RANKL inhibition through osteoprotegerin blocks bone loss in experimental periodontitis.
BACKGROUND
Prevention of alveolar bone destruction is a clinical challenge in periodontal disease treatment. The receptor activator of nuclear factor-kappa B ligand (RANKL) inhibitor osteoprotegerin (OPG) inhibits osteoclastogenesis and suppresses bone resorption.


METHODS
To study the effects of RANKL inhibition on alveolar bone loss, an experimental ligature-induced model of periodontitis was used. A total of 32 rats were administered human OPG-Fc fusion protein (10 mg/kg) or vehicle by subcutaneous delivery twice weekly for 6 weeks. Negative or positive controls received no treatment or disease through vehicle delivery, respectively. Biopsies were harvested after 3 and 6 weeks, and mandibulae were evaluated by microcomputed tomography (microCT) and histology. Serum levels of human OPG-Fc and tartrate-resistant acid phosphatase-5b (TRAP-5b) were measured throughout the study by enzyme-linked immunosorbent assay (ELISA). Statistical analyses included analysis of variance (ANOVA) and Tukey tests.


RESULTS
Human OPG-Fc was detected in the sera of OPG-Fc-treated animals by 3 days and throughout the study. Serum TRAP-5b was sharply decreased by OPG-Fc treatment soon after OPG-Fc delivery and remained low for the observation period. Significant preservation of alveolar bone volume was observed among OPG-Fc-treated animals compared to the controls at weeks 3 and 6 (P <0.05). Descriptive histology revealed that OPG-Fc significantly suppressed osteoclast surface area at the alveolar crest.


CONCLUSIONS
Systemic delivery of OPG-Fc inhibits alveolar bone resorption in experimental periodontitis, suggesting that RANKL inhibition may represent an important therapeutic strategy for the prevention of progressive alveolar bone loss.
Jin
Qiming
Q
Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USA.
Cirelli
Joni A
JA
Park
Chan Ho
CH
Sugai
James V
JV
Taba
Mario
M
Kostenuik
Paul J
PJ
Giannobile
William V
WV
D000135:Acid Phosphatase / Q000378:metabolism; D016301:Alveolar Bone Loss / Q000378:metabolism / Q000517:prevention & control*; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008334:Mandible; D053244:Osteoprotegerin / Q000097:blood / Q000502:physiology*; D010518:Periodontitis / Q000378:metabolism*; D053245:RANK Ligand / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D018709:Statistics, Nonparametric; D000071681:Tartrate-Resistant Acid Phosphatase
D007527:Isoenzymes; D053244:Osteoprotegerin; D053245:RANK Ligand; D011994:Recombinant Proteins; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase