Skip to main content Accessibility help
  • Print publication year: 2015
  • Online publication date: September 2015

Chapter 9 - Differential diagnosis III: osteogenesis imperfecta

from Section I - Skeletal trauma
    • By Deborah Krakow, Professor of Orthopaedic Surgery, Human Genetics and Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA, Ralph S. Lachman, Pediatric Radiologist at Harbor/UCLA Medical Center, International Skeletal Dysplasia Registry at Cedars-Sinai Medical Center and Professor of Radiology and Pediatrics at the University of California, Los Angeles School of Medicine, Los Angeles, California, USA, Paul K. Kleinman, Department of Radiology, Boston Children’s Hospital, and Harvard Medical School, Boston, Massachusetts, USA
  • Edited by Paul K. Kleinman
  • Publisher: Cambridge University Press
  • DOI:
  • pp 254-267


Osteogenesis imperfecta

Of the many conditions that may be confused with child abuse, osteogenesis imperfecta (OI) deserves special consideration. Although this is a relatively rare disorder (1 in 20,000 births), cases of OI have been initially confused with inflicted skeletal injury. As will be apparent from the discussion in this chapter, such confusion is avoidable in most cases if a thorough clinical, radiologic, and molecular evaluation is carried out. A heightened public awareness of OI has created considerable controversy and has added a new dimension to the diagnostic imaging of suspected child abuse (1–13).

In recent years, many cases of children with features of inflicted trauma have had the flag of the OI defense raised by the children’s caretakers and their attorneys, as well as the plaintiffs’ legal representatives in other civil litigations. It has been well known since the earliest description of OI by Ekman in 1788 and Axmann’s (his own and his family’s) description in 1831 that fractures with minimal trauma are an important part of this disease complex (14, 15).

To differentiate OI from child abuse, it is necessary to understand the disease not only radiologically and clinically, but also appreciate the distinct histologic, biochemical, and molecular abnormalities associated with this important condition.

Related content

Powered by UNSILO
Greeley, CS, Donaruma-Kwoh, M, Vettimattam, M, Lobo, C, Williard, C, Mazur, L. Fractures at diagnosis in infants and children with osteogenesis imperfecta. J Pediatr Orthop. 2013;33(1):32–6.
Egge, MK, Berkowitz, CD. Controversies in the evaluation of young children with fractures. Adv Pediatr. 2010;57(1):63–83.
Bitton, A, Yialamas, M, Levy, BD, Katz, JT, Loscalzo, J. Clinical problem-solving. A fragile balance. N Engl J Med. 2009;361(1):74–9.
Cabral, WA, Milgrom, S, Letocha, AD, Moriarty, E, Marini, JC. Biochemical screening of type I collagen in osteogenesis imperfecta: detection of glycine substitutions in the amino end of the alpha chains requires supplementation by molecular analysis. J Med Genet. 2006;43(8):685–90.
Alvarez, R, Garcia, R, Luis, J, Lopez, J, Gutierrez, A, Gonzalez, M, et al. [Bone mineral density in children with osteogenesis imperfecta.]Rev Esp Med Nucl. 2003;22(4):224–8.
Lapillonne, A, Travers, R, DiMaio, M, Salle, BL, Glorieux, FH. Urinary excretion of cross-linked N-telopeptides of type 1 collagen to assess bone resorption in infants from birth to 1 year of age. Pediatrics. 2002;110(1 Pt. 1):105–9.
Sewell, RD, Steinberg, M. Chest compressions in an infant with osteogenesis imperfecta type II: No new rib fractures. Pediatrics. 2000;106(5):e71.
Blacksin, MF, Pletcher, BA, David, M. Osteogenesis imperfecta with joint contractures: bruck syndrome. Pediatr Radiol. 1998;28(2):117–19.
Wardinsky, T, Vizcarrondo, F, Cruz, B. The mistaken diagnosis of child abuse: a three-year USAF medical center analysis and literature review. Mil Med. 1995;160(1):15–20.
Shaw, DG, Hall, CM, Carty, H. Osteogenesis imperfecta: the distinction from child abuse and the recognition of a variant form. Am J Med Genet. 1995;56(1):116–18.
Minnis, H, Ramsay, R, Ewije, P, Kumar, C. Osteogenesis imperfecta and non-accidental injury. Br J Psychiatry. 1995;166(6):824–5.
Steiner, R, Pepin, M, Byers, PH. Studies of collagen synthesis and structure in the differentiation of child abuse from osteogenesis imperfecta. J Pediatr. 1996;128(4):542–7.
Renaud, A, Aucourt, J, Weill, J, Bigot, J, Dieux, A, Devisme, L, et al. Radiographic features of osteogenesis imperfecta. Insights Imaging. 2013;4(4):417–29.
Cole, ZA, Gale, CR, Javaid, MK, Robinson, SM, Law, C, Boucher, BJ, et al. Maternal dietary patterns during pregnancy and childhood bone mass: a longitudinal study. J Bone Miner Res. 2009;24(4):663–8.
Marlowe, A, Pepin, MG, Byers, PH. Testing for osteogenesis imperfecta in cases of suspected non-accidental injury. J Med Genet. 2002;39(6):382–6.
Sillence, DO, Rimoin, DL. Classification of osteogenesis imperfecta. Lancet. 1978;1(8072):1041–2.
Van Dijk, FS, Pals, G, Van Rijn, RR, Nikkels, PG, Cobben, JM. Classification of osteogenesis imperfecta revisited. Eur J Med Genet. 2010;53(1):1–5.
Marini, JC, Blissett, AR. New genes in bone development: what’s new in osteogenesis imperfecta. J Clin Endocrinol Metab. 2013;98(8):3095–103.
Forlino, A, Marini, JC. Osteogenesis imperfecta: prospects for molecular therapeutics. Mol Genet Metab. 2000;71(1–2):225–32.
Taitz, LS. Child abuse and metabolic bone disease: are they often confused?BMJ. 1991;302(6787):1244.
Rohrbach, M, Giunta, C. Recessive osteogenesis imperfecta: clinical, radiological, and molecular findings. Am J Med Genet C Semin Med Genet. 2012;160C(3):175–89.
Rauch, F, Moffatt, P, Cheung, M, Roughley, P, Lalic, L, Lund, AM, et al. Osteogenesis imperfecta type V: marked phenotypic variability despite the presence of the IFITM5 c. –14C>T mutation in all patients. J Med Genet. 2013;50(1):21–4.
Semler, O, Garbes, L, Keupp, K, Swan, D, Zimmermann, K, Becker, J, et al. A mutation in the 5ʹ-UTR of IFITM5 creates an in-frame start codon and causes autosomal-dominant osteogenesis imperfecta type V with hyperplastic callus. Am J Hum Genet. 2012;91(2):349–57.
Sillence, DO, Senn, A, Danks, DM. Genetic heterogeneity in osteogenesis imperfecta. J Med Genet. 1979;16(2):101–16.
Leidig-Bruckner, G, Grauer, A. Images in clinical medicine. Blue sclerae in osteogenesis imperfecta. N Engl J Med. 1998;339(14):966.
Carr, AJ, Chiodo, AA, Hilton, JM, Chow, CW, Hockey, A, Cole, WG. The clinical features of Ehlers–Danlos syndrome type VIIB resulting from a base substitution at the splice acceptor site of intron 5 of the COL1A2 gene. J Med Genet. 1994;31(4):306–11.
Byers, PH, Murray, ML. Heritable collagen disorders: the paradigm of the Ehlers–Danlos syndrome. J Invest Dermatol. 2012;132(E1):E6–11.
Santos, F, McCall, AA, Chien, W, Merchant, S. Otopathology in osteogenesis imperfecta. Otol Neurotol. 2012;33(9):1562–6.
Teixeira, CS, Santos Felippe, MC, Tadeu Felippe, W, Silva-Sousa, YT, Sousa-Neto, MD. The role of dentists in diagnosing osteogenesis imperfecta in patients with dentinogenesis imperfecta. J Am Dent Assoc. 2008;139(7):906–14; quiz 994.
Kim, JW, Simmer, JP. Hereditary dentin defects. J Dent Res. 2007;86(5):392–9.
Baumgartner, D, Gassner, I, Sperl, W, Salzer-Kuntschik, M, Judmaier, W, Steinmann, B. Calvarial “doughnut lesions”: clinical spectrum of the syndrome, report on a case, and review of the literature. Am J Med Genet. 2001;99(3):238–43.
Moog, U, Maroteaux, P, Schrander-Stumpel, CT, van Ooij, A, Schrander, JJ, Fryns, JP. Two sibs with an unusual pattern of skeletal malformations resembling osteogenesis imperfecta: a new type of skeletal dysplasia?J Med Genet. 1999;36(11):856–8.
Unger, S, Antoniazzi, F, Brugnara, M, Alanay, Y, Caglayan, A, Lachlan, K, et al. Clinical and radiographic delineation of odontochondrodysplasia. Am J Med Genet A. 2008;146A(6):770–8.
Lachman, RS. Taybi and Lachman’s Radiology of Syndromes, Metabolic Disorders and Skeletal Dysplasias, 5th edn. St. Louis, MO: Mosby; 2007.
Byers, PH, Pyott, SM. Recessively inherited forms of osteogenesis imperfecta. Annu Rev Genet. 2012;46:475–97.
Puig-Hervas, MT, Temtamy, S, Aglan, M, Valencia, M, Martinez-Glez, V, Ballesta-Martinez, MJ, et al. Mutations in PLOD2 cause autosomal-recessive connective tissue disorders within the Bruck syndrome–osteogenesis imperfecta phenotypic spectrum. Hum Mutat. 2012;33(10):1444–9.
Schwarze, U, Cundy, T, Pyott, SM, Christiansen, HE, Hegde, MR, Bank, RA, et al. Mutations in FKBP10, which result in Bruck syndrome and recessive forms of osteogenesis imperfecta, inhibit the hydroxylation of telopeptide lysines in bone collagen. Hum Mol Genet. 2013;22(1):1–17.
Kelley, BP, Malfait, F, Bonafe, L, Baldridge, D, Homan, E, Symoens, S, et al. Mutations in FKBP10 cause recessive osteogenesis imperfecta and Bruck syndrome. J Bone Miner Res. 2011;26(3):666–72.
Aslam, SI, Sivakumar, S. A case report of a rare type of skeletal dysplasia diagnosed by a common blood test. Arch Dis Child. 2011;96(Suppl. 1):A77.
Matsushita, M, Kitoh, H, Michigami, T, Tachikawa, K, Ishiguro, N. Benign prenatal hypophosphatasia: a treatable disease not to be missed. Pediatr Radiol. 2014;44(3):340–3.
Marini, JC, Forlino, A, Cabral, WA, Barnes, AM, San Antonio, JD, Milgrom, S, et al. Consortium for osteogenesis imperfecta mutations in the helical domain of type I collagen: regions rich in lethal mutations align with collagen binding sites for integrins and proteoglycans. Hum Mutat. 2007;28(3):209–21.
Pyott, SM, Pepin, MG, Schwarze, U, Yang, K, Smith, G, Byers, PH. Recurrence of perinatal lethal osteogenesis imperfecta in sibships: parsing the risk between parental mosaicism for dominant mutations and autosomal recessive inheritance. Genet Med. 2011;13(2):125–30.
Rimoin, DL. Histopathology and ultrastructure of cartilage in the chondrodystrophies. Birth Defects Orig Artic Ser. 1974;10(9):1–18.
Khoury, DJ, Szalay, EA. Bone mineral density correlation with fractures in nonambulatory pediatric patients. J Pediatr Orthop. 2007;27(5):562–6.
Ben Amor, IM, Glorieux, FH, Rauch, F. Genotype–phenotype correlations in autosomal dominant osteogenesis imperfecta. J Osteoporos. 2011;2011:540178.
Rauch, F, Lalic, L, Roughley, P, Glorieux, FH. Genotype–phenotype correlations in nonlethal osteogenesis imperfecta caused by mutations in the helical domain of collagen type I. Eur J Hum Genet. 2010;18(6):642–7.
Tedeschi, E, Antoniazzi, F, Venturi, G, Zamboni, G, Tato, L. Osteogenesis imperfecta and its molecular diagnosis by determination of mutations of type I collagen genes. Pediatr Endocrinol Rev. 2006;4(1):40–6.
Willing, MC, Deschenes, SP, Slayton, RL, Roberts, EJ. Premature chain termination is a unifying mechanism for COL1A1 null alleles in osteogenesis imperfecta type I cell strains. Am J Hum Genet. 1996;59(4):799–809.
Bateman, JF, Lamande, SR, Dahl, HH, Chan, D, Mascara, T, Cole, WG. A frameshift mutation results in a truncated nonfunctional carboxyl-terminal pro alpha 1(I) propeptide of type I collagen in osteogenesis imperfecta. J Biol Chem. 1989;264(19):10,960–4.
Gahagan, S, Rimsza, ME. Child abuse and osteogenesis imperfecta: how can we tell?Pediatrics. 1991;88:987–92.
Paterson, CR, Mole, PA. Bone density in osteogenesis imperfecta may well be normal. Postgrad Med J. 1994;70:104–7.
Dent, JA, Paterson, CR. Fractures in early childhood: OI or child abuse?J Pediatr Orthop. 1991;11:184–6.
Bulloch, B, Schubert, CJ, Brophy, PD, Johnson, N, Reed, MH, Shapiro, RA. Cause and clinical characteristics of rib fractures in infants. Pediatrics. 2000;105(4):E48.
Marti, B, Sirinelli, D, Maurin, L, Carpentier, E. Wormian bones in a general paediatric population. Diagn Interv Imaging. 2013;94(4):428–32.
Semler, O, Cheung, MS, Glorieux, FH, Rauch, F. Wormian bones in osteogenesis imperfecta: correlation to clinical findings and genotype. Am J Med Genet A. 2010;152A(7):1681–7.
Cremin, B, Goodman, H, Spranger, J, Beighton, P. Wormian bones in osteogenesis imperfecta and other disorders. Skeletal Radiol. 1982;8(1):35–8.
Parmar, CD, Sinha, AK, Hayhurst, C, May, PL, O’Brien, DF. Epidural hematoma formation following trivial head trauma in a child with osteogenesis imperfecta. Case report. J Neurosurg. 2007;106(1 Suppl.):57–60.
Tsipouras, P, Barabas, G, Matthews, WS. Neurologic correlates of osteogenesis imperfecta. Arch Neurol. 1986;43(2):150–2.
Khandanpour, N, Connolly, DJA, Raghavan, A, Griffiths, PD, Hoggard, N. Craniospinal abnormalities and neurologic complications of osteogenesis imperfecta: imaging overview. Radiographics. 2012;32(7):2101–12.
Burchardt, AJ, Wagner, AA, Basse, P. Hyperplastic callus formation in osteogenesis imperfecta. A case report. Acta Radiol. 1994;35(5):426–8.
Ramirez, N, Vilella, FE, Colon, M, Flynn, JM. Osteogenesis imperfecta and hyperplastic callus formation in a family: a report of three cases and a review of the literature. J Pediatr Orthop B. 2003;12(2):88–96.
Folkestad, L, Hald, JD, Hansen, S, Gram, J, Langdahl, B, Abrahamsen, B, et al. Bone geometry, density, and microarchitecture in the distal radius and tibia in adults with osteogenesis imperfecta type I assessed by high-resolution pQCT. J Bone Miner Res. 2012;27(6):1405–12.
Herman, TE, McAlister, WH. Inherited diseases of bone density in children. Radiol Clin North Am. 1991;29(1):149–64.
Miller, ME, Hangartner, TN. Bone density measurements by computed tomography in osteogenesis imperfecta type I. Osteoporos Int. 1999;9(5):427–32.
Miller, M, Hangartner, TN. CT bone density in a case of osteogenesis imperfecta – type I (OI) presenting with suspected child abuse. Pediatr Res. 1998;43(4):116A [Abstract].
Davie, MW, Haddaway, MJ. Bone mineral content and density in healthy subjects and in osteogenesis imperfecta. Arch Dis Child. 1994;70(4):331–4.
Engelke, K, Libanati, C, Fuerst, T, Zysset, P, Genant, HK. Advanced CT based in vivo methods for the assessment of bone density, structure, and strength. Curr Osteoporos Rep. 2013;11(3):246–55.
Kocher, MS, Dichtel, L. Osteogenesis imperfecta misdiagnosed as child abuse. J Pediatr Orthop. 2011;20(6):440–3.
Knight, DJ, Bennet, GC. Nonaccidental injury in osteogenesis imperfecta: a case report. J Pediatr Orthop. 1990;10(4):542–4.