Effects of 25-hydroxyvitamin D and vitamin D-binding protein on bone mineral density and disease activity in Malaysian patients with rheumatoid arthritis
Tze Hao Wong
Pathology Division, School of Medicine, International Medical University, Kuala Lumpur, Malaysia
Search for more papers by this authorEsha Das Gupta
Internal Medicine Department, School of Medicine, International Medical University, Seremban, Malaysia
Search for more papers by this authorAmmu K. Radhakrishnan
Pathology Division, School of Medicine, International Medical University, Kuala Lumpur, Malaysia
Search for more papers by this authorSuk Chyn Gun
Internal Medicine Department, Hospital Tuanku Jaafar, Seremban, Malaysia
Search for more papers by this authorGandhi Chembalingam
Internal Medicine Department, Hospital Tuanku Jaafar, Seremban, Malaysia
Search for more papers by this authorCorresponding Author
Swan Sim Yeap
Department of Medicine, Subang Jaya Medical Centre, Subang Jaya, Malaysia
Correspondence: Dr Swan Sim Yeap, Consultant Rheumatologist, Subang Jaya Medical Centre, No. 1, Jalan SS 12/1A, 47500 Subang Jaya, Selangor, Malaysia. Email: [email protected]Search for more papers by this authorTze Hao Wong
Pathology Division, School of Medicine, International Medical University, Kuala Lumpur, Malaysia
Search for more papers by this authorEsha Das Gupta
Internal Medicine Department, School of Medicine, International Medical University, Seremban, Malaysia
Search for more papers by this authorAmmu K. Radhakrishnan
Pathology Division, School of Medicine, International Medical University, Kuala Lumpur, Malaysia
Search for more papers by this authorSuk Chyn Gun
Internal Medicine Department, Hospital Tuanku Jaafar, Seremban, Malaysia
Search for more papers by this authorGandhi Chembalingam
Internal Medicine Department, Hospital Tuanku Jaafar, Seremban, Malaysia
Search for more papers by this authorCorresponding Author
Swan Sim Yeap
Department of Medicine, Subang Jaya Medical Centre, Subang Jaya, Malaysia
Correspondence: Dr Swan Sim Yeap, Consultant Rheumatologist, Subang Jaya Medical Centre, No. 1, Jalan SS 12/1A, 47500 Subang Jaya, Selangor, Malaysia. Email: [email protected]Search for more papers by this authorAbstract
Aim
Vitamin D3 [25(OH)D] has been shown to be important in bone health and can influence rheumatoid arthritis (RA) disease activity. Vitamin D-binding protein (VDBP) levels vary with race and may modulate ‘bioavailable’ levels of 25(OH)D. The aim of this study was to explore the relationships between 25(OH)D, VDBP and clinical factors on bone mineral density (BMD) in a group of multi-ethnic Malaysian RA patients and healthy controls.
Methods
A cross-sectional study of 77 female RA patients and 29 controls was performed. Serum 25(OH)D was measured using the Elecsys® Vitamin D total assay. Serum VDBP was measured using a Quantikine® enzyme-linked immunosorbent assay kit. BMD was assessed using dual-energy X-ray absorptiometry (DXA).
Results
Overall, mean 25(OH)D levels were 42.66 ± 21.75 nmol/L with no significant difference between RA patients and controls. 25(OH)D levels were significantly higher in Chinese, compared to Malay/Indian subjects. In RA patients, menopausal status and body mass index (BMI) were significantly associated with BMD but not 25(OH)D or RA Disease Activity Score of 28 joints (DAS28). There was no significant correlation between 25(OH)D and DAS28, even after correction for menopausal status and BMI. VDBP levels were not significantly different between the races and did not significantly correlate with BMD, 25(OH)D overall, or DAS28 in RA patients.
Conclusions
In Malaysian RA patients, menopausal status and BMI were more important influences on BMD than 25(OH)D or RA disease activity. The utility of measuring VDBP levels in this population remains uncertain.
References
- 1Holick MF (2007) Vitamin D deficiency. N Engl J Med 357, 266–81.
- 2Hewison M (2010) Vitamin D and the immune system: new perspectives on an old theme. Endocrinol Metab Clin North Am 39 (2), 365–79.
- 3Holick MF (2009) Vitamin D status: measurement, interpretation and clinical application. Ann Epidemiol 19, 73–8.
- 4Bischoff-Ferrari HA, Dietrich T, Orav EJ, Dawson-Hughes B (2004) Positive association between 25-hydroxy vitamin D levels and bone mineral density: a population-based study of younger and older adults. Am J Med 116, 634–9.
- 5von Mühlen DG, Greendale GA, Garland CF, Wan L, Barrett-Connor E (2005) Vitamin D, parathyroid hormone levels and bone mineral density in community-dwelling older women: the Rancho Bernardo Study. Osteoporos Int 16, 1721–6.
- 6Kuchuk NO, Pluijm SMF, van Schoor NM, Looman CWN, Smit JH, Lips P (2009) Relationships of serum 25-hydroxyvitamin D to bone mineral density and serum parathyroid hormone and markers of bone turnover in older persons. J Clin Endocrinol Metab 94, 1244–50.
- 7Lin J, Liu J, Davies ML, Chen W (2016) Serum vitamin D level and rheumatoid arthritis disease activity: review and meta-analysis. PLoS One 11 (1), e0146351.
- 8Chen J, Liu W, Lin Q, Chen L, Yin J, Huang H (2014) Vitamin D deficiency and low bone mineral density in native Chinese rheumatoid arthritis patients. Int J Rheum Dis 17 (1), 66–70.
- 9Hong Q, Xu J, Xu S, Lian L, Zhang M, Ding C (2014) Associations between serum 25-hydroxyvitamin D and disease activity, inflammatory cytokines and bone loss in patients with rheumatoid arthritis. Rheumatology (Oxford) 53, 1994–2001.
- 10Sharma R, Saigal R, Goyal L et al. (2014) Estimation of vitamin D levels in rheumatoid arthritis patients and its correlation with the disease activity. J Assoc Physicians India 62, 678–81.
- 11Matsumoto Y, Sugioka Y, Tada M et al. (2015) Relationships between serum 25-hydroxycalciferol, vitamin D intake and disease activity in patients with rheumatoid arthritis—TOMORROW study. Mod Rheumatol 25 (2), 246–50.
- 12Pakchotanon R, Chaiamnuay S, Narongroeknawin P, Asavatanabodee P (2016) The association between serum vitamin D Level and disease activity in Thai rheumatoid arthritis patients. Int J Rheum Dis 19, 355–61.
- 13Bikle DD, Gee E, Halloran B, Kowalski MA, Ryzen E, Haddad JG (1986) Assessment of the free fraction of 25-hydroxyvitamin D in serum and its regulation by albumin and the vitamin D-binding protein. J Clin Endocrinol Metab 63, 954–9.
- 14Adebanjo OA, Moonga BS, Haddad JG, Huang CL-H, Zaidi M (1998) A possible new role for vitamin D-binding protein in osteoclast control: inhibition of extracellular Ca2+ sensing at low physiological concentrations. Biochem Biophys Res Commun 249, 668–71.
- 15Papiha SS, Allcroft LC, Kanan RM, Francis RM, Datta HK (1999) Vitamin D binding protein gene in male osteoporosis: association of plasma DBP and bone mineral density with (TAAA)(n)-Alu polymorphism in DBP. Calcif Tissue Int 65, 262–6.
- 16Taes YE, Goemaere S, Huang G et al. (2006) Vitamin D binding protein, bone status and body composition in community-dwelling elderly men. Bone 38, 701–7.
- 17Arnaud J, Constans J (1993) Affinity differences for vitamin D metabolites associated with the genetic isoforms of the human serum carrier protein (DBP). Hum Genet 92, 183–8.
- 18Powe CE, Evans MK, Wenger J et al. (2013) Vitamin D-binding protein and vitamin D status of Black Americans and White Americans. N Engl J Med 369, 1991–2000.
- 19Arnett FC, Edworthy SM, Bloch DA et al. (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31, 315–24.
- 20Aletaha D, Neogi T, Silman AJ et al. (2010) 2010 Rheumatoid arthritis classification criteria. Arthritis Rheum 62, 2569–81.
- 21Aletaha D, Ward MM, Machold KP, Nell VP, Stamm T, Smolen JS (2005) Remission and active disease in rheumatoid arthritis: defining criteria for disease activity states. Arthritis Rheum 52, 2625–36.
- 22 WHO (1994) WHO Technical Report Series 843. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. World Health Organisation, Geneva.
- 23Ross AC, Manson JE, Abrams SA et al. (2011) The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab 96 (1), 53–8.
- 24Holick MF, Binkley NC, Bischoff-Ferrari HA et al. (2011) Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 96, 1911–30.
- 25Holick MF, Siris ES, Binkley N et al. (2005) Prevalence of vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy. J Clin Endocrinol Metab 90, 3215–24.
- 26Green TJ, Skeaff CM, Rockell JEP et al. (2008) Vitamin D status and its association with parathyroid hormone concentrations in women of child-bearing age living in Jakarta and Kuala Lumpur. Eur J Clin Nutr 62, 373–8.
- 27Hawkins R (2013) Total 25-OH vitamin D concentrations in Chinese, Malays and Indians. Ann Lab Med 33 (2), 156–8.
- 28Choi HS (2013) Vitamin D status in Korea. Endocrinol Metab 28, 12–6.
10.3803/EnM.2013.28.1.12 Google Scholar
- 29Li S, Ou Y, Zhang H et al. (2014) Vitamin D status and its relationship with body composition, bone mineral density and fracture risk in urban central south Chinese postmenopausal women. Ann Nutr Metab 64, 13–9.
- 30Wat WZ, Leung JY, Tam S, Kung AW (2007) Prevalence and impact of vitamin D insufficiency in southern Chinese adults. Ann Nutr Metab 51 (1), 59–64.
- 31Ho-Pham LT, Nguyen ND, Lai TQ, Eisman JA, Nguyen TV (2011) Vitamin D status and parathyroid hormone in a urban population in Vietnam. Osteoporos Int 22 (1), 241–8.
- 32Kitamura K, Nakamura K, Saito T et al. (2013) High serum 25-hydroxyvitamin D levels do not retard postmenopausal bone loss in Japanese women: the Yokogoshi study. Arch Osteoporos 8, 153.
- 33Tanaka S, Kuroda T, Yamazaki Y, Shiraki Y, Yoshimura N, Shiraki M (2014) Serum 25-hydroxyvitamin D below 25 ng/mL is a risk factor for long bone fracture comparable to bone mineral density in Japanese postmenopausal women. J Bone Miner Metab 32, 514–23.
- 34Garg MK, Tandon N, Marwaha RK, Menon AS, Mahalle N (2014) The relationship between serum 25-hydroxy vitamin D, parathormone and bone mineral density in Indian population. Clin Endocrinol (Oxford) 80 (1), 41–6.
- 35 National Osteoporosis Foundation (2014) Clinician's Guide to Prevention and Treatment of Osteoporosis. National Osteoporosis Foundation, Washington, DC.
- 36Garnero P, Munoz F, Sornay-Rendu E, Delmas PD (2007) Associations of vitamin D status with bone mineral density, bone turnover, bone loss and fracture risk in healthy postmenopausal women. The OFELY study. Bone 40 (3), 716–22.
- 37Hwang S, Choi HS, Kim KM, Rhee Y, Lim SK (2015) Associations between serum 25-hydroxyvitamin D and bone mineral density and proximal femur geometry in Koreans: the Korean National Health and Nutrition Examination Survey (KNHANES) 2008–2009. Osteoporos Int 26, 163–71.
- 38George JA, Micklesfield LK, Norris SA, Crowther NJ (2014) The association between body composition, 25(OH)D, and PTH and bone mineral density in black African and Asian Indian population groups. J Clin Endocrinol Metab 99, 2146–54.
- 39Kostoglou-Athanassiou I, Athanassiou P, Lyraki A, Raftakis I, Antoniadis C (2012) Vitamin D and rheumatoid arthritis. Ther Adv Endocrinol Metab 3, 181–7.
- 40Baykal T, Senel K, Alp F, Erdal A, Ugur M (2012) Is there an association between serum 25-hydroxyvitamin D concentrations and disease activity in rheumatoid arthritis? Bratisl Lek Listy 113, 610–1.
- 41Cutolo M, Otsa K, Laas K et al. (2006) Circannual vitamin D serum levels and disease activity in rheumatoid arthritis: northern versus southern Europe. Clin Exp Rheumatol 24, 702–4.
- 42Rossini M, Maddali Bongi S, La Montagna G et al. (2010) Vitamin D deficiency in rheumatoid arthritis: prevalence, determinants and associations with disease activity and disability. Arthritis Res Ther 12, R216.
- 43Roux C (2011) Osteoporosis in inflammatory joint diseases. Osteoporos Int 22, 421–33.
- 44Peng J, Gong Y, Zhang Y, Xiao Z, Zeng Q, Chen S (2016) Bone mineral density in patients with rheumatoid arthritis and 4-year follow-up results. J Clin Rheumatol 22 (2), 71–4.
- 45Lee SG, Park YE, Park SH et al. (2012) Increased frequency of osteoporosis and BMD below the expected range for age among South Korean women with rheumatoid arthritis. Int J Rheum Dis 15 (3), 289–96.
- 46Brance ML, Brun LR, Lioi S, Sánchez A, Abdala M, Oliveri B (2015) Vitamin D levels and bone mass in rheumatoid arthritis. Rheumatol Int 35, 499–505.
- 47Hilmi I, Sunderesvaran K, Ananda V, Sarji SA, Arumugam K, Goh KL (2013) Increased fracture risk and osteoporosis not associated with vitamin D levels in Malaysian patients with inflammatory bowel disease. J Clin Endocrinol Metab 98, 2415–21.
- 48Yeap SS, Othman AZ, Zain AA, Chan SP (2012) Vitamin D levels: its relationship to bone mineral density response and disease activity in premenopausal Malaysian systemic lupus erythematosus patients on corticosteroids. Int J Rheum Dis 15 (1), 17–24.
- 49Ahn J, Yu K, Stolzenberg-Solomon R et al. (2010) Genome-wide association study of circulating vitamin D levels. Hum Mol Genet 19, 2739–45.
- 50Dastani Z, Berger C, Langsetmo L et al. (2014) In healthy adults, biological activity of vitamin D, as assessed by serum PTH, is largely independent of DBP concentrations. J Bone Miner Res 29, 494–9.
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