Prostaglandin-Induced Hyperostosis as A Dose-Related Condition

Background: Prostaglandin-induced hyperostosis is caused by prolonged infusion of prostaglandin E (PGE). It commonly involves diaphysis of the long bones of the upper and lower limbs, clavicles, ribs, and scapulae. PGE therapy is commonly used to maintain the patency of ductus arteriosus in neonates with ductal-dependent congenital heart defects (CHDs). Reversible cortical hyperostosis of long bones is a side-effect of PGE injections. Some studies suggested that periostitis was more dependent on duration than on dosage of the prostaglandins administered. However, infants with cyanotic CHD, which causes decreased pulmonary blood flow and reduced PGE clearance, may have higher systemic concentration of PGE. Aim: To determine the minimal injected dose of PGE for risk of developing prostaglandin-induced periostitis in infants with ductal-dependent CHD. Methods: Forty-eight infants with ductal-dependent CHDs and previous preoperative PGE infusion (> 2 d) who underwent reconstructive cardiac surgery were retrospectively included and separated into two groups. The study group included 20 patients (6 females) meeting the inclusion criteria of PGE-induced hyperostosis of long bones, the diaphysis of upper and/or lower limbs, clavicles, or ribs, which was diagnosed by X-ray. The remaining 28 patients were included in the control group (13 females). Patients with hyperostosis of any other localization were excluded. Results: Receiver operating characteristic analysis was performed to determine the minimal injected dose in which there was a risk of developing prostaglandin-induced periostitis. Periostitis was graded as 1 and its absence as 0. Estimated data showed that if the injected dose had increased to 172.5 ng/kg/min, hyperostosis would likely appear in 90% of patients (area under the curve: 0.918; P < 0.0010), with sensitivity of 90.0% and specificity of 92.9%. The odds ratio of hyperostosis development was 75.0 (P < 0.0001) in the group with a total injected dose ≥ 172.5 ng/kg/min. The relative risk in the same group was 11.6 (P = 0.0004). Conclusion: Our study showed that prostaglandin-induced hyperostosis is a dose-related condition. The minimum injected dose of 172.5 ng/kg/min was estimated as a risk of hyperostosis development