Skip to main content
Erschienen in: Osteoporosis International 2/2016

01.02.2016 | Original Article

Reducing glucocorticoid dosage improves serum osteocalcin in patients with rheumatoid arthritis—results from the TOMORROW study

verfasst von: M. Tada, K. Inui, Y. Sugioka, K. Mamoto, T. Okano, T. Koike, H. Nakamura

Erschienen in: Osteoporosis International | Ausgabe 2/2016

Einloggen, um Zugang zu erhalten

Abstract

Summary

Decreasing the daily dose of glucocorticoids improved bone metabolic marker levels in patients with rheumatoid arthritis. However, changes in disease activity did not influence bone metabolism. Bone metabolism might thus remain uncontrolled even if disease activity is under good control. Decreasing glucocorticoid dosage appears important for improving bone metabolism.

Introduction

Patients with rheumatoid arthritis (RA) develop osteoporosis more frequently than healthy individuals. Bone resorption is increased and bone formation is inhibited in patients with RA, and glucocorticoid negatively affects bone metabolism. We aimed to investigate factors influencing bone metabolic markers in patients with RA.

Methods

We started the 10-year prospective cohort Total Management of Risk Factors in Rheumatoid Arthritis Patients to Lower Morbidity and Mortality (TOMORROW) study in 2010. We compared changes in urinary cross-linked N-telopeptide of type I collagen (uNTx) and serum osteocalcin (OC), as markers of bone resorption and formation, respectively, in 202 RA patients and age- and sex-matched volunteers between 2010 and 2011. We also investigated factors influencing ΔuNTx and ΔOC in the RA group using multivariate analysis.

Results

Values of ΔuNTx were significantly lower in patients with RA than in healthy controls (−0.51 vs. 7.41 nmol bone collagen equivalents (BCE)/mmol creatinine (Cr); p = 0.0013), whereas ΔOC values were significantly higher in RA patients (0.94 vs. 0.37 ng/ml; p = 0.0065). Changes in prednisolone dosage correlated negatively with ΔOC (β = −0.229, p = 0.001), whereas changes in disease activity score, bisphosphonate therapy, and period of biologics therapy did not correlate significantly with ΔOC. No significant correlation was seen between ΔuNTx and change in prednisolone dosage.

Conclusions

Decreased glucocorticoid dosage improved bone metabolic markers in RA, but disease activity, bisphosphonate therapy, and period of biologics therapy did not influence levels of bone metabolic markers. Decreasing glucocorticoid dosage appears important for improving bone metabolic marker profiles in patients with RA.
Literatur
1.
Zurück zum Zitat Deodhar AA, Woolf AD (1996) Bone mass measurement and bone metabolism in rheumatoid arthritis: a review. Br J Rheumatol 35:309–322CrossRefPubMed Deodhar AA, Woolf AD (1996) Bone mass measurement and bone metabolism in rheumatoid arthritis: a review. Br J Rheumatol 35:309–322CrossRefPubMed
2.
Zurück zum Zitat Peel NF, Moore DJ, Barrington NA, Bax DE, Eastell R (1995) Risk of vertebral fracture and relationship to bone mineral density in steroid treated rheumatoid arthritis. Ann Rheum Dis 54:801–806PubMedCentralCrossRefPubMed Peel NF, Moore DJ, Barrington NA, Bax DE, Eastell R (1995) Risk of vertebral fracture and relationship to bone mineral density in steroid treated rheumatoid arthritis. Ann Rheum Dis 54:801–806PubMedCentralCrossRefPubMed
3.
Zurück zum Zitat van Staa TP, Geusens P, Bijlsma JW, Leufkens HG, Cooper C (2006) Clinical assessment of the long-term risk of fracture in patients with rheumatoid arthritis. Arthritis Rheum 54:3104–3112CrossRefPubMed van Staa TP, Geusens P, Bijlsma JW, Leufkens HG, Cooper C (2006) Clinical assessment of the long-term risk of fracture in patients with rheumatoid arthritis. Arthritis Rheum 54:3104–3112CrossRefPubMed
4.
Zurück zum Zitat Wright NC, Lisse JR, Walitt BT, Eaton CB, Chen Z (2011) Arthritis increases the risk for fractures—results from the women’s health initiative. J Rheumatol 38:1680–1688PubMedCentralCrossRefPubMed Wright NC, Lisse JR, Walitt BT, Eaton CB, Chen Z (2011) Arthritis increases the risk for fractures—results from the women’s health initiative. J Rheumatol 38:1680–1688PubMedCentralCrossRefPubMed
5.
Zurück zum Zitat Kannus P, Sievanen H, Palvanen M, Jarvinen T, Parkkari J (2005) Prevention of falls and consequent injuries in elderly people. Lancet 366:1885–1893CrossRefPubMed Kannus P, Sievanen H, Palvanen M, Jarvinen T, Parkkari J (2005) Prevention of falls and consequent injuries in elderly people. Lancet 366:1885–1893CrossRefPubMed
6.
Zurück zum Zitat Haugeberg G, Uhlig T, Falch JA, Halse JI, Kvien TK (2000) Bone mineral density and frequency of osteoporosis in female patients with rheumatoid arthritis: results from 394 patients in the Oslo County Rheumatoid Arthritis register. Arthritis Rheum 43:522–530CrossRefPubMed Haugeberg G, Uhlig T, Falch JA, Halse JI, Kvien TK (2000) Bone mineral density and frequency of osteoporosis in female patients with rheumatoid arthritis: results from 394 patients in the Oslo County Rheumatoid Arthritis register. Arthritis Rheum 43:522–530CrossRefPubMed
7.
Zurück zum Zitat Lodder MC, Haugeberg G, Lems WF, Uhlig T, Orstavik RE, Kostense PJ, Dijkmans BA, Kvien TK, Woolf AD (2003) Radiographic damage associated with low bone mineral density and vertebral deformities in rheumatoid arthritis: the Oslo-Truro-Amsterdam (OSTRA) collaborative study. Arthritis Rheum 49:209–215CrossRefPubMed Lodder MC, Haugeberg G, Lems WF, Uhlig T, Orstavik RE, Kostense PJ, Dijkmans BA, Kvien TK, Woolf AD (2003) Radiographic damage associated with low bone mineral density and vertebral deformities in rheumatoid arthritis: the Oslo-Truro-Amsterdam (OSTRA) collaborative study. Arthritis Rheum 49:209–215CrossRefPubMed
8.
Zurück zum Zitat Braun T, Schett G (2012) Pathways for bone loss in inflammatory disease. Curr Osteoporos Rep 10:101–108CrossRefPubMed Braun T, Schett G (2012) Pathways for bone loss in inflammatory disease. Curr Osteoporos Rep 10:101–108CrossRefPubMed
9.
Zurück zum Zitat Van Staa TP, Leufkens HG, Abenhaim L, Zhang B, Cooper C (2000) Use of oral corticosteroids and risk of fractures. J Bone Miner Res 15:993–1000CrossRefPubMed Van Staa TP, Leufkens HG, Abenhaim L, Zhang B, Cooper C (2000) Use of oral corticosteroids and risk of fractures. J Bone Miner Res 15:993–1000CrossRefPubMed
10.
Zurück zum Zitat van Staa TP, Leufkens HG, Cooper C (2002) The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int 13:777–787CrossRefPubMed van Staa TP, Leufkens HG, Cooper C (2002) The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int 13:777–787CrossRefPubMed
11.
Zurück zum Zitat Grossman JM, Gordon R, Ranganath VK, Deal C, Caplan L, Chen W, Curtis JR, Furst DE, McMahon M, Patkar NM, Volkmann E, Saag KG (2010) American College of Rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res 62:1515–1526CrossRef Grossman JM, Gordon R, Ranganath VK, Deal C, Caplan L, Chen W, Curtis JR, Furst DE, McMahon M, Patkar NM, Volkmann E, Saag KG (2010) American College of Rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res 62:1515–1526CrossRef
12.
Zurück zum Zitat Nawata H, Soen S, Takayanagi R, Tanaka I, Takaoka K, Fukunaga M, Matsumoto T, Suzuki Y, Tanaka H, Fujiwara S, Miki T, Sagawa A, Nishizawa Y, Seino Y (2005) Guidelines on the management and treatment of glucocorticoid-induced osteoporosis of the Japanese Society for Bone and Mineral Research (2004). J Bone Miner Metab 23:105–109CrossRefPubMed Nawata H, Soen S, Takayanagi R, Tanaka I, Takaoka K, Fukunaga M, Matsumoto T, Suzuki Y, Tanaka H, Fujiwara S, Miki T, Sagawa A, Nishizawa Y, Seino Y (2005) Guidelines on the management and treatment of glucocorticoid-induced osteoporosis of the Japanese Society for Bone and Mineral Research (2004). J Bone Miner Metab 23:105–109CrossRefPubMed
13.
Zurück zum Zitat Vis M, Havaardsholm EA, Haugeberg G, Uhlig T, Voskuyl AE, van de Stadt RJ, Dijkmans BA, Woolf AD, Kvien TK, Lems WF (2006) Evaluation of bone mineral density, bone metabolism, osteoprotegerin and receptor activator of the NFkappaB ligand serum levels during treatment with infliximab in patients with rheumatoid arthritis. Ann Rheum Dis 65:1495–1499PubMedCentralCrossRefPubMed Vis M, Havaardsholm EA, Haugeberg G, Uhlig T, Voskuyl AE, van de Stadt RJ, Dijkmans BA, Woolf AD, Kvien TK, Lems WF (2006) Evaluation of bone mineral density, bone metabolism, osteoprotegerin and receptor activator of the NFkappaB ligand serum levels during treatment with infliximab in patients with rheumatoid arthritis. Ann Rheum Dis 65:1495–1499PubMedCentralCrossRefPubMed
14.
Zurück zum Zitat Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324CrossRefPubMed Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324CrossRefPubMed
15.
Zurück zum Zitat Prevoo ML, van’t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL (1995) Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 38:44–48CrossRefPubMed Prevoo ML, van’t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL (1995) Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 38:44–48CrossRefPubMed
16.
Zurück zum Zitat Pincus T, Summey JA, Soraci SA Jr, Wallston KA, Hummon NP (1983) Assessment of patient satisfaction in activities of daily living using a modified Stanford Health Assessment Questionnaire. Arthritis Rheum 26:1346–1353CrossRefPubMed Pincus T, Summey JA, Soraci SA Jr, Wallston KA, Hummon NP (1983) Assessment of patient satisfaction in activities of daily living using a modified Stanford Health Assessment Questionnaire. Arthritis Rheum 26:1346–1353CrossRefPubMed
17.
Zurück zum Zitat Okano T, Koike T, Tada M, Sugioka Y, Mamoto K, Wakitani S, Nakamura H (2014) The limited effects of anti-tumor necrosis factor blockade on bone health in patients with rheumatoid arthritis under the use of glucocorticoid. J Bone Miner Metab 32:593–600CrossRefPubMed Okano T, Koike T, Tada M, Sugioka Y, Mamoto K, Wakitani S, Nakamura H (2014) The limited effects of anti-tumor necrosis factor blockade on bone health in patients with rheumatoid arthritis under the use of glucocorticoid. J Bone Miner Metab 32:593–600CrossRefPubMed
18.
Zurück zum Zitat Laan RF, Buijs WC, Verbeek AL, Draad MP, Corstens FH, van de Putte LB, van Riel PL (1993) Bone mineral density in patients with recent onset rheumatoid arthritis: influence of disease activity and functional capacity. Ann Rheum Dis 52:21–26PubMedCentralCrossRefPubMed Laan RF, Buijs WC, Verbeek AL, Draad MP, Corstens FH, van de Putte LB, van Riel PL (1993) Bone mineral density in patients with recent onset rheumatoid arthritis: influence of disease activity and functional capacity. Ann Rheum Dis 52:21–26PubMedCentralCrossRefPubMed
19.
Zurück zum Zitat Hall GM, Spector TD, Griffin AJ, Jawad AS, Hall ML, Doyle DV (1993) The effect of rheumatoid arthritis and steroid therapy on bone density in postmenopausal women. Arthritis Rheum 36:1510–1516CrossRefPubMed Hall GM, Spector TD, Griffin AJ, Jawad AS, Hall ML, Doyle DV (1993) The effect of rheumatoid arthritis and steroid therapy on bone density in postmenopausal women. Arthritis Rheum 36:1510–1516CrossRefPubMed
20.
Zurück zum Zitat Haugeberg G, Ørstavik RE, Uhlig T, Falch JA, Halse JI, Kvien TK (2002) Bone loss in patients with rheumatoid arthritis: results from a population-based cohort of 366 patients followed up for two years. Arthritis Rheum 46:1720–1728CrossRefPubMed Haugeberg G, Ørstavik RE, Uhlig T, Falch JA, Halse JI, Kvien TK (2002) Bone loss in patients with rheumatoid arthritis: results from a population-based cohort of 366 patients followed up for two years. Arthritis Rheum 46:1720–1728CrossRefPubMed
21.
Zurück zum Zitat Vis M, Guler-Yuksel M, Lems WF (2013) Can bone loss in rheumatoid arthritis be prevented? Osteoporos Int 24:2541–2553CrossRefPubMed Vis M, Guler-Yuksel M, Lems WF (2013) Can bone loss in rheumatoid arthritis be prevented? Osteoporos Int 24:2541–2553CrossRefPubMed
22.
Zurück zum Zitat Lange U, Teichmann J, Muller-Ladner U, Strunk J (2005) Increase in bone mineral density of patients with rheumatoid arthritis treated with anti-TNF-alpha antibody: a prospective open-label pilot study. Rheumatology (Oxford) 44:1546–1548CrossRef Lange U, Teichmann J, Muller-Ladner U, Strunk J (2005) Increase in bone mineral density of patients with rheumatoid arthritis treated with anti-TNF-alpha antibody: a prospective open-label pilot study. Rheumatology (Oxford) 44:1546–1548CrossRef
23.
Zurück zum Zitat Garnero P, Thompson E, Woodworth T, Smolen JS (2010) Rapid and sustained improvement in bone and cartilage turnover markers with the anti-interleukin-6 receptor inhibitor tocilizumab plus methotrexate in rheumatoid arthritis patients with an inadequate response to methotrexate: results from a substudy of the multicenter double-blind, placebo-controlled trial of tocilizumab in inadequate responders to methotrexate alone. Arthritis Rheum 62:33–43CrossRefPubMed Garnero P, Thompson E, Woodworth T, Smolen JS (2010) Rapid and sustained improvement in bone and cartilage turnover markers with the anti-interleukin-6 receptor inhibitor tocilizumab plus methotrexate in rheumatoid arthritis patients with an inadequate response to methotrexate: results from a substudy of the multicenter double-blind, placebo-controlled trial of tocilizumab in inadequate responders to methotrexate alone. Arthritis Rheum 62:33–43CrossRefPubMed
25.
Zurück zum Zitat O’Brien CA, Jia D, Plotkin LI, Bellido T, Powers CC, Stewart SA, Manolagas SC, Weinstein RS (2004) Glucocorticoids act directly on osteoblasts and osteocytes to induce their apoptosis and reduce bone formation and strength. Endocrinology 145:1835–1841CrossRefPubMed O’Brien CA, Jia D, Plotkin LI, Bellido T, Powers CC, Stewart SA, Manolagas SC, Weinstein RS (2004) Glucocorticoids act directly on osteoblasts and osteocytes to induce their apoptosis and reduce bone formation and strength. Endocrinology 145:1835–1841CrossRefPubMed
26.
Zurück zum Zitat Weinstein RS, Jilka RL, Parfitt AM, Manolagas SC (1998) Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. J Clin Invest 102:274–282PubMedCentralCrossRefPubMed Weinstein RS, Jilka RL, Parfitt AM, Manolagas SC (1998) Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. J Clin Invest 102:274–282PubMedCentralCrossRefPubMed
27.
Zurück zum Zitat Neovius M, Sundstrom A, Simard J, Wettermark B, Cars T, Feltelius N, Askling J, Klareskog L (2011) Small-area variations in sales of TNF inhibitors in Sweden between 2000 and 2009. Scand J Rheumatol 40:8–15CrossRefPubMed Neovius M, Sundstrom A, Simard J, Wettermark B, Cars T, Feltelius N, Askling J, Klareskog L (2011) Small-area variations in sales of TNF inhibitors in Sweden between 2000 and 2009. Scand J Rheumatol 40:8–15CrossRefPubMed
28.
Zurück zum Zitat Yamanaka H, Seto Y, Tanaka E, Furuya T, Nakajima A, Ikari K, Taniguchi A, Momohara S (2013) Management of rheumatoid arthritis: the 2012 perspective. Mod Rheumatol 23:1–7CrossRefPubMed Yamanaka H, Seto Y, Tanaka E, Furuya T, Nakajima A, Ikari K, Taniguchi A, Momohara S (2013) Management of rheumatoid arthritis: the 2012 perspective. Mod Rheumatol 23:1–7CrossRefPubMed
Metadaten
Titel
Reducing glucocorticoid dosage improves serum osteocalcin in patients with rheumatoid arthritis—results from the TOMORROW study
verfasst von
M. Tada
K. Inui
Y. Sugioka
K. Mamoto
T. Okano
T. Koike
H. Nakamura
Publikationsdatum
01.02.2016
Verlag
Springer London
Erschienen in
Osteoporosis International / Ausgabe 2/2016
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-015-3291-y

Weitere Artikel der Ausgabe 2/2016

Osteoporosis International 2/2016 Zur Ausgabe

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen. 
» Jetzt entdecken

Ein Drittel der jungen Ärztinnen und Ärzte erwägt abzuwandern

07.05.2024 Klinik aktuell Nachrichten

Extreme Arbeitsverdichtung und kaum Supervision: Dr. Andrea Martini, Sprecherin des Bündnisses Junge Ärztinnen und Ärzte (BJÄ) über den Frust des ärztlichen Nachwuchses und die Vorteile des Rucksack-Modells.

Aquatherapie bei Fibromyalgie wirksamer als Trockenübungen

03.05.2024 Fibromyalgiesyndrom Nachrichten

Bewegungs-, Dehnungs- und Entspannungsübungen im Wasser lindern die Beschwerden von Patientinnen mit Fibromyalgie besser als das Üben auf trockenem Land. Das geht aus einer spanisch-brasilianischen Vergleichsstudie hervor.

Endlich: Zi zeigt, mit welchen PVS Praxen zufrieden sind

IT für Ärzte Nachrichten

Darauf haben viele Praxen gewartet: Das Zi hat eine Liste von Praxisverwaltungssystemen veröffentlicht, die von Nutzern positiv bewertet werden. Eine gute Grundlage für wechselwillige Ärztinnen und Psychotherapeuten.

Proximale Humerusfraktur: Auch 100-Jährige operieren?

01.05.2024 DCK 2024 Kongressbericht

Mit dem demographischen Wandel versorgt auch die Chirurgie immer mehr betagte Menschen. Von Entwicklungen wie Fast-Track können auch ältere Menschen profitieren und bei proximaler Humerusfraktur können selbst manche 100-Jährige noch sicher operiert werden.

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.