Dextromethorphan upregulates osteoblast and osteoclast activity but does not attenuate ovariectomy-induced osteoporosis.
OBJECTIVE
Study on the in vivo regulatory role of glutamate in osteoblast (OB) and osteoclast (OC) differentiation is less advanced. The present study investigated the effect of dextromethorphan (DXM), an N-methyl-d-aspartate receptors (NMDARs) antagonist, on osteoporosis development.


METHODS
In order to examine the role of glutamate in bone metabolism, ovariectomized (Ovx) female Wistar rats were injected three times per week for 8weeks with either saline, or 15μg/kg of β-estrodiol, or DXM (40mg/kg) intraperitoneally. Serum samples were collected every two weeks for measuring osteocalcin and C-terminal telopeptide of type I collagen (CTX-1) level. Rats were then sacrificed at week 8 and the femurs harvested for micro-CT scanning and mechanical strength.


RESULTS
In saline-treated group, osteocalcin level significantly lower than that of sham-operated rats at 8weeks after operation, while CTX-1 levels were not affected. Estrogen treatment, as a positive control, partially inhibited the Ovx-induced reduction of osteocalcin serum level. DXM injection prevented the Ovx-induced reduction of osteocalcin expression and significantly upregulated CTX-1 expression. The micro-CT scan showed that the bone volume density decreased significantly in DXM treated rats compared to the sham-operated rats. In the mechanical strength assay, the maximum failure load for DXM treatment was significantly lower than the other groups.


CONCLUSIONS
Treatment with DXM upregulated OB and OC markers in Ovx rats, however with a greater effect on the OC marker, and had no significant benefit on bone volume density or bone strength.
Department of Orthopedics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Orthopedics, Taipei Medical University Hospital, Taipei, Taiwan.
Jia-Lin
JL
Wu
Department of Anesthesiology, Cathay General Hospital, Taipei, Taiwan.
Wei-Yuan
WY
Tsai
School of Physical Therapy, Chung Shan Medical University, Taichung, Taiwan.
Jian-Horng
JH
Chen
Department of Anesthesiology, Cathay General Hospital, Taipei, Taiwan. Electronic address: w82556@gmail.com.
Chih-Shung
CS
Wong
D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D024042:Collagen Type I / Q000378:metabolism; D003915:Dextromethorphan / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D010006:Osteoblasts / Q000378:metabolism* / Q000473:pathology; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology; D010024:Osteoporosis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D010052:Ovariectomy; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
C000615613:CTX-I peptide, rat; D024042:Collagen Type I; D010446:Peptide Fragments; D003915:Dextromethorphan
Cefazolin (PubChem CID:23675322); Dextromethorphan; Dextromethorphan (PubChem CID: 5360696); Glutamate; Osteoblast; Osteoclast; Osteoporosis; Thiopental (PubChem CID:000715); β-estrodiol (PubChem CID:5757)