Internal Calvarial Bone Distraction in Rabbits with Delayed-Onset Coronal Suture Synostosis

Abstract

Recent studies have identified a subpopulation of craniosynostotic individuals who exhibit progressive or delayed-onset synostosis and mild craniofacial growth abnormalities. These individuals may be good candidates for nonextirpation, distraction osteogenesis therapy. The present study was designed to test this hypothesis by using internal calvarial bone distraction in a rabbit model with familial delayed-onset craniosynostosis. Data were collected from 159 rabbits: 71 normal controls, 72 with delayed-onset coronal suture synostosis, 8 with delayed-onset coronal suture synostosis and coronal suturectomy, and 8 with delayed-onset coronal suture synostosis and distraction. At 10 days of age, all rabbits had amalgam markers placed on both sides of the frontonasal, coronal, and anterior lambdoidal sutures. At 25 days of age, correction was accomplished through either a 5-mm-wide suturectomy or distraction osteogenesis. An internal distraction appliance was fixed to the frontal and parietal bones and percutaneously and intermittently activated at an average of 0.10 mm/day for 42 days (4.11 mm total). Serial radiographs were taken at 10, 25, 42, and 84 days of age. Results revealed that rabbits with delayed-onset synostosis had significantly (p < 0.01) reduced coronal suture growth rates (0.04 mm/day) compared with the other three groups (0.07 mm/day). Rabbits with suturectomy and rabbits with distraction showed similar coronal suture responses. However, from 42 to 84 days of age, rabbits with distraction showed reduced growth at the vault sutures and abnormal growth patterns in cranial vault width, cranial vault shape, and cranial base angulation compared with the other three groups. Results demonstrated that, although the normal coronal suture growth rate was maintained in rabbits with delayed-onset synostosis using intermittent distraction osteogenesis, normal adult craniofacial structure was not achieved. Such anomalous growth was probably a result of altered growth vectors and compressive forces at adjacent sutures during distraction. These findings suggest that distraction osteogenesis without corticotomy may be a treatment alternative in individuals with progressive, delayed-onset synostosis, but that internal appliances that generate low-level, continuous distractive forces should be investigated and developed.

Rescue of coronal suture fusion using transforming growth factor‐beta 3 (Tgf‐β3) in rabbits with delayed‐onset craniosynostosis

“…It has been suggested that the delayed-onset condition may be a variable phenotypic expression of a familial craniosynostotic condition, and may represent part of a synostotic continuum (Reddy et al, 1990;Hoffman and Reddy, 1991;Cohen et al, 1993;Mooney et al, 1994aMooney et al, ,b, 1996aMooney et al, , 2002bBurrows et al, 1995;Losken et al, 1998Losken et al, , 1999. It is thought that this continuum ranges from 1) normal growing sutures in affected genotypes on one end to 2) delayed-onset and single-suture synostosis in the middle of the continuum, and then to 3) early-onset and multiple-suture synostosis at the other extreme.…”

“…1) at 10 days of age and the quantitative assessment of coronal suture growth from serial radiographs (Mooney et al, 1994b(Mooney et al, , 1996aBurrows et al, 1995;Losken et al, 1998Losken et al, , 1999. Cephalographs of the rabbits were taken at 10 and 25 days of age, and rabbits in which coronal suture marker separation fell below the 95% confidence interval of the mean for unaffected rabbits were classified as having delayed-onset synostosis.…”

“…Rabbits with delayed-onset synostosis average about 70 -75% of normal coronal suture growth, and usually fuse by 42 days of age ( Fig. 1) (Mooney et al, 1994a;Burrows et al, 1995;Losken et al, 1998Losken et al, , 1999.…”

“…Serial lateral and dorsoventral head radiographs were taken with the rabbits tranquilized with an IM injection (0.40 ml/kg) of a solution of 9l% Ketaset (ketamine hydrochloride, 100 mg/ ml; Aveco Co. Inc., Fort Dodge, IA) and 9% Rompun (xy- lazine, 20 mg/ml; Mobay Corp., Shawnee, KS). The heads were immobilized in a specially designed cephalostat, and a Philips Oralix 70 dental x-ray unit (Shelton, CT) was used at an exposure of 50kV, 7mA, with a .17-.50-sec exposure time, and a tube-to-cassette distance held constant at 152 cm (Mooney et al, 1994b;Burrows et al, 1995;Losken et al, 1998Losken et al, , 1999. The radiographs were viewed on a light box, and the amalgam markers at the coronal suture were identified and traced on acetate tracing paper (Figs.…”

“…In particular, a number of clinical (Reddy et al, 1990;Hoffman and Reddy, 1991;Cohen et al, 1993;Cohen and MacLean, 2000) and animal (Mooney et al, 1994a(Mooney et al, , 1996a(Mooney et al, , 2002bBurrows et al, 1995;Losken et al, 1998Losken et al, , 1999) studies have identified and described a subset of craniosynostotic individuals with familial, nonsyndromic, delayed-onset (i.e., postgestational) craniosynostosis. Although the pathogenesis of delayed-onset or progressive synostosis is not known, it has been suggested that this condition may be a variable phenotypic expression of a familial craniosynostotic condition, and may represent part of a synostotic continuum (Reddy et al, 1990;Hoffman and Reddy, 1991;Cohen et al, 1993;Mooney et al, 1994aMooney et al, , 1996aMooney et al, , 2002Losken et al, 1998Losken et al, , 1999. While the suture is not completely synostosed in craniosynostotic individuals, dense collagen bundles and small bony bridges have been observed crossing the suture (Mooney et al, 1996a,b;Losken et al, 1999).…”