Reduced Bone Mineral Density in Women with Multiple Sclerosis

Czech version

Authors: M. Týblová ¹; doc. MUDr. Vít Zikán, Ph.D. ²; M. Luchavová ²; E. Havrdová ¹; I. Raška Jr ²; D. Michalská ²; A. A. Kuběna ³
Authors‘ workplace: Neurologická klinika 1. LF UK a VFN v Praze ¹; III. interní klinika 1. LF UK a VFN v Praze ²; Katedra sociální a klinické farmacie, Farmaceutická fakulta UK v Hradci Králové ³
Published in: Cesk Slov Neurol N 2013; 76/109(1): 35-44
Category: Original Paper

Overview

Aim:
The aim of this study was to compare the bone mineral density (BMD) and muscle mass in women with multiple sclerosis (MS) in an outpatient setting and control subjects, and to examine the effect of motor disability, muscle mass and/or glucocorticoids (GC) use on BMD.

Methods:
Body composition and BMD were measured by dual-energy X-ray absorptiometry in 250 MS women (153 premenopausal and 97 postmenopausal women) with EDSS (Expanded Disability Status Scale) ≤ 6.5 treated in an outpatient setting and in 193 controls.

Results:
Compared to controls, patients had significantly lower values for total body bone mineral content and BMD at all measured sites except for the distal radius. Patients with MS had significantly lower amount of total muscle mass as well as total leg muscle mass when compared to the control group. The EDSS score was negatively associated with BMD at the proximal femur in both premenopausal and postmenopausal women, while the deficit of total body muscle mass was significantly associated with a loss of BMD at the lumbar spine and whole body BMD in premenopausal women only. GC treatment was negatively associated with BMD at the lumbar spine in premenopausal women.

Conclusion:
The total body muscle mass was an important predictive factor for the total body BMD and the lumbar spine BMD in premenopausal women with MS. Further prospective studies are required to verify the protective effect of muscle mass on BMD in patients with MS and to assess the role of systemic factors modulating the bone-muscle relationship (e.g. vitamin D or estrogen deficiency).

Key words:
body composition – bone mineral density – multiple sclerosis – glucocorticoids

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.

Sources

1. Compston A, Coles A. Multiple sclerosis. Lancet 2008; 372(9648): 1502–1517.

2. Hughes JM, Petit MA. Biological underpinnings of Frost‘s mechanostat thresholds: the important role of osteocytes. J Musculoskelet Neuronal Interact 2010; 10(2): 128–135.

3. Sibley WA, Bamford CR, Clark K, Smith MS, Laguna JF. A prospective study of physical trauma and multiple sclerosis. J Neurol Neurosurg Psychiatry 1991; 54(7): 584–589.

4. Troiano RA, Jotkowitz A, Cook SD, Bansil S, Zito G. Rate and types of fractures in corticosteroid-treated multiple sclerosis patients. Neurology 1992; 42(7): 1389–1391.

5. 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(9): 1687–1692.

6. Cosman F, Nieves J, Herbert J, Shen V, Lindsay R. High-dose glucocorticoids in multiple sclerosis patients exert direct effects on the kidney and skeleton. J Bone Miner Res 1994; 9(7): 1097–1105.

7. Cosman F, Nieves J, Komar L, Ferrer G, Herbert J, Formica C et al. Fracture history and bone loss in patients with MS. Neurology 1998; 51(4): 1161–1165.

8. Weinstock-Guttman B, Gallagher E, Baier M, Green L, Feichter J, Patrick K et al. Risk of bone loss in men with multiple sclerosis. Mult Scler 2004; 10(2): 170–175.

9. Logan WC jr, Sloane R, Lyles KW, Goldstein B, Hoenig HM. Incidence of fractures in a cohort of veterans with chronic multiple sclerosis or traumatic spinal cord injury. Arch Phys Med Rehabil 2008; 89(2): 237–243.

10. Marrie RA, Cutter G, Tyry T, Vollmer T. A cross-sectional study of bone health in multiple sclerosis. Neurology 2009; 73(17):1394–1398.

11. Havrdová E, Týblová M, Štěpán J, Horáková D, Tichá V, Nováková I et al. Výskyt osteoporózy u pacientů s roztroušenou sklerózou v závislosti na míře kortikoterapie a stupni hybného postižení. Cesk Slov Neurol N 2004; 67/100(4): 234–240.

12. Nilsagard Y, Lundholm C, Denison E, Gunnarsson LG. Predicting accidental falls in people with multiple sclerosis – a longitudinal study. Clin Rehabil 2009; 23(3): 259–269.

13. Peterson EW, Cho CC, von Koch L, Finlayson ML. Injurious falls among middle aged and older adults with multiple sclerosis. Arch Phys Med Rehabil 2008; 89(6): 1031–1037.

14. Finlayson ML, Peterson EW, Cho CC. Risk factors for falling among people aged 45 to 90 years with multiple sclerosis. Arch Phys Med Rehabil 2006; 87(9): 1274–1279.

15. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983; 33(11): 1444–1452.

16. Schwid SR, Goodman AD, Edward PJ, McDermott MP, Mattson DH. Sporadic corticosteroid pulses and osteoporosis in multiple sclerosis. Arch Neurol 1996; 53(8): 753–757.

17. 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(4): 309–313.

18. Hotermans C, Dive D, Rinkin, Leroy M, Malaise M, Moonen G et al. Hip bone mineral density is correlated with EDSS in patients with multiple sclerosis. J Neurol 2006; 253: ii126 Abstract.

19. Terzi T, Terzi M, Tander B, Cantürk 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(10): 1260–1264.

20. van der Mei IA, Ponsonby AL, Dwyer T, Blizzard L, Taylor BV, Kilpatrick T et al. Vitamin D levels in people with multiple sclerosis and community controls in Tasmania, Australia. J Neurol 2007; 254(5): 581–590.

21. Formica CA, Cosman F, Nieves J, Herbert J, Lindsay R. Reduced bone mass and fat-free mass in women with multiple sclerosis: effects of ambulatory status and glucocorticoid use. Calcif Tissue Int 1997; 61(2): 129–133.

22. Wei T, Lightman SL. The neuroendocrine axis in patients with multiple sclerosis. Brain 1997; 120(Pt 6): 1067–1076.

23. Moen SM, Celius EG, Sandvik L, Nordsletten L, Eriksen EF, Holmøy T. Low bone mass in newly diagnosed multiple sclerosis and clinically isolated syndrome. Neurology 2011; 77(2): 151–157.

24. Lambert CP, Lee Archer R, Evans WJ. Body composition in ambulatory women with multiple sclerosis. Arch Phys Med Rehabil 2002; 83(11): 1559–1561.

25. Mojtahedi MC, Snook EM, Motl RW, Evans EM. Bone health in ambulatory individuals with multiple sclerosis: impact of physical activity, glucocorticoid use, and body composition. J Rehabil Res Dev 2008; 45(6): 851–861.

26. Sioka C, Fotopoulos A, Georgiou A, Papakonstantinou S, Pelidou SH, Kyritsis AP et al. Body composition in ambulatory patients with multiple sclerosis. J Clin Densitom 2011; 14(4): 465–470.

27. Kanis JA, Glüer CC. An update on the diagnosis and assessment of osteoporosis with densitometry. Committee of Scientific Advisors, International Osteoporosis Foundation. Osteoporos Int 2000; 11(3): 192–202.

28. Cohen J. Statistical power analysis for the behavioral sciences. 2nd ed. Hillsdale, NJ: Lawrence Erlbaum Associates 1988.

29. Jiang SD, Dai LY, Jiang LS. Osteoporosis after spinal cord injury. Osteoporos Int 2006; 17(2): 180–192.

30. Slade JM, Bickel CS, Modlesky CM, Majumdar S, Dudley GA. Trabecular bone is more deteriorated in spinal cord injured versus estrogen-free postmenopausal women. Osteoporos Int 2005; 16(3): 263–272.

31. Jørgensen L, Jacobsen BK, Wilsgaard T, Magnus JH. Walking after stroke: does it matter? Changes in bone mineral density within the first 12 months after stroke. A longitudinal study. Osteoporos Int 2000; 11(5): 381–387.

32. Lee KC, Lanyon LE. Mechanical loading influences bone mass through estrogen receptor alpha. Exerc Sport Sci Rev 2004; 32(2): 64–68.

33. Taaffe DR, Cauley JA, Danielson M, Nevitt MC, Lang TF, Bauer DC et al. Race and sex effects on the association between muscle strength, soft tissue, and bone mineral density in healthy elders: the health, aging, and body composition study. J Bone Miner Res 2001; 16(7): 1343–1352.

34. Marone JR, Falduto MT, Essig DA, Hickson RC. Effects of glucocorticoids and endurance training on cytochrome oxidase expression in skeletal muscle. J Appl Physiol 1994; 77(4): 1685–1690.

35. Lobo MJ, Remesar X, Alemany M. Effect of chronic intravenous injection of steroid hormones on body weight and composition of female rats. Biochem Mol Biol Int 1993; 29(2): 349–358.

36. Schwarz P. Physical activity and bone strength. Scand J Med Sci Sports 2004; 14: 1.

37. Lemmey AB, Glassford J, Flick-Smith HC, Holly JM, Pell JM. Differential regulation of tissue insulin-like growth factor-binding protein (IGFBP)-3, IGF-I and IGF type 1 receptor mRNA levels, and serum IGF-I and IGFBP concentrations by growth hormone and IGF-I. J Endocrinol 1997; 154(2): 319–328.

38. Karasik D, Kiel DP. Evidence for pleiotropic factors in genetics of the musculoskeletal system. Bone 2010; 46(5): 1226–1237.

39. Stepan JJ, Havrdova E, Tyblova M, Horakova D, Ticha V, Novakova I et al. Markers of bone remodeling predict rate of bone loss in multiple sclerosis patients treated with low dose glucocorticoids. Clin Chim Acta 2004; 348(1–2): 147–154.

40. Dovio A, Perazzolo L, Osella G, Ventura M, Termine A, Milano E et al. Immediate fall of bone formation and transient increase of bone resorption in the course of high-dose, short-term glucocorticoid therapy in young patients with multiple sclerosis. J Clin Endocrinol Metab 2004; 89(10): 4923–4928.

41. Then Bergh F, Kümpfel T, Schumann E, Held U, Schwan M, Blazevic M et al. Monthly intravenous methylprednisolone in relapsing-remitting multiple sclerosis – reduction of enhancing lesions, T2 lesion volume and plasma prolactin concentrations. BMC Neurol 2006; 6: 19.

42. Frediani B, Falsetti P, Bisogno S, Baldi F, Acciai C, Filippou G et al. Effects of high dose methylprednisolone pulse therapy on bone mass and biochemical markers of bone metabolism in patients with active rheumatoid arthritis: a 12-month randomized prospective controlled study. J Rheumatol 2004; 31(6): 1083–1087.

43. Van Staa TP, Laan RF, Barton IP, Cohen S, Reid DM, Cooper C. Bone density threshold and other predictors of vertebral fracture in patients receiving oral glucocorticoid therapy. Arthritis Rheum 2003; 48(11): 3224–3229.

44. Van Staa TP, Leufkens HG, Abenhaim L, Zhang B, Cooper C. Oral corticosteroids and fracture risk: relationship to daily and cumulative doses. Rheumatology (Oxford) 2000; 39(12): 1383–1389.

45. 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(3): 410–418.

46. Holick MF, Siris ES, Binkley N, Beard MK, Khan A, Katzer JT et al. Prevalence of Vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy. J Clin Endocrinol Metab 2005; 90(6): 3215–3224.

47. Ginde AA, Liu MC, Camargo CA Jr. Demographic differences and trends of vitamin D insufficiency in the US population, 1988–2004. Arch Intern Med 2009; 169(6): 626–632.

48. Yildiz M, Tettenborn B, Putzki N. Vitamin D levels in Swiss multiple sclerosis patients. Swiss Med Wkly 2011; 141: w13192.

49. Ryan AS, Ivey FM, Hurlbut DE, Martel GF, Lemmer JT, Sorkin JD et al. Regional bone mineral density after resistive training in young and older men and women. Scand J Med Sci Sports 2004; 14(1): 16–23.

50. Dalgas U, Stenager E, Jakobsen J, Petersen T, Hansen HJ, Knudsen C et al. Resistance training improves muscle strength and functional capacity in multiple sclerosis. Neurology 2009; 73(18): 1478–1484.

51. Snook EM, Motl RW. Effect of exercise training on walking mobility in multiple sclerosis: a meta-analysis. Neurorehabil Neural Repair 2009; 23(2): 108–116.