High dose vitamin D supplementation does not affect biochemical bone markers in multiple sclerosis - a randomized controlled trial

Trygve Holmøy, Jonas Christoffer Lindstrøm, Erik Fink Eriksen, Linn Hofsøy Steffensen, Margitta T Kampman, Trygve Holmøy, Jonas Christoffer Lindstrøm, Erik Fink Eriksen, Linn Hofsøy Steffensen, Margitta T Kampman

Abstract

Background: People with multiple sclerosis have high risk of osteoporosis and fractures. A poor vitamin D status is a risk factor for MS, and vitamin D supplementation has been recommended both to prevent MS progression and to maintain bone health.

Methods: We assessed the effect of 20,000 IU vitamin D3 weekly compared to placebo on biochemical markers of bone metabolism in 68 persons with relapsing remitting multiple sclerosis.

Results: Serum levels of 25-hydroxyvitamin D more than doubled in the vitamin D group, and parathyroid hormone decreased in the vitamin D group compared to the placebo group at week 48 and week 96. There was however no effect on bone formation as measured by procollagen type I N propeptide (PINP), or on bone resorption as measured by C-terminal cross-linking telopeptide of type I collagen (CTX1). Neither PINP nor CTX1 predicted bone loss from baseline to week 96.

Conclusions: These findings corroborate the previously reported lack of effect of weekly high dose vitamin D supplementation on bone mass density in the same patients, and suggest that such vitamin D supplementation does not prevent bone loss in persons with MS who are not vitamin D deficient.

Trial registration: The trial was registered at ClinicalTrials.gov on April 4 2008, registration number NCT00785473 .

Keywords: Multiple sclerosis; osteoporosis; randomized controlled trial; vitamin D.

References

    1. Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006;296:2832–2838. doi: 10.1001/jama.296.23.2832.
    1. Løken-Amsrud KI, Holmøy T, Bakke SJ, Beiske AG, Bjerve KS, Bjørnarå BT, et al. Vitamin D and disease activity in multiple sclerosis before and during interferon beta treatment. Neurology. 2012;79:267–273. doi: 10.1212/WNL.0b013e31825fdf01.
    1. Simpson S, Jr, Taylor B, Blizzard L, Ponsonby AL, Pittas F, Tremlett H, et al. Higher 25-hydroxyvitamin D is associated with lower relapse risk in multiple sclerosis. Ann Neurol. 2010;68:193–203.
    1. Huang Z, Qi Y, Du S, Chen G, Yan W. Bone mineral density levels in adults with multiple sclerosis: A meta-analysis. Int J Neurosci. 2015;125:904–912. doi: 10.3109/00207454.2014.988332.
    1. Gupta S, Ahsan I, Mahfooz N, Abdelhamid N, Ramanathan M, Weinstock-Guttman B. Osteoporosis and multiple sclerosis: risk factors, pathophysiology, and therapeutic interventions. CNS Drugs. 2014;28:731–742. doi: 10.1007/s40263-014-0173-3.
    1. Steffensen LH, Mellgren SI, Kampman MT. Predictors and prevalence of low bone mineral density in fully ambulatory persons with multiple sclerosis. J Neurol. 2010;257:410–418. doi: 10.1007/s00415-009-5337-6.
    1. Moen SM, Celius EG, Sandvik L, Nordsletten L, Eriksen EF, Holmoy T. Low bone mass in newly diagnosed multiple sclerosis and clinically isolated syndrome. Neurology. 2011;77:151–157. doi: 10.1212/WNL.0b013e3182242d34.
    1. Silk LN, Greene DA, Baker MK, Jander CB. The effect of calcium and vitamin D supplementation on bone health of male Jockeys. J Sci Med Sport. 2016
    1. Bazelier MT, van Staa TP, Uitdehaag BM, Cooper C, Leufkens HG, Vestergaard P, et al. The risk of fracture in patients with multiple sclerosis: the UK general practice research database. J Bone Miner Res. 2011;26:2271–2279. doi: 10.1002/jbmr.418.
    1. Bazelier MT, de Vries F, Bentzen J, Vestergaard P, Leufkens HG, van Staa TP, et al. Incidence of fractures in patients with multiple sclerosis: the Danish National Health Registers. Mult Scler. 2012;18:622–627. doi: 10.1177/1352458511426739.
    1. Bazelier MT, van Staa TP, Uitdehaag BM, Cooper C, Leufkens HG, Vestergaard P, et al. Risk of fractures in patients with multiple sclerosis: a population-based cohort study. Neurology. 2012;78:1967–1973. doi: 10.1212/WNL.0b013e318259e0ff.
    1. Ramagopalan SV, Seminog O, Goldacre R, Goldacre MJ. Risk of fractures in patients with multiple sclerosis: record-linkage study. BMC Neurol. 2012;12:135. doi: 10.1186/1471-2377-12-135.
    1. James E, Dobson R, Kuhle J, Baker D, Giovannoni G, Ramagopalan SV. The effect of vitamin D-related interventions on multiple sclerosis relapses: a meta-analysis. Mult Scler. 2013;19:1571–1579. doi: 10.1177/1352458513489756.
    1. Hearn AP, Silber E. Osteoporosis in multiple sclerosis. Mult Scler. 2010;16:1031–1043. doi: 10.1177/1352458510368985.
    1. Dobson R, Ramagopalan S, Giovannoni G. Bone health and multiple sclerosis. Mult Scler. 2012;18:1522–1528. doi: 10.1177/1352458512453362.
    1. Kampman MT, Eriksen EF, Holmoy T. Multiple sclerosis, a cause of secondary osteoporosis? What is the evidence and what are the clinical implications? Acta Neurol Scand Suppl. 2011:44–9.
    1. RossCA TCL, Yaktine AL, Del Valle HB. Institute of Medicine. Daily reference values for calcium and vitamin D. Washington DC: The National Academic Press; 2011.
    1. Priemel M, von DC, Klatte TO. Kessler S, Schlie J, Meier S, et al. Bone mineralization defects and vitamin D deficiency: histomorphometric analysis of iliac crest bone biopsies and circulating 25-hydroxyvitamin D in 675 patients. J Bone Miner Res. 2010;25:305–312. doi: 10.1359/jbmr.090728.
    1. Vieth R. Why the minimum desirable serum 25-hydroxyvitamin D level should be 75 nmol/L (30 ng/ml) Best Pract Res Clin Endocrinol Metab. 2011;25:681–691. doi: 10.1016/j.beem.2011.06.009.
    1. Pludowski P, Holick MF, Grant WB, Konstantynowicz J, Mascarenhas MR, Haq A, et al. Vitamin D supplementation guidelines. J Steroid Biochem Mol Biol. 2017
    1. Steffensen LH, Jorgensen L, Straume B, Mellgren SI, Kampman MT. Can vitamin D(3) supplementation prevent bone loss in persons with MS? A placebo-controlled trial. J Neurol. 2011;258:1624–1631. doi: 10.1007/s00415-011-5980-6.
    1. Jorde R, Grimnes G, Hutchinson MS, Kjaergaard M, Kamycheva E, Svartberg J. Supplementation with vitamin D does not increase serum testosterone levels in healthy males. Horm Metab Res. 2013;45:675–681. doi: 10.1055/s-0033-1345139.
    1. Bhargava P, Steele SU, Waubant E, Revirajan NR, Marcus J, Dembele M, et al. Multiple sclerosis patients have a diminished serologic response to vitamin D supplementation compared to healthy controls. Mult Scler. 2016;22:753–760. doi: 10.1177/1352458515600248.
    1. Johansson H, Oden A, Kanis JA, McCloskey EV, Morris HA, Cooper C, et al. A meta-analysis of reference markers of bone turnover for prediction of fracture. Calcif Tissue Int. 2014;94:560–567. doi: 10.1007/s00223-014-9842-y.
    1. Vasikaran S, Eastell R, Bruyere O, Foldes AJ, Garnero P, Griesmacher A, et al. Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporos Int. 2011;22:391–420. doi: 10.1007/s00198-010-1501-1.
    1. Kampman MT, Steffensen LH, Mellgren SI, Jorgensen L. Effect of vitamin D3 supplementation on relapses, disease progression and measures of function in persons with multiple sclerosis: exploratory outcomes from a double-blind randomised controlled trial. Mult Scler. 2012;18:1144–1151. doi: 10.1177/1352458511434607.
    1. Hjartaker A, Andersen LF, Lund E. Comparison of diet measures from a food-frequency questionnaire with measures from repeated 24-hour dietary recalls. The Norwegian Women and Cancer Study. Public Health Nutr. 2007;10:1094–1103. doi: 10.1017/S1368980007702872.
    1. Rosjo E, Lossius A, Abdelmagid N, Lindstrom JC, Kampman MT, Jorgensen L, et al. Effect of high-dose vitamin D3 supplementation on antibody responses against Epstein-Barr virus in relapsing-remitting multiple sclerosis. Mult Scler Mult Scler. 2017;23:395–402. doi: 10.1177/1352458516654310.
    1. Aloia J, Bojadzievski T, Yusupov E, Shahzad G, Pollack S, Mikhail M, et al. The relative influence of calcium intake and vitamin D status on serum parathyroid hormone and bone turnover biomarkers in a double-blind, placebo-controlled parallel group, longitudinal factorial design. J Clin Endocrinol Metab. 2010;95:3216–3224. doi: 10.1210/jc.2009-1294.
    1. McKenna MJ, Murray B, Lonergan R, Redmond JM. Immunomodulators for multiple sclerosis may ameliorate spinal bone loss. Ir J Med Sci. 2013;182:29–32. doi: 10.1007/s11845-012-0818-5.
    1. Abraham AK, Ramanathan M, Weinstock-Guttman B, Mager DE. Mechanisms of interferon-beta effects on bone homeostasis. Biochem Pharmacol. 2009;77:175762. doi: 10.1016/j.bcp.2009.01.007.
    1. Kampman MT, Steffensen LH. Comment on Shuhaibar et al: Favourable effect of immunomodulator therapy on bone mineral density in multiple sclerosis. Ir J Med Sci. 2009;178:235–236. doi: 10.1007/s11845-009-0275-y.
    1. Saltyte Benth J, Myhr KM, Loken-Amsrud KI, Beiske AG, Bjerve KS, Hovdal H, et al. Modelling and prediction of 25-hydroxyvitamin D levels in Norwegian relapsing-remitting multiple sclerosis patients. Neuroepidemiology. 2012;39:84–93. doi: 10.1159/000339360.
    1. Huang Z, Qi Y, Du S, Chen G, Yan W. BMI levels with MS Bone mineral density levels in adults with multiple sclerosis: a meta-analysis. Int J Neurosci. 2015;125:904–912. doi: 10.3109/00207454.2014.988332.
    1. Bischoff-Ferrari HA, Willett WC, Orav EJ, Lips P, Meunier PJ, Lyons RA, et al. A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med. 2012;367:40–49. doi: 10.1056/NEJMoa1109617.
    1. Souberbielle JC, Body JJ, Lappe JM, Plebani M, Shoenfeld Y, Wang TJ, et al. Vitamin D and musculoskeletal health, cardiovascular disease, autoimmunity and cancer: Recommendations for clinical practice. Autoimmun Rev. 2010;9:709–715. doi: 10.1016/j.autrev.2010.06.009.
    1. Hollis BW, Wagner CL. Clinical review: The role of the parent compound vitamin D with respect to metabolism and function: Why clinical dose intervals can affect clinical outcomes. J Clin Endocrinol Metab. 2013;98:4619–4628. doi: 10.1210/jc.2013-2653.

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅