis : 36-Month Results from the European Forsteo Observational Study (EFOS)
- 2012
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Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 90:5, s. 373-383
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Tidskriftsartikel (refereegranskat)abstract
- This predefined analysis of the European Forsteo Observational Study (EFOS) aimed to describe clinical fracture incidence, back pain, and health-related quality of life (HRQoL) during 18 months of teriparatide treatment and 18 months post-teriparatide in the subgroup of 589 postmenopausal women with osteoporosis aged a parts per thousand yen75 years. Data on clinical fractures, back pain (visual analogue scale, VAS), and HRQoL (EQ-5D) were collected over 36 months. Fracture data were summarized in 6-month intervals and analyzed using logistic regression with repeated measures. A repeated-measures model analyzed changes from baseline in back pain VAS and EQ-VAS. During the 36-month observation period, 87 (14.8 %) women aged a parts per thousand yen75 years sustained a total of 111 new fractures: 37 (33.3 %) vertebral fractures and 74 (66.7 %) nonvertebral fractures. Adjusted odds of fracture was decreased by 80 % in the 30 to < 36-month interval compared with the first 6-month interval (P < 0.009). Although the older subgroup had higher back pain scores and poorer HRQoL at baseline than the younger subgroup, both age groups showed significant reductions in back pain and improvements in HRQoL postbaseline. In conclusion, women aged a parts per thousand yen75 years with severe postmenopausal osteoporosis treated with teriparatide in normal clinical practice showed a reduced clinical fracture incidence by 30 months compared with baseline. An improvement in HRQoL and, possibly, an early and significant reduction in back pain were also observed, which lasted for at least 18 months after teriparatide discontinuation when patients were taking other osteoporosis medication. The results should be interpreted in the context of an uncontrolled observational study.
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