Can vitamin D supplementation prevent bone loss in persons with MS? A placebo-controlled trial

Linn H Steffensen, Lone Jørgensen, Bjørn Straume, Svein Ivar Mellgren, Margitta T Kampman, Linn H Steffensen, Lone Jørgensen, Bjørn Straume, Svein Ivar Mellgren, Margitta T Kampman

Abstract

Multiple sclerosis (MS) is a possible cause of secondary osteoporosis. In this phase II trial we assessed whether a weekly dose of 20,000 IU vitamin D(3) prevents bone loss in ambulatory persons with MS age 18-50 years. ClinicalTrials.gov ID NCT00785473. All patients managed at the University Hospital of North Norway who fulfilled the main inclusion criteria were invited to participate in this double-blinded trial. Participants were randomised to receive 20,000 IU vitamin D(3) or placebo once a week and 500 mg calcium daily for 96 weeks. The primary outcome was the effect of the intervention on percentage change in bone mineral density (BMD) at the hip, the spine, and the ultradistal radius over the study period. Of 71 participants randomised, 68 completed. Mean serum 25-hydroxyvitamin D [25(OH)D] levels in the intervention group increased from 55 nmol/L at baseline to 123 nmol/L at week 96. After 96 weeks, percentage change in BMD did not differ between groups at any site. BMD decreased at the hip, by 1.4% in the placebo group (95% CI -2.3 to -0.4, SD 2.7, p = 0.006) and by 0.7% in the treatment group (-1.6 to 0.2, 2.7, p = 0.118), difference 0.7% (-1.9 to 0.7, p = 0.332). Findings were not altered by adjustment for sex or serum 25(OH)D. Supplementation with 20,000 IU vitamin D(3) a week did not prevent bone loss in this small population. Larger studies are warranted to assess the effect of vitamin D on bone health in persons with MS.

Figures

Fig. 1
Fig. 1
Flow of the participants through the study

References

    1. Ascherio A, Munger KL, Simon KC. Vitamin D and multiple sclerosis. Lancet Neurol. 2010;9:599–612. doi: 10.1016/S1474-4422(10)70086-7.
    1. Berger C, Goltzman D, Langsetmo L, Joseph L, Jackson S, Kreiger N, Tenenhouse A, Davison KS, Josse RG, Prior JC, Hanley DA. Peak bone mass from longitudinal data: implications for the prevalence, pathophysiology, and diagnosis of osteoporosis. J Bone Miner Res. 2010;25:1948–1957. doi: 10.1002/jbmr.95.
    1. Berger C, Langsetmo L, Joseph L, Hanley DA, Davison KS, Josse R, Kreiger N, Tenenhouse A, Goltzman D. Change in bone mineral density as a function of age in women and men and association with the use of antiresorptive agents. CMAJ. 2008;178:1660–1668. doi: 10.1503/cmaj.071416.
    1. Bischoff-Ferrari HA. How to select the doses of vitamin D in the management of osteoporosis. Osteoporos Int. 2007;18:401–407. doi: 10.1007/s00198-006-0293-9.
    1. Bischoff-Ferrari HA, Dietrich T, Orav EJ, Dawson-Hughes B. Positive association between 25-hydroxy vitamin D levels and bone mineral density: a population-based study of younger and older adults. Am J Med. 2004;116:634–639. doi: 10.1016/j.amjmed.2003.12.029.
    1. Bischoff-Ferrari HA, Willett WC, Wong JB, Stuck AE, Staehelin HB, Orav EJ, Thoma A, Kiel DP, Henschkowski J. Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch Intern Med. 2009;169:551–561. doi: 10.1001/archinternmed.2008.600.
    1. Burton JM, Kimball S, Vieth R, Bar-Or A, Dosch HM, Cheung R, Gagne D, D’Souza C, Ursell M, O’Connor P. A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis. Neurology. 2010;74:1852–1859. doi: 10.1212/WNL.0b013e3181e1cec2.
    1. Chapurlat RD, Garnero P, Sornay-Rendu E, Arlot ME, Claustrat B, Delmas PD. Longitudinal study of bone loss in pre- and perimenopausal women: evidence for bone loss in perimenopausal women. Osteoporos Int. 2000;11:493–498. doi: 10.1007/s001980070091.
    1. Chel V, Wijnhoven HA, Smit JH, Ooms M, Lips P. Efficacy of different doses and time intervals of oral vitamin D supplementation with or without calcium in elderly nursing home residents. Osteoporos Int. 2008;19:663–671. doi: 10.1007/s00198-007-0465-2.
    1. Cosman F, Nieves J, Komar L, Ferrer G, Herbert J, Formica C, Shen V, Lindsay R. Fracture history and bone loss in patients with MS. Neurology. 1998;51:1161–1165.
    1. Cranney A, Weiler HA, O’Donnell S, Puil L. Summary of evidence-based review on vitamin D efficacy and safety in relation to bone health. Am J Clin Nutr. 2008;88:513S–519S.
    1. Dawson-Hughes B, Heaney RP, Holick MF, Lips P, Meunier PJ, Vieth R. Estimates of optimal vitamin D status. Osteoporos Int. 2005;16:713–716. doi: 10.1007/s00198-005-1867-7.
    1. Emaus N, Berntsen GK, Joakimsen RM, Fonnebo V. Longitudinal changes in forearm bone mineral density in women and men aged 25–44 years: the Tromso study: a population-based study. Am J Epidemiol. 2005;162:633–643. doi: 10.1093/aje/kwi258.
    1. Emaus N, Omsland TK, Ahmed LA, Grimnes G, Sneve M, Berntsen GK. Bone mineral density at the hip in Norwegian women and men-prevalence of osteoporosis depends on chosen references: the Tromso Study. Eur J Epidemiol. 2009;24:321–328. doi: 10.1007/s10654-009-9333-z.
    1. Grimnes G, Almaas B, Eggen AE, Emaus N, Figenschau Y, Hopstock LA, Hutchinson MS, Methlie P, Mihailova A, Sneve M, Torjesen P, Wilsgaard T, Jorde R. Effect of smoking on the serum levels of 25-hydroxyvitamin D depends on the assay employed. Eur J Endocrinol. 2010;163:339–348. doi: 10.1530/EJE-10-0150.
    1. Harlow SD, Crawford S, Dennerstein L, Burger HG, Mitchell ES, Sowers MF. Recommendations from a multi-study evaluation of proposed criteria for staging reproductive aging. Climacteric. 2007;10:112–119. doi: 10.1080/13697130701258838.
    1. Hearn AP, Silber E. Osteoporosis in multiple sclerosis. Mult Scler. 2010;16:1031–1043. doi: 10.1177/1352458510368985.
    1. Henry MJ, Pasco JA, Korn S, Gibson JE, Kotowicz MA, Nicholson GC. Bone mineral density reference ranges for Australian men: Geelong Osteoporosis Study. Osteoporos Int. 2010;21:909–917. doi: 10.1007/s00198-009-1042-7.
    1. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266–281. doi: 10.1056/NEJMra070553.
    1. Kampman MT, Steffensen LH. The role of vitamin D in multiple sclerosis. J Photochem Photobiol B. 2010;101:137–141. doi: 10.1016/j.jphotobiol.2010.04.003.
    1. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS) Neurology. 1983;33:1444–1452.
    1. Lanham-New SA. Importance of calcium, vitamin D and vitamin K for osteoporosis prevention and treatment. Proc Nutr Soc. 2008;67:163–176. doi: 10.1017/S0029665108007003.
    1. McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, McFarland HF, Paty DW, Polman CH, Reingold SC, Sandberg-Wollheim M, Sibley W, Thompson A, van den NS, Weinshenker BY, Wolinsky JS. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50:121–127. doi: 10.1002/ana.1032.
    1. National osteoporosis foundation. Clinician’s guide to prevention and treatment of osteoporosis. Available at: . Revised January 2010. Accessed February 01, 2011
    1. Neer RM. Bone loss across the menopausal transition. Ann N Y Acad Sci. 2010;1192:66–71. doi: 10.1111/j.1749-6632.2009.05233.x.
    1. Nieves J, Cosman F, Herbert J, Shen V, Lindsay R. High prevalence of vitamin D deficiency and reduced bone mass in multiple sclerosis. Neurology. 1994;44:1687–1692.
    1. Ozgocmen S, Bulut S, Ilhan N, Gulkesen A, Ardicoglu O, Ozkan Y. Vitamin D deficiency and reduced bone mineral density in multiple sclerosis: effect of ambulatory status and functional capacity. J Bone Miner Metab. 2005;23:309–313. doi: 10.1007/s00774-005-0604-9.
    1. Pierrot-Deseilligny C, Souberbielle JC. Is hypovitaminosis D one of the environmental risk factors for multiple sclerosis? Brain. 2010;133:1869–1888. doi: 10.1093/brain/awq147.
    1. Poole KE, Compston JE. Osteoporosis and its management. BMJ. 2006;333:1251–1256. doi: 10.1136/bmj.39050.597350.47.
    1. Pugliatti M, Riise T, Nortvedt MW, Carpentras G, Sotgiu MA, Sotgiu S, Rosati G. Self-perceived physical functioning and health status among fully ambulatory multiple sclerosis patients. J Neurol. 2008;255:157–162. doi: 10.1007/s00415-008-0543-1.
    1. Ravnborg M, Sorensen PS, Andersson M, Celius EG, Jongen PJ, Elovaara I, Bartholome E, Constantinescu CS, Beer K, Garde E, Sperling B. Methylprednisolone in combination with interferon beta-1a for relapsing-remitting multiple sclerosis (MECOMBIN study): a multicentre, double-blind, randomised, placebo-controlled, parallel-group trial. Lancet Neurol. 2010;9:672–680. doi: 10.1016/S1474-4422(10)70132-0.
    1. Recker R, Lappe J, Davies K, Heaney R. Characterization of perimenopausal bone loss: a prospective study. J Bone Miner Res. 2000;15:1965–1973. doi: 10.1359/jbmr.2000.15.10.1965.
    1. Sneve M, Figenschau Y, Jorde R. Supplementation with cholecalciferol does not result in weight reduction in overweight and obese subjects. Eur J Endocrinol. 2008;159:675–684. doi: 10.1530/EJE-08-0339.
    1. Sorensen PS, Mellgren SI, Svenningsson A, Elovaara I, Frederiksen JL, Beiske AG, Myhr KM, Sogaard LV, Olsen IC, Sandberg-Wollheim M. NORdic trial of oral Methylprednisolone as add-on therapy to interferon beta-1a for treatment of relapsing-remitting Multiple Sclerosis (NORMIMS study): a randomised, placebo-controlled trial. Lancet Neurol. 2009;8:519–529. doi: 10.1016/S1474-4422(09)70085-7.
    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. Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet. 2007;370:657–666. doi: 10.1016/S0140-6736(07)61342-7.
    1. Terzi T, Terzi M, Tander B, Canturk F, Onar M. Changes in bone mineral density and bone metabolism markers in premenopausal women with multiple sclerosis and the relationship to clinical variables. J Clin Neurosci. 2010;17:1260–1264. doi: 10.1016/j.jocn.2010.01.044.
    1. Tuzun S, Altintas A, Karacan I, Tangurek S, Saip S, Siva A. Bone status in multiple sclerosis: beyond corticosteroids. Mult Scler. 2003;9:600–604. doi: 10.1191/1352458503ms966oa.
    1. Weinstock-Guttman B, Gallagher E, Baier M, Green L, Feichter J, Patrick K, Miller C, Wrest K, Ramanathan M. Risk of bone loss in men with multiple sclerosis. Mult Scler. 2004;10:170–175. doi: 10.1191/1352458504ms993oa.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다