Abstract
Vertebral fractures due to osteoporosis are a common but frequently unrecognized complication in established ankylosing spondylitis (AS). It is known that inflammatory activity in rheumatic diseases (i.e., proinflammatory cytokines) itself plays a possible role in the pathophysiology of bone loss. The aim of this study was to analyze whether inflammatory activity and an alteration of the vitamin D metabolism play a substantial role in the loss of bone mass in AS. In this cross-sectional study, 58 patients with established AS and an age- and sex-matched control group were examined. The vitamin D status was investigated, as was, in parallel, the relationship to disease activity (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]), markers of bone metabolism (parathyroid hormone [PTH], 1.25 vitamin D3, 25 vitamin D3), calcium, bone alkaline phosphatase (bone-AP), urine cross-links, and plasma tumor necrosis factor α(TNFα). Bone mineral density was measured by quantitative computed tomography (QCT) of the lumbar spine. Osteoporosis was diagnosed in early as well as in progressive stages of AS (23/58=39.6%). Furthermore, serum levels of 1.25 vitamin D3 and PTH were negatively correlated with disease activity and TNFα. The excretion of cross-links showed a positive correlation with disease activity and TNFα, and 1.25 vitamin D3 and PTH were positively correlated with bone-AP. TNFα also positively correlated with disease activity. AS patients with osteoporosis showed significantly increased CRP, ESR, cross-links and PTH and a significantly decreased 1.25 D3. Osteoporosis is frequent in AS and high disease activity is associated with an alteration in vitamin D metabolites and increased levels of bone resorption in active AS. Our findings propose a close association of BMD, bone metabolism and inflammatory activity, possibly related to vitamin D inflammation interactions.
Similar content being viewed by others
References
Will R, Palmer R, Bhalla AK, Ring F, Colin A (1989) Osteoporosis in early ankylosing spondylitis: a primary pathological event? Lancet 2:1483–1485
Bhalla AK, Shenstone B (1992) Bone densitometry measurements in early inflammatory disease. Baillières Clin Rheumatol 2(6):405–414
Gratacós J, Collado A, Pons F, Osaba M, Sanmarti R, Roqué M et al (1999) Significant loss of bone mass in patients with early active ankylosing spondylitis. Arthritis Rheum 42:2319–2324
Manolagas SCV (1995) Role of cytokines in bone resorption. Bone 16 [Suppl 1]:63–67
Manolagas SCV (1995) Bone marrow, clastic and blastic cell system: Quo vadis? Calcif Tissue Int 56 [Suppl 1]:2–53
Pacifici R (1995)Cytokines and osteoclast activity. Calcif Tissue Int 56 [Suppl 1]:27–28
Hahn G, Stuhlmueller B, Hain N, Kalden JR, Pfizemaier K, Burmester GR (1993) Modulation of monocyte activation in patients with rheumatoid arthritis by leukapheresis therapy. J Clin Invest 91:862–870
Nguyen L, Dewhirst FE, Hauschka PV, Stashenko P (1991) Interleukin-1β stimulates bone resorption and inhibits bone formation in vivo. Lymphokine Cytokine Res 10:15–21
Lange U, Jung O, Teichmann J, Neeck G (2001) Relationship between disease activity and serum levels of vitamin D metabolites and parathyroid hormone in ankylosing spondylitis. Osteoporos Int 12:1031–1035
Moll LMH, Wright V (1973) New York clinical criteria for ankylosing spondylitis. A statistical evaluation. Ann Rheum Dis 32:354
Dougados M, van der Linden S, Juhlin R, Huitfeldt B, Amor B, Calin A, Cats A et al (1991) The European Spondylarthropathy Study Group preliminary criteria for the classification of spondylarthropathy. Arthritis Rheum 34(10):1218–1227
Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisfrod P, Calin A (1994) A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol 21:2286–2291
Payne RB, Carrver ME, Morgan DB (1979) Interpretation of serum total calcium: effects of adjustment for albumin concentration on frequency of abnormal values and on detection of change in the individual. J Clin Pathol 32:56–60
Melton LJ 3rd, Lane AW, Cooper C, Eastell R, O’Fallon WM, Riggs BL (1993) Prevalence and incidence of vertebral deformities. Osteoporos Int 3:113–119
Karberg K, Zochling J, Sieper J, Felsenberg D, Braun J (2005) Bone loss is more frequently detected in ankylosing spondylitis patients with syndesmophytes. J Rheumatol 32(7):1290–1298
Lange U, Kluge A, Teichmann J, Stracke H, Rau WS, Schmidt KL (2001) Bone density measurement by dual X-ray absorptiometry (DXA) and single energy-quantitative computed tomography (SE-QCT) in ankylosing spondylitis—critical comments. Akt Rheumatol 26:1–6
Lange U, Kluge A., Strunk J, Teichmann J, Bachmann G (2004) Ankylosing spondylitis and bone mineral density—What is the ideal tool for measurement? Rheumatol Int (epub ahead of print; (11)5:S0172–8172)
Ott V (1972) Klinik und Therapie der ankylosierenden Spondylitis (Morbus Strümpell-Marie-Bechterew) In: Brügel H (ed) Fortschritte auf dem Gebiet der rheumatischen Erkrankungen und der degenerativen Gelenkerkrankungen. Schattauer, Stuttgart, pp 92–104
Amento EP (1987) Vitamin D and the immune system. Steroids 49:55–72
Overbergh L, Decallonne B, Valckx D et al (1998) Identification and immune regulation of 25-hydroxyvitamin D-1-alpha-hydroxylase in murine macrophages. Clin Exp Immunol 120:139–146
Obermayer-Pietsch BM, Lange U, Tauber G, Frühauf G, Fahrleitner A, Dobnig H, Hermann J, Aglas F, Teichmann J, Neeck G, Leb G (2003) Vitamin D receptor initiation codon polymorphism, bone density and inflammatory activity of patients with ankylosing spondylitis. Osteoporos Int 14:995–1000
Quinn JM, Itoh K, Udagawa N (2001) Transforming growth factor beta affects osteoclast differentiation via direct and indirect interactions. J Bone Miner Res 16:1787–1794
Lange U, Teichmann J, Stracke H (2000) Correlation between plasma TNF-alpha, IGF-1, biochemical markers of bone metabolism, markers of inflammation/disease activity, and clinical manifestations in ankylosing spondylitis. Eur J Med Res 5:507–511
Baeten D, Kruithof E, Van den Bosch F et al (2001) Immunomodulatory effects of anti-tumor necrosis factor alpha therapy on synovium in spondylarthropathy: histologic findings in eight patients from an open-label pilot study. Arthritis Rheum 44:186–195
Fernandez-Martin JL, Kurian S, Farmer P et al (1998) Tumor necrosis factor activates a nuclear inhibitor of vitamin D and retinoid -X receptors. Mol Cell Endocrinol 25:65–72
Kuno H, Kurian SM, Hendy GN et al (1994) Inhibition of 1,25-dihydroxyvitamin D3 stimulated osteocalcin gene transcription by tumor necrosis factor-alpha: structural determinants within the vitamin D response element. Endocrinology 134:2524–2531
Schacht E (2000) Osteoporosis in rheumatoid arthritis: significance of alfacalcidol in prevention and therapy. Z Rheumatol 59:10–20
Shany S, Levy Y, Lahav-Cohen M (2001) The effects of 1alpha,24(S)-dihydroxyvitamin D(2) analog on cancer cell proliferation and cytokine expression. Steroids 66:319–325
Fuss M, Pepersack T, Gillet C, Karmali R, Corvilain J (1992) Calcium and vitamin D metabolism in granulomatous diseases. Clin Rheumatol 11:28–36
Wemeau JL (1995) Calciotropic hormones and ageing. Horm Res 43:76–79
Bouillon R, Okmamura WH, Norman AW (1995) Structure-function relationships in the vitamin D endocrine system. Endocr Rev 16:200–257
Toussirot E, Ricard-Blum S, Dumoulin G, Cedoz JP, Wendling D (1999) Relationship between urinary pyridinium cross-links, disease activity and disease subsets of ankylosing spondylitis. Rheumatology 38:21–27
Compston JE, Vedi S, Croucher PI, Garrahan NJ, O Sullivan MM (1994) Bone turnover in non-steroid-treated rheumatoid arthritis. Ann Rheum Dis 53:1263–1266
Ekenstam E (1991) Influence of inflammation and corticosteroid treatment on indices of bone turnover and parathyroid function. Scand J Rheumatol 20:200
Langman CB, Ford, KK, Pachman LM, Glorieux F (1990) Vitamin D metabolism in rats with adjuvant-induced arthritis. J Bone Miner Res 5:905–913
Uzawa T, Hori M, Ejiri S, Ozawa H (1995) Comparison of the effects of intermittent and continuous administration of human parathyroid hormone (1–34) on rat bone. Bone 16:477–484
Teichmann J, Lange U, Stracke H, Doppl W, Klör HU, Federlin K (1997) Rapid trabecular bone loss in female patients with ileitis Crohn and additional sacroiliac joint inflammation. Rheumatol Int 17:45–48
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lange, U., Teichmann, J., Strunk, J. et al. Association of 1.25 vitamin D3 deficiency, disease activity and low bone mass in ankylosing spondylitis. Osteoporos Int 16, 1999–2004 (2005). https://doi.org/10.1007/s00198-005-1990-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00198-005-1990-5