Visualisation of the unmet treatment need of osteoporotic fracture in Taiwan: A nationwide cohort study.

AIMS: Recent clinical guidelines have suggested that patients experience an osteoporotic fracture should initiate anti-osteoporosis medications (AOMs). However, whether clinical guidelines translate well in "real-world" practices remain questioned. This study aimed to evaluate the "real-world" prescription pattern of AOMs and visualise the unmet treatment needs in different geographical areas in Taiwan. METHODS: Using Taiwan's National Health Insurance Research Database, we identified patients diagnosed with a hip or vertebral fracture between 2009 and 2012. The treatment rate was defined as the proportion of patients receiving AOMs within 1 year after their index fracture. The qualitative geographical information systems approach was adopted to visualise the treatment needs of postfracture patients in different geographical areas. RESULTS: Our study included 276,492 patients diagnosed with a hip or vertebral fracture between 2009 and 2012. The proportion of patients who received AOMs within 1 year after their index fracture increased with age and differed with fracture types and sex. For patients with hip fractures, the treatment rate ranged from 3.43% to 20.88% for female patients and from 0.69% to 10.04% for male patients in different age groups. For patients with vertebral fractures, the treatment rate ranged from 3.23% to 37.08% for female patients and from 1.85% to 23.05% for male patients. Cities in the mid-northern and southern areas of Taiwan had the highest unmet treatment need, with a treatment rate of less than 15%. CONCLUSION: The treatment rate of osteoporotic fractures with AOMs was diverse and suboptimal in Taiwan, especially among male patients. This study used a visualisation technique to display information about the treatment status in different geographical areas and help policymakers allocate resource appropriately.

Integrated care for geriatric frailty and sarcopenia: a randomized control trial.

BACKGROUND: Exercise, nutrition, and psychological interventions may all have positive impacts on frailty and sarcopenia. However, it is not known whether an integrated care programme with all three components can be beneficial and the intensity of such programme is also not certain. In this study, we aim to determine the effectiveness of two levels of integrated care on frailty and sarcopenia. METHODS: A randomized control trial was conducted at two community hospitals in Taiwan. Older adults (65-79 years of age, N = 289) who scored ≥1 on the Cardiovascular Health Study Phenotypic Classification of Frailty (CHS_PCF) were enrolled in the trial. Low-level care (LLC) participants received a 2 h education course on frailty, sarcopenia, coping strategy, nutrition, and demonstration of study exercise programme. Educational multimedia material was distributed as reference for home practice with bi-monthly telephone follow-ups on adherences. High-level care (HLC) participants, in addition to LLC instructions, received six sessions of on-site problem solving therapy and 48 exercise sessions within 6 months. Brief nutrition consultation was also provided during the exercise sessions. Primary outcome was improvement of the CHS_PCF by at least one category (from pre-frail to robust, or from frail to pre-frail or robust) from baseline. Secondary outcomes included changes of individual frailty, and sarcopenia indicators. Assessments were done at 3, 6, and 12 months by trained research assistants blinded to randomization status. Intention-to-treat analysis was applied. RESULTS: Mean age was 71.6 ± 4.3 years, with 53% females. For the entire cohort, improvement of primary outcome was 35% at 3 months, increased to 40% at 6 months, and remained stable at 39% at 12 months. Improvement rates were similar in both groups. Compared with the LLC group, HLC participants had greater improvements in the following indices: energy expenditure of walking, 5 m walking time, dominant hand grip strength, timed-up-and-go-test, and one-leg-stand time - mainly at 6 and 12 month assessments. CONCLUSIONS: The 6 month integrated care improved frailty and sarcopenia status among community-dwelling elders, with high-intensity training yielding greater improvements. Low-level care could be promoted as a basic intervention, while HLC could be reserved for those at high risk and with high motivation.

Sarcopenia Screened With SARC-F Questionnaire Is Associated With Quality of Life and 4-Year Mortality.

OBJECTIVES: There is no gold standard in diagnosing sarcopenia. We aimed to assess the validity of screening sarcopenia using SARC-F (sluggishness, assistance in walking, rise from a chair, climb stairs, falls). DESIGN: Prospective cohort study. SETTING: Community hospital in Taiwan. PARTICIPANTS: Community-dwelling senior citizens. MEASUREMENTS: Participants were interviewed with a structured questionnaire annually. The questionnaire items were recoded into the 5 items of SARC-F (sluggishness, assistance in walking, rise from a chair, climb stairs, falls). In the baseline year, a subgroup was tested for grip strength and body composition. Healthcare utilization and mortality were based on self-report and hospital records. Our main outcome was 4-year mortality. Secondary outcomes included hospitalization, emergency care use, and quality of life (QOL) measured using the CASP-12 scale (control, autonomy, self-realization, pleasure (control, autonomy, self-realization, pressure). RESULTS: There were 670 participants. The mean age was 76.1 (standard deviation 6.36). One-half were men (n = 340, 50.7%). The prevalence of sarcopenia was 6.1% (n = 41). SARC-F scores were inversely associated with grip strength (P = .001) and skeletal muscle composition (P = .045). Participants with sarcopenia were mostly women (P = .005) and older (P < .001). In univariate analysis, sarcopenia was associated with 1- to 4-year mortalities (P = .033, .001, .001, <.001, respectively), overall hospitalization (P = .004), overall emergency care use (P = .017), and QOL (P < .001). In multivariate model, sarcopenia [odds ratio (OR) 7.35, 95% confidence interval (CI) 2.67-20.18], age (OR 1.19, 95% CI 1.09-1.29 for each year), and taking vitamin D supplements (OR 0.29, 95% CI 0.11-0.74) were factors associated with mortality. CONCLUSIONS: Sarcopenia screened using SARC-F was associated with subsequent QOL, overall hospitalization, overall emergency care use, and 4-year mortality. SARC-F can serve as a quick screening tool of sarcopenia.

Drynaria fortunei J. Sm. improves the bone mass of ovariectomized rats through osteocalcin-involved endochondral ossification.

AIM OF THIS STUDY: Our previous study showed that Drynaria fortunei J. Sm. (Kunze), a traditional Chinese medical herb, can promote osteoblast differentiation and maturation. This study was further aimed to confirm the traditional effects of Kunze on the bone mass of ovariectomized rats. MATERIALS AND METHODS: Female Wistar rats were given an ovariectomy and then administered the water extract of Kunze (WEK). Systemic and tissue toxicities of WEK were assessed. A biomechanical test, bone mineral contents, and bone histomorphometry were analyzed to determine the effects of the WEK on the bone mass. Levels of osteocalcin (OCN) in bone tissues were determined by immunohistochemistry and immunoblotting. The effects of naringin, one of the bioactive compounds of the WEK, on the bone mass were evaluated. RESULTS: A bilateral ovariectomy in rats caused a time-dependent decrease in levels of serum 17ß-estradiol. Exposure of ovariectomized rats to the WEK at 0.5 and 1g/kg body weight/day for 1, 2, 3, and 6 months did not induce systemic or tissue toxicities. Biomechanical testing and a bone mineral content analysis showed that the ovariectomy decreased the bone torsion force and bone ash in time-dependent manners. In comparison, after exposure to the WEK, the ovariectomy-induced reductions in the bone torsion force and bone ash were significantly alleviated. In parallel, results of a bone histomorphometric assay further revealed that the ovariectomy caused significant diminution in the production of prehypertrophic chondrocytes and trabecular bone but enhanced hypertrophic chondrocyte numbers in the growth plate. However, exposure to the WEK lowered ovariectomy-induced changes in these cellular events. As to the mechanism, the WEK increased OCN biosynthesis in bone tissues of ovariectomized rats. Administration of naringin to ovariectomized rats caused significant amelioration of the bone strength, bone mineral contents, and trabecular bone amounts. CONCLUSIONS: This study shows that the WEK can translationally promote the bone mass in ovariectomized rats through stimulating OCN-involved endochondral ossification.

Honokiol, a low molecular weight natural product, prevents inflammatory response and cartilage matrix degradation in human osteoarthritis chondrocytes.

Proinflammatory cytokine interleukin-1ß (IL-1ß) stimulates several mediators of cartilage degradation and plays an important role in the pathogenesis of osteoarthritis (OA). Honokiol, a low molecular weight natural product isolated from the Magnolia officinalis, has been shown to possess anti-inflammatory effect. Here, we used an in vitro model of cartilage inflammation to investigate the therapeutic potential of honokiol in OA. Human OA chondrocytes were cultured and pretreated with honokiol (2.5-10 µM) with or without IL-1ß (10 ng/ml). Nitric oxide (NO) production was quantified by Griess reagent. Prostaglandin (PG)E2 , metalloproteinase-13 (MMP-13), and interleukin-6 (IL-6) productions were quantified by enzyme-linked immunosorbent assay. The expressions of collagen II, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and nuclear factor κB (NF-κB)-related signaling molecules were determined by Western blotting. Our data showed that IL-1ß markedly stimulated the expressions of iNOS and COX-2 and the productions of NO, PGE2 , and IL-6, which could be significantly reversed by honokiol. Honokiol could also suppress the IL-1ß-triggered activation of IKK/IκBα/NF-κB signaling pathway. Moreover, honokiol significantly inhibited the IL-1ß-induced MMP-13 production and collagen II reduction. Taken together, the present study suggests that honokiol may have a chondroprotective effect and may be a potential therapeutic choice in the treatment of OA patients.

Ethanol Extracts of Fresh Davallia formosana (WL1101) Inhibit Osteoclast Differentiation by Suppressing RANKL-Induced Nuclear Factor- κ B Activation.

The rhizome of Davallia formosana is commonly used to treat bone disease including bone fracture, arthritis, and osteoporosis in Chinese herbal medicine. Here, we report the effects of WL1101, the ethanol extracts of fresh rhizomes of Davallia formosana on ovariectomy-induced osteoporosis. In addition, excess activated bone-resorbing osteoclasts play crucial roles in inflammation-induced bone loss diseases, including rheumatoid arthritis and osteoporosis. In this study, we examined the effects of WL1101 on receptor activator of nuclear factor- κ B ligand (RANKL)-induced osteoclastogenesis. Treatment with WL1101 significantly inhibited RANKL-stimulated osteoclastogenesis. Two isolated active compounds, ((-)-epicatechin) or WL14 (4-hydroxy-3-aminobenzoic acid) could also inhibit RANKL-induced osteoclastogenesis. WL1101 suppressed the RANKL-induced nuclear factor- κ B (NF- κ B) activation and nuclear translocation, which is the key process during osteoclastogenesis, by inhibiting the activation of I κ B kinase (IKK) and I κ B α . In animal model, oral administration of WL1101 (50 or 200 mg/kg/day) effectively decreased the excess bone resorption and significantly antagonized the trabecular bone loss in ovariectomized rats. Our results demonstrate that the ethanol extracts of fresh rhizomes of Davallia formosana inhibit osteoclast differentiation via the inhibition of NF- κ B activation and effectively ameliorate ovariectomy-induced osteoporosis. WL1101 may thus have therapeutic potential for the treatment of diseases associated with excessive osteoclastic activity.

Enhancement of PLGF production by 15-(S)-HETE via PI3K-Akt, NF-κB and COX-2 pathways in rheumatoid arthritis synovial fibroblast.

Metabolites from arachidonic acids play the pivotal roles in inflammatory arthritis. Arachidonic acid could be metabolized by cyclooxygenase (COX) and lipoxygenase (LOX) to produce the bioactive eicosanoids. Although the down-stream products of COX including prostaglandin E2 are well-known inflammatory stimulators, the role of LOX products in inflammatory arthritis is still unclear. Here we found that the downstream product of 15-LOX, 15-S-hydroxyeicosatetraenoic acid (15-(S)-HETE), can enhance the expression of placenta growth factor (PLGF), which is recently considered to play an important role in rheumatoid arthritis. 15-(S)-HETE increased the expression of PLGF in human rheumatoid arthritis synovial fibroblasts in a time-dependent and concentration-dependent manner. PI3K-Akt, NF-κB signaling pathways were involved in the potentiation effects of 15-(S)-HETE. In addition, COX-2 was up-regulated by the treatment of 15-(S)-HETE and the increase of COX-2 expression participated in 15-(S)-HETE-induced PLGF expression, which was confirmed by COX-2 shRNA or pharmacological COX-2 inhibitor. Moreover, it was found that treatment of prostaglandin E2 (PGE2), which was the main down-stream metabolite of COX-2, increased the expression of PLGF. EP1, EP2, EP3 and EP4 agonists could up-regulate PLGF as well. In animal studies, we found that the adjuvant-induced expression of PLGF and COX-2 was inhibited in 15-LOX knockout mice. These results indicated that PLGF up-regulation by 15-LOX downstream product may be involved in inflammatory arthritis.

EGb761 inhibits inflammatory responses in human chondrocytes and shows chondroprotection in osteoarthritic rat knee.

Osteoarthritis (OA) is a degenerative joint disease involving a combination of cartilage degradation and inflammation. EGb761, a standardized extract of Ginkgo biloba leaves, holds an anti-inflammatory potency. Here, we determined whether EGb761 could inhibit lipopolysaccharide (LPS)- and IL-1ß-induced inflammatory responses in human articular chondrocytes and apply the chondroprotection in OA rats. We found that LPS markedly induced the productions of PGE2 and NO and the protein expressions of COX-2 and iNOS in human chondrocytes. LPS was also seen to up-regulate the expressions of toll-like receptor-4 (TLR4), its downstream signal TNF receptor-associated factor 6 (TRAF6), and nuclear factor (NF)-κB signaling. These LPS-induced inflammatory responses were efficaciously reversed by EGb761 and its active components quercetin and kampferol. The similar results could be observed by using IL-1ß as an in vitro model to mimic an inflammatory response. In an OA rat model, PGE2 and NO levels in blood, the histological alterations, and COX-2 and nitrotyrosine expressions in cartilages were markedly increased, which were effectively reversed by EGb761. Our results suggested that EGb761 exerts the anti-inflammatory effects on human articular chondrocytes and OA rats.

Dextromethorphan inhibits osteoclast differentiation by suppressing RANKL-induced nuclear factor-κB activation.

UNLABELLED: Dextromethorphan (DXM), a commonly used antitussive, is a dextrorotatory morphinan. Here, we report that DXM inhibits the receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastogenesis and bone resorption by abrogating the activation of NF-κB signalling in vitro. Oral administration of DXM ameliorates ovariectomy (OVX)-induced osteoporosis in vivo. INTRODUCTION: DXM was reported to possess anti-inflammatory properties through inhibition of the release of pro-inflammatory factors. However, the potential role and action mechanism of DXM on osteoclasts and osteoblasts remain unclear. In this study, in vitro and in vivo studies were performed to investigate the potential effects of DXM on osteoclastogenesis and OVX-induced bone loss. METHODS: Osteoclastogenesis was examined by the TRAP staining, pit resorption, TNF-α release, and CCR2 and CALCR gene expression. Osteoblast differentiation was analyzed by calcium deposition. Osteogenic and adipogenic genes were measured by real-time PCR. Signaling pathways were explored using Western blot. ICR mice were used in an OVX-induced osteoporosis model. Tibiae were measured by µCT and serum markers were examined with ELISA kits. RESULTS: DXM inhibited RANKL-induced osteoclastogenesis. DXM mainly inhibited osteoclastogenesis via abrogation of IKK-IκBα-NF-κB pathways. However, a higher dosage of DXM antagonized the differentiation of osteoblasts via the inhibition of osteogenic signals and increase of adipogenic signals. Oral administration of DXM (20 mg/kg/day) partially reduced trabecular bone loss in ovariectomized mice. CONCLUSION: DXM inhibits osteoclast differentiation and activity by affecting NF-κB signaling. Therefore, DXM at suitable doses may have new therapeutic applications for the treatment of diseases associated with excessive osteoclastic activity.

Osteoporosis Prevention by Adlay ( Yì Yǐ: The Seeds of Coix Lachryma-Jobi L. var. ma-yuen Stapf) in a Mouse Model.

Osteoporosis is characterized by reduced bone mass and quality due to an imbalanced bone remodeling. A grass crop, adlay (Coix lachryma-jobi), is a kind of nourishing food, which has also been used in traditional Chinese medicine. In this study, we investigated the effect of adlay (C. lachryma-jobi L. var. ma-yuen Stapf) on osteoporosis using an ovariectomized mouse model. The adlay diet (10% and 30% adlay in mouse diet) or water extract of adlay (0.3 g/kg/day) was given to ovariectomized mice for 4 weeks. In some experiments, the primary rat osteoblast cells were used to test the possible mechanism of adlay on osteoporosis. The body weight was slightly increased and uterus weight was markedly decreased in ovariectomized mice, which were not affected by adlay treatment. Adlay diet (30%) and adlay extract feedings significantly reversed the decreased bone alkaline phosphatase activity and calcium contents and bone mineral density in ovariectomized mice. Moreover, adlay extracts increased the osteoblast cell proliferation in a dose-dependent manner. Adlay extracts also increased the protein expressions of proliferating cell nuclear antigen and phosphorylated extracellular signal-regulated kinase (ERK) 1/2 in osteoblast cells. ERK inhibitor PD98059 significantly reversed the increased osteoblast cell proliferation by adlay extracts. Taken together, these findings indicate that adlay effectively alleviates the osteoporotic status in ovariectomized mice. Adlay is capable of increasing the proliferation of osteoblast cells via an ERK-regulated signaling pathway. Adlay may be a helpful healthy food for osteoporosis prevention.

Antidiabetic effects of pterosin A, a small-molecular-weight natural product, on diabetic mouse models.

The therapeutic effect of pterosin A, a small-molecular-weight natural product, on diabetes was investigated. Pterosin A, administered orally for 4 weeks, effectively improved hyperglycemia and glucose intolerance in streptozotocin, high-fat diet-fed, and db/db diabetic mice. There were no adverse effects in normal or diabetic mice treated with pterosin A for 4 weeks. Pterosin A significantly reversed the increased serum insulin and insulin resistance (IR) in dexamethasone-IR mice and in db/db mice. Pterosin A significantly reversed the reduced muscle GLUT-4 translocation and the increased liver phosphoenolpyruvate carboxyl kinase (PEPCK) expression in diabetic mice. Pterosin A also significantly reversed the decreased phosphorylations of AMP-activated protein kinase (AMPK) and Akt in muscles of diabetic mice. The decreased AMPK phosphorylation and increased p38 phosphorylation in livers of db/db mice were effectively reversed by pterosin A. Pterosin A enhanced glucose uptake and AMPK phosphorylation in cultured human muscle cells. In cultured liver cells, pterosin A inhibited inducer-enhanced PEPCK expression, triggered the phosphorylations of AMPK, acetyl CoA carboxylase, and glycogen synthase kinase-3, decreased glycogen synthase phosphorylation, and increased the intracellular glycogen level. These findings indicate that pterosin A may be a potential therapeutic option for diabetes.

Involvement of 15-lipoxygenase in the inflammatory arthritis.

15-Lipoxygenase (15-LOX) is involved in many pathological processes. The aim of this study is to examine the role of 15-LOX in the matrix metalloproteinase (MMP) expression and inflammatory arthritis. It was found that treatment of 15-LOX downstream product of 15-(S)-HETE (15-S-hydroxyeicosatetraenoic acid) increased the mRNA and protein levels of MMP-2 in rheumatoid arthritis synovial fibroblast (RASF) derived from rheumatoid arthritis patients. The enhancement effect of 15-(S)-HETE was antagonized by the addition of LY294002 (PI3K inhibitor) and PDTC (NF-κB inhibitor). Treatment of 15-(S)-HETE increased the phosphorylation of AKT, nuclear translocation of p65 and the breakdown of IκBα. TNF-α and IL-1ß are the key cytokines involved in arthritis and also increase the activity of MMP-2 in RASF, which was antagonized by pretreatment with 15-LOX inhibitor PD146176 or knockdown of 15-LOX. It was also found that these two cytokines increased the expression of 15-LOX in RASF. Treatment of glucocorticoid but not NSAIDs inhibited 15-(S)-HETE-induced expression of MMP-2. In comparison with wild-type mice, adjuvant-induced arthritis and MMP-2 expression in synovial membrane were markedly inhibited in 15-LOX knockout (KO) mice. These results indicate that 15-LOX plays an important role in the disease progression of arthritis and may be involved in the inflammatory action induced by TNF-α and IL-1ß. 15-LOX is thus a good target for developing drugs in the treatment of inflammatory arthritis.

Acute effects of plyometric jumping and intermittent running on serum bone markers in young males.

The purpose of this study was to investigate whether different modes of single-bout exercise would cause different responses in short-term bone metabolism. 24 untrained male college students (19.1 ± 0.1 years old) were recruited and randomly assigned to three groups: (1) a single-bout plyometric exercise group (the PL group, n = 8), (2) a 200-meter × 10 intermittent running group (the IR group, n = 8) and (3) a sedentary control group, which followed the same time schedule of experimentation without performing any exercise (the CON group, n = 8). Serial blood samples were collected before (baseline) and 5 min, 15 min, 1 h, 3 h, 6 h, 24 h, 48 h, and 72 h after exercise trials. Within 15 min of exercise, the PL and IR groups showed significantly higher serum phosphorus than did the control group (P < 0.05). Osteocalcin levels were significantly higher in the PL group at 5 min and 1 h after exercise (P < 0.05), while serum tartrate-resistant acid phosphatase (TRAP) showed no differences among groups. Exercises with different mechanical impact levels responded differently in serum bone formation markers as shown by osteocalcin. Because the increase in osteocalcin in the PL group was revealed shortly after the exercise bout, the changes might due to an exercise-induced mechanical impact rather than bone cellular activities.

Evidence for improved neuropharmacological efficacy and decreased neurotoxicity in mice with traditional processing of Rhizoma Arisaematis.

Rhizoma Arisaematis (RA, the rhizome of Pinellia pedatisecta Schott) is a traditional Chinese medicine commonly used in the treatment of convulsions, inflammation, and cancer. Despite the fact that it has been used for more than 2000 years, the pharmacological and toxic effects of traditionally processed products of RA are still unclear. In this study, we attempted to investigate the effects exerted by untreated crude RA and different preparations of RA treated with alumen in combination with ginger juice (Zhinanxing) or bile juice (Dannanxing) in ICR mice. The results showed that both the Zhinanxing and Dannanxing water extracts exerted significantly increased sedative effects, as indicated by the inhibitory effects on ambulatory distances, jumps, vertical-plane entries, and prolonged pentobarbital-induced sleeping time. The extracts also exerted significantly increased analgesic effects (increase of tail flick latency in nociceptive testing) in mice than did the unprocessed crude RA after oral administration for one to three days, and effects persisted 18 days after the cessation of treatment. By contrast, the toxic effects, such as an increase in stereotype-1 episodes of locomotor activities and reduction of the retention time on a rotating rod (motor equilibrium dysfunction), were observed only in mice treated with the unprocessed crude RA for three consecutive days, and effects persisted for 18 days after the cessation of treatment. These neurotoxic effects were accompanied by an increase in plasma lipid peroxidation (LPO), decrease in whole blood nitric oxide (NO(x)) levels, and inhibition of Na(+)/K(+)-ATPase activities in membrane fractions of erythrocytes and in the cerebral cortex. In conclusion, these findings provide scientific evidence that the processed RA indeed possesses not only enhanced neuropharmacological efficacy but also reduced neurotoxic effects as compared to the unprocessed crude RA. The signaling of NO(x)/oxidative stress/Na(+)-K(+)- ATPase activities played a role, at least in part, in the underlying mechanisms of neurotoxic effects induced by the crude RA.

Treatment of unicameral bone cyst: surgical technique.

BACKGROUND: There is a variety of treatment modalities for unicameral bone cysts, with variable outcomes reported in the literature. Although good initial outcomes have been reported, the success rate has often changed with longer-term follow-up. We introduce a novel, minimally invasive treatment method and compare its clinical outcomes with those of other methods of treatment of this lesion. METHODS: From February 1994 to April 2008, forty patients with a unicameral bone cyst were treated with one of four techniques: serial percutaneous steroid and autogenous bone-marrow injection (Group 1, nine patients); open curettage and grafting with a calcium sulfate bone substitute either without instrumentation (Group 2, twelve patients) or with internal instrumentation (Group 3, seven patients); or minimally invasive curettage, ethanol cauterization, disruption of the cystic boundary, insertion of a synthetic calcium sulfate bone-graft substitute, and placement of a cannulated screw to provide drainage (Group 4, twelve patients). Success was defined as radiographic evidence of a healed cyst or of a healed cyst with some defect according to the modified Neer classification, and failure was defined as a persistent or recurrent cyst that needed additional treatment. Patients who sustained a fracture during treatment were also considered to have had a failure. The outcome parameters included the radiographically determined healing rate, the time to solid union, and the total number of procedures needed. RESULTS: The follow-up time ranged from eighteen to eighty-four months. Group-4 patients had the highest radiographically determined healing rate. Healing was seen in eleven of the twelve patients in that group compared with three of the nine in Group 1, eight of the twelve in Group 2, and six of the seven in Group 3. Group-4 patients also had the shortest mean time to union: 3.7 ± 2.3 months compared with 23.4 ± 14.9, 12.2 ± 8.5, and 6.6 ± 4.3 months in Groups 1, 2, and 3, respectively. CONCLUSIONS: This new minimally invasive method achieved a favorable outcome, with a higher radiographically determined healing rate and a shorter time to union. Thus, it can be considered an option for initial treatment of unicameral bone cysts.

Caffeine enhances osteoclast differentiation from bone marrow hematopoietic cells and reduces bone mineral density in growing rats.

Caffeine-containing beverage consumption has been associated with low bone mass and increased fracture risk in some, but not most, observational studies. The effects of caffeine on bone metabolism are still controversial. We investigated the effects of caffeine on the differentiation of bone progenitor cells and bone mineral density (BMD) by in vitro and in vivo experiments. Low-concentration caffeine (0.005-0.1 mM) did not affect the bone marrow cell viability and alkaline phosphatase activity during osteoblast differentiation from bone marrow stromal cells, but it effectively enhanced the osteoclastogenesis from bone marrow hematopoietic cells and the bone resorption activity by pit formation assay. Moreover, caffeine effectively enhanced the receptor activator of NF-κB ligand (RANKL), but reduced the osteoprotegerin protein expressions in osteoblast MC3T3-E1 cells. Caffeine could also increase the cyclooxygenase-2 (COX-2) protein expression and prostaglandin (PG)E(2) production in cultured neonatal mouse calvariae. In animal study, BMD in lumbar vertebra, femur, or tibia was significantly lowered in growing rats supplemented with 0.2% caffeine in diets for 20 weeks compared with the control group. The calcium contents in tibia and femur of caffeine-treated rats were also lower than that in the control group. The osteoclastogenesis of bone marrow cells isolated from caffeine-treated rats was markedly enhanced as compared with the control group. Taken together, these results suggest that caffeine may reduce BMD in growing rats through the enhancement in osteoclastogenesis. Caffeine may possess the ability to enhance a COX-2/PGE(2) -regulated RANKL-mediated osteoclastogenesis.

Extract isolated from Angelica hirsutiflora with insulin secretagogue activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Angelica genus (Umbelliferae) has traditionally been used as the medicine and health food considered alleviating several disorders including diabetes mellitus. Angelica hirsutiflora Liu Chao & Chuang is an endemic species and a folk medicine in Taiwan. AIM OF THE STUDY: The scientific evidence of anti-diabetic effect for Angelica hirsutiflora remains unknown. The methanolic extracts isolated from Angelica hirsutiflora were studied for its insulin secretagogue and hypoglycemic activities. MATERIALS AND METHODS: The in vitro effects and possible mechanisms of Angelica hirsutiflora extract on the insulin secretion in isolated mouse and human islets and pancreatic beta-cell line HIT-T15 were determined; and tested the regulation of blood glucose in fasted mice and high-fat diet-induced diabetic mice. RESULTS: Angelica hirsutiflora extract potently stimulated the release of insulin from cultured HIT-T15 cells and isolated mouse and human islets. The intracellular calcium levels were also increased in HIT-T15 cells and isolated human islets treated with Angelica hirsutiflora extract. Angelica hirsutiflora extract was capable of enhancing the phosphorylation of extracellular signal-regulated protein kinases (ERK)1/2 protein in HIT-T15 cells. Specific ERK inhibitor PD98059 inhibited the increase of insulin secretion by Angelica hirsutiflora extract in HIT-T15 cells and isolated mouse islets. When Angelica hirsutiflora extract was administered to the fasted mice, it decreased the rise in blood glucose level after starch loading. The plasma insulin level was also increased by Angelica hirsutiflora extract treatment. In high-fat diet-induced diabetic mice, Angelica hirsutiflora extract markedly improved the oral glucose intolerance as compared with the vehicle control. CONCLUSIONS: These findings support that Angelica hirsutiflora extract may be useful in the control of hyperglycemia in non-insulin-dependent diabetes mellitus by acting as an insulin secretagogue.

Cycling and Tai Chi Chuan exercises exert greater immunomodulatory effect on surface antigen expression of human hepatitis B virus.

BACKGROUND: Both athletes with intensive exercise and aged people may have weakened immunity against virus infection. This study aimed to evaluate whether people undergoing aerobic exercises including competitive cyclists with moderate training (CMT) and middle-aged people practicing Tai Chi Chuan (TCC) exercise have higher immunity against hepatitis B virus than age-matched sedentary controls including college students (CSC) and middle-aged people (MSC). METHODS: Human peripheral blood mononuclear cells from competitive cyclists and sedentary controls were stimulated by phytohemagglutinin (PHA) to prepare conditioned medium (MNC-CM) for the assessment of inhibitory effects on hepatitis B surface antigen (HBsAg) expression in human hepatoma Hep3B cells. RESULTS: The inhibitory effects on the relative HBsAg expression of CMT's and TCC's MNC-CM were greater than those of the controls. The CMT's MNC-CM prepared from 5 microg/ml PHA decreased HBsAg expression to 61.5%, whereas that of CSC remained at 83.8%. Similarly, this expression by treatment of TCC group' MNC-CM was 68.4% whereas that of MSC group was 84.3%. The levels of cytokines such as interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), IFN-alpha and interleukin-1beta (IL-1beta) in the MNC-CM from the CMT and TCC groups were greater than those in the controls. Antibody neutralization of CMT's MNC-CM and addition of recombinant cytokines into CSC's MNC-CM indicated that IFN-gamma, TNF-alpha and IFN-alpha had synergistic effects against HBsAg expression. Similar blocking effect was noted in TCC versus MSC groups. CONCLUSION: These results suggest that the immunomodulatory response to suppress HBsAg expression in CMT and TCC with moderate aerobic exercise is greater than that in age-matched sedentary controls.

Evaluation of osteoporosis prevention by adlay using a tissue culture model.

Adlay (Coix lachryma-jobi L. var. ma-yuen Stapf ) is a grass crop, which has been used in traditional Chinese medicine and also as a nourishing food. Recently, some studies have indicated that adlay possesses some pharmacological effects including anti-allergic, anti-mutagenic, hypolipemic, and anti-diabetic effects. However, the effect of adlay on osteoporosis is still unknown. In this study, we investigated and evaluated the effect of adlay seed on the osteoporosis prevention. The methods of in vitro cultures of neonatal rat calvaria tissues or adult rat femoral metaphyseal tissues of bones isolated from normal or ovariectomized female rats were used for further investigation. Treatment with water extract of adlay seed could reverse the decreased alkaline phosphatase activities and calcium levels and increased tartrate-resistant acidic phosphatase activities induced by parathyroid hormone in cultured metaphyseal tissues. In ovariectomized rats, the alkaline phosphatase activities and calcium levels were significantly decreased and tartrate-resistant acidic phosphatase activities were increased in femoral metaphyseal tissues as compared with sham-control. Treatment with water extract of adlay seed could counteract these effects in ovariectomized rats. Taken together, these findings imply that adlay is capable of reversing the osteoporotic status in rats, and may be a helpful healthy food for osteoporosis prevention.

Onion decreases the ovariectomy-induced osteopenia in young adult rats.

It has been suggested that fruit and vegetable consumption are associated with good bone health. Onion, in particular, has been verified in its efficacy in bone resorption activity. In this study, we further investigated the effects of an onion-containing diet on ovariectomy-induced bone loss using methods of serum marker assay, histomorphometric analysis and biomechanical tests. Sixty-four female Wistar rats (14-week-old) with sham operations or ovariectomy were assigned to 6 groups: CON, sham-operated control group; OVX, ovariectomized group; ALN, ovariectomized rats treated with alendronate (1 mg/kg/day, p.o.); and 3% ON, 7% ON and 14% ON, ovariectomized rats fed with diets containing 3%, 7% and 14% (wt/wt) onion powder, respectively. Animals were sacrificed after a six-week treatment course. In the serum marker assay, alendronate and all three onion-enriched diets significantly decreased serum calcium level (p<0.05). Both 14% ON group and the ALN group even showed similarly lower level of serum osteocalcin (p<0.05), suggesting a down-regulation of bone turnover. The histomorphometric analysis showed that ovariectomy markedly decrease bone trabeculae. The ALN and 14% ON rats were 80% and 46% higher, respectively, in BV/TV than the OVX rats (p<0.05), and the rats fed with onion-enriched food showed a lesser ovariectomy-induced bone loss in a dose-dependent manner. Additionally, both ALN and 14% ON groups had significantly more trabecular number, less separated trabeculae, and fewer osteoclasts (p<0.05), but the protective efficacy from the 14% onion-enriched diet was slightly inferior to that of alendronate. Ovariectomy also significantly decreased tissue weight and biomechanical strength in the OVX group (p<0.05). The ALN and 14% ON groups equivalently showed a lesser decrease in tissue weight, though the difference was not significant. On the other hand, both the ALN and 14% ON groups represented similar biomaterial properties of femurs, and both reduced the ovariectomy-induced decrease in bending load and bending energy (p<0.05). The present study further verified that an onion-enriched diet could counteract ovariectomy-induced bone loss and deterioration of biomechanical properties.