Histomorphometry evaluation of bone anabolism promoted by prostaglandin E1 and its relation to hypercalcemia

Francisco H. Velásquez-Forero, Unidad de Investigación y Diagnóstico en Nefrología y Metabolismo Mineral Óseo, Hospital Infantil de México Federico Gómez, Ciudad de México, México
Pedro F. Valencia-Mayoral, Dirección de Planeación, Hospital Infantil de México Federico Gómez, Mexico City, Mexico

Background: At present, parathyroid hormone is the only existing anabolic bone therapy but produces hypercalcemia. Prostaglandin E1 (PGE1) has been suggested as a bone anabolic agent that allows bone modeling formation without producing hypercalcemia. This study aimed to corroborate these PGE1 properties. Methods: For 22 days, rabbits (n = 30) were divided into three groups (n = 10 each group) and received intravenous solutions: vehicle (control group), palate disjunction + vehicle (sham group), and palate disjunction + 50 μg of PGE1 (PGE1 group). On days 1, 3, and 22, palatine suture X-rays weretaken. On day 22, bone formation markers were analyzed, and the rabbits were sacrificed. Bone palate undecalcified samples were processed. Histomorphometry software was used to analyze bone parameters, and the mineralization front was stained with toluidine blue. Scalloped lines reflect remodeling-based bone formation (RBF), and smooth lines reflect modeling-based formation (MBF). Results: X-rays showed more significant palatal disjunction in the PGE1 group; this group exhibited significant calcitriol serum increments. Hypercalciuria was observed in the PGE1 group, and resorption markers (N-telopeptides) remained stable. Sutural bones in the PGE1 group exhibited significant anabolism in structural parameters. RBF was 20%, and MBF was 6% in the sham group; in the PGE1 group, RBF was 8.6%, and MBF was 17%. In the PGE1 group, mineralization was significantly accelerated, but resorption remained stable. Conclusions: This model suggests that PGE1 favors palate disjunction, calcitriol synthesis, and shortens the mineralization. Therefore, PGE1 is an important bone anabolic molecule predominantly of modeling-based form and no hypercalcemia.

Keywords: Prostaglandin E1 bone anabolism. Calcitriol increments. Anabolism without hypercalcemia. Modeling-based bone formation. Remodeling-based bone formation and shortening bone mineralization.