Review Article The Spine in Patients With Osteogenesis Imperfecta Abstract Maegen J. Wallace, MD Osteogenesis imperfecta is a genetic disorder of type I collagen. Richard W. Kruse, DO, MBA Although multiple genotypes and phenotypes are associated with osteogenesis imperfecta, approximately 90% of the mutations are in Suken A. Shah, MD the COL1A1 and COL1A2 genes. Osteogenesis imperfecta is characterized by bone fragility. Patients typically have multiple fractures or limb deformity; however, the spine can also be affected. Spinal manifestations include scoliosis, kyphosis, craniocervical junction abnormalities, and lumbosacral pathology. The incidence of lumbosacral spondylolysis and spondylolisthesis is higher in patients with osteogenesis imperfecta than in the general population. Use of From the Department of Orthopedics, diphosphonates has been found to decrease the rate of progression Nemours/Alfred I. duPont Hospital for of scoliosis in patients with osteogenesis imperfecta. A lateral Children, Wilmington, DE. cervical radiograph is recommended in patients with this condition Dr. Kruse or an immediate family before age 6 years for surveillance of craniocervical junction member serves as an unpaid abnormalities, such as basilar impression. Intraoperative and consultant to DePuy Synthes and serves as a board member, owner, anesthetic considerations in patients with osteogenesis imperfecta officer, or committee member of the include challenges related to fracture risk, airway management, American Academy of Orthopaedic pulmonary function, and blood loss. Surgeons and the Pediatric Orthopaedic Society of North America. Dr. Shah or an immediate family member has received royalties from Arthrex and DePuy Synthes; steogenesis imperfecta (OI) is a aremorecommoninchildrenwith serves as a paid consultant to DePuy Ogenetic disorder of type I colla- dentinogenesis imperfecta than in Synthes and Stryker; has stock or gen, which is located mainly in bone, children without dentinogenesis stock options held in Globus Medical; has received research or institutional ligaments, dentin, and sclerae. Mul- imperfecta. Children with cranio- support from DePuy Synthes; and tiple genotypes and phenotypes are cervical junction abnormalities are serves as a board member, owner, associated with OI, and the condition not likely to have generalized officer, or committee member of the is characterized by bone fragility. hypermobility.4 AllchildrenwithOI American Academy of Orthopaedic Surgeons, the Scoliosis Research Patients typically have multiple should undergo regular physical Society, the Pediatric Orthopaedic fractures or limb deformity; how- examination of their extremities and Society of North America, and the ever, the spine can also be affected.1,2 spinetoscreenforandmonitor Setting Scoliosis Straight Foundation. Neither Dr. Wallace nor any Spinal manifestations include scoli- progression of scoliosis. immediate family member has osis, kyphosis, craniocervical junc- Seventeen genetic causes of OI have received anything of value from or has tion abnormalities, such as basilar been identified. Approximately 90% stock or stock options held in a impression, basilar invagination of the mutations are found in commercial company or institution related directly or indirectly to the and platybasia, and lumbosacral the COL1A1 and COL1A2 genes. subject of this article. pathology, such as spondylolis- COL1A1 and COL1A2 genes 3 J Am Acad Orthop Surg 2017;25: thesis. Other clinical signs of OI encode for the alpha-1 and alpha-2 100-109 include blue sclerae, early hearing chains of type I collagen.2 The DOI: 10.5435/JAAOS-D-15-00169 loss, dentinogenesis imperfecta, phenotypic expression of OI was joint hypermobility, and short stat- originally classified by Sillence et al.1 Copyright 2016 by the American 2 Academy of Orthopaedic Surgeons. ure. Scoliosis, kyphosis, and cra- Type I is nondeforming OI with blue niocervical junction abnormalities sclerae, type II is perinatally lethal OI 100 Journal of the American Academy of Orthopaedic Surgeons Copyright ª the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited. Maegen J. Wallace, MD, et al with multiple intrauterine fractures, Table 1 type III can result in fractures at birth Sillence Classification of Osteogenesis Imperfecta1,2 and causes progressive deformity, and type IV OI is characterized by normal Type Severity Features Inheritance sclerae and variable long bone defor- I Mild Blue sclerae, mild bone fragility, Autosomal dominant or mities2 (Table 1). Additional types fractures after walking, new mutations have been described as knowledge of minimal deformity the genetics of OI has increased. II Lethal Blue sclerae, multiple Autosomal recessive or Diphosphonate therapy has been intrauterine fractures, severe new mutations found to have a positive effect on deformity, stillbirth or neonatal death vertebral morphology, including III Severe Normal sclerae, dentinogenesis Autosomal recessive or remodeling of deformed vertebrae in deforming imperfecta, frequent fractures, new mutations older children and preservation of deformity of long bones, short vertebral shape when started early in stature, scoliosis life.5,6 Diphosphonates are often IV Intermediate Normal sclerae, moderate bone Autosomal dominant or startedininfancyinpatientswith fragility, moderate deformity, new mutations short stature, possible type III, type IV, or severe type I dentinogenesis imperfecta OI.7,8 Kusumi et al8 reported on a group of 18 patients with OI (5 type I,7typeIII,and6typeIV)with an average age of 12 months (range, study.3 Scoliosis is rarely observed in theorized that ligamentous laxity 11 days to 23 months). They patients younger than 6 years and plays a substantial role because the showed considerable improvement can progress rapidly after it is diag- lack of stability between vertebrae in bone density via dual-energy nosed.9 Engelbert et al10 and allows scoliosis to progress. x-ray absorptiometry (DEXA) and others11 showed that children with a decreased fracture rate with no OI in whom scoliosis developed had Progression major side effects of treatment. In markedly lower DEXA Z scores one study, infants who were treated compared with those of children Untreated scoliosis is known to with diphosphonates showed no with OI in whom scoliosis did not progress in growing children with OI 13 development of scoliosis, kyphosis, or develop. Single thoracic curves are and even into adulthood. Scoliosis craniocervical junction abnormalities the most frequent type of scoliosis curve progression can be as high as ° during treatment or follow-up from curve found in patients with type I 6 per year in patients with type III ° age 3 to 6 years, although clinically OI: 97% of curves in patients with OI, 4 per year in patients with type ° relevant scoliosis generally is not type I OI who have scoliosis are IV OI, and as low as 1 per year in 7,9 12 seen before 6 years of age. single thoracic curves, whereas in patients with type I OI (Table 2). 11 Furthermore, all 11 children who patients with type III OI, 58% of Watanabe et al found that, as the were treated in the study (average curves are in the thoracic region.12 DEXA Z score worsened, the scoli- age, 4.8 years) were ambulatory. In osis progressed, suggesting that a historical cohort of children with poorer bone quality leads to more OI of similar severity who were not Etiology severe scoliosis. Ishikawa et al14 treated with diphosphonates, only The etiology of scoliosis in patients found that biconcave vertebrae, in 2of11childrencouldwalkatan with OI is controversial, with theories which the height of the midportion average age of 4.6 years, and including vertebral body fragility, of the body is ,70% of the mean of 6 other children had lost a motor vertebral body shape, ligamentous the anterior and posterior vertebral milestone previously gained during laxity, muscle weakness, limb-length body heights, were common in childhood.7 discrepancy, and pelvic obliq- patients with OI (Figure 1). The uity.11,13 Vertebral fractures are presence of six or more biconcave thought to be a leading cause of vertebrae before puberty suggested Kyphoscoliosis scoliosis because of the severe fra- that severe scoliosis would develop. gility of the vertebral growth plates Anissipour et al12 found that The prevalence of scoliosis in the and the progression that occurs with patients with type III OI who began population of patients with OI ranges continued growth.14 Benson and diphosphonate treatment before age from 39% to 80%, depending on the Newman9 and Engelbert et al10 6 years had slower curve progression February 2017, Vol 25, No 2 101 Copyright ª the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited. The Spine in Patients With Osteogenesis Imperfecta Table 2 Prevalence of and Progression of Scoliosis in Patients With Osteogenesis Imperfecta12 No Diphosphonate Treatment Before Diphosphonate Treatment Before Age 6 Years Age 6 Years Type of Osteogenesis Prevalence of Rate of Scoliosis P Rate of Scoliosis P Imperfecta Scoliosis Progression (degrees/yr) Value Progression (degrees/yr) Value I 39% 1 0.01 2.3 0.19 III 68% 6 ,0.01 2.3 0.01 IV 54% 4 ,0.01 3.1 0.91 ° ’ Figure 1 patients with type I or IV OI did not curves reach 45 , but the patient s have a statistically significant effect age and truncal height need to be on the progression of scoliosis. taken into account to avoid thoracic insufficiency syndrome.