Abstract
Osteogenesis Imperfecta (OI) is a rare heritable condition characterized by bone fragility and reduced bone mass. Traditionally OI was classified into OI types I to IV and thought to be only due to a defect in the collagen gene, however through the discovery of the new types of OI–V to VII, breakthroughs have been made in understanding the pathophysiology of autosomal recessive OI and new genetic mutations, such as in CRTAP and P3H1 genes. OI can present at any age and be difficult to diagnose because of the wide phenotypic variation. Awareness of the new forms of OI, the differential diagnosis and the limitations of diagnostic tools, all help to correctly diagnose and manage a patient with OI. Cyclical intravenous pamidronate is now the standard of care for moderately to severely affected children with OI, given in combination with good orthopedic, physiotherapy and rehabilitation programs. The benefits and short term safety of cyclic bisphosphonates have been amply reported in the literature; however their long term effects are still under investigation. Newer more potent forms of bisphosphonates such as zoledronic acid have undergone and are still being subject to international multicentric drug trials and are beginning to replace pamidronate in some centers.
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Rauch F, Glorieux FH. Osteogenesis imperfecta. Lancet 2004;363:1377–85.
Roughley PJ, Rauch F, Glorieux FH. Osteogenesis imperfecta—clinical and molecular diversity. Eur Cell Mater. 2003;5:41–7. discussion 47.
Boyde A, Travers R, Glorieux FH, Jones SJ. The mineralization density of iliac crest bone from children with osteogenesis imperfecta. Calcif Tissue Int. 1999;64:185–90.
Glorieux FH, Rauch F, Plotkin H, Ward L, Travers R, Roughley P, Lalic L, Glorieux DF, Fassier F, Bishop NJ. Type V osteogenesis imperfecta: a new form of brittle bone disease. J Bone Miner Res. 2000;15:1650–8.
Glorieux FH, Ward LM, Rauch F, Lalic L, Roughley PJ, Travers R. Osteogenesis imperfecta type VI: a form of brittle bone disease with a mineralization defect. J Bone Miner Res. 2002;17:30–8.
Ward LM, Rauch F, Travers R, Chabot G, Azouz EM, Lalic L, Roughley PJ, Glorieux FH. Osteogenesis imperfecta type VII: an autosomal recessive form of brittle bone disease. Bone 2002;31:12–8.
Morello R, Bertin TK, Chen Y, Hicks J, Tonachini L, Monticone M, Castagnola P, Rauch F, Glorieux FH, Vranka J, Bachinger HP, Pace JM, Schwarze U, Byers PH, Weis M, Fernandes RJ, Eyre DR, Yao Z, Boyce BF, Lee B. CRTAP is required for prolyl 3-hydroxylation and mutations cause recessive osteogenesis imperfecta. Cell 2006;127:291–304.
Cabral WA, Chang W, Barnes AM, Weis M, Scott MA, Leikin S, Makareeva E, Kuznetsova NV, Rosenbaum KN, Tifft CJ, Bulas DI, Kozma C, Smith PA, Eyre DR, Marini JC. Prolyl 3-hydroxylase 1 deficiency causes a recessive metabolic bone disorder resembling lethal/severe osteogenesis imperfecta. Nat Genet. 2007;39:359–65.
Byers PH, Krakow D, Nunes ME, Pepin M. Genetic evaluation of suspected osteogenesis imperfecta (OI). Genet Med. 2006;8:383–8.
Cubert R, Cheng EY, Mack S, Pepin MG, Byers PH. Osteogenesis imperfecta: mode of delivery and neonatal outcome. Obstet Gynecol. 2001;97:66–9.
Munns CF, Rauch F, Travers R, Glorieux FH. Effects of intravenous pamidronate treatment in infants with osteogenesis imperfecta: clinical and histomorphometric outcome. J Bone Miner Res. 2005;20:1235–43.
Koay MA, Brown MA. Genetic disorders of the LRP5-Wnt signalling pathway affecting the skeleton. Trends Mol Med. 2005;11:129–37.
Breslau-Siderius EJ, Engelbert RH, Pals G, van der Sluijs JA. Bruck syndrome: a rare combination of bone fragility and multiple congenital joint contractures. J Pediatr Orthop B. 1998;7:35–8.
Cole DE, Carpenter TO. Bone fragility, craniosynostosis, ocular proptosis, hydrocephalus, and distinctive facial features: a newly recognized type of osteogenesis imperfecta. J Pediatr. 1987;110:76–80.
Rauch F, Travers R, Norman ME, Taylor A, Parfitt AM, Glorieux FH. Deficient bone formation in idiopathic juvenile osteoporosis: a histomorphometric study of cancellous iliac bone. J Bone Miner Res. 2000;15:957–63.
Rauch F, Plotkin H, Travers R, Zeitlin L, Glorieux FH. Osteogenesis imperfecta types I, III and IV: effect of pamidronate therapy on bone and mineral metabolism. J Clin Endocrinol Metab. 2003;88:986–92.
Munns CF, Rajab MH, Hong J, Briody J, Hogler W, McQuade M, Little DG, Cowell CT. Acute phase response and mineral status following low dose intravenous zoledronic acid in children. Bone 2007;41:366–70.
Glorieux FH, Bishop NJ, Plotkin H, Chabot G, Lanoue G, Travers R. Cyclic administration of pamidronate in children with severe osteogenesis imperfecta. N Engl J Med. 1998;339:947–52.
Montpetit K, Plotkin H, Rauch F, Bilodeau N, Cloutier S, Rabzel M, Glorieux FH. Rapid increase in grip force after start of pamidronate therapy in children and adolescents with severe osteogenesis imperfecta. Pediatrics. 2003;111:e601–3.
Zeitlin L, Rauch F, Plotkin H, Glorieux FH. Height and weight development during long-term therapy with cyclical intravenous pamidronate in children and adolescents with osteogenesis imperfecta types I, III and IV. Pediatrics 2003;111:1030–6.
Land C, Rauch F, Travers R, Glorieux FH. Osteogenesis imperfecta type VI in childhood and adolescence: effects of cyclical intravenous pamidronate treatment. Bone 2007;40:638–44.
Rauch F, Travers R, Munns C, Glorieux FH. Sclerotic metaphyseal lines in a child treated with pamidronate: histomorphometric analysis. J Bone Miner Res. 2004;19:1191–3.
Land C, Rauch F, Munns CF, Sahebjam S, Glorieux FH. Vertebral morphometry in children and adolescents with osteogenesis imperfecta: Effect of intravenous pamidronate treatment. Bone 2006;39:901–6.
Rauch F, Travers R, Glorieux FH. Pamidronate in children with osteogenesis imperfecta: histomorphometric effects of long-term therapy. J Clin Endocrinol Metab. 2006;91:511–6.
Munns CF, Rauch F, Mier RJ, Glorieux FH. Respiratory distress with pamidronate treatment in infants with severe osteogenesis imperfecta. Bone 2004;35:231–4.
Land C, Rauch F, Glorieux FH. Cyclical intravenous pamidronate treatment affects metaphyseal modeling in growing patients with osteogenesis imperfecta. J Bone Miner Res. 2006;21:374–9.
Migliorati CA, Siegel MA, Elting LS. Bisphosphonate-associated osteonecrosis: a long-term complication of bisphosphonate treatment. Lancet Oncol. 2006;7:508–14.
Munns CF, Rauch F, Zeitlin L, Fassier F, Glorieux FH. Delayed osteotomy but not fracture healing in pediatric osteogenesis imperfecta patients receiving pamidronate. J Bone Miner Res. 2004;19:1779–86.
Munns CF, Rauch F, Ward L, Glorieux FH. Maternal and fetal outcome after long-term pamidronate treatment before conception: a report of two cases. J Bone Miner Res. 2004;19:1742–5.
Aarabi M, Rauch F, Hamdy RC, Fassier F. High prevalence of coxa vara in patients with severe osteogenesis imperfecta. J Pediatr Orthop. 2006;26:24–8.
Violas P, Fassier F, Hamdy R, Duhaime M, Glorieux FH. Acetabular protrusion in osteogenesis imperfecta. J Pediatr Orthop. 2002;22:622–5.
Marini JC, Hopkins E, Glorieux FH, Chrousos GP, Reynolds JC, Gundberg CM, Reing CM. Positive linear growth and bone responses to growth hormone treatment in children with types III and IV osteogenesis imperfecta: high predictive value of the carboxyterminal propeptide of type I procollagen. J Bone Miner Res. 2003;18:237–43.
Vahle JL, Sato M, Long GG, Young JK, Francis PC, Engelhardt JA, Westmore MS, Linda Y, Nold JB. Skeletal changes in rats given daily subcutaneous injections of recombinant human parathyroid hormone (1–34) for 2 years and relevance to human safety. Toxicol Pathol. 2002;30:312–21.
Horwitz EM, Prockop DJ, Fitzpatrick LA, Koo WW, Gordon PL, Neel M, Sussman M, Orchard P, Marx JC, Pyeritz RE, Brenner MK. Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med. 1999;5:309–13.
Horwitz EM, Prockop DJ, Gordon PL, Koo WW, Fitzpatrick LA, Neel MD, McCarville ME, Orchard PJ, Pyeritz RE, Brenner MK. Clinical responses to bone marrow transplantation in children with severe osteogenesis imperfecta. Blood 2001;97:1227–31.
Acknowledgements
This work was supported by the Shriners of North America. We thank Guylaine Bédard for preparation of the figures.
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Cheung, M.S., Glorieux, F.H. Osteogenesis Imperfecta: Update on presentation and management. Rev Endocr Metab Disord 9, 153–160 (2008). https://doi.org/10.1007/s11154-008-9074-4
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DOI: https://doi.org/10.1007/s11154-008-9074-4