Diabetes, a chronic hyperglycemic condition, is caused by insufficient insulin secretion or functional impairment. Long-term inadequate regulation of blood glucose levels or hyperglycemia can lead to various complications, such as retinopathy, nephropathy, and cardiovascular disease. Recent studies have explored the molecular mechanisms linking diabetes to bone loss and an increased susceptibility to fractures. This study reviews the characteristics and molecular mechanisms of diabetes-induced bone disease. Depending on the type of diabetes, changes in bone tissue vary. The molecular mechanisms responsible for bone loss in diabetes include the accumulation of advanced glycation end products (AGEs), upregulation of inflammatory cytokines, induction of oxidative stress, and deficiencies in insulin/IGF-1. In diabetes, alveolar bone loss results from complex interactions involving oral bacterial infections, host responses, and hyperglycemic stress in periodontal tissues. Therapeutic strategies for diabetes-induced bone loss may include blocking the AGEs signaling pathway, decreasing inflammatory cytokine activity, inhibiting reactive oxygen species generation and activity, and controlling glucose levels; however, further research is warranted.

Developments in cancer therapies and diagnostic techniques have improved the long-term survival of cancer patients. Certain cancer treatments, such as radiotherapy, often harm normal tissue as well as the specifically targeted cancer cells. High doses of radiation induce bone loss. This study investigated the effects of pentoxifylline (PTX) on radiation-induced bone loss in C3H/HeN mice. C3H/HeN mice were divided into sham and irradiation (3 Gy, gamma-ray, IR) groups. The irradiated mice were treated for 12 weeks with vehicle, PTX (p.o.) or PTX (s.c.). Grip strength, uterus weight, serum alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) level were measured. Tibiae were analyzed using micro-computed tomography. There were no significant differences in the degree of grip strength, body weight and uterine weight between IR group and PTX-treated group. Treatment of PTX significantly preserved trabecular bone volume, trabecular number, trabecular separation and bone mineral density of proximal tibia metaphysic. The administration of PTX lowered serum TRAP in IR mice, suggesting that PTX can reduce the bone resorptive rate in mice. Our experimental data support the protective role of PTX against bone loss in irradiated mice. Based on the findings of this study, development of PTXbased treatments is anticipated to address bone loss after radiotherapy. Prospective dose escalation studies are required to determine the appropriate dosage of PTX.

Homer proteins are scaffold proteins that regulate calcium (Ca2+) signaling by modulating the activity of multiple Ca2+ signaling proteins. In our previous report, Homer2 and Homer3 regulated NFATc1 function through its interaction with calcineurin, which then acted to regulate receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis and bone metabolism. However, to date, the role of Homers in osteoclastogenesis remains unknown. In this study, we investigated the roles of Homer2 and Homer3 in aging-dependent bone remodeling. Deletion of Homer2 /Homer3 (Homer2/3 DKO) markedly decreased the bone density of the femur. The decrease in bone density was not seen in mice with Homer2 (Homer2−/−) and Homer3 (Homer3−/−) deletion. Moreover, RANKL treatment of bone marrow-derived monocytes/macrophages in Homer2/3 DKO mice significantly increased the formation of multinucleated cells and resorption areas. Finally, Homer2/3 DKO mice decreased bone density in an aging-dependent manner. These findings suggest a novel potent mode of bone homeostasis regulation through osteoclasts differentiation during aging by Homer proteins, specifically Homer2 and Homer3.

The purpose of this study was to evaluate the effect of mangosteen extract complex (MEC; Garcinia mangostana L. and propolis extracts) on the inhibition of inflammation and prevention of alveolar bone loss using a ligature-induced periodontitis model. Rat molars were ligatured with silk, and 1 μg/mL of lipopolysaccharide of Porphyromonas gingivalis was injected into the buccal and palatal gingivae of the teeth with or without treatment with the MEC. Changes in the expression levels of prostaglandin E2 (PGE2), interleukin-8 (IL-8), inducible nitric oxide synthase (iNOS), matrix metalloproteinase-8 (MMP-8), cyclooxygenase (COX)-1, and COX-2 in gingival tissues were evaluated using enzyme-linked immunosorbent assays. Alveolar bone loss around the ligated molars was examined using micro-computed tomography. The expression levels of PGE2, IL-8, iNOS, MMP-8, COX-1, and COX-2 in gingival tissues were significantly reduced in the group treated with a mixture of 16 μg of mangosteen extract powder and 544 μg of propolis extract powder (ligation [Lig] + lipopolysaccharide extracted from P. gingivalis KCOM 2804 [L] + MEC 1:34). Additionally, alveolar bone loss was significantly reduced in the Lig + L + MEC 1:34 group compared with that in other groups. These results indicate that the MEC could be useful in preventing and treating periodontitis.

Osteoporosis is a major worldwide public health problem that poses a great economic burden to society. Puerariae Radix, the dried root of Pueraria lobata (Wild.) Ohwi, has been widely used in Asia. This study investigated the effects of Puerariae Radix (PR) on bone loss in ovariectomized (OVX) mice. C3H/HeN mice (10 weeks old) were divided into sham and OVX groups. The OVX mice were treated with vehicle, 17β-estradiol (E2), PR (oral administration, 250 mg/ kg/day) or PR (intraperitoneal administration, 50 mg/ kg/every other day) for 6 weeks. Grip strength, uterus weight, serum alkaline phosphatase (ALP), estradiol concentration and osteoclast surface levels were measured. Tibiae were analyzed using microcomputed tomography. There were no significant differences in the degree of grip strength, body weight and uterine weight between OVX group and PR-treated group. As compared with the OVX group, the serum estradiol levels were significantly increased in the PR-treated group. PR (i.p.) significantly preserved trabecular bone volume, trabecular bone number, structure model index and bone mineral density of proximal tibiae metaphysic. The administration of PR lowered serum ALP and osteoclast surface levels in OVX mice, suggesting that PR can reduce the bone turnover rate in mice. The results indicate that the supply of PR can prevent OVX-induced bone loss in mice.

One of functions of Galla Rhois (GR) is reportedly an anti-inflammatory effect on the several inflammatory diseases. However, an effect of GR related to periodontitis has not been investigated. In the present study, we examined the effect of the hexane extract of Galla Rhois (GR-H) on periodontitis. Cytotoxicity was assessed by MTS analysis using human gingival fibroblast (hGF) cells. Experimental periodontitis was induced by injecting E.coli LPS into the palatal gingiva maxillary molar thrice weekly for 3 weeks (LPS group). GR-H diluted in 1xPBS was orally administrated using a syringe at 30 mg/kg body weight and 100 mg/kg body weight once a day (GR-H group). GR-H effect on the alveolar bone loss (ABL) was digitized with a micro-CT. GR-H treatment at concentrations exceeding 0.5 mg/ml showed cytotoxic effect in hGF cells. The micro-CT among groups were presented for the different distances from cemento-enamel junction (CEJ) to alveolar bone crest (ABC). The results indicated an inhibitory effect on alveolar bone loss for orally administered GR-H in a model of LPS-induced periodontitis.

This study was conducted to investigate the dietary and other factors affecting bone mineral density (BMD) in older Korean women. A total of 340 women aged 65 to 74 were recruited from the Kugoksoondam area (Kurye, Goksung, Soonchang and Damyang counties), known as the longevity-belt region in Jeonla province, Korea. They were categorized into two groups according to bone status by T-score : a nonosteoporotic group and an osteoporotic group. Demographic characteristics were collected, as well as information on physical measurements, blood tests for biochemical indicators, health status health-related life style, dietary behavior, favorite food groups, nutrient intake and mini nutrition assessment (MNA). The results are as follows: The mean age of 185 nonosteoporotic women was 69.6 years and that of 155 osteoporotic women was 70.9 years (p<0.001). The mean T-score of the nonosteoporotic group was －1.5 mg/cm3 and that of theosteoporotic group was －3.2 mg/cm3 (p<0.001). Height and body weight in the nonosteoporotic group were significantly higher than in the osteoporotic group (p<0.001, respectively). There was no significant difference in BMI, although the BMI in the nonosteoporotic group was slightly higher. Waist and hip circumferences in the nonosteoporotic group were significantly higher than in the osteoporotic group (p<0.01, respectively), and the mid upper arm and calf circumferences were also significantly higher than in the osteoporotic group (p<0.001, p<0.01, respectively). The 5 m walking ability was significantly superior compared to the osteoporotic group. Serum levels did not show any significant differences between the groups and were within normal range. The serum total protein, albumin and Insulin-like growth factor (IGFs) levels of the nonosteoporotic group were significantly higher than those of the osteoporotic group (p<0.05, p<0.05, p<0.001, respectively). IGF was 104.7 ng/mL for the nonosteoporotic group and 88.1 ng/mL for the osteoporotic group. Physical activity and appetite in the nonosteoporotic group were significantly higher (p<0.01, p<0.05, respectively). The favorite food groups of the nonosteoporotic group comprised more meats and fish than those of the osteoporotic group (p<0.05, respectively). Nutrient intake was not significantly different, with the exception of niacin intake (p<0.05), but the nutrient intake of the nonosteoporotic group was slightly higher than that of the osteoporotic group. The niacin intake of the nonosteoporotic group and the osteoporotic group were 11.4 mgNE and 10.0 mgNE, corresponding to 103.6% and 90.9% of the Korean EAR, respectively. The MNA score of the nonosteoporotic group was significantly more favorable than for the osteoporotic group. In conclusion, it is necessary to maintain adequate body weight and muscle mass. Habitual physical activity may have a beneficial effect on BMD for older women. Dietary factors, such as meat and fish, higher intake of niacin rich foods and nutrient status for older women also appear to have favorable effects on bone mineral density.

Panax ginseng, also known as Korean ginseng, has long been used as a broad tonic in Oriental medicine to augment vitality, health, and longevity, particularly in older people. This study investigated the effects of Korean red ginseng (RG) on bone loss in ovariectomized (OVX) mice. C3H/HeN mice (10-weeks-old) were divided into sham and OVX groups. OVX mice were treated with vehicle, 17β-estradiol (E2), RG (oral administration, 250 mg/kg/day), or RG (intraperitoneal administration, 50 mg/kg/every other day) for 6 weeks. Serum E2 concentration and alkaline phosphatase (ALP) activity were measured. Tibiae were analyzed using microcomputed tomography. Biomechanical properties and osteoclast surface level were measured. There was no significant difference in the degree of grip strength, body weight, uterine weight, mechanical property, tibiae length, or tibiae weight between the OVX and RG-treated groups. Compared with the OVX group, the serum ALP level was significantly lower in the RG-treated groups. Serum E2 levels and osteoclast surface levels did not change between the OVX and RG-treated groups. RG could not preserve trabecular bone volume, trabecular bone number, trabecular separation, trabecular thickness, structure model index, or bone mineral density of the proximal tibiae metaphysic. In conclusion, there was no definite effect of RG on OVX-induced bone loss in C3H/HeN mice.

Periodontal disease induces an increased incidence of tooth loss, particularly in cases with an associated loss of alveolar bone and periodontal ligaments. In this study, alveolar bone loss was detected by micro-computed tomography (CT) following exposure to E. coli lipopolysaccharide (LPS) in a streptozotocin (STZ)-induced diabetic mouse model. A 10 mg/ml dosage of E. coli LPS was applied between the first, second and third molars of the mice three times a week for 10 weeks. The loss of periodontal ligaments and alveolar processes was then evaluated by micro-CT using two and three dimensional microstructure morphometric parameters. In the diabetic mice, E. coli LPS induced the destruction of periodontal ligaments and loss of alveolar process spaces. The distances between periodontal ligaments were significantly widened in the STZ-LPS group compared with the untreated STZ group. The 10 mg/ml exposure to E. coli LPS in the STZ mice also resulted in a significant decrease in the alveolar bone volume fraction. The results of our study suggest that alveolar bone loss can be readily detected by volumetric micro-CT analysis as an increase in the distance between periodontal ligaments and in the alveolar process length.

It has been documented that SPA0355 exerts anti-inflammatory effects via the inhibition of nuclear factor¬kappaB activation. In present study, we investigated the inhibitory effects of SPA0355 on periodontitis in an animal model. Periodontitis was induced by ligation of the cervix of the 1st molar in the left mandible in rats. After ligature, the rats were randomly divided into four groups and topically applied with SPA0355 (0.5, 1, and 2%) or the vehicle alone once daily for 10 days. Body weight and food intake were measured daily throughout the experimental period. At day 10 post-ligature, the infiltration of inflammatory cells and distance of the cementoenamel junction (CEJ) to the alveolar bone crest (ABC) in the distal area of ligatured tooth were estimated histopathologically. No changes in body weight or food intake were found between the control and SPA0355 groups. The degree of inflammation was decreased in all three SPA0355 application groups. A decrease CEJ-ABC distance was observed in the 0.5% and 1% SPA0355 groups. These results indicate that SPA0355 inhibits the infiltration of inflammatory cells and alveolar bone resorption and suggests its potential as a therapeutic agent for periodontitis.

he purpose of this experiment was to examine the antimicrobial effect of the natural flavonoid hesperidin on dental caries and alveolar bone resorption in the albinorats. Twenty five day old male rats were fed with the experimental diets for 42 days. At the end of the 42 day experimental period, the molar tooth occlusal surface was examined by a dissecting microscope. The sulcular caries lesions were recorded: the first molar caries incidence was higher than that of the second molar and the third molar. Alvelolar bone resorption was measured on the buccal and lingual aspects of each molars. Three measurements were taken on the first molar (mesialpoint, midpoint, distalpoint). The results of this experiment, showed that hesperidin is effective in reducing dental caries and alveolar bone resorption.