Zoledronate reverses mandibular bone loss in osteoprotegerin-deficient mice.
To characterize the changes in osteoprotegerin-deficient (OPG-/-) mice mandibles and the possible mandibular bone loss prevention by zoledronate. This preventive effect in the mandible differed from that in the proximal tibia and was independent of the OPG pathway.


BACKGROUND
The study aimed to characterize both the changes in the mandible in osteoprotegerin-deficient (OPG-/-) mice and possible mandibular bone loss prevention by zoledronate.


METHODS
Twenty-eight 6-week-old female mice (C57BL/6J), including OPG-/- (n = 21) and wild-type (WT) (n = 7) mice, were assigned to four groups after 2 weeks of acclimatization to local vivarium conditions: wild mice with vehicle (WT group); OPG-/- mice with vehicle (OPG-/- group); and OPG-/- mice that were subcutaneously injected with either 50 or 150 microg/kg zoledronate (Zol-50 and Zol-150 groups, respectively). Mice were sacrificed at 4 weeks after these treatments and after fasting for 12 h. Sera were harvested for biochemical analyses. The right mandible and tibia of each mouse were selected for microCT analysis. Student's t-test was performed for comparisons of bone parameters at different sites in the WT group. Analysis of variance (ANOVA) was used to compare the biomarkers and bone parameters in the different treatment groups.


RESULTS
Serum bone-specific alkaline phosphatase (B-ALP) and tartrate-resistant acid phosphatase 5b (TRACP-5b) were significantly decreased in WT mice as compared to the levels in the OPG-/- mice (P < 0.05). Zoledronate treatment decreased the high serum B-ALP activity observed in OPG-/- mice to the levels seen in WT mice, while serum TRACP-5b concentrations were decreased to levels even lower than those in WT mice. There were substantial variations in BMD and microstructure of the mandibular and proximal tibial trabeculae. Mandibular bone loss was less affected by OPG gene deprivation than the proximal tibia was. Both zoledronate groups showed greater BMD, trabecular BV/TV, Tb.Th, Tb.N, and Conn.D and a significant decrease in Tb.Sp and SMI as compared to the findings in OPG-/- mice (P < 0.05). However, higher apparent BMD and more compact plate-like trabeculae were observed in the mandible after treatment with zoledronate as compared to the findings in the proximal tibia. No significant differences were found in any parameter in both zoledronate groups.


CONCLUSIONS
The present study showed that zoledronate could reverse the significant bone loss in mice mandibles that was induced by OPG gene deficiency. This preventive effect, which was accompanied with considerable inhibition of bone turnover, differed in the mandible and in the proximal tibia and was independent of the OPG pathway.
Sheng
Z-F
ZF
Institute of Metabolism and Endocrinology, The Second Xiang-Ya Hospital, Central South University, Renmin road 139#, Changsha, 410011, Hunan, People's Republic of China.
Xu
K
K
Ma
Y-L
YL
Liu
J-H
JH
Dai
R-C
RC
Zhang
Y-H
YH
Jiang
Y-B
YB
Liao
E-Y
EY
D000135:Acid Phosphatase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D016301:Alveolar Bone Loss / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001862:Bone Resorption / Q000517:prevention & control; D004164:Diphosphonates / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D005260:Female; D007093:Imidazoles / Q000627:therapeutic use*; D007527:Isoenzymes / Q000097:blood; D008334:Mandible / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053244:Osteoprotegerin / Q000172:deficiency* / Q000235:genetics; D011897:Random Allocation; D000071681:Tartrate-Resistant Acid Phosphatase; D013977:Tibia / Q000473:pathology; D000077211:Zoledronic Acid
D015415:Biomarkers; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D007527:Isoenzymes; D053244:Osteoprotegerin; D000077211:Zoledronic Acid; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase