Reduced Bone Mass and Fat-Free Mass in Women with Multiple Sclerosis: Effects of Ambulatory Status and Glucocorticoid Use

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Abstract
Multiple sclerosis (MS) is associated with reduced bone mass and vitamin D deficiency. The underlying pathophysiology of the bone disease is uncertain, however, acute and long-term glucocorticoid use, progressive immobilization, vitamin D deficiency, and possibly skeletal muscle atrophy are likely to be determinants. The aims of this study were to determine (a) whether multiple sclerosis is associated with reduced fat-free mass and (b) whether in patients with multiple sclerosis, ambulation ability or glucocorticoid use is associated with bone mass and/or fat-free mass. Seventy-one female patients with MS were compared with 71 healthy, age-matched female controls. Total body bone mineral content (TBBMC, kg), fat mass (FM, kg), and fat-free mass (FFM, kg) were measured using dual X-ray absorptiometry. Disability status was graded according to the Kurtzke Expanded Disability Status Scale (EDSS) as ambulatory, with or without aide (EDSS score of 0 to 6.5), or predominantly wheelchair bound (EDSS score > 6.5). The patients with MS, when compared to age-comparable controls, had deficits in TBBMC (≈ 8%, −0.3 ± 0.1 SD, P < 0.04) and FFM (≈ 5%, −0.3 ± 0.1 SD, P < 0.01). Both TBBMC and FFM were negatively associated with EDSS score (r= 0.33, P < 0.01, and r= 0.41, P < 0.01, respectively). Patients with MS who were nonambulatory had even greater deficits in TBBMC and FFM as compared with age-matched controls (−0.6 ± 0.1 SD, P < 0.01, and −0.6 ± 0.1 SD, P < 0.01, respectively). By contrast, as compared with age-comparable controls, ambulatory patients with MS had no deficits in bone mass or soft tissue mass. When compared with ambulatory patients with MS, nonambulatory patients with MS had deficits in TBBMC and FFM (P < 0.01 and P < 0.01, respectively). The difference in TBBMC was largely caused by the difference in fat-free mass, whereas the difference in FFM was largely caused by the difference in glucocorticoid use based on analysis of covariance. We conclude that in patients with multiple sclerosis, physical disuse is the main determinant for the reduction in bone mass. Glucocorticoid treatment is the major determinant of the reduction in fat-free mass and thus also contributes to the reduction in bone mass.

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