| Adachi et al.1414 Adachi H, Igarashi K, Mitani H, Shinoda H. Effects of topical administration of a bisphosphonate (risedronate) on orthodontic tooth movements in rats. J Dent Res. 1994 Aug;73(8):1478-86. (1994, Japan) |
Experimental (split-mouth design). Standardized expansion spring, made of 0.012-in Nickel-Titanium (NiTi) wire |
126 male Wistar rats |
9-10 weeks |
Group A - Anchorage effect of risedronate: Group A1: Orthodontic tooth movement effect of risedronate: 50µL of risedronate solution (0.9% NaCl, pH 7.4) at a concentration of either 0 (0.9% NaCl), 125, 250, or 500 µmol/L (left side). Injection of 50µL of 0.9% NaCl solution into the corresponding area used as control (right side). n=41 animals.
Group A2: Histological analysis: risedronate at a concentration of 500 µmol/L (left side) and control (0.9% NaCl) (right side) (n=23 animals). Group B - Retentive effect of risedronate: Group B1: Orthodontic tooth movement of risedronate: 50µL of risedronate solution (0.9% NaCl, pH 7.4) at a concentration of either 0 (0.9% NaCl), 125, 250, or 500 µmol/L (left side). Injection of 50 µL of 0.9% NaCl solution into the corresponding area used as control (right side) (n=40). Group B2: Histological analysis: risedronate at a concentration of 500 gmol/L (left side) and control (0.9% NaCl)(right side) (n=22 animals). |
Group A: 3 weeks. The administrations started 3 days prior to the set of appliance + application every 3 days.
Group A1: 0, 3, 7, 14 or 21 days after application of orthodontic force.
Group B: 3 weeks without test drug. Then, the application of risedronate initiated.
Group B1: The right and left upper first molars were first moved to the buccal side with the spring without any test drug. Three weeks later, the spring was removed, and administration of risedronate was initiated 0, 3, 7, 14 or 21 days after appliance was removed. |
Stone model with sliding calipers: measurement of the distance between the crests of the mesiopalatal cusps of the first molars before and after tooth movement.
a = tooth movement or relapse movement on the control side.
b = tooth movement or relapse movement on the risedronate-injected side.
% inhibition = b/a x 100.
Histology: osteoclasts count and measurement of the sizes of active bone-resorptive lacunae. |
Group A1: decreased tooth movement on the risedronate-injected side. The percent inhibition (b/a x 100) was 102.1%, 91.2%, 71.1%, and 49.6%X, of the control side at concentrations of 0, 125, 250, and 500µmol/L, respectively.
Group A2: Risedronate-treated side had decreased osteoclast count per area at the periods of 3, 7 and 14 days. Decreased percentage of the size of the lacunae and resorptive area on the risedronate-injected side.
Group B1: The relapse of the tooth on the risedronate-injected side was significantly less than control. The percent inhibition (b/a x 100) was 96.1%, 79.8%, 73.7%, and 56.7% of the control side at concentrations of 0, 125, 250, and 500 µmol/L, respectively.
Group B2: Except on day 14, risedronate had decreased number of osteoclasts in all time points. Sizes of active bone-resorptive lacunae could not be determined. |
Wu et al.1515 Wu D, Meng B, Cheng Y, Gan L, Huang P, Cao Y. The effect of risedronate on orthodontic tooth movement in ovariectomized rats. Arch Oral Biol. 2019 Sep;105:59-64. (2019,
China) |
Experimental (split mouth design). Nickel-Titanium alloy closed-coil springs |
45 Sprague-Dawley rats |
10 weeks |
Group A: ovariectomy (saline i.p.).
Group B: ovariectomy + risedronate (10ug/kg risedronate dissolved in saline i.p.).
Group C: sham (saline i.p.)
(n=15 per group) |
The administrations started 2 weeks after ovariectomy, and drug administration was every 3 days. On days 3, 7 and 14, five rats from each group were euthanized. |
Digital caliper: distance of tooth movement. TRAP staining: osteoclasts count. Immunohistochemical analysis: analysis of RANKL, OPG and CTPSK. |
Ovariectomy increased OTM, osteoclasts count, RANKL and CTPSK levels, and decreased OPG levels. Risedronate treatment into the OVX rats reversed all phenotypes. |
Utari et al.1616 Utari TR, Ana ID, Pudyani PS, Asmara W. The intrasulcular application effect of bisphosphonate hydrogel toward osteoclast activity and relapse movement. Saudi Dent J. 2021 Jul;33(5):292-8. (2021,
Indonesia) |
Experimental (control group and release of risedronate). Nickel-Titanium open coil spring |
75 male guinea pigs |
5 weeks |
Group Bis-CR250 (250mmol/L; 1mg pure risedronate after hydrogel preparation) (n=25)
Group Bis-CR500 (500mmol/L; 1.92mg pure risedronate after hydrogel preparation) (n=25)
Group Bis-CR000 (control) (n=25) |
After reaching ± 3mm of distance between the lower incisor bonding cleat, the distance was maintained for 14 days as a stabilization period, then it was removed. The administrations were every 3 days. On days 3, 7, 14 and 21 relapse movement and interincisal distance were measured. |
Sliding caliper: relapse movement and interincisal distance. TRAP staining: osteoclasts count Histological analysis: to calculate the average number of osteoclasts on the mesial (compression side) of the alveolar bone. |
Effect to relapse distance: the control had the highest relapse rate at days 14 and 21. There was a significantly less relapse movement in the treatment group on days 14 and 21 compared to control. Bis-CR500 inhibited the relapse movement more effectively than Bis-CR250 on day 21, indicating a dose dependency in the biphosphonate hydrogel application. Number of osteoclasts: osteoclast were abundant along the alveolar bone in Bis-CR000 but decreased in the Bis-CR250 and Bis-CR500 groups. |
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