ABSTRACT
OBJECTIVE: To study the curative effect of bionic tiger-bone powder on osteoporosis in ovariectomized rats and investigate its mechanism. METHODS: Overall, a 120 female Wistar rats were randomly divided into Sham (sham-operated group), ovariectomy (OVX, ovariectomized group), TB (bionic tiger-bone powder treatment group after ovariectomy) and TB + VD groups (bionic tiger-bone powder + vitamin D treatment group after ovariectomy). The osteoporotic rat model was established 3 months after ovariectomy, and rats were intragastrically administrated with the corresponding drugs. Serum and bone tissue samples were collected from 10 rats in each group at weeks 4, 12 and 24 after intragastric administration. The bone microstructure of L6 vertebrae was analyzed by MicroCT, the biomechanical strength of left femurs was measured by the three-point bending test, and serum bone metabolism markers (P1NP and CTX) were detected by ELISA. Changes in bone collagen were analyzed by Masson's trichrome staining and hydroxyproline detection, and members of the BMP2/SMAD/RUNX2 and OPG/RANKL/RANK signal pathways were detected by immunoblotting. RESULTS: Compared with the OVX group, the serum level of P1NP in the TB and TB + VD groups was higher (P < 0.05), while the CTX level was lower (P < 0.05). Bone collagen fiber structures in the TB and TB + VD groups were repaired, and the collagen content was significantly higher than that in the OVX group (P < 0.05). In the TB group, BMP-2, P-SMAD1/5, RUNX2 and OPG levels were increased in bone tissue (P < 0.01), RANKL levels were decreased (P < 0.01), and the bone microstructure and biomechanical strength were improved. CONCLUSION: Bionic tiger-bone powder promotes osteogenesis by activating the BMP2/SMAD/RUNX2 signaling pathway, suppresses osteoclasts by downregulating the OPG/RANK/RANKL signaling pathway, increases bone collagen content, and improves bone microstructure and bone biomechanical strength.
Subject(s)
Bone Density/drug effects , Bone Substitutes/pharmacology , Medicine, Chinese Traditional/methods , Osteoporosis/drug therapy , Animals , Disease Models, Animal , Female , Femur/drug effects , Lumbar Vertebrae/drug effects , Ovariectomy , Powders , Rats , Rats, Wistar , Vitamin D/pharmacologyABSTRACT
Mixed results have been reported regarding whether habitual tea intake affects bone health. This study investigated the relationship between green tea intake and bone mineral density (BMD) in postmenopausal Korean women. We used data from the Korean National Health and Nutrition Examination Surveys from 2008 to 2011 and divided the participants into three groups according to their frequency of green tea intake over the past 12 months. BMD of the lumbar spine, total femur, and femur neck was measured using dual-energy X-ray absorptiometry. The odds ratios (ORs) and 95% confidence intervals (CIs) of osteoporosis and osteopenia according to green tea consumption were analyzed. Participants who did not consume green tea or consumed less than one cup per day were more likely to have osteopenia of the lumbar spine or femur than those who consumed it once to three times a day (OR 1.81 and 1.85, 95% CI, 1.20-2.71; and 1.23-2.77). Moreover, ORs for osteoporosis were 1.91 (95% CI 1.13-3.23) and 1.82 (95% CI 1.09-3.05) in non-consumers and consumers who drank less than one cup per day, respectively, compared with the reference group. These results support that green tea consumption may have benefits on bone health.
Subject(s)
Bone Density/drug effects , Osteoporosis, Postmenopausal/epidemiology , Osteoporosis, Postmenopausal/prevention & control , Postmenopause , Tea , Aged , Asian People , Bone Diseases, Metabolic/prevention & control , Female , Femur Neck/drug effects , Humans , Lumbar Vertebrae/drug effects , Middle Aged , Republic of Korea/epidemiologyABSTRACT
AIMS: Intermittent cyclic tension stimulation(ICMT) was shown to promote degeneration of endplate chondrocytes and induce autophagy. However, enhancing autophagy can alleviate degeneration partly. Studies have shown that curcumin can induce autophagy and protect chondrocytes, we speculated that regulation of autophagy by curcumin might be an effective method to improve the stress resistance of endplate cartilage. In this study, human cervical endplate cartilage specimens were collected, and expression of autophagy markers was detected and compared. MAIN METHODS: Human cervical endplate chondrocytes were cultured to establish a tension-induced degeneration model, for which changes of functional metabolism and autophagy levels were detected under different tension loading conditions. Changes in functional metabolism of endplate chondrocytes were observed under high-intensity tension loading in the presence of inhibitors, inducers, and curcumin to regulate the autophagy level of cells. In addition, a rat model of lumbar instability was established to observe the degeneration of lumbar disc after curcumin administration. KEY FINDINGS: Through a series of experiments, we found that low-intensity tension stimulation can maintain a stable phenotype of endplate chondrocytes, but high-intensity tension stimulation has a negative effect. Moreover, with increasing tension intensity, the degree of degeneration of endplate chondrocytes was gradually aggravated and the level of autophagy increased. Besides, curcumin upregulated autophagy, inhibited apoptosis, and reduced phenotype loss of endplate chondrocytes induced by high-intensity tension loading, thereby relieving intervertebral disc degeneration induced by mechanical imbalance. SIGNIFICANCE: Curcumin mediated autophagy and enhanced the adaptability of endplate chondrocytes to high-intensity tension load, thereby relieving intervertebral disc degeneration.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Autophagy/drug effects , Cartilage/drug effects , Curcumin/therapeutic use , Intervertebral Disc Degeneration/drug therapy , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Autophagy/physiology , Cartilage/pathology , Curcumin/pharmacology , Female , Intervertebral Disc Degeneration/pathology , Lumbar Vertebrae/drug effects , Lumbar Vertebrae/pathology , Male , Rats , Rats, Sprague-DawleyABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Morinda officinalis is a well-known Chinese tonic herb that has shown clinical efficacy in the treatment of bone disease. However, its anti-osteoporotic potential and the M. officinalis polysaccharides (MOPs) responsible for activity require further investigation. AIM OF THE STUDY: This study aimed to investigate the anti-osteoporotic effects of different MOP fractions in ovariectomized (OVX) rats, and to identify the osteoprotective components by bioassay-guided isolation. MATERIALS AND METHODS: MOPs were prepared by hot water and alkali extraction, separated into three fractions (MO50, MO70, and MOB) and evaluated in the classic OVX rat model and in MC3T3-E1 cells for anti-osteoporotic activity. RESULTS: Administration of MOPs (400â¯mg/kg/day) provided significant protection against ovariectomy-induced bone loss and biomechanical dysfunction in rats. Treated animals exhibited reduced deterioration of trabecular microarchitecture and lower levels of bone turnover markers. Bioactivity-guided fractionation led to the isolation of two inulin-type fructans from MO50, MOW50-1 and MOP50-2, with potential anti-osteoporotic activities. These consisted of (2â¯ââ¯1)-linked ß-D-fructosyl residues with degrees of polymerization (DP) of 7 and 13, respectively. Furthermore, MOW50-1 promoted osteogenic differentiation of MC3T3-E1 cells by increasing alkaline phosphatase activity. CONCLUSIONS: These data suggest very strongly that MOPs, especially MO50 and MOW50-1, may play important roles in the prevention and treatment of osteoporosis.
Subject(s)
Biological Assay , Bone Density Conservation Agents/pharmacology , Bone Remodeling/drug effects , Femur/drug effects , Lumbar Vertebrae/drug effects , Morinda , Osteoblasts/drug effects , Osteoporosis, Postmenopausal/prevention & control , Polysaccharides/pharmacology , 3T3 Cells , Animals , Bone Density/drug effects , Bone Density Conservation Agents/isolation & purification , Chemical Fractionation , Disease Models, Animal , Female , Femur/pathology , Femur/physiopathology , Humans , Lumbar Vertebrae/pathology , Lumbar Vertebrae/physiopathology , Mice , Morinda/chemistry , Osteoblasts/metabolism , Osteoblasts/pathology , Osteogenesis/drug effects , Osteoporosis, Postmenopausal/pathology , Osteoporosis, Postmenopausal/physiopathology , Ovariectomy , Polysaccharides/isolation & purification , Rats, Sprague-DawleyABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Yaobitong capsule (YBTC) was a traditional Chinese medicine (TCM) and it had clinically used to treat lumbar disc degeneration (LDH) for a long time. However, the active ingredients of YBTC absorption into the plasma and its pharmacological mechanism of treatment for LDH still remained unclear. AIM OF THE STUDY: In this study, our research committed to identify the absorbed active ingredients of YBTC in rat plasma, and it may be a potential mechanism of action on LDH by the biological targets regulating related pathways. MATERIALS AND METHODS: An ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established to identify the absorption components and metabolites of YBTC in rat plasma, and the network pharmacology was further investigated to illuminate its potential mechanism of treatment for LDH by the biological targets regulating related pathways. RESULTS: The network analysis found that 56 components were identified as its main active ingredients including ginsenoside Rg1, ginsenoside Rb1, senkyunolide H, and tetrahydropalmatine, etc. Combining with biological process, cellular component and molecular functions of GO, and kyotoencyclopedia of genes and genomes pathway enrichment analysis to perform network topology analysis on core targets. These active ingredients regulated 29 mainly pathways by 87 direct target genes including MAPK, Ras, PI3K-Akt, and NF-kappa B signaling pathway, etc. CONCLUSION: In this study, the absorption active ingredients of YBTC in rat plasma were firstly combined with the network pharmacology investigation to elucidate its biological mechanism of treatment for LDH in vivo. It inhibited excessive inflammatory reactions, thereby reducing the sensitivity of the nerves to reduce pain and relieve LDH, and potential medicine targets could be identified to clarify the molecular mechanism of YBTCs' regulation of LDH.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Drugs, Chinese Herbal/pharmacology , Intervertebral Disc Displacement/drug therapy , Intervertebral Disc/drug effects , Lumbar Vertebrae/drug effects , Systems Biology , Administration, Oral , Animals , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/blood , Chromatography, High Pressure Liquid , Databases, Genetic , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/metabolism , Gastrointestinal Absorption , Gene Expression Regulation , Gene Regulatory Networks , Intervertebral Disc/metabolism , Intervertebral Disc/pathology , Intervertebral Disc Displacement/blood , Intervertebral Disc Displacement/genetics , Intervertebral Disc Displacement/pathology , Lumbar Vertebrae/metabolism , Lumbar Vertebrae/pathology , Male , Protein Interaction Maps , Rats, Sprague-Dawley , Signal Transduction , Spectrometry, Mass, Electrospray Ionization , Tandem Mass SpectrometryABSTRACT
BACKGROUND: Ovarian suppression from chemotherapy results in bone loss in premenopausal women with breast cancer (BC). Less is known about bone microarchitecture changes. We used high-resolution peripheral quantitative computed tomography (HR-pQCT) to measure volumetric bone density and trabecular and cortical microarchitecture in this population. MATERIALS AND METHODS: The primary endpoint was to assess changes in cortical thickness and trabecular bone density by HR-pQCT. Premenopausal women with stage I to III BC undergoing adjuvant chemotherapy underwent a bone mineral density (BMD) dual energy x-ray absorptiometry scan and HR-pQCT (voxel size, 82 microns) at baseline and 12 months. Paired t tests were used to observe the change over time in bone microarchitecture and areal and volumetric density. RESULTS: Eighteen patients were evaluated, of which 12 patients had baseline and matched 12-month imaging. The mean age was 45.2 years (range, 35-51 years), 17 (94%) patients had hormone receptor-positive BC, and 16 (89%) initiated tamoxifen. At 12 months, there was a significant decrease in femoral neck (P < .05) and lumbar spine and total hip (P < .01) BMD. Changes detected by HR-pQCT at 12 months included significant decreases in cortical thickness and area at the tibia (P < .05), and total and cortical volumetric BMD at the radius and tibia (P < .01), as well as an increase in tibial trabecular area (P < .05). CONCLUSION: Premenopausal women undergoing chemotherapy experience BMD decline and trabecular and cortical bone microarchitecture deterioration. In this population, future efforts should focus on therapy-induced bone loss and optimizing bone density-related management.
Subject(s)
Bone Density/drug effects , Breast Neoplasms/therapy , Cancellous Bone/drug effects , Cortical Bone/drug effects , Osteoporosis/diagnosis , Absorptiometry, Photon , Adult , Cancellous Bone/diagnostic imaging , Cancellous Bone/physiopathology , Chemotherapy, Adjuvant/adverse effects , Chemotherapy, Adjuvant/methods , Cortical Bone/diagnostic imaging , Cortical Bone/physiopathology , Female , Femur Neck/diagnostic imaging , Femur Neck/drug effects , Hip Joint/diagnostic imaging , Hip Joint/drug effects , Humans , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/drug effects , Mastectomy , Middle Aged , Osteoporosis/chemically induced , Premenopause , Prospective Studies , Radius/diagnostic imaging , Radius/drug effects , Tibia/diagnostic imaging , Tibia/drug effects , Tomography, X-Ray ComputedABSTRACT
CONTEXT: In the Denosumab and High-Dose Teriparatide Administration (DATA-HD) study, we reported that 15 months of combined high-dose (HD) teriparatide and denosumab increased mean areal bone mineral density (aBMD) at the hip and spine more than combined denosumab and standard-dose (SD) teriparatide. OBJECTIVE: In the current analysis, we compare the individual rates of aBMD response between the treatment groups. DESIGN: Single-site, open-label, randomized controlled trial in which postmenopausal women received either teriparatide 20-µg daily (SD) or 40-µg daily (HD) given months 0 through 9, overlapped with denosumab 60 mg, given months 3 through 15 (15 months' total duration). The proportion of participants in the SD and HD groups experiencing total hip, femoral neck, and lumbar spine aBMD gains of >3%, >6%, and >9% were compared. PARTICIPANTS: Postmenopausal women with osteoporosis completing all study visits (n = 60). MAIN OUTCOME MEASURE(S): aBMD (dual x-ray absorptiometry). RESULTS: At the end of the 15-month treatment period, a higher proportion of women in the HD group had aBMD increases >3% (83% vs. 58%, P = .037) and >6% (45% vs. 19%, P = .034) at the total hip, and >3% at the femoral neck (86% vs. 63%, P = .044). At the lumbar spine, >3% response rates were similar, whereas the >6% and >9% response rates were greater in the HD group (100% vs. 79%, P = .012 and 93% vs. 59%, P = .003, respectively). CONCLUSION: Compared with the SD regimen, more women treated with the HD regimen achieved clinically meaningful and rapid gains in hip and spine aBMD. These results suggest that this approach may provide unique benefits in the treatment of postmenopausal osteoporosis.
Subject(s)
Bone Density Conservation Agents/administration & dosage , Bone Density/drug effects , Denosumab/administration & dosage , Osteoporosis, Postmenopausal/drug therapy , Teriparatide/administration & dosage , Absorptiometry, Photon , Aged , Dose-Response Relationship, Drug , Drug Therapy, Combination/methods , Female , Femur Neck/diagnostic imaging , Femur Neck/drug effects , Femur Neck/physiopathology , Humans , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/drug effects , Lumbar Vertebrae/physiopathology , Middle Aged , Osteoporosis, Postmenopausal/complications , Osteoporosis, Postmenopausal/diagnosis , Osteoporosis, Postmenopausal/physiopathology , Treatment OutcomeABSTRACT
Eldecalcitol increased bone mineral density (BMD) and prevented vertebral fractures in vitamin D-sufficient osteoporotic subjects. However, the effect of eldecalcitol on BMD under vitamin D insufficiency is unknown. We examined the effect of eldecalcitol on BMD compared with alfacalcidol in osteoporotic patients without vitamin D or calcium supplementation. This is a randomized, double-blind, active comparator trial. 265 Chinese osteoporotic patients were randomly assigned to receive 0.75 µg eldecalcitol or 1.0 µg alfacalcidol for 12 months without vitamin D or calcium supplementation. Baseline calcium intakes were less than 550 mg/day and mean serum 25-hydroxyvitamin D [25(OH)D] was below 43 nmol/L in both groups. Baseline BMD tended to be lower in patients with lower calcium intake and serum 25(OH)D. Lumbar BMD increased by 2.05% higher in eldecalcitol than alfacalcidol group at 12 months. Total hip and femoral neck BMD also increased by 1.33 and 1.78%, respectively, in the eldecalcitol than the alfacalcidol group. The effect of eldecalcitol on BMD was not affected by serum 25(OH)D or calcium intake. The incidence of adverse events was not different between the two groups. Incidence of hypercalcemia in the edecalcitol group was not affected by serum 25(OH)D. In conclusion, baseline BMD tended to be lower in patients with low calcium intake and serum 25(OH)D. Eldecalcitol increased lumbar and hip BMD more than alfacalcidol regardless of serum 25(OH)D or calcium intake without vitamin D or calcium supplementation. These results suggest that eldecalcitol is effective in increasing the BMD of osteoporotic patients regardless of vitamin D status or calcium intake.Clinical Trial Registration number JAPIC CTI 152904.
Subject(s)
Bone Density/drug effects , Calcium/pharmacology , Dietary Supplements , Osteoporosis/drug therapy , Osteoporosis/physiopathology , Vitamin D/analogs & derivatives , Vitamin D/pharmacology , Aged , Biomarkers/blood , Bone Density Conservation Agents/pharmacology , Bone Remodeling/drug effects , Calcium/blood , Calcium/urine , Double-Blind Method , Female , Femur Neck/drug effects , Femur Neck/physiopathology , Hip/physiopathology , Humans , Lumbar Vertebrae/drug effects , Lumbar Vertebrae/physiopathology , Male , Middle Aged , Osteoporosis/blood , Osteoporosis/urine , Vitamin D/adverse effects , Vitamin D/blood , Vitamin D/therapeutic useABSTRACT
Aromatase inhibitors (AIs) are the gold standard therapy for breast cancer in postmenopausal women. AI suppresses the conversion of androgens to estrogens; however, this results in osteopenia, osteoporosis, and bone fracture, thus reducing the patient's quality of life. The use of adjuvant denosumab reduces the risk of clinical fractures in postmenopausal patients with breast cancer receiving AI. However, the efficacy of denosumab in the treatment of AI-associated bone loss has not been prospectively evaluated in Japan. In this study, we aimed to investigate the predictive factors for the efficacy of denosumab in postmenopausal patients with breast cancer treated with AI by analyzing the results of two prospective trials. The patients received 60 mg denosumab subcutaneously every 6 months. The primary endpoint was percentage change in lumbar spine bone mineral density (BMD) from baseline to month 12 in lumbar spine. Post hoc analysis and T tests were performed. A total of 205 patients were enrolled. At 12 and 24 months, the lumbar spine BMD increased by 5.6% [95% confidence interval (CI) 4.9-6.3] and 8.3% (95% CI 7.5-9.1), respectively. Subgroup analysis was conducted according to the time of AI therapy initiation, type of AI therapy, age, time since menopause, baseline body mass index, and BMD. The results showed that baseline lumbar and left femoral BMD was significantly associated with a percentage change in these sites, respectively. In addition, baseline left femoral BMD was also associated with a change in lumbar BMD. In conclusion, the baseline BMD in the lumbar spine was a predictive indicator for the efficacy of denosumab in this site and the baseline BMD in left femoral neck was a predictive indicator in lumbar spine and left femur.
Subject(s)
Aromatase Inhibitors/therapeutic use , Asian People , Breast Neoplasms/drug therapy , Denosumab/therapeutic use , Postmenopause , Aged , Aromatase Inhibitors/adverse effects , Aromatase Inhibitors/pharmacology , Bone Density/drug effects , Bone Density Conservation Agents/therapeutic use , Breast Neoplasms/physiopathology , Chemotherapy, Adjuvant , Denosumab/adverse effects , Denosumab/pharmacology , Female , Femur Neck/drug effects , Femur Neck/physiopathology , Fractures, Bone/chemically induced , Fractures, Bone/drug therapy , Humans , Japan , Lumbar Vertebrae/drug effects , Lumbar Vertebrae/physiopathology , Middle Aged , Multivariate Analysis , Postmenopause/drug effects , Prospective Studies , Treatment OutcomeABSTRACT
In women, age-related bone loss is associated with increased risk of bone fracture. Existing therapies are associated with severe side effects; thus, there is a need to find alternative medicines with less or optimal side effects. Cissus quadrangularis (CQ), an Ayurvedic medicine used to enhance fracture healing, was tested for its bone protective properties and studied to discern the mechanism by which it is beneficial to bone. Female Sprague Dawley rats were either sham operated or ovariectomized and were fed CQ for 3 months. Several biochemical markers, cytokines and hormones were assayed. Femur, tibia and lumbar vertebrae were subjected to pQCT and µCT densitometry. MC3T3 cells were cultured, treated with CQ and used to analyze miRNA content and subjected to qPCR for gene expression analysis related to bone metabolism. CQO rats showed protected bone mass and microarchitecture of trabecular bone in the distal femoral metaphysis and the proximal tibial metaphysis. The lumbar vertebrae, however, showed no significant changes. Serum protein expression levels of P1NP increased and Trap5b and CTX levels decreased with in vivo CQ treatment. Some influence on the anti- and pro-inflammatory markers was also observed. Significantly high level of estradiol in the CQO rats was observed. In vitro expression of a few genes related to bone metabolism showed that osteocalcin increased significantly. The other genes-collagen I expression, SPP1, BMP2, DCAT1-decreased significantly. Certain miRNA that regulate bone turnover using the BMP pathway and Wnt signaling pathways were upregulated by CQ. qPCR after acute treatment with CQ showed significantly increased levels of osteocalcin and decreased levels of Wnt/ß catenin antagonist DCAT1. Overall, CQ protected the microarchitecture of the long bones from ovariectomy-induced bone loss. This may be because of decreased inflammation and modulation through the BMP and Wnt signaling pathways. We conclude that CQ is a potential therapeutic agent to treat postmenopausal osteoporosis with no side effects.
Subject(s)
Bone Remodeling , Cissus/chemistry , Ovariectomy , Plant Extracts/pharmacology , Animals , Biomarkers/blood , Body Weight/drug effects , Bone Remodeling/drug effects , Cell Line , Cytokines/blood , Feeding Behavior , Female , Hormones/blood , Humans , Lipids/blood , Liver/drug effects , Liver/pathology , Lumbar Vertebrae/drug effects , Mice , MicroRNAs/genetics , MicroRNAs/metabolism , Organ Size/drug effects , Ovariectomy/adverse effects , Rats, Sprague-Dawley , Spleen/drug effects , Spleen/pathologyABSTRACT
PURPOSE: To evaluate the influence of intravenous methylprednisolone (IVMP) pulse administration on bone mineral density (BMD) of the lumbar spine and the femoral neck in patients with moderate-to-severe Graves' orbitopathy (GO). METHODS: Thirty-five patients with GO in euthyreosis were treated with 12 IVMP pulses (6 × 0.5 g, 6 × 0.25 g on a weekly schedule). Supplementation with 1.0 g of calcium and 800 IU of vitamin D was initiated in all patients before beginning therapy. BMD of the lumbar spine (L1-L4) and the femoral neck were assessed at baseline and after the last IVMP pulse using dual-energy X-ray absorptiometry. To determine differences in BMD between values at baseline and after treatment, we used the least significant change (LSC) methodology. LSC values were calculated to be 3 and 5% for the lumbar spine and the femoral neck, respectively. Change in BMD equal to or exceeding the LSC was assessed as either increase or decrease of BMD. We then compared pre-treatment and post-treatment mean BMD values at the lumbar spine and the femoral neck. RESULTS: We did not observe a decrease of BMD at any site equal to or exceeding the LSC. We found an increase of BMD in at least one measurement site equal to or exceeding the LSC value in 43% of patients, mostly in the lumbar spine (31%). Mean femoral neck BMD did not change while mean lumbar BMD increased. CONCLUSIONS: IVMP given in weekly intravenous pulses does not lead to loss of BMD of the lumbar spine and the femoral neck.
Subject(s)
Bone Density/drug effects , Glucocorticoids/adverse effects , Graves Ophthalmopathy/drug therapy , Methylprednisolone/adverse effects , Osteoporosis/chemically induced , Absorptiometry, Photon , Adult , Aged , Femur Neck/diagnostic imaging , Femur Neck/drug effects , Glucocorticoids/administration & dosage , Glucocorticoids/therapeutic use , Humans , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/drug effects , Methylprednisolone/administration & dosage , Methylprednisolone/therapeutic use , Middle Aged , Osteoporosis/diagnostic imaging , Young AdultABSTRACT
Epilepsy might have adverse effect on bone density due to underlying disease, drugs, vitamin D deficiency, immobilization and malnutrition. We investigated the bone mineral density in ambulatory vitamin-D supplemented children with epilepsy. This case-control study was conducted on 90 epileptic children aged 11.4 ± 3.3 years, and age and gender matched controls in pediatric neurology clinics of Shiraz, in Southern Iran, 2016. Anthropometric measurements, puberty, sun exposure, physical activity and biochemical variables were assessed. Bone mineral density was evaluated by dual-energy X-ray absorptiometry method. Data were analyzed by SPSS.v21. Prevalence of low bone mass in femur was more in patients (27%) than the controls (9%) (P value = 0.002). Age, weight Z score and height Z score were the most significant associated factors on lumbar BMD, BMAD, and femur BMD. Seizure duration and how it responded to anticonvulsants were the most associated factors with both lumbar and femur bone density. Sodium valproate and carbomazepin usage had negative association with lumbar Z score (beta = - 0.216, P = 0.017 and beta = - 0.336, P = 0.027, respectively). We hypothesized that epilepsy per se could affect bone density by an unknown pathophysiology, which was independent from vitamin D deficiency, effects of anticonvulsant and physical activity.
Subject(s)
Bone Density , Dietary Supplements , Epilepsy/drug therapy , Epilepsy/physiopathology , Vitamin D/therapeutic use , Walking , Absorptiometry, Photon , Adolescent , Bone Density/drug effects , Case-Control Studies , Child , Epilepsy/epidemiology , Female , Femur/diagnostic imaging , Femur/drug effects , Femur/pathology , Femur/physiopathology , Humans , Iran/epidemiology , Linear Models , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/drug effects , Lumbar Vertebrae/pathology , Lumbar Vertebrae/physiopathology , Male , Prevalence , Vitamin D/pharmacologyABSTRACT
OBJECTIVE: To investigate the impact of Qing'e Pill (, QEP) on the cancellous bone microstructure and its effect on the level of ß-catenin in a mouse model of postmenopausal osteoporosis. METHODS: Ninety-six 8-week-old specific pathogen free C57BL/6 mice were randomly divided into 4 groups (24/group): sham, ovariectomised osteoporosis model, oestradiol-treated, and QEP-treated groups. Three months after surgery, the third lumbar vertebra and left femur of the animals were dissected and scanned using micro-computed tomography (micro-CT) to acquire three-dimensional (3D) parameters of their cancellous bone microstructure. The impact of ovariectomy, the effect of oestradiol and QEP intervention on cancellous bone microstructure, and the expression of ß-catenin were evaluated. RESULTS: The oestradioland the QEP-treated groups exhibited a significant increase in the bone volume fraction, trabecular number, trabecular thickneßs, bone surface to bone volume ratio (BS/BV), and ß-catenin expression compared with those of the model group (P <0.05). In contrast, the structure model index, trabecular separation, and BS/BV were significantly decreased compared with those of the ovariectomised osteoporosis model group (P <0.05). No differences were observed in the above parameters between animals of the QEP- and oestradiol-treated groups. CONCLUSIONS: The increased ß-catenin expression may be the mechanism underlying QEP's improvement of the cancellous bone microstructure in ovariectomised mice. Our findings provide a scientific rationale for using QEP as a dietary supplement to prevent bone loss in postmenopausal women.
Subject(s)
Bone Diseases, Metabolic/pathology , Bone Diseases, Metabolic/physiopathology , Cancellous Bone/pathology , Cancellous Bone/physiopathology , Drugs, Chinese Herbal/pharmacology , Animals , Biomechanical Phenomena/drug effects , Cancellous Bone/diagnostic imaging , Cancellous Bone/drug effects , Femur/diagnostic imaging , Femur/drug effects , Femur/pathology , Femur/physiopathology , Imaging, Three-Dimensional , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/drug effects , Lumbar Vertebrae/pathology , Lumbar Vertebrae/physiopathology , Mice, Inbred C57BL , Ovariectomy , Survival Analysis , X-Ray Microtomography , beta Catenin/metabolismABSTRACT
OBJECTIVES: The aim of the study was to evaluate the influence of the depth of local anesthesia application on procedural pain during lumbar transforaminal epidural steroid injection. DESIGN: Sixty-eight patients were enrolled who were scheduled for single-level, unilateral fluoroscopically guided lumbar transforaminal epidural steroid injection. Patients were randomly allocated to receive either subcutaneous local anesthesia (group S) or deep local anesthesia (group D) for transforaminal epidural steroid injection. The data related to pain and technical performance during the procedure was compared. In addition, the incidence of injection site soreness was assessed 2 wks after transforaminal epidural steroid injection. RESULTS: Sixty-seven patients completed all assessments (group S, n = 33; group D, n = 34). There was no significant difference in procedural pain and discomfort level between the groups (P = 0.151, P = 0.183, respectively). Patients in group D showed lower behavioral pain scores (P = 0.017). There was no significant difference in the numbers of needle manipulations, fluoroscopy time, and radiation dose during the procedure between the groups. Two patients in group S and three in group D complained of injection site soreness after transforaminal epidural steroid injection for a few days, but there was no significant difference in its incidence (P = 0.667). CONCLUSIONS: Deep local anesthesia to reduce procedural pain during transforaminal epidural steroid injection seems to have no significant clinical benefit compared with conventional subcutaneous local anesthesia. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Reduce procedural pain by considering clinical factors of the patient during fluoroscopically guided lumbar transforaminal epidural injections.Upon completion of this article, the reader should be able to: (1) Understand the potential impact of procedural pain on the performance of transforaminal epidural steroid injections; (2) Distinguish cutaneous nociceptive afferents from nociceptive afferents in muscle; and (3) Explain the factors to reduce procedural pain during fluoroscopically guided lumbar transforaminal epidural injections. LEVEL: Advanced ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.
Subject(s)
Anesthesia, Local/methods , Fluoroscopy/adverse effects , Injections, Epidural/adverse effects , Pain, Procedural/drug therapy , Adult , Aged , Aged, 80 and over , Female , Fluoroscopy/methods , Humans , Injections, Epidural/methods , Lumbar Vertebrae/drug effects , Male , Middle Aged , Pain Measurement , Pain, Procedural/etiology , Treatment Outcome , Young AdultABSTRACT
Bone fragility, despite relatively high BMD values, is an important complication related to insulin resistance and oxidative stress in diabetes mellitus type 1. The present study aimed to compare the effects of soy milk (SM), soy milk containing Lactobacillus casei (PSM), and soy milk enriched with Lactobacillus casei and omega-3 (OPSM) on the stereology of the tibia and vertebra, and antioxidant activity in type 1 diabetic rats. Sixty-five male Sprague Dawley rats were randomly assigned into 5 groups of 13 animals each. Diabetes was induced by a single injection of STZ (60 mg/kg); two control groups (non-diabetic: CN and diabetic: CD) were selected and then fed with 1 mL of distilled water. Three treatment groups were fed 1 ml of SM, PSM, and OPSM via intragastric gavage for 60 days. Treatment with SM, PSM, and OPSM significantly decreased (P < 0.05) the number of the osteoclasts in both tibia and L5 vertebra, and plasma alkaline phosphatase level. Also, the osteoblast number, calcium level, catalase activity, and total antioxidant capacity were increased in the SM, PSM, and OPSM groups compared to the STZ group. OPSM had the greatest effects on the stereological and biochemical parameters compared to the SM and PSM groups. Soy milk combination with Lactobacillus casei and omega-3 can ameliorate the stereological changes in the tibia and vertebra. In addition, this combination increased the antioxidant activity and improved the redox homeostasis in diabetic rats. These results suggest the potential role of soy milk containing Lactobacillus casei enriched with omega-3 in preventing and delaying osteoporosis in diabetic patients.
Subject(s)
Bone Diseases, Metabolic/drug therapy , Diabetes Mellitus, Type 1/complications , Fatty Acids, Omega-3/metabolism , Probiotics/administration & dosage , Soy Milk/metabolism , Tibia/metabolism , Alkaline Phosphatase/blood , Animals , Bone Density/drug effects , Bone Diseases, Metabolic/blood , Bone Diseases, Metabolic/etiology , Bone Diseases, Metabolic/physiopathology , Calcium/blood , Food Additives/analysis , Food Additives/metabolism , Humans , Lacticaseibacillus casei/physiology , Lumbar Vertebrae/chemistry , Lumbar Vertebrae/drug effects , Male , Probiotics/analysis , Rats , Rats, Sprague-Dawley , Soy Milk/chemistry , Tibia/chemistryABSTRACT
The aim of the the study is to compare the effects of cholecalciferol and calcitriol on bone mineral metabolism in women with vitamin D deficiency. Calcitriol was associated with a significant increase in bone mineral density at the lumbar spine in patients with low vitamin D levels. PURPOSE/INTRODUCTION: Active vitamin D analogs may have larger impact in decreasing bone loss and fracture rate compared to cholecalciferol in osteoporosis. However, their effects in the treatment of vitamin D deficiency compared to cholecalciferol are not clear. The aim of the present study is to compare the effects of cholecalciferol and calcitriol on bone mineral metabolism and bone mineral density in pre- and postmenopausal women with vitamin D deficiency. METHODS: This was a 6-month prospective, open-label, controlled clinical trial. Eligible 120 participants were pre- and postmenopausal women diagnosed with vitamin D deficiency. Forty-three subjects (group 1) received 1000 IU of cholecalciferol and 1 g of calcium daily. The other 77 subjects (group 2) received 0.5 µg calcitriol in addition to 400 IU of cholecalciferol and 1 g of calcium daily. RESULTS: Oral vitamin D supplementation did not increase bone mineral density after 6 months of intervention in group 1. On the other hand, bone mineral density at the lumbar spine increased from 0.809 ± 0.172 to 0.848 ± 0.161 g/cm2 in group 2 patients (p < 0.017 vs baseline). CONCLUSIONS: Oral daily calcitriol was associated with a significant increase in bone mineral density at the lumbar spine in patients with low vitamin D, elevated PTH, and osteoporosis.
Subject(s)
Bone Density Conservation Agents/administration & dosage , Calcitriol/administration & dosage , Cholecalciferol/administration & dosage , Dietary Supplements , Vitamin D Deficiency/therapy , Bone Density/drug effects , Calcium/administration & dosage , Female , Humans , Lumbar Vertebrae/drug effects , Middle Aged , Osteoporosis/complications , Osteoporosis/therapy , Prospective Studies , Treatment Outcome , Vitamin D/analogs & derivatives , Vitamin D Deficiency/complicationsABSTRACT
BACKGROUND: Osteoporosis is becoming more prevalent in aging societies worldwide, and the economic burden attributable to osteoporotic fractures is substantial. The medications presently available to treat osteoporosis have side effects, and the development of safer and more effective treatments is urgently needed. The aim of this study is to evaluate the efficacy and safety of BHH10, a traditional Korean herbal medicine, in the treatment of postmenopausal osteoporosis. METHODS/DESIGN: This is a phase II, multicenter, randomized, double-blinded, placebo-controlled clinical trial and will include 168 postmenopausal women aged 55 years and older with osteoporosis. The participants will be recruited competitively from two sites of the Acupuncture and Moxibustion Department of Kyung Hee University Hospital of Korean Medicine, either Hoegidong or Gangdong in Seoul, Korea. Participants will be assigned randomly to one of two groups, the BHH10 group or the placebo group, in a 1:1 ratio, and will have five scheduled visits. Participants will take two tablets of BHH10 or placebo three times daily for 12 weeks. The primary efficacy outcome is the change in bone mineral density at the lumbar spine (L1-4) between baseline (visit 1) and 12 weeks after randomization (visit 5). Other outcome variables include changes in bone turnover markers, the Deficiency Syndrome of the Kidney Index, EuroQol five-dimension questionnaire score, and laboratory parameters, as well as adverse events. DISCUSSION: To our knowledge, this will be the first clinical trial to assess the efficacy and safety of BHH10 in postmenopausal women with osteoporosis. It is anticipated that the results will contribute to the development of traditional herbal medicines that can be used to treat osteoporosis in postmenopausal women in Korea. If the superiority of BHH10 over placebo is demonstrated, this study could provide the foundation for a phase III clinical trial. The results of the study will be published in a peer-reviewed journal. TRIAL REGISTRATION: Clinical Research Information Service, KCT0001842 . Registered on 14 March 2016.
Subject(s)
Bone Density Conservation Agents/therapeutic use , Bone Density/drug effects , Lumbar Vertebrae/drug effects , Osteoporosis, Postmenopausal/drug therapy , Plant Extracts/therapeutic use , Aged , Aged, 80 and over , Bone Density Conservation Agents/adverse effects , Clinical Trials, Phase II as Topic , Double-Blind Method , Female , Humans , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/physiopathology , Middle Aged , Multicenter Studies as Topic , Osteoporosis, Postmenopausal/diagnostic imaging , Osteoporosis, Postmenopausal/physiopathology , Plant Extracts/adverse effects , Randomized Controlled Trials as Topic , Seoul , Time Factors , Treatment OutcomeABSTRACT
The rationale behind intradiscal O2-O3 therapy is the pain elicited by the mechanical compression of the nerve root, which is associated with periganglionic and periradicular inflammation. This study aimed to determine the effect of intradiscal ozone injection on pain score and satisfaction of patients with low back pain (LBP) secondary to disc herniation. Patients with LBP diagnosed with disc herniation were enrolled in this clinical trial. After prepping and draping the area, intradiscal injection of ozone/oxygen mixture (10 ml, 25µg/ml) was performed under fluoroscopy guide (c-arm). Pain score and patient satisfaction were assessed prior to the injection (baseline) and 1, 3, 6, 12 and 24 months after the injection. Sixty three patients (24 males, 39 females) with mean age of 53.3 ±2.0 y enrolled in the study. The mean±standard deviation (SD) of pain score before intervention was 6.968 ±0.11. Pain score was reduced to 4.25±0.19 at 1 month, 4.33±0.20 at 3 months, 4.87 ±0.21 at 6 months and 5.22 ±0.20 at 24 months. According to the modified MacNab scale success of pain relief was as follows: excellent: 4 (6.3%), good: 17 (26.98 %), sufficient: 13 (20.63 %), poor: 13 (20.63 %), no result: 11 (17.46%), negative: 4 (6.3 %). Intradiscal ozone therapy was determined to provide improved outcomes in patients with single level of bulging and protrusion.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Intervertebral Disc Displacement/drug therapy , Low Back Pain/drug therapy , Oxygen/therapeutic use , Ozone/therapeutic use , Female , Fluoroscopy , Humans , Injections, Intralesional , Intervertebral Disc/diagnostic imaging , Intervertebral Disc/drug effects , Intervertebral Disc/innervation , Intervertebral Disc/pathology , Intervertebral Disc Displacement/diagnostic imaging , Intervertebral Disc Displacement/pathology , Low Back Pain/diagnostic imaging , Low Back Pain/pathology , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/drug effects , Lumbar Vertebrae/innervation , Lumbar Vertebrae/pathology , Male , Middle Aged , Pain Measurement/statistics & numerical data , Patient Satisfaction/statistics & numerical data , Treatment OutcomeABSTRACT
Lower back pain (LBP) is the most common disease in orthopedic clinics world-wide. A classic Fangji of traditional Chinese medicine, Duhuo Jisheng Decoction (DHJSD), has been proven clinically effective for LBP but its therapeutic mechanisms remain unclear. We hypothesized that DHJSD might relieve LBP through inhibiting the exaggerated proinflammatory cytokines and extracellular matrix (ECM) degradation. Thus, we studied the effects of DHJSD on stromal cell-derived factor-1 (SDF-1)-induced inflammation and ECM degradation in human nucleus pulposus cells (hNPCs). The primary hNPCs were isolated from either degenerated human intervertebral disc (HID) of LBP patients or normal HID of lumbar vertebral fracture patients, and cultured in vitro. The cells were treated with SDF-1 (10 ng/mL) and subsequently with different concentrations (100-500 µg/mL) of DHJSD for 24 h, respectively. We found that application of DHJSD significantly antagonized the SDF-1-induced production of proinflammatory cytokines and reduction of aggrecan and type II collagen in the hNPCs. DHJSD also markedly reduced the SDF-1-induced increase of CXCR4 and p-p65 and inhibited the nuclear translocation of p65 in the hNPCs. DHJSD, CXCR4-siRNA, and NF-κB inhibitor (BAY11-7082) caused the same inhibition of exaggerated proinflammatory cytokines in the SDF-1-treated hNPCs. These results provided compelling evidence that DHJSD may inhibit the generation of proinflammatory mediators and ECM degradation of HID through an orchestrated targeting at multiple molecules in the SDF-1/CXCR4/NF-κB pathway, thus offered novel mechanistic insights into the clinical effectiveness of DHJSD on LBP.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Chemokine CXCL12/pharmacology , Drugs, Chinese Herbal/pharmacology , Extracellular Matrix/metabolism , Intervertebral Disc Degeneration/drug therapy , Low Back Pain/drug therapy , Lumbar Vertebrae/drug effects , NF-kappa B/metabolism , Nucleus Pulposus/drug effects , Receptors, CXCR4/metabolism , Adult , Aged , Case-Control Studies , Cells, Cultured , Cytokines/metabolism , Dose-Response Relationship, Drug , Female , Humans , Inflammation Mediators/metabolism , Intervertebral Disc Degeneration/immunology , Intervertebral Disc Degeneration/metabolism , Intervertebral Disc Degeneration/pathology , Low Back Pain/immunology , Low Back Pain/metabolism , Low Back Pain/pathology , Lumbar Vertebrae/immunology , Lumbar Vertebrae/metabolism , Lumbar Vertebrae/pathology , Male , Matrix Metalloproteinases, Secreted/metabolism , Middle Aged , Nucleus Pulposus/immunology , Nucleus Pulposus/metabolism , Nucleus Pulposus/pathology , Receptors, CXCR4/genetics , Signal Transduction/drug effects , Transcription Factor RelA/metabolism , Young AdultABSTRACT
This study investigated whether or not vitamin D and calcium supplementation affected bone metabolism and bone mineral density (BMD) over a period of four years of denosumab therapy in patients with primary osteoporosis. Patients were divided into a denosumab monotherapy group (22 cases) or a denosumab plus vitamin D and calcium supplementation group (combination group, 21 cases). We measured serum bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase (TRACP)-5b, urinary N-terminal telopeptide of type-I collagen (NTX), and BMD of the lumbar 1-4 vertebrae (L-BMD) and bilateral hips (H-BMD) at baseline and at 12, 24, 36, and 48 months of treatment. There were no significant differences in patient background. Serum BAP, TRACP-5b, and urinary NTX were significantly and comparably inhibited in both groups from 12 to 48 months versus baseline values. L-BMD was significantly increased at every time point in both groups, while H-BMD was significantly increased at every time point in the combination group only. There were significant differences between the groups for L-BMD at 24, 36, and 48 months (P < 0.05) and for H-BMD at 12 months (P < 0.05). Compared with denosumab monotherapy, combination therapy of denosumab plus vitamin D and calcium significantly increased H-BMD at 12 months and L-BMD from 24 to 48 months. These findings indicate that continuous vitamin D and calcium supplementation is important, especially for 12 months to improve H-BMD and from 24 to 48 months to improve L-BMD.