Lactation induces increases in the RANK/RANKL/OPG system in maxillary bone

• Published in: Bone (New York, N.Y.) Vol. 110; pp. 160 - 169
• Main Authors: Macari, Soraia, Sharma, Lavanya A., Wyatt, Amanda, da Silva, Janine Maíra, Dias, George J., Silva, Tarcília A., Szawka, Raphael E., Grattan, David R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-05-2018
• Subjects: Alveolar bone; Animals; Bone Diseases, Metabolic - metabolism; Bone Remodeling; Cell Differentiation; Female; Lactation; Maxilla - diagnostic imaging; Maxilla - metabolism; Mice; Mice, Inbred C57BL; Osteoblasts - metabolism; Osteoclasts - metabolism; Osteoprotegerin; Osteoprotegerin - metabolism; Phenotype; Prolactin - metabolism; RANK; RANK Ligand - metabolism; RANKL; Receptor Activator of Nuclear Factor-kappa B - metabolism; X-Ray Microtomography; RANKL; RANK; Bone remodeling; Lactation; Alveolar bone; Osteoprotegerin
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/j.bone.2018.01.032

The underlying causes of maxillary bone loss during lactation remain poorly understood. We evaluated the impact of lactation on physiological and mechanically-induced alveolar bone remodeling. Nulliparous non-lactating (N-LAC) and 21-day lactating (LAC) mice underwent mechanically-induced bone remodeling by orthodontic tooth movement (OTM). Micro-computed tomography (microCT) was performed in the maxilla, femur and vertebra. Tartrate-resistant-acid phosphatase (TRAP) and Masson's trichrome labelling was performed in the maxillary bone and gene expression was determined in the periodontal ligament. The effect of prolactin on osteoclast (OCL) and osteoblast (OBL) differentiation was also investigated in N-LAC and LAC mice. Lactation increased alveolar bone loss in the maxilla, femur and vertebra, while OTM was enhanced. The number of OCL and OBL was higher in the maxilla of LAC mice. OTM increased OCL in both groups; while OBL was increased only in N-LAC but not in LAC mice, in which cell numbers were already elevated. The alveolar bone loss during lactation was associated with increased expression of receptor activator of nuclear factor-KappaB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) in the maxilla. OTM induced the same responses in N-LAC mice, whereas it had no further effect in LAC mice. Lactation enhanced differentiation of OCL and OBL from bone marrow cells, and prolactin recapitulated OCL differentiation in N-LAC mice. Thus, lactation increases physiological maxillary bone remodeling and OTM, and both require activation of RANK/RANKL/OPG system. These findings expand our knowledge of lactation-induced osteopenia and have possible impact on clinical practice regarding orthodontic treatments and dental implants in lactating women.
•Lactation induces osteopenic effects on maxillary alveolar bone.•Lactation-induced bone loss in femur is correlated with maxillary osteopenic phenotype.•Lactation enhances mechanically-induced bone remodeling and osteoclast and osteoblast numbers.•Lactation and mechanically-induced bone remodeling increase RANK/RANKL/OPG pathway in the maxillary alveolar bone.•Osteoclast differentiation is enhanced by lactation and prolactin.