Effects of Low-level Mechanical Vibration on Bone Density in Ambulant Children Affected by Duchenne Muscular Dystrophy

Effects of Low-level Mechanical Vibration on Bone Density in Ambulant Children Affected by Duchenne Muscular Dystrophy

Low-level Mechanical Vibration, Bone Density, Bone Resorption and Muscular Strength in Ambulant Children Affected by Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a X-linked recessive disorder due to a mutation of the dystrophin gene (Xp21). Dystrophin is a sarcolemmal protein of skeletal and cardiac muscle, and its absence causes progressive muscle degeneration and substitution with fat and connective tissue. The progressive muscle degeneration leads to loss of autonomous walking before the age of 15 years and death for cardiac and/or respiratory failure. There are no specific treatment for DMD, and the standard of care is now based on long-term corticosteroid (CS) use. The studies on bone mass in DMD are very few, but they agree in reporting the presence of a reduced bone mass and an increased rate of fractures probably due to long-term steroid therapy and disuse-osteopenia. The aim of this study, involving 20 ambulant DMD boys (age 7-10 years) has been the evaluation of the effects of low-level mechanical vibrations on bone in a group of ambulant DMD children for 1 year, with RDA-adjusted dietary calcium intake and 25OH vitamin D supplementation.

All children were instructed to have a daily intake of calcium equal to the 100% of the RDA and were supplemented with calcifediol (0.7 mcg/kg/die). The 20 boys were randomly assigned to two groups: group 1 (mechanical intervention group) = a mechanical device (a small platform designed to induce vertical, sinusoidal acceleration) was installed in the home of each boy of group 1. group 2 (placebo control group) = a placebo device was installed in the home of each boy of group 2 All boys were instructed to stand on the platform for 10 minutes each day for 12 months. Compliance was followed and stimulated through weekly telephone contacts with parents and children.

Duchenne Muscular Dystrophy, children, low bone mass, osteoporosis, low-level mechanical vibration, bone turnover markers

20 subjects participated to the study (1 year double-blind, randomized, placebo controlled, parallel group study) and 10 subjects were randomized to this arm. Intervention: to stand on the active platform (inducing vertical, sinusoidal acceleration) for 10 minutes each day for 12 months.

20 subjects participated to the study (1 year double-blind, randomized, placebo controlled, parallel group study) and 10 subjects were randomized to this arm. Intervention: to stand on the placebo platform (not inducing vertical, sinusoidal acceleration) for 10 minutes each day for 12 months.

Bone mineral density evaluated by DXA. Bone mineral apparent density calculated to correct for bone size (growing subjects). Z-score calculated. Measurements: baseline and 12 months.

Inclusion Criteria: Diagnosis of DMD Ability to stand up and walk (some balance assistance allowed, but full weight-bearing necessary) All the children must already be on glucocorticoid therapy for at least 6 months before the start of the study. Exclusion Criteria: Presence of other diseases interfering with bone density and bone turnover The inability to regularly use the vibratory platform.

Khan MA. Corticosteroid therapy in Duchenne muscular dystrophy. J Neurol Sci. 1993 Dec 1;120(1):8-14. doi: 10.1016/0022-510x(93)90017-s.

Mendell JR, Moxley RT, Griggs RC, Brooke MH, Fenichel GM, Miller JP, King W, Signore L, Pandya S, Florence J, et al. Randomized, double-blind six-month trial of prednisone in Duchenne's muscular dystrophy. N Engl J Med. 1989 Jun 15;320(24):1592-7. doi: 10.1056/NEJM198906153202405.

Bonifati MD, Ruzza G, Bonometto P, Berardinelli A, Gorni K, Orcesi S, Lanzi G, Angelini C. A multicenter, double-blind, randomized trial of deflazacort versus prednisone in Duchenne muscular dystrophy. Muscle Nerve. 2000 Sep;23(9):1344-7. doi: 10.1002/1097-4598(200009)23:93.0.co;2-f.

Biggar WD, Gingras M, Fehlings DL, Harris VA, Steele CA. Deflazacort treatment of Duchenne muscular dystrophy. J Pediatr. 2001 Jan;138(1):45-50. doi: 10.1067/mpd.2001.109601.

Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med. 1993 Jun;94(6):646-50. doi: 10.1016/0002-9343(93)90218-e. No abstract available.

Baylink DJ. Glucocorticoid-induced osteoporosis. N Engl J Med. 1983 Aug 4;309(5):306-8. doi: 10.1056/NEJM198308043090509. No abstract available.

Chesney RW, Mazess RB, Rose P, Jax DK. Effect of prednisone on growth and bone mineral content in childhood glomerular disease. Am J Dis Child. 1978 Aug;132(8):768-72. doi: 10.1001/archpedi.1978.02120330040010.

Jones G, Ponsonby AL, Smith BJ, Carmichael A. Asthma, inhaled corticosteroid use, and bone mass in prepubertal children. J Asthma. 2000;37(7):603-11. doi: 10.3109/02770900009090816.

Naganathan V, Jones G, Nash P, Nicholson G, Eisman J, Sambrook PN. Vertebral fracture risk with long-term corticosteroid therapy: prevalence and relation to age, bone density, and corticosteroid use. Arch Intern Med. 2000 Oct 23;160(19):2917-22. doi: 10.1001/archinte.160.19.2917.

Whalen RT, Carter DR, Steele CR. Influence of physical activity on the regulation of bone density. J Biomech. 1988;21(10):825-37. doi: 10.1016/0021-9290(88)90015-2.

Slemenda CW, Miller JZ, Hui SL, Reister TK, Johnston CC Jr. Role of physical activity in the development of skeletal mass in children. J Bone Miner Res. 1991 Nov;6(11):1227-33. doi: 10.1002/jbmr.5650061113.

Slemenda CW, Reister TK, Hui SL, Miller JZ, Christian JC, Johnston CC Jr. Influences on skeletal mineralization in children and adolescents: evidence for varying effects of sexual maturation and physical activity. J Pediatr. 1994 Aug;125(2):201-7. doi: 10.1016/s0022-3476(94)70193-8.

Courteix D, Lespessailles E, Peres SL, Obert P, Germain P, Benhamou CL. Effect of physical training on bone mineral density in prepubertal girls: a comparative study between impact-loading and non-impact-loading sports. Osteoporos Int. 1998;8(2):152-8. doi: 10.1007/BF02672512.

Palmieri GM, Bertorini TE, Griffin JW, Igarashi M, Karas JG. Assessment of whole body composition with dual energy x-ray absorptiometry in Duchenne muscular dystrophy: correlation of lean body mass with muscle function. Muscle Nerve. 1996 Jun;19(6):777-9. doi: 10.1002/(SICI)1097-4598(199606)19:63.0.CO;2-I. No abstract available.

Larson CM, Henderson RC. Bone mineral density and fractures in boys with Duchenne muscular dystrophy. J Pediatr Orthop. 2000 Jan-Feb;20(1):71-4.

Aparicio LF, Jurkovic M, DeLullo J. Decreased bone density in ambulatory patients with duchenne muscular dystrophy. J Pediatr Orthop. 2002 Mar-Apr;22(2):179-81.

McDonald DG, Kinali M, Gallagher AC, Mercuri E, Muntoni F, Roper H, Jardine P, Jones DH, Pike MG. Fracture prevalence in Duchenne muscular dystrophy. Dev Med Child Neurol. 2002 Oct;44(10):695-8. doi: 10.1017/s0012162201002778.

Welten DC, Kemper HC, Post GB, Van Mechelen W, Twisk J, Lips P, Teule GJ. Weight-bearing activity during youth is a more important factor for peak bone mass than calcium intake. J Bone Miner Res. 1994 Jul;9(7):1089-96. doi: 10.1002/jbmr.5650090717.

Vestergaard P, Glerup H, Steffensen BF, Rejnmark L, Rahbek J, Moseklide L. Fracture risk in patients with muscular dystrophy and spinal muscular atrophy. J Rehabil Med. 2001 Jul;33(4):150-5.

Talim B, Malaguti C, Gnudi S, Politano L, Merlini L. Vertebral compression in Duchenne muscular dystrophy following deflazacort. Neuromuscul Disord. 2002 Mar;12(3):294-5. doi: 10.1016/s0960-8966(01)00307-8. No abstract available.

Bianchi ML, Mazzanti A, Galbiati E, Saraifoger S, Dubini A, Cornelio F, Morandi L. Bone mineral density and bone metabolism in Duchenne muscular dystrophy. Osteoporos Int. 2003 Sep;14(9):761-7. doi: 10.1007/s00198-003-1443-y. Epub 2003 Jul 29.

Merlini L, Mazzone ES, Solari A, Morandi L. Reliability of hand-held dynamometry in spinal muscular atrophy. Muscle Nerve. 2002 Jul;26(1):64-70. doi: 10.1002/mus.10166.

Xie L, Jacobson JM, Choi ES, Busa B, Donahue LR, Miller LM, Rubin CT, Judex S. Low-level mechanical vibrations can influence bone resorption and bone formation in the growing skeleton. Bone. 2006 Nov;39(5):1059-1066. doi: 10.1016/j.bone.2006.05.012. Epub 2006 Jul 7.

Gilsanz V, Wren TA, Sanchez M, Dorey F, Judex S, Rubin C. Low-level, high-frequency mechanical signals enhance musculoskeletal development of young women with low BMD. J Bone Miner Res. 2006 Sep;21(9):1464-74. doi: 10.1359/jbmr.060612.

Ward K, Alsop C, Caulton J, Rubin C, Adams J, Mughal Z. Low magnitude mechanical loading is osteogenic in children with disabling conditions. J Bone Miner Res. 2004 Mar;19(3):360-9. doi: 10.1359/JBMR.040129. Epub 2004 Jan 27.