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Osteoporosis in Multiple Sclerosis

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Osteoporosis Rehabilitation

Abstract

Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system involving lymphocytes that damage myelin and axons and a process resulting in sensory, motor, and eventual cognitive deficits. There are four basic types of multiple sclerosis: relapsing remitting, secondary progressive, primary progressive, and progressive relapsing. Relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS) forms constitute 85 % of cases and are predominantly seen in females. In contrast, primary progressive multiple sclerosis (PPMS), characterized by a continual decline without remissions and exacerbations, represents only 10 % of the cases and is seen in equal numbers of males and females.

Cellular and autoimmune abnormalities favor bone resorption in those with MS, even before functional deficits are appreciated. Decreased physical functioning, pain, excessive fatigue, suboptimal nutrition (particularly low vitamin D), and adverse effects of medications are among the many factors contributing to bone loss in MS. Fear of falling remains a primary concern and can prevent a patient from mobilizing due to limited help or apprehensiveness. Falls also directly contribute to fractures in MS patients. Several medications have been studied to assist with osteoporosis in MS. This chapter will describe each of the above points and will propose functional and pharmacological strategies for osteoporosis management in the patient with MS. Finally, it will propose a strategy for timely assessment and early management of osteoporosis due to all forms of MS, processes which can be initiated during inpatient rehabilitation and continued in either long-term care or in a community setting.

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References

  1. Campagnolo DI, Vollmen TL. Multiple sclerosis. In: Kirshblum S, Campagnolo DI, editors. Spinal cord medicine. Philadelphia: Lippincott, Williams and Wilkins; 2011. p. 617–31.

    Google Scholar 

  2. National MS Society. http://www.nationalmssociety.org/What-is-MS/Types-of-MS. Accessed 22 Dec 2015.

  3. Thomson A. FTY720 in multiple sclerosis: the emerging evidence of its therapeutic value. Core Evid. 2006;1(3):157–67.

    PubMed  PubMed Central  Google Scholar 

  4. Gregson CL, Dennison EM, Compston JE, Adami S, Adachi JD, Anderson Jr FA, et al. Disease-specific perception of fracture risk and incident fracture rates: GLOW cohort study. Osteoporos Int. 2014;25(1):85–95.

    Article  CAS  PubMed  Google Scholar 

  5. Hughes S, Spelman T, Trojano M, Lugaresi A, Izquierdo G, Grand Maison F, et al. The Kurtzke EDSS rank stability increased 4 years after the onset of multiple sclerosis: results from the MSBase Registry. J Neurol Neurosurg Psychiatry. 2012;83(3):305–10.

    Article  PubMed  Google Scholar 

  6. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33(11):1444–52.

    Article  CAS  PubMed  Google Scholar 

  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):1161–5.

    Article  CAS  PubMed  Google Scholar 

  8. Weinstock-Guttman B, Gallagher E, Baier M, Green L, Feichter J, Patrick K, et al. Risk of bone loss in mean with multiple sclerosis. Mult Scler. 2004;10(2):170–5.

    Article  PubMed  Google Scholar 

  9. Formica CA, Cosman F, Neives 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):129–33.

    Article  CAS  PubMed  Google Scholar 

  10. Terzi T, Terzi M, Tander B, Cantürk F, Onar M. Changes in bone mineral density and bone metabolism markers in premenopausal women in multiple sclerosis and the relationship to clinical variables. J Clin Neurosci. 2010;17(10):1260–4.

    Article  PubMed  Google Scholar 

  11. 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(8):731–42.

    Article  CAS  PubMed  Google Scholar 

  12. Vogt MHJ, ten Kate J, Dent RJM, Polman CH, Hupperts R. Increased osteopontin plasma levels in multiple sclerosis patients correlate with bone-specific markers. Mult Scler. 2010;16(4):443–9.

    Article  CAS  PubMed  Google Scholar 

  13. Josyula S, Mehta BK, Karmon Y, Teter B, Batista S, Ostroff J, et al. The nervous system’s potential role in multiple sclerosis associated bone loss. J Neurol Sci. 2012;319(1–2):8–14.

    Article  PubMed  Google Scholar 

  14. Smolders J, Damoiseaux J, Menheere P, Hupperts R. Vitamin D as an immune modulator in multiple sclerosis, a review. J Neuroimmunol. 2008;194(1–2):7–17.

    Article  CAS  PubMed  Google Scholar 

  15. Bikle D, Adams JS, Christakos S. Vitamin D: production, metabolism, mechanism of action, and clinical requirements. In: Rosen CJ, editor. Primer on the metabolic: bone diseases and disorders of mineral metabolism. Ames: Wiley; 2013. p. 235–44.

    Chapter  Google Scholar 

  16. Garcion E, Wion-Barbot N, Montero-Menei CN, Berger F, Wion D. New clues about vitamin D functions in the nervous system. Trends Endocrinol Metab. 2002;13(3):100–5.

    Article  CAS  PubMed  Google Scholar 

  17. Chen S, Sims GP, Chen XX, Gu YY, Chen S, Lipsky PE. Modulatory effects of 1,12-dihydrozyvitamin D3 on human B cell differentiation. J Immunol. 2007;179(3):1634–47.

    Article  CAS  PubMed  Google Scholar 

  18. Nakashima T, Takayanagi H. Osteoimmunology: crosstalk between the immune and bone systems. J Clin Immunol. 2009;29(5):555–67.

    Article  PubMed  Google Scholar 

  19. Sioka C, Kyritsis AP, Fotopoulos A. Multiple sclerosis, osteoporosis, and vitamin D. J Neurol Sci. 2009;287(1–2):1–6.

    Article  CAS  PubMed  Google Scholar 

  20. Zikan V. Bone health in patients with multiple sclerosis. J Osteoporos. 2011;2011:1–9.

    Article  Google Scholar 

  21. Mitchell DR, Lyles KW. Glucocorticoid-induced osteoporosis: mechanisms for bone loss; evaluation of strategies for prevention. J Gerontol. 1990;45(5):M153–8.

    Article  CAS  PubMed  Google Scholar 

  22. Ziegler R, Kasperk C. Glucocorticoid-induced osteoporosis: prevention and treatment. Steroids. 1998;63(5):344–8.

    Article  CAS  PubMed  Google Scholar 

  23. De Vries F, Bracke M, Leufkens HGA, Lammers JWJ, Cooper C, van Staa TP. Fracture risk with intermittent high-dose oral glucocorticoid therapy. Arthritis Rheum. 2007;56(1):208–14.

    Article  PubMed  Google Scholar 

  24. Berris KK, Repp AL, Kleerekoper M. Glucocorticoid-induced osteoporosis. Curr Opin Endocrinol Diabetes Obes. 2007;14(6):446–50.

    Article  CAS  PubMed  Google Scholar 

  25. 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):309–13.

    Article  PubMed  Google Scholar 

  26. Ayatollahi A, Mohajeri-Tehrani MR, Nafissi S. Factors affecting bone mineral density in multiple sclerosis patients. Iran J Neurol. 2013;12(1):19–22.

    PubMed  PubMed Central  Google Scholar 

  27. Tüzün Ş, AltWntaş A, Karacan İ, Tangürek S, Saip S, Siva A. Bone status in multiple sclerosis: beyond corticosteroids. Mult Scler. 2003;9(6):600–4.

    Article  PubMed  Google Scholar 

  28. Schwid SR, Goodman AD, Puzas JE, McDermott MP, Mattson DH. Sporadic corticosteroid pulses and osteoporosis in multiple sclerosis. Arch Neurol. 1996;53(8):753–7.

    Article  CAS  PubMed  Google Scholar 

  29. Panday K, Gona A, Humphrey MB. Medication-induced osteoporosis: screening and treatment strategies. Ther Adv Musculoskel Disord. 2014;6(5):185–202.

    Article  CAS  Google Scholar 

  30. Brazelier MT, van Staa TP, Uitdehaag BM, Cooper C, Leufkens H, Vestergaard P, et al. A simple score for estimating the long-term risk of fracture in patients with multiple sclerosis. Neurology. 2012;79(9):922–8.

    Article  Google Scholar 

  31. Richards JS, Kogos SC, Ness TJ, Oleson CV. Smoking and neuropathic SCI pain: two case studies. J Spinal Cord Med. 2005;28(4):330–2.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Patten SB, Metz LM, Reimer MA. Biopsychosocial correlates of lifetime major depression in a multiple sclerosis population. Mult Scler. 2000;6(2):115–20.

    Article  CAS  PubMed  Google Scholar 

  33. Ehde DM, Bombardier CH. Depression in persons with multiple sclerosis. Phys Med Rehabil Clin N Am. 2005;16(2):437–48.

    Article  PubMed  Google Scholar 

  34. Ensrud KE, Blackwell T, Mangione CM, Bowman PJ, Bauer DC, Schwartz A, et al. Central nervous system active medications and risk for fractures in older women. Arch Intern Med. 2003;163(8):949–57.

    Article  PubMed  Google Scholar 

  35. Inose H, Zhou B, Yadav VK, Guo XE, Karsenty G, Ducy P. Efficacy of serotonin inhibition in mouse models of bone loss. J Bone Miner Res. 2011;26(9):2002–11.

    Article  CAS  PubMed  Google Scholar 

  36. Karsenty G, Yadav VK. Regulation of bone mass by serotonin molecular biology and therapeutic implications. Annu Rev Med. 2011;62:323–31.

    Article  CAS  PubMed  Google Scholar 

  37. Wu Q, Bencaz AF, Hentz JG, Crowell MD. Selective serotonin reuptake inhibitor treatment and risk of fractures: a meta-analysis of cohort and case–control studies. Osteoporos Int. 2012;23(1):365–75.

    Article  CAS  PubMed  Google Scholar 

  38. Birnbaum G. Management of multiple sclerosis symptoms. In: Birnbaum G, editor. Multiple sclerosis: clinician’s guide to diagnosis and treatment. New York: Oxford University Press; 2009. p. 97–110.

    Google Scholar 

  39. Adams AL, Black MH, Zhang JL, Shi JM, Jacobsen SJ. Proton-pump inhibitor use and hip fractures in men: a population-based case-control study. Ann Epidemiol. 2014;24(4):286–90.

    Article  PubMed  Google Scholar 

  40. Yu E, Blackwell T, Ensrud K, Hiller T, Lane N, Orwoll E, et al. Acid-suppressive medications and risk of bone loss and fracture in older adults. Calcif Tissue Int. 2008;83(4):251–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Vestergaard P, Rejnmark L, Mosekilde L. Proton pump inhibitors, histamine H2 receptor antagonists, and other antacid medications and the risk of fracture. Calcif Tissue Int. 2006;79(2):76–83.

    Article  CAS  PubMed  Google Scholar 

  42. Lau YT, Ahmed NN. Fracture risk and bone mineral density reduction associated with proton pump inhibitors. Pharmacotherapy. 2012;32(1):67–79.

    Article  CAS  PubMed  Google Scholar 

  43. Pouwels S, Lalmohamed A, Souverein P, Cooper C, Veldt BJ, Leufkens HG. Use of proton pump inhibitors and risk of hip/femur fracture: a population-based case-control study. Osteoporos Int. 2011;22(3):903–10.

    Article  CAS  PubMed  Google Scholar 

  44. Ahmad NA, Anderson J, Brenner DM, Chan AT, Chan FK, Chang L, et al. Selected summaries: the final word on proton pump inhibitors and osteoporosis. Gastroenterology. 2013;144:650–3.

    Article  Google Scholar 

  45. Consortium for Spinal Cord Medicine. Clinical Practice Guidelines: prevention of thromboembolism in spinal cord injury. 2nd ed. Washington, DC: Paralyzed Veterans Association; 2003.

    Google Scholar 

  46. Van Der Kallen J, Giles M, Cooper K, Gill K, Parker V, Tembo A, et al. A fracture prevention service reduces further fractures two years after incident minimal trauma fracture. Int J Rheum Dis. 2014;17(2):195–203.

    Article  PubMed  Google Scholar 

  47. Lee J, Youn K, Choi N, Lee J, Kang D, Song H, et al. A population-based case-control study: proton pump inhibition and risk of hip fracture by bisphosphonate. J Gastroenterol. 2013;48(9):1016–22.

    Article  CAS  PubMed  Google Scholar 

  48. Kwok C, Yeong J, Loke Y. Meta-analysis: risk of fractures with acid-suppressing medication. Bone. 2011;48(4):768–76.

    Article  CAS  PubMed  Google Scholar 

  49. Yang Y, Lewis J, Epstein S, Metz D. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006;296(24):2947–53.

    Article  CAS  PubMed  Google Scholar 

  50. Gerson LB. The final word on proton pump inhibitors and osteoporosis? Gastroenterology. 2013;144(3):650–3.

    Article  PubMed  Google Scholar 

  51. Targownik LE, Leslie WD, Davison KS, Goltzman D, Jamal SA, Kreiger N, et al. The relationship between proton pump inhibitor use and longitudinal change in bone mineral density: a population-based from the Canadian Multicentre Osteoporosis Study (CaMos). Am J Gastroenterol. 2012;107(9):1361–9.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Corley D, Kubo A, Zhao W, Quesenberry C. Proton pump inhibitors and histamine-2 receptor antagonists are associated with hip fracture among at-risk patients. Gastroenterology. 2010;139(1):93–101.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Rajgopal R, Bear M, Butcher M, Shaughnessy S. The effects of heparin and low molecular weight heparins on bone. Thromb Res. 2008;122(3):293–8.

    Article  CAS  PubMed  Google Scholar 

  54. Hawkins D, Evans J. Minimising the risk of heparin-induced osteoporosis during pregnancy. Expert Opin Drug Saf. 2005;4(3):583–90.

    Article  CAS  PubMed  Google Scholar 

  55. Bilen O, Teruya J. Complications of anticoagulation. Dis Mon. 2012;58(8):440–7.

    Article  PubMed  Google Scholar 

  56. Hirsh J, Bauer KA, Donati MB, Gould M, Samama MM, Weitz JI. Parenteral anticoagulants: American College of Chest Physicians evidence-based clinical practice guidelines. Chest J. 2008;133(6):141S–59.

    Article  CAS  Google Scholar 

  57. Monreal M, Lafoz E, Olive A, del Rio L, Vedia C. Comparison of subcutaneous unfractionated heparin with a low molecular weight heparin (Fragmin) in patients with venous thromboembolism and contraindications to coumarin. Thromb Haemost. 1994;71(1):7–11.

    CAS  PubMed  Google Scholar 

  58. Backos M, Rai R, Thomas E, Murphy M, Dore C, Regan L. Bone density changes in pregnant women treated with heparin: a prospective, longitudinal study. Hum Reprod. 1999;14(11):2876–80.

    Article  CAS  PubMed  Google Scholar 

  59. Handschin AE, Trentz OA, Hoerstrup SP, Kock HJ, Wanner GA, Trentz O. Effect of low molecular weight heparin (dalteparin) and fondaparinux (Arixtra ®) on human osteoblasts in vitro. Br J Surg. 2005;92(2):177–83.

    Article  CAS  PubMed  Google Scholar 

  60. Carabello PJ, Heit JA, Atkinson EJ, Silverstein MD, O’Fallon WM, Castro MR, et al. Long-term use of oral anticoagulants and the risk of fracture. Arch Intern Med. 1999;159(15):1750–6.

    Article  Google Scholar 

  61. Woo C, Chang LL, Ewing SK, Bauer DC. Single-point assessment of warfarin use and risk of osteoporosis in elderly men. JAGS. 2008;56(7):1171–6.

    Article  Google Scholar 

  62. PDR Network. Physicians’ Desk Reference, 70th ed. Montvale, NJ. 2016.

    Google Scholar 

  63. National Multiple Sclerosis Society: Amantadine. www.nationalmssociety.org/Treating-MS/Medications/Amantidine. Accessed 1 Jan 2015.

  64. Asano M, Finlayson ML. Meta-analysis of three different types of fatigue management interventions for people with multiple sclerosis: exercise, education, and medication. Mult Scler Int. 2014. doi:10.1155/2014/798285.

    PubMed  PubMed Central  Google Scholar 

  65. Cohen RA, Fisher M. Amantadine treatment of fatigue associated with multiple sclerosis. Arch Neurol. 1989;46(6):676–80.

    Article  CAS  PubMed  Google Scholar 

  66. Lovera JF, Frohman E, Brown TR, Bandari D, Nguyen L, Yadav V, et al. Memantime for cognitive impairment in multiple sclerosis: a randomized placebo-controlled trial. Mult Scler. 2010;16(6):715–23. doi:10.1177/1352458510367662.

    Article  CAS  PubMed  Google Scholar 

  67. Sailer M, Heinze HJ, Schoenfeld MA, Hauser U, Smid HG. Amantadine influences cognitive processing in patients with multiple sclerosis. Pharmacopsychiatry. 2000;33(1):28–37.

    Article  CAS  PubMed  Google Scholar 

  68. Sandoval AEG. Exercise in multiple sclerosis. Phys Med Rehabil Clin N Am. 2013;24(4):605–18. doi:10.1016/j.pmr.2013.07.002.

    Article  PubMed  Google Scholar 

  69. Stevens V, Goodman K, Rough K, Kraft GH. Gait impairment and optimizing mobility in multiple sclerosis. Phys Med Rehabil Clin N Am. 2013;24(4):573–92. doi:10.1016/j.pmr.2013.07.002.

    Article  PubMed  Google Scholar 

  70. Sosnoff JJ, Sandroff BM, Pula JH, Morrison SM, Moti RW. Falls and physical activity in persons with multiple sclerosis. Mult Scler Int. 2012;2012:315620. doi:10.1155/2012/315620.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Rodman GA, Fleisch HA. Bisphosphonates: mechanisms of action. J Clin Invest. 1996;97(12):2692–6.

    Article  Google Scholar 

  72. Fleish HA. Bisphosphonates: mechanisms of action. Endocr Rev. 1998;19(1):80–100.

    Article  Google Scholar 

  73. Hughes DE, Wright KR, Uy HL, Sasaki A, Yoneda T, Roodman DG, et al. Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo. J Bone Miner Res. 1995;10(10):1478–87.

    Article  CAS  PubMed  Google Scholar 

  74. Zehnder Y, Risi S, Michel D, Knecht H, Perrelet R, Kraenzlin M, et al. Prevention of bone loss in paraplegics over 2 years with alendronate. J Bone Miner Res. 2004;19(7):1067–74.

    Article  CAS  PubMed  Google Scholar 

  75. Shapiro J, Smith B, Beck T, Ballard P, Dapthary M, BrintzenhofeSzoc K, et al. Treatment with zoledronic acid ameliorates negative geometric changes in the proximal femur following acute spinal cord injury. Calcif Tissue Int. 2007;80(5):316–22.

    Article  CAS  PubMed  Google Scholar 

  76. Bekker PJ, Holloway DL, Rasmussen AS, Murphy R, Martin SW, Leese PT, et al. A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res. 2005;20(12):2275–82.

    Article  PubMed  Google Scholar 

  77. Hamdy NA. Targeting the RANK/RANKL/OPG signaling pathway: a novel approach in the management of osteoporosis. Curr Opin Investig Drugs. 2007;8(4):299–303.

    CAS  PubMed  Google Scholar 

  78. Jamal SA, Ljunggren Ö, Stehman-Breen C, Cummings SR, McClung MR, Goemaere S, et al. Effects of denosumab on fracture and bone mineral density by level of kidney function. J Bone Miner Res. 2011;26(8):1829–35.

    Article  CAS  PubMed  Google Scholar 

  79. Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361(8):756–65.

    Article  CAS  PubMed  Google Scholar 

  80. Papapoulos S, Lippuner K, Roux C, Hall J, Kendler D, Lewiecki EM, et al. Eight years of denosumab treatment in postmenopausal women with osteoporosis: results from the first five years of the FREEDOM extension. J Bone Miner Res. 2013;28 Suppl 1:S503.

    Google Scholar 

  81. Reid IR. Efficacy, effectiveness and side effects of medications used to prevent fractures. J Int Med. 2014. doi:10.1111/joim.12339.

    Google Scholar 

  82. Fahrleitner-Pammer A, Langdahl BL, Marin F, Jakob F, Karras D, Barrett A, et al. Fracture rate and back pain during and after discontinuation of teriparatide: 36-month data from the European Forsteo Observational Study (EFOS). Osteoporos Int. 2011;22(10):2709–19. doi:10.1007/s00198-010-1498-5.

    Article  CAS  PubMed  Google Scholar 

  83. Daddona PE, Matriano JA, Mandema J, Maa YF. Parathyroid hormone (1–34)-coated microneedle patch system: clinical pharmacokinetics for treatment of osteoporosis. Pharm Res. 2011;28(1):159–65.

    Article  CAS  PubMed  Google Scholar 

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  1. Department of Rehabilitation Medicine, Thomas Jefferson University, Philadelphia, PA, USA

    Christina V. Oleson

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Oleson, C.V. (2017). Osteoporosis in Multiple Sclerosis. In: Osteoporosis Rehabilitation. Springer, Cham. https://doi.org/10.1007/978-3-319-45084-1_10

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