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The Effect of Calmodulin Antagonists on Experimental Scoliosis: A Pinealectomized Chicken Model

Akel, Ibrahim, MD*; Kocak, Ozgur, MD*; Bozkurt, Gokhan, MD; Alanay, Ahmet, MD*; Marcucio, Ralph, PhD; Acaroglu, Emre, MD*

doi: 10.1097/BRS.0b013e31818be0b1
Basic Science
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Study Design. Randomized controlled.

Objective. To evaluate the effects of Tamoxifen (TMX) and trifluoperozine (TFP) on pinealectomized chicken scoliosis.

Summary of Background Data. Pinealectomized chicken develops scoliosis probably due to the lack of melatonin. In addition to other functions, melatonin also acts as a calmodulin antagonist. We postulate that loss of this antagonistic effect may be the cause of scoliosis in this model. TMX and TFP are known calmodulin antagonists, which may alter the incidence and severity of scoliosis.

Methods. Seventy-two newly hatched chicken that underwent surgical pinealectomy within 72 hours of hatching were divided into 3 groups of 24 animals in each as group I (control), group II (TMX), and group III (TFP). TMX and TFP were given to groups II and III, respectively, for 10 weeks with the dose of 0.1 mg/kg/d, whereas the control group received no medication. AP scoliosis radiographs were obtained at seventh and 10th week to evaluate coronal spinal alignment.

Results. Three chickens in group I, 2 chickens in group II, and 1 chicken in group III died in the first postoperative week. Scoliosis incidences and magnitudes were similar among groups at seventh and 10th week. TMX and TFP groups showed decreases of incidence of upper cervical, lower cervical, lower cervical-thoracic-lumbar curves at 10th week compared with seventh week. TMX group showed a decline in thoracic region mean Cobb angle, whereas control group showed an increase (P = 0.048). TMX group showed a more prominent decline in cervicothoracic region mean Cobb angle compared with control group (P = 0.009).

Conclusion. The incidence and magnitude of scoliosis in pinealectomized chicken may be decreased by the administration of TMX, presumably because of this drugs' calmodulin antagonism. Further studies on higher animals and dosage and timing are required.

The development of scoliosis after pinealectomy in chicken may be caused by the relative over activity of calmodulin. This study investigated the effect of calmodulin inhibitors and demonstrated that Tamoxifen is effective in decreasing the incidence as well as the magnitude of scoliosis at a certain time point.

From the Departments of *Orthopedics and Traumatology and †Neurosurgery, Hacettepe University, Ankara, Turkey; and ‡University of California San Francisco, Department of Orthopedic Surgery, San Francisco, CA.

Acknowledgment date: February 28, 2008. Revision date: July 3, 2008. Acceptance date: August 5, 2008.

The legal regulatory status of the device(s)/drug(s) that is/are the subject of this manuscript is not applicable in the authors' country.

No funds were received in support of this work. No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript.

Supported by a grant from Scoliosis Research Society via Cotrel Foundation.

Address correspondence and reprint requests to Emre Acaroglu, MD, Hacettepe University, Faculty of Medicine, Department of Orthopedics and Traumatology, Sihhiye, Ankara, 06100 Turkey; E-mail: eacarogl@hacettepe.edu.tr.

© 2009 Lippincott Williams & Wilkins, Inc.