Abstract
Pompe disease (lysosomal acid alpha-glucosidase deficiency) in adolescents and adults presents primarily with muscle weakness. Bone weakness is an under-recognized finding in patients with Pompe disease, but there is emerging evidence that loss of muscle function and mobility can lead to loss of mineral content and a higher risk of fracture. In addition to the mineral content, architecture is also important in determining the overall strength of the bone. We present the results of the longest longitudinal duration study to date using a novel application of high-resolution peripheral quantitative computed tomography (HR-pQCT) in four patients with Pompe disease over 4 years of observation during the normal course of their disease management. The subjects varied in treatment status with recombinant human alpha-glucosidase (rhGAA), use of anti-resorptive therapy (such as bisphosphonates), mobility and weight-bearing status, and the use of side-alternating vibration therapy. Our observations were that HR-pQCT can measure trends in mineral density and architecture over a long period of observation and may be an early indicator of the response to interventional therapies. In addition, a combination of decreased loading forces due to decreased mobility likely contributes to the compromise of bone integrity in Pompe disease. These trends can be reversed by applying increased loading forces such as vibration therapy and maintaining weight-bearing and mobility. We conclude that HR-pQCT can serve as a valuable tool to monitor bone health in patients with Pompe disease.
Competing interests: None declared
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Boutroy S, Bouxsein ML, Munoz F, Delmas PD (Dec 2005) In vivo assessment of trabecular bone microarchitecture by high-resolution peripheral quantitative computed tomography. J Clin Endocrinol Metab [Comparative Study Evaluation Studies Research Support, Non-U.S. Gov't]90(12):6508–6515
Burghardt AJ, Kazakia GJ, Sode M, de Papp AE, Link TM, Majumdar S (Dec 2010) A longitudinal HR-pQCT study of alendronate treatment in postmenopausal women with low bone density: Relations among density, cortical and trabecular microarchitecture, biomechanics, and bone turnover. J Bone Miner Res [Randomized Controlled Trial Research Support, N.I.H., Extramural]25(12):2558–2571
Cefalu CA (March 2004) Is bone mineral density predictive of fracture risk reduction? Curr Med Res Opin [Review]20(3):341–349
Cortet B, Dubois P, Boutry N, Bourel P, Cotten A, Marchandise X (1999) Image analysis of the distal radius trabecular network using computed tomography. Osteoporos Int 9(5):410–419
Faulkner RA, McCulloch RG, Fyke SL, De Coteau WE, McKay HA, Bailey DA et al (1995) Comparison of areal and estimated volumetric bone mineral density values between older men and women. Osteoporos Int [Comparative Study Research Support, Non-U.S. Gov't]5(4):271–275
Goulet RW, Goldstein SA, Ciarelli MJ, Kuhn JL, Brown MB, Feldkamp LA (Apr 1994) The relationship between the structural and orthogonal compressive properties of trabecular bone. J Biomech [Research Support, U.S. Gov't, P.H.S.]27(4):375–389
Griffith JF, Genant HK (Oct 2008) Bone mass and architecture determination: state of the art. Best Pract Res Clin Endocrinol Metab [Review]22(5):737–764
Hagemans ML, Winkel LP, Van Doorn PA, Hop WJ, Loonen MC, Reuser AJ et al (March 2005) Clinical manifestation and natural course of late-onset Pompe's disease in 54 Dutch patients. Brain [Research Support, Non-U.S. Gov't]128(Pt 3):671–677
Hasegawa Y, Schneider P, Reiners C, Kushida K, Yamazaki K, Hasegawa K et al (2000) Estimation of the architectural properties of cortical bone using peripheral quantitative computed tomography. Osteoporos Int [Research Support, Non-U.S. Gov't]11(1):36–42
Khan A, Ramage B, Robu I, Benard L (2009) Side-alternating vibration training improves muscle performance in a patient with late-onset pompe disease. Case Report Med 2009:741087
Kishnani PS, Hwu WL, Mandel H, Nicolino M, Yong F, Corzo D (May 2006) A retrospective, multinational, multicenter study on the natural history of infantile-onset Pompe disease. J Pediatr [Multicenter Study Research Support, Non-U.S. Gov't]148(5):671–676
Kishnani PS, Corzo D, Nicolino M, Byrne B, Mandel H, Hwu WL et al (Jan 2007) Recombinant human acid [alpha]-glucosidase: major clinical benefits in infantile-onset Pompe disease. Neurology [Multicenter Study Randomized Controlled Trial]68(2):99–109
Macdonald HM, Nishiyama KK, Kang J, Hanley DA, Boyd SK (Jan 2011) Age-related patterns of trabecular and cortical bone loss differ between sexes and skeletal sites: a population-based HR-pQCT study. J Bone Miner Res [Research Support, Non-U.S. Gov't]26(1):50–62
Macdonald HM, Nishiyama KK, Hanley DA, Boyd SK (Jan 2011) Changes in trabecular and cortical bone microarchitecture at peripheral sites associated with 18 months of teriparatide therapy in postmenopausal women with osteoporosis. Osteoporos Int [Clinical Trial Research Support, Non-U.S. Gov't]22(1):357–362
MacNeil JA, Boyd SK (2007) Accuracy of high-resolution peripheral quantitative computed tomography for measurement of bone quality. Med Eng Phys 29(10):1096–1105
Marshall D, Johnell O, Wedel H (May 1996) Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ [Meta-Analysis Research Support, Non-U.S. Gov't]312(7041):1254–1259
Orlikowski D, Pellegrini N, Prigent H, Laforet P, Carlier R, Carlier P et al (2011) Recombinant human acid alpha-glucosidase (rhGAA) in adult patients with severe respiratory failure due to Pompe disease. Neuromuscul Disord 21(7):477–482
Papadimas GK, Terzis G, Spengos K, Methenitis S, Papadopoulos C, Vassilopoulou S et al (Feb 2011) Bone mineral density in adult patients with Pompe disease. Bone [Comment Letter]48(2):417; author reply 8–9
Papadimas GK, Spengos K, Konstantinopoulou A, Vassilopoulou S, Vontzalidis A, Papadopoulos C et al (2011b) Adult Pompe disease: clinical manifestations and outcome of the first Greek patients receiving enzyme replacement therapy. Clin Neurol Neurosurg 113(4):303–307
Rizzoli R, Laroche M, Krieg MA, Frieling I, Thomas T, Delmas P et al (Aug 2010) Strontium ranelate and alendronate have differing effects on distal tibia bone microstructure in women with osteoporosis. Rheumatol Int [Randomized Controlled Trial Research Support, Non-U.S. Gov't]30(10):1341–1348
Ruegsegger P, Koller B, Muller R (Jan 1996) A microtomographic system for the nondestructive evaluation of bone architecture. Calcif Tissue Int [Research Support, Non-U.S. Gov't]58(1):24–29
van Capelle CI, van der Beek NA, Hagemans ML, Arts WF, Hop WC, Lee P et al (Dec 2010) Effect of enzyme therapy in juvenile patients with Pompe disease: a three-year open-label study. Neuromuscul Disord [Clinical Trial, Phase II Research Support, Non-U.S. Gov't]20(12):775–782
van den Berg LE, Zandbergen AA, van Capelle CI, de Vries JM, Hop WC, van den Hout JM et al (Sept 2010) Low bone mass in Pompe disease: muscular strength as a predictor of bone mineral density. Bone [Research Support, Non-U.S. Gov't]47(3):643–649
van den Hout HM, Hop W, van Diggelen OP, Smeitink JA, Smit GP, Poll-The BT et al (Aug 2003) The natural course of infantile Pompe’s disease: 20 original cases compared with 133 cases from the literature. Pediatrics [Research Support, Non-U.S. Gov't Review]112(2):332–340
Vielhaber S, Brejova A, Debska-Vielhaber G, Kaufmann J, Feistner H, Schoenfeld MA et al (2011) 24-months results in two adults with Pompe disease on enzyme replacement therapy. Clin Neurol Neurosurg 113(5):350–357
Acknowledgments
Images in Fig. 1 are courtesy of Yves Pauchard, University of Calgary. We would like to thank Ion Robu for his engineering and technical expertise in the vibration training setup. This research was supported by funding from the Alberta Children’s Hospital Research Foundation, Alberta Health Innovates Health Solutions (formerly Alberta Heritage Foundation for Medical Research), and through the support of Alberta Health Services.
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Communicated by: Ed Wraith
Synopsis
Synopsis
High-resolution peripheral computed tomography can be used to monitor peripheral limb bone health in patients with Pompe disease.
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Khan, A. et al. (2012). In Vivo Bone Architecture in Pompe Disease Using High-Resolution Peripheral Computed Tomography. In: Brown, G., Morava, E., Peters, V., Gibson, K., Zschocke, J. (eds) JIMD Reports - Case and Research Reports, 2012/4. JIMD Reports, vol 7. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2012_146
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DOI: https://doi.org/10.1007/8904_2012_146
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