The effects of propranolol (PRO), a nonselective β-adrenergic receptor (β-AR) antagonist with membrane-stabilizing action on bone metabolism, were examined in spontaneously hypertensive rats (SHR) showing osteoporosis with hyperactivity of the sympathetic nervous system. Treatment of SHR with PRO at 1 and 5 mg/kg p.o. for 12 weeks increased bone mass of the lumbar vertebra and proximal tibia without affecting blood pressure, but PRO at 50 and 100 mg/kg with hypotensive action did not increase bone mass. Next, the effects of PRO at 0.1, 1, and 10 mg/kg on bone status were examined in more detail. Compared with the SHR control, not only bone mass but also biomechanical parameters of strength and toughness of the lumbar vertebrae were increased in SHR treated with PRO at 0.1 and 1 mg/kg, suggesting antiosteoporotic action. PRO at 1 mg/kg statistically increased histomorphometry indices of bone formation, whereas PRO at doses of 0.1, 1, and 10 mg/kg decreased those of bone resorption. Antiosteoporotic effect of PRO is attenuated at 10 mg/kg compared with 0.1 and 1 mg/kg. In addition, treatment with timolol, a nonselective β-AR antagonist without membrane-stabilizing action, or butoxamine, a selective β2-AR antagonist, at 1 mg/kg increased bone mass in SHR. These results suggested that treatment of SHR with β-blockers at low dose improved bone loss and bone fragility. This antiosteoporotic effect of β-blockers seems to be caused by the blocking action of β2-AR, regardless of the membrane-stabilizing action.

Recently, involvement of the sympathetic nervous system in bone metabolism has attracted attention. β2-Adrenergic receptor (β2-AR) is presented on osteoblastic and osteoclastic cells. We previously demonstrated that β-AR blockers at low dose improve osteoporosis with hyperactivity of the sympathetic nervous system via β2-AR blocking, while they may have a somewhat inhibitory effect on osteoblastic activity at high doses. In this study, the effects of butoxamine (BUT), a specific β2-AR antagonist, on tooth movement were examined in spontaneously hypertensive rats (SHR) showing osteoporosis with hyperactivity of the sympathetic nervous system. We administered BUT (1 mg/kg) orally, and closed-coil springs were inserted into the upper-left first molar. After sacrifice, we calculated the amount of tooth movement and analyzed the trabecular microarchitecture and histomorphometry. The distance in the SHR control was greater than that in the Wistar-Kyoto rat group, but no significant difference was found in the SHR treated with BUT compared with the Wistar-Kyoto rat control. Analysis of bone volume per tissue volume, trabecular number, and osteoclast surface per bone surface in the alveolar bone showed clear bone loss by an increase of bone resorption in SHR. In addition, BUT treatment resulted in a recovery of alveolar bone loss. Furthermore, TH-immunoreactive nerves in the periodontal ligament were increased by tooth movement, and BUT administration decreased TH-immunoreactive nerves. These results suggest that BUT prevents alveolar bone loss and orthodontic tooth movement via β2-AR blocking.

The purpose of this study was to compare the treatment duration and dentoskeletal changes between two different anchorage systems used to treat maxillary dentoalveolar protrusion and to examine the effectiveness of en-masse retraction using two miniscrews placed in the midpalatal suture. Fifty-seven patients (9 men, 48 women), who had undergone level anchorage system treatment at Aichi-Gakuin University Dental Hospital (Nagoya, Japan) were divided into two groups according to the method of maxillary posterior anchorage reinforcement: midpalatal miniscrews (25 patients, mean age 22 years) and conventional anchorage (32 patients, mean age 19 years). The en-masse retraction period, overall treatment duration, pre-treatment effective ANB angle, and change in the effective ANB angle were compared with an independent-samples t-test. Compared to the headgear group, the duration of en-masse retraction was longer by approximately 4 months in the miniscrew group (p < 0.001). However, we found no significant difference in the total treatment duration between the groups. Moreover, a greater change in the effective ANB angle was observed in patients treated with miniscrews than in those treated with the conventional method (p < 0.05). The level anchorage system treatment using miniscrews placed in the midpalatal area will allow orthodontists more time to control the anterior teeth during en-masse retraction, without increasing the total treatment duration. Furthermore, it achieves better dentoskeletal control than does the conventional anchorage method, thereby improving the quality of the treatment results.

Gangliosides are widely expressed in almost all tissues and cells and are also considered to be essential in the development and maintenance of various organs and tissues. However, little is known about their roles in bone metabolism. In this study, we investigated the effects of genetic deletion of ganglioside D3 (GD3) synthase, which is responsible for the generation of all b-series gangliosides, on bone metabolism. Although b-series gangliosides were not expressed in osteoblasts, these gangliosides were expressed in pre-osteoclasts. However, the expression of these gangliosides was decreased after induction of osteoclastogenesis by receptor activator of nuclear factor kappa-B ligand (RANKL). Three-dimensional micro-computed tomography (3D-μCT) analysis revealed that femoral cancellous bone mass in GD3 synthase-knockout (GD3S KO) mice was higher than that in wild type (WT) mice at the age of 40 weeks, although there were no differences in that between GD3S KO and WT mice at 15 weeks old. Whereas bone formation parameters (osteoblast numbers/bone surface and osteoblast surface/bone surface) in GD3S KO mice did not differ from WT mice, bone resorption parameters (osteoclast numbers/bone surface and osteoclast surface/bone surface) in GD3S KO mice became significantly lower than those in WT mice at 40 weeks of age. Collectively, this study demonstrates that deletion of GD3 synthase attenuates bone loss that emerges with aging.