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Muscle-Bone Interactions in Pediatric Bone Diseases

  • Pediatrics (L Ward and E Imel, Section Editors)
  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

Abstract

Purpose

Here, we review the skeletal effects of pediatric muscle disorders as well as muscle impairment in pediatric bone disorders.

Recent Findings

When starting in utero, muscle disorders can lead to congenital multiple contractures. Pediatric-onset muscle weakness such as cerebral palsy, Duchenne muscular dystrophy, spinal muscular atrophy, or spina bifida typically are associated with small diameter of long-bone shafts, low density of metaphyseal bone, and increased fracture incidence in the lower extremities, in particular, the distal femur. Primary bone diseases can affect muscles through generic mechanisms, such as decreased physical activity or in disease-specific ways. For example, the collagen defect underlying the bone fragility of osteogenesis imperfecta may also affect muscle force generation or transmission. Transforming growth factor beta released from bone in Camurati Engelman disease may decrease muscle function.

Future Directions

Considering muscle-bone interactions does not only contribute to the understanding of musculoskeletal disorders but also can identify new targets for therapeutic interventions.

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References

Papers of particular interest, published recently, have been highlighted as: •Of importance ••Of major importance

  1. Frost HM. Bone’s mechanostat: a 2003 update. Anat Rec A Discov Mol Cell Evol Biol. 2003;275:1081–101.

    Article  PubMed  Google Scholar 

  2. Hall JG, Aldinger KA, Tanaka KI. Amyoplasia revisited. Am J Med Genet A. 2014;164a:700–30.

    Article  PubMed  Google Scholar 

  3. Hall JG. Arthrogryposis (multiple congenital contractures): diagnostic approach to etiology, classification, genetics, and general principles. Eur J Med Genet. 2014;57:464–72.

    Article  PubMed  Google Scholar 

  4. Spencer HT, Bowen RE, Caputo K, Green TA, Lawrence JF. Bone mineral density and functional measures in patients with arthrogryposis. J Pediatr Orthop. 2010;30:514–8.

    Article  PubMed  Google Scholar 

  5. Simone C, Ramirez A, Bucchia M, Rinchetti P, Rideout H, Papadimitriou D, et al. Is spinal muscular atrophy a disease of the motor neurons only: pathogenesis and therapeutic implications? Cell Mol Life Sci. 2016;73:1003–20.

    Article  CAS  PubMed  Google Scholar 

  6. Knierim E, Hirata H, Wolf NI, Morales-Gonzalez S, Schottmann G, Tanaka Y, et al. Mutations in subunits of the activating signal cointegrator 1 complex are associated with prenatal spinal muscular atrophy and congenital bone fractures. Am J Hum Genet. 2016;98:473–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Moon RJ, Harvey NC, Curtis EM, de Vries F, van Staa T, Cooper C. Ethnic and geographic variations in the epidemiology of childhood fractures in the United Kingdom. Bone. 2016;85:9–14.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Colver A, Fairhurst C, Pharoah PO. Cerebral palsy. Lancet. 2014;383:1240–9.

    Article  PubMed  Google Scholar 

  9. Mughal MZ. Fractures in children with cerebral palsy. Curr Osteoporos Rep. 2014;12:313–8.

    Article  PubMed  Google Scholar 

  10. Uddenfeldt Wort U, Nordmark E, Wagner P, Duppe H, Westbom L. Fractures in children with cerebral palsy: a total population study. Dev Med Child Neurol. 2013;55:821–6.

    Article  PubMed  Google Scholar 

  11. • Modlesky CM, Whitney DG, Singh H, Barbe MF, Kirby JT, Miller F. Underdevelopment of trabecular bone microarchitecture in the distal femur of nonambulatory children with cerebral palsy becomes more pronounced with distance from the growth plate. Osteoporos Int. 2015;26:505–12. This study provides MRI-based structural data that underpin the low metaphyseal femoral bone density in children with cerebral palsy.

    Article  CAS  PubMed  Google Scholar 

  12. Modlesky CM, Kanoff SA, Johnson DL, Subramanian P, Miller F. Evaluation of the femoral midshaft in children with cerebral palsy using magnetic resonance imaging. Osteoporos Int. 2009;20:609–15.

    Article  CAS  PubMed  Google Scholar 

  13. Binkley T, Johnson J, Vogel L, Kecskemethy H, Henderson R, Specker B. Bone measurements by peripheral quantitative computed tomography (pQCT) in children with cerebral palsy. J Pediatr. 2005;147:791–6.

    Article  PubMed  Google Scholar 

  14. Whitney DG, Singh H, Miller F, Barbe MF, Slade JM, Pohlig RT, et al. Cortical bone deficit and fat infiltration of bone marrow and skeletal muscle in ambulatory children with mild spastic cerebral palsy. Bone. 2017;94:90–7.

    Article  PubMed  Google Scholar 

  15. Trudel G, Payne M, Madler B, Ramachandran N, Lecompte M, Wade C, et al. Bone marrow fat accumulation after 60 days of bed rest persisted 1 year after activities were resumed along with hemopoietic stimulation: the women international space simulation for exploration study. J Appl Physiol. 2009;107:540–8.

    Article  PubMed  Google Scholar 

  16. Rantalainen T, Nikander R, Heinonen A, Cervinka T, Sievanen H, Daly RM. Differential effects of exercise on tibial shaft marrow density in young female athletes. J Clin Endocrinol Metab. 2013;98:2037–44.

    Article  CAS  PubMed  Google Scholar 

  17. Mah JK. Current and emerging treatment strategies for Duchenne muscular dystrophy. Neuropsychiatr Dis Treat. 2016;12:1795–807.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Matthews E, Brassington R, Kuntzer T, Jichi F, Manzur AY. Corticosteroids for the treatment of Duchenne muscular dystrophy. Cochrane Database Syst Rev. 2016;5:Cd003725.

    Google Scholar 

  19. Tian C, Wong BL, Hornung L, Khoury JC, Miller L, Bange J, et al. Bone health measures in glucocorticoid-treated ambulatory boys with Duchenne muscular dystrophy. Neuromuscul Disord. 2016;26:760–7.

    Article  PubMed  Google Scholar 

  20. Ma J, McMillan HJ, Karaguzel G, Goodin C, Wasson J, Matzinger MA, et al. The time to and determinants of first fractures in boys with Duchenne muscular dystrophy. Osteoporos Int. 2017;28:597–608.

    Article  CAS  PubMed  Google Scholar 

  21. Singh A, Schaeffer EK, Reilly CW. Vertebral fractures in Duchenne muscular dystrophy patients managed with deflazacort. J Pediatr Orthop. 2016. doi:https://doi.org/10.1097/BPO.0000000000000817

  22. King WM, Kissel JT, Visy D, Goel PK, Matkovic V. Skeletal health in Duchenne dystrophy: bone-size and subcranial dual-energy X-ray absorptiometry analyses. Muscle Nerve. 2014;49:512–9.

    Article  PubMed  Google Scholar 

  23. Wong BL, Rybalsky I, Shellenbarger KC, Tian C, McMahon MA, Rutter MM, et al. Long-term outcome of interdisciplinary management of patients with Duchenne muscular dystrophy receiving daily glucocorticoid treatment. J Pediatr. 2017;182:296–303 e1.

    Article  CAS  PubMed  Google Scholar 

  24. • Misof BM, Roschger P, McMillan HJ, Ma J, Klaushofer K, Rauch F, et al. Histomorphometry and bone matrix mineralization before and after bisphosphonate treatment in boys with Duchenne muscular dystrophy: a paired transiliac biopsy study. J Bone Miner Res. 2016;31:1060–9. This bone tissue study shows that bone turnover is low in boys with Duchenne muscular dystrophy but that material bone properties are largely normal.

    Article  CAS  PubMed  Google Scholar 

  25. Vai S, Bianchi ML, Moroni I, Mastella C, Broggi F, Morandi L, et al. Bone and spinal muscular atrophy. Bone. 2015;79:116–20.

    Article  CAS  PubMed  Google Scholar 

  26. 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;33:150–5.

    Article  CAS  PubMed  Google Scholar 

  27. Trinh A, Wong P, Brown J, Hennel S, Ebeling PR, Fuller PJ, et al. Fractures in spina bifida from childhood to young adulthood. Osteoporos Int. 2017;28:399–406.

    Article  CAS  PubMed  Google Scholar 

  28. Dosa NP, Eckrich M, Katz DA, Turk M, Liptak GS. Incidence, prevalence, and characteristics of fractures in children, adolescents, and adults with spina bifida. J Spinal Cord Med. 2007;30(Suppl 1):S5–9.

    Article  PubMed  PubMed Central  Google Scholar 

  29. • Horenstein RE, Shefelbine SJ, Mueske NM, Fisher CL, Wren TA. An approach for determining quantitative measures for bone volume and bone mass in the pediatric spina bifida population. Clin Biomech (Bristol, Avon). 2015;30:748–54. This study used CT images to study three-dimensional geometry and density along the entire tibia in children with spina bifida. Non-ambulatory children had decreased bone mass in the diaphysis and proximal and distal epiphyses compared to ambulatory and control children.

    Article  PubMed Central  Google Scholar 

  30. Folkestad L, Hald JD, Ersboll AK, Gram J, Hermann AP, Langdahl B, et al. Fracture rates and fracture sites in patients with osteogenesis Imperfecta: a nationwide register-based cohort study. J Bone Miner Res. 2017;32:125–34.

    Article  PubMed  Google Scholar 

  31. Trejo P, Rauch F. Osteogenesis imperfecta in children and adolescents-new developments in diagnosis and treatment. Osteoporos Int. 2016;27:3427–37.

    Article  CAS  PubMed  Google Scholar 

  32. Ben Amor IM, Roughley P, Glorieux FH, Rauch F. Skeletal clinical characteristics of osteogenesis imperfecta caused by haploinsufficiency mutations in COL1A1. J Bone Miner Res. 2013;28:2001–7.

    Article  CAS  PubMed  Google Scholar 

  33. Graf A, Hassani S, Krzak J, Caudill A, Flanagan A, Bajorunaite R, et al. Gait characteristics and functional assessment of children with type I osteogenesis imperfecta. J Orthop Res. 2009;27:1182–90.

    Article  PubMed  Google Scholar 

  34. Caudill A, Flanagan A, Hassani S, Graf A, Bajorunaite R, Harris G, et al. Ankle strength and functional limitations in children and adolescents with type I osteogenesis imperfecta. Pediatr Phys Ther. 2010;22:288–95.

    Article  PubMed  Google Scholar 

  35. Veilleux LN, Lemay M, Pouliot-Laforte A, Cheung MS, Glorieux FH, Rauch F. Muscle anatomy and dynamic muscle function in osteogenesis imperfecta type I. J Clin Endocrinol Metab. 2014;99:E356–62.

    Article  CAS  PubMed  Google Scholar 

  36. Pouliot-Laforte A, Veilleux LN, Rauch F, Lemay M. Physical activity in youth with osteogenesis imperfecta type I. J Musculoskelet Neuronal Interact. 2015;15:171–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Veilleux LN, Pouliot-Laforte A, Lemay M, Cheung MS, Glorieux FH, Rauch F. The functional muscle-bone unit in patients with osteogenesis imperfecta type I. Bone. 2015;79:52–7.

    Article  CAS  PubMed  Google Scholar 

  38. Gillies AR, Lieber RL. Structure and function of the skeletal muscle extracellular matrix. Muscle Nerve. 2011;44:318–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Light N, Champion AE. Characterization of muscle epimysium, perimysium and endomysium collagens. Biochem J. 1984;219:1017–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Huijing PA. Muscle as a collagen fiber reinforced composite: a review of force transmission in muscle and whole limb. J Biomech. 1999;32:329–45.

    Article  CAS  PubMed  Google Scholar 

  41. Misof K, Landis WJ, Klaushofer K, Fratzl P. Collagen from the osteogenesis imperfecta mouse model (oim) shows reduced resistance against tensile stress. J Clin Invest. 1997;100:40–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Sims TJ, Miles CA, Bailey AJ, Camacho NP. Properties of collagen in OIM mouse tissues. Connect Tissue Res. 2003;44(Suppl 1):202–5.

    Article  CAS  PubMed  Google Scholar 

  43. Montpetit K, Plotkin H, Rauch F, Bilodeau N, Cloutier S, Rabzel M, et al. Rapid increase in grip force after start of pamidronate therapy in children and adolescents with severe osteogenesis imperfecta. Pediatrics. 2003;111:E601–3.

    Article  PubMed  Google Scholar 

  44. Hoggarth CR, Bennett R, Daley-Yates PT. The pharmacokinetics and distribution of pamidronate for a range of doses in the mouse. Calcif Tissue Int. 1991;49:416–20.

    Article  CAS  PubMed  Google Scholar 

  45. Hodges PW, Smeets RJ. Interaction between pain, movement, and physical activity: short-term benefits, long-term consequences, and targets for treatment. Clin J Pain. 2015;31:97–107.

    Article  PubMed  Google Scholar 

  46. •• Waning DL, Mohammad KS, Reiken S, Xie W, Andersson DC, John S, et al. Excess TGF-beta mediates muscle weakness associated with bone metastases in mice. Nat Med. 2015;21:1262–71. This is an experimental study demonstrating the adverse muscle effect of transforming growth factor beta released from bone.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Imel EA, Carpenter TO. A practical clinical approach to paediatric phosphate disorders. Endocr Dev. 2015;28:134–61.

    Article  PubMed  Google Scholar 

  48. Amanzadeh J, Reilly RF Jr. Hypophosphatemia: an evidence-based approach to its clinical consequences and management. Nat Clin Pract Nephrol. 2006;2:136–48.

    Article  CAS  PubMed  Google Scholar 

  49. Singhal PC, Kumar A, Desroches L, Gibbons N, Mattana J. Prevalence and predictors of rhabdomyolysis in patients with hypophosphatemia. Am J Med. 1992;92:458–64.

    Article  CAS  PubMed  Google Scholar 

  50. Veilleux LN, Cheung MS, Glorieux FH, Rauch F. The muscle-bone relationship in x-linked hypophosphatemic rickets. J Clin Endocrinol Metab. 2013;98:E990–5.

    Article  PubMed  Google Scholar 

  51. Thom JM, Morse CI, Birch KM, Narici MV. Triceps surae muscle power, volume, and quality in older versus younger healthy men. J Gerontol A Biol Sci Med Sci. 2005;60:1111–7.

    Article  PubMed  Google Scholar 

  52. Ducher G, Daly RM, Hill B, Eser P, Naughton GA, Gravenmaker KJ, et al. Relationship between indices of adiposity obtained by peripheral quantitative computed tomography and dual-energy X-ray absorptiometry in pre-pubertal children. Ann Hum Biol. 2009;36:705–16.

    Article  CAS  PubMed  Google Scholar 

  53. Farr JN, Funk JL, Chen Z, Lisse JR, Blew RM, Lee VR, et al. Skeletal muscle fat content is inversely associated with bone strength in young girls. J Bone Miner Res. 2011;26:2217–25.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Goodpaster BH, Kelley DE, Thaete FL, He J, Ross R. Skeletal muscle attenuation determined by computed tomography is associated with skeletal muscle lipid content. J Appl Physiol. 2000;89:104–10.

    CAS  PubMed  Google Scholar 

  55. Finol H, De Venanzi F, Pereyra B, Alfonso C, Sanchez J. Effects of phosphorus deficiency on the ultrastructure of the rat fast twitch skeletal muscle. Interciencia. 2001;26:62–6.

    Google Scholar 

  56. Fuller TJ, Carter NW, Barcenas C, Knochel JP. Reversible changes of the muscle cell in experimental phosphorus deficiency. J Clin Invest. 1976;57:1019–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Whyte MP. Hypophosphatasia—aetiology, nosology, pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. 2016;12:233–46.

    Article  CAS  PubMed  Google Scholar 

  58. Phillips D, Case LE, Griffin D, Hamilton K, Lara SL, Leiro B, et al. Physical therapy management of infants and children with hypophosphatasia. Mol Genet Metab. 2016;119:14–9.

    Article  CAS  PubMed  Google Scholar 

  59. Weber TJ, Sawyer EK, Moseley S, Odrljin T, Kishnani PS. Burden of disease in adult patients with hypophosphatasia: results from two patient-reported surveys. Metabolism. 2016;65:1522–30.

    Article  CAS  PubMed  Google Scholar 

  60. Whyte MP, Madson KL, Phillips D, Reeves AL, McAlister WH, Yakimoski A, et al. Asfotase alfa therapy for children with hypophosphatasia. JCI Insight. 2016;1:e85971.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Janssens K, Vanhoenacker F, Bonduelle M, Verbruggen L, Van Maldergem L, Ralston S, et al. Camurati-Engelmann disease: review of the clinical, radiological, and molecular data of 24 families and implications for diagnosis and treatment. J Med Genet. 2006;43:1–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Ayyavoo A, Derraik JG, Cutfield WS, Hofman PL. Elimination of pain and improvement of exercise capacity in Camurati-Engelmann disease with losartan. J Clin Endocrinol Metab. 2014;99:3978–82.

    Article  CAS  PubMed  Google Scholar 

  63. Simsek-Kiper PO, Dikoglu E, Campos-Xavier B, Utine GE, Bonafe L, Unger S, et al. Positive effects of an angiotensin II type 1 receptor antagonist in Camurati-Engelmann disease: a single case observation. Am J Med Genet A. 2014;164a:2667–71.

    Article  PubMed  Google Scholar 

  64. Werkstetter KJ, Pozza SB, Filipiak-Pittroff B, Schatz SB, Prell C, Bufler P, et al. Long-term development of bone geometry and muscle in pediatric inflammatory bowel disease. Am J Gastroenterol. 2011;106:988–98.

    Article  PubMed  Google Scholar 

  65. Lee DY, Wetzsteon RJ, Zemel BS, Shults J, Organ JM, Foster BJ, et al. Muscle torque relative to cross-sectional area and the functional muscle-bone unit in children and adolescents with chronic disease. J Bone Miner Res. 2015;30:575–83.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Griffin LM, Thayu M, Baldassano RN, DeBoer MD, Zemel BS, Denburg MR, et al. Improvements in bone density and structure during anti-TNF-alpha therapy in pediatric Crohn’s disease. J Clin Endocrinol Metab. 2015;100:2630–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Oestreich AK, Carleton SM, Yao X, Gentry BA, Raw CE, Brown M, et al. Myostatin deficiency partially rescues the bone phenotype of osteogenesis imperfecta model mice. Osteoporos Int. 2016;27:161–70.

    Article  CAS  PubMed  Google Scholar 

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  1. Shriners Hospital for Children, 1003 Boulevard Decarie, Montreal, QC, H4A 0A9, Canada

    Louis-Nicolas Veilleux & Frank Rauch

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Correspondence to Louis-Nicolas Veilleux.

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Louis-Nicolas Veilleux and Frank Rauch declare no conflict of interest.

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This article is part of the Topical Collection on Pediatrics

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Veilleux, LN., Rauch, F. Muscle-Bone Interactions in Pediatric Bone Diseases. Curr Osteoporos Rep 15, 425–432 (2017). https://doi.org/10.1007/s11914-017-0396-6

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