Reduced Bone Mineral Density and Radial Bone Growth in Young Rabbits Treated with Dexamethasone Eye Drops

Objective: To investigate the effect of dexamethasone eye drops on bone metabolism in newborn rabbits. Methods: Thirty-four 3-week-old rabbits had unilateral clear lens extraction and were randomized into three groups. Postoperatively, group 1 received high-dose and group 2 low-dose dexamethasone eye drops (average doses 0.27 and 0.10 mg/kg body weight/day, respectively). These rabbits also received a postoperative subconjunctival injection of betamethasone. Group 3 (control) received vehicle eye drops only. After 8 weeks of treatment, all animals were killed and the left femurs were isolated and subjected to peripheral quantitative computerized tomography (pQCT) and dual X-ray absorptiometry (DXA) analyses. Results: DXA showed that rabbits treated with either a high or low dose of dexamethasone eye drops had significantly reduced areal bone mineral density (BMD), area and total bone mineral content (BMC) of the femur. Measurements with pQCT demonstrated a dose-dependent reduction in cortical BMC, cortical volumetric BMD and cortical area. These effects were associated with an inhibition of radial femur growth, cortical thickness and periosteal and endosteal circumferences. Conclusion: Dexamethasone eye drops have systemic effects affecting several bone parameters in young rabbits. Any long-term systemic effects of ocular glucocorticoids need to be further studied.

[1]  C. Ohlsson,et al.  Glucocorticoid eye drops inhibit growth in the newborn rabbit. , 2005, Acta paediatrica.

[2]  A. Vasavada,et al.  Visual axis opacification after AcrySof intraocular lens implantation in children , 2004, Journal of cataract and refractive surgery.

[3]  O. Butenandt Rheumatoid arthritis and growth retardation in children: Treatment with human growth hormone , 1979, European Journal of Pediatrics.

[4]  C. Cooper,et al.  Bone density threshold and other predictors of vertebral fracture in patients receiving oral glucocorticoid therapy. , 2003, Arthritis and rheumatism.

[5]  H. Saadi,et al.  Cushing's syndrome caused by unsupervised use of ocular glucocorticoids. , 2003, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[6]  G. Saggese,et al.  Assessment of Bone Quality by Quantitative Ultrasound of Proximal Phalanges of the Hand and Fracture Rate in Children and Adolescents with Bone and Mineral Disorders , 2003, Pediatric Research.

[7]  H. Mcilwain,et al.  Glucocorticoid-induced osteoporosis: pathogenesis, diagnosis, and management. , 2003, Preventive medicine.

[8]  J. V. van Meurs,et al.  Intraocular penetration and systemic absorption after topical application of dexamethasone disodium phosphate. , 2002, Ophthalmology.

[9]  J. Baron,et al.  Recovery from osteoporosis through skeletal growth: early bone mass acquisition has little effect on adult bone density , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[10]  C. McGhee,et al.  Locally Administered Ocular Corticosteroids , 2002, Drug safety.

[11]  S. Szefler,et al.  Pharmacokinetics of intranasal corticosteroids. , 2001, The Journal of allergy and clinical immunology.

[12]  C. Zetterström,et al.  Intraocular lens designed for the newborn infant eye , 2001, Journal of cataract and refractive surgery.

[13]  D. Allen Systemic effects of intranasal steroids: an endocrinologist's perspective. , 2000, The Journal of allergy and clinical immunology.

[14]  J. Gustafsson,et al.  Estrogen receptor specificity in the regulation of skeletal growth and maturation in male mice. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[15]  S. Holmes,et al.  Effects of high‐dose inhaled corticosteroids on bone metabolism in prepubertal children with asthma , 2000, Pediatric Pulmonology.

[16]  E. Meltzer,et al.  Detection of growth suppression in children during treatment with intranasal beclomethasone dipropionate. , 2000, Pediatrics.

[17]  C. Zetterström,et al.  Complications after early surgery for congenital cataracts. , 1999, Acta ophthalmologica Scandinavica.

[18]  J. Gustafsson,et al.  Increased cortical bone mineral content but unchanged trabecular bone mineral density in female ERbeta(-/-) mice. , 1999, The Journal of clinical investigation.

[19]  E. Bérard,et al.  Effects of growth hormone in short children after renal transplantation , 1998, Pediatric Nephrology.

[20]  E. Bérard,et al.  Effects of growth hormone in short children after renal transplantation. French Society of Pediatric Nephrology. , 1998, Pediatric nephrology.

[21]  R. Roorda,et al.  One year treatment with salmeterol compared with beclomethasone in children with asthma. The Dutch Paediatric Asthma Study Group. , 1997, American journal of respiratory and critical care medicine.

[22]  S. Holgate,et al.  Growth of prepubertal children with mild asthma treated with inhaled beclomethasone dipropionate. , 1995, American journal of respiratory and critical care medicine.

[23]  J. Rootman,et al.  Ocular pharmacokinetics of subconjunctivally administered cyclosporine in the rabbit. , 1991, Canadian journal of ophthalmology. Journal canadien d'ophtalmologie.

[24]  J. Dutton,et al.  Visual rehabilitation of aphakic children. , 1990, Survey of ophthalmology.