Korean J Orthod.  2020 Jan;50(1):42-51. 10.4041/kjod.2020.50.1.42.

The effect of cetirizine, a histamine 1 receptor antagonist, on bone remodeling after calvarial suture expansion

  • 1Department of Orthodontics, Gangnam Severance Dental Hospital, College of Dentistry, Yonsei University, Seoul, Korea. khkim@yuhs.ac
  • 2Department of Orthodontics and Institute of Craniofacial Deformity, College of Dentistry, Yonsei University, Seoul, Korea.


The objective of this study was to evaluate the effects of cetirizine, a histamine 1 receptor antagonist, on bone remodeling after calvarial suture expansion.
Sixty male Sprague-Dawley rats were divided into 4 groups; the phosphate-buffered saline (PBS)-injected no expansion group, cetirizine-injected no expansion group, PBS-injected expansion group, and cetirizine-injected expansion group, and were observed at 7, 14, and 28 days. Five rats per group were examined at each observation day. Daily injections of cetirizine or PBS were administered to the relevant groups starting 2 weeks prior to expander insertion. A rapid expander was inserted in the calvarial bone to deliver 100 cN of force to the parietal suture. The specimens were prepared for hematoxylin and eosin and tartrate-resistant acid phosphatase (TRAP) staining. Suture opening and bone regeneration were evaluated using microcomputed tomography and bone histomorphometric analysis. Serum blood levels of osteocalcin and carboxy-terminal collagen crosslinks (CTX) were also evaluated.
TRAP-positive cell counts and CTX levels decreased while osteocalcin levels increased in the cetirizine-injected expansion group at observation day 28. In the expansion groups, the mineralized area gradually increased throughout the observation period. At day 28, the cetirizine-injected expansion group showed greater bone volume density, greater mineralized area, and narrower average suture width than did the PBS-injected expansion group.
Cetirizine injection facilitated bone formation after suture expansion, mostly by suppressing osteoclastic activity. Histamine 1 receptor antagonists may aid in bone formation after calvarial suture expansion in the rat model.


Cetirizine; Calvarial suture; Rapid expansion; Rat model

MeSH Terms

Acid Phosphatase
Bone Regeneration
Bone Remodeling*
Cell Count
Eosine Yellowish-(YS)
Models, Animal
X-Ray Microtomography
Acid Phosphatase
Eosine Yellowish-(YS)


  • Figure 1 Three-dimensional microcomputed tomography (micro-CT) reconstruction of the phosphate-buffered saline (PBS)/cetirizine groups after active expansion of the parietal suture at 7 (A, D), 14 (B, E), and 28 (C, F) days. Parietal suture showing the region of interest (ROI) used in the micro-CT analysis (G). Parietal suture with the expansion appliance (H). Images of the PBS- and cetirizine-injected no expansion groups (I, J).

  • Figure 2 Effect of cetirizine/phosphate-buffered saline (PBS) and active/inactive expansion on body weight.

  • Figure 3 Changes of the suture on histological sections. Hematoxylin and eosin staining of the parietal suture. Sevenday phosphate-buffered saline (PBS) no expansion (A), 7-day PBS expansion (A′), 14-day PBS no expansion (B), 14-day PBS expansion (B′), 28-day PBS no expansion (C), 28-day PBS expansion (C′), 7-day cetirizine no expansion (D), 7-day cetirizine expansion (D′), 14-day cetirizine no expansion (E), 14-day cetirizine expansion (E′), 28-day cetirizine no expansion (F), and 28-day cetirizine expansion (F′). Scale bar = 100 µm.

  • Figure 4 Region of interest used in the histomorphometric analysis. Representations of the mineralized area (A), voided areas (B), and fibrous area (C). H&E staining (left, ×20 magnification; right, ×40 magnification). Scale bar = 100 µm.

  • Figure 5 Tartrate-resistant acid phosphatase (TRAP)-positive cell count comparison between the phosphate-buffered saline (PBS)- and cetirizine-injected rats in the no expansion and expansion groups. TRAP staining. Scale bar = 20 µm. ***p < 0.001.

  • Figure 6 Comparison of osteocalcin and carboxy-terminal collagen crosslink (CTX) levels between the phosphate-buffered saline (PBS)- and cetirizine-injected rats in the no expansion (A, B) and expansion (C, D) groups. *p < 0.05, **p < 0.01, ***p < 0.001.


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