Evaluation of bone mineral density, bone metabolism, osteoprotegerin and RANKL serum levels during treatment with infliximab in patients with rheumatoid arthritis

M Vis ^1*, E A Haavardsholm ², G Haugeberg ², T Uhlig ², A E Voskuyl ³, R J van de Stadt ⁴, B AC Dijkmans ³, A D Woolf ⁵, T K Kvien ² and W F Lems ³

¹ VU University Medical Center, Netherlands
² Diakonhjemmet Hospital, Norway
³ VU University Medical Centre, Netherlands
⁴ Jan van Breemen Institute, Netherlands
⁵ Royal Cornwall Hospital, United Kingdom

^* To whom correspondence should be addressed. E-mail: m.vis{at}vumc.nl.

Accepted 12 February 2006

Abstract

Introduction: The aim of the study was to examine whether treatment with anti-TNF-¥á prevents loss of bone mineral density at the spine and hip (generalized) and in the hands (local) in patients with rheumatoid arthritis (RA) and to study the changes in markers of bone metabolism, including receptor activator of NF¥êB ligand (RANKL) and osteoprotegerin (OPG), during anti- TNF treatment.

Patients and Methods: 102 patients with active RA, who were treated with infliximab during one year, were included into this open cohort study. The BMD of the spine and hip (DEXA) and hands (DXR) was measured before the start of treatment and after one year. Osteocalcin (formation), ©¬-CTx (resorption), receptor activator of Nf¥êb ligand (RANKL) and osteoprotegerin (OPG) were determined at 0, 14, 30 and 46 weeks.

Results: The BMD of the spine and hip was unchanged during treatment with infliximab, whereas BMD of the hand decreased significantly by 0.8 percent (p<0.01). The BMD of the hip in patients with an EULAR good response showed a favorable change compared with patients not achieving such a response. Serum ¥â-CTx and RANKL were both significantly decreased compared to baseline at all time points. The decrease in ¥â-CTx was associated to the decrease in DAS-28 and CRP during the 0 to 14 weeks interval.

Conclusion: In RA patients treated with infliximab, spine and hip bone loss is arrested, while metacarpal cortical hand bone loss is not stopped. The outcome of the study also supports a relationship between clinical response, in terms of reduced inflammatory activity, and changes in bone loss of spine, hip and hands.

Keywords: RANKL, anti-TNF, bone metabolism, bone mineral density, rheumatoid arthritis

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Haugeberg, G, Conaghan, P G, Quinn, M, Emery, P (2009). Bone loss in patients with active early rheumatoid arthritis: infliximab and methotrexate compared with methotrexate treatment alone. Explorative analysis from a 12-month randomised, double-blind, placebo-controlled study. Ann Rheum Dis 68: 1898-1901 [Abstract] [Full Text]  
• Hoff, M, Kvien, T K, Kalvesten, J, Elden, A, Haugeberg, G (2009). Adalimumab therapy reduces hand bone loss in early rheumatoid arthritis: explorative analyses from the PREMIER study. Ann Rheum Dis 68: 1171-1176 [Abstract] [Full Text]  
• Hardy, R, Cooper, M S (2009). Bone loss in inflammatory disorders. J Endocrinol 201: 309-320 [Abstract] [Full Text]  
• Guler-Yuksel, M, Allaart, C F, Goekoop-Ruiterman, Y P M, de Vries-Bouwstra, J K, van Groenendael, J H L M, Mallee, C, de Bois, M H W, Breedveld, F C, Dijkmans, B A C, Lems, W F (2009). Changes in hand and generalised bone mineral density in patients with recent-onset rheumatoid arthritis. Ann Rheum Dis 68: 330-336 [Abstract] [Full Text]  
• Wijbrandts, C A, Klaasen, R, Dijkgraaf, M G W, Gerlag, D M, van Eck-Smit, B L F, Tak, P P (2009). Bone mineral density in rheumatoid arthritis patients 1 year after adalimumab therapy: arrest of bone loss. Ann Rheum Dis 68: 373-376 [Abstract] [Full Text]  
• Visvanathan, S, van der Heijde, D, Deodhar, A, Wagner, C, Baker, D G, Han, J, Braun, J (2009). Effects of infliximab on markers of inflammation and bone turnover and associations with bone mineral density in patients with ankylosing spondylitis. Ann Rheum Dis 68: 175-182 [Abstract] [Full Text]  
• Castellino, G, Corallini, F, Trotta, F, Secchiero, P (2008). Is there any role for tumour necrosis factor related apoptosis inducing ligand-osteoprotegerin (TRAIL-OPG) interaction in rheumatoid arthritis?. Ann Rheum Dis 67: 1196-1197 [Full Text]  
• Guler-Yuksel, M, Bijsterbosch, J, Goekoop-Ruiterman, Y P M, de Vries-Bouwstra, J K, Hulsmans, H M J, de Beus, W M, Han, K H, Breedveld, F C, Dijkmans, B A C, Allaart, C F, Lems, W F (2008). Changes in bone mineral density in patients with recent onset, active rheumatoid arthritis. Ann Rheum Dis 67: 823-828 [Abstract] [Full Text]  
• Tilg, H, Moschen, A R, Kaser, A, Pines, A, Dotan, I (2008). Gut, inflammation and osteoporosis: basic and clinical concepts. Gut 57: 684-694 [Abstract] [Full Text]  
• Ding, C., Parameswaran, V., Udayan, R., Burgess, J., Jones, G. (2008). Circulating Levels of Inflammatory Markers Predict Change in Bone Mineral Density and Resorption in Older Adults: A Longitudinal Study. J. Clin. Endocrinol. Metab. 93: 1952-1958 [Abstract] [Full Text]  
• Chopin, F, Garnero, P, le Henanff, A, Debiais, F, Daragon, A, Roux, C, Sany, J, Wendling, D, Zarnitsky, C, Ravaud, P, Thomas, T (2008). Long-term effects of infliximab on bone and cartilage turnover markers in patients with rheumatoid arthritis. Ann Rheum Dis 67: 353-357 [Abstract] [Full Text]  
• Lilleby, V. (2007). Review: Bone status in juvenile systemic lupus erythematosus. Lupus 16: 580-586 [Abstract]