Research on Molecular Mechanism of Fructus Ligustri Lucidi against Osteoporosis based on Network Pharmacology

Abstract TCMSP platform of systematic pharmacology of traditional Chinese medicine This study aimed to investigate the molecular mechanism of Fructus Ligustri Lucidi (NZZ, Chinese abbreviation) against osteoporosis (OP) by means of network pharmacology.ChemDraw Professional 15.1 software and Molinspiration Smiles database were used to draw the chemical formulas of the components. The active ingredients and related target proteins of NZZ were searched in platform of systematic pharmacology of traditional Chinese medicine database, Drugbank, Therapeutic Target Database, SymMap and other databases. Gene Ontology(GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out on the selected target through Enrichr and KEGG Automatic Annotation databases, and their mechanism was studied. A total of 29 compounds and 140 corresponding targets, including 14 key targets and 14 protein factors in protein-protein interaction core network were obtained. The key targets were tumor necrosis factor(TNF), interleukin(IL)-6R and sestrogen receptor alpha. The number of GO items was 466 (P<0.05), including 399 items of biological process (BP), 54 items of cell composition (MF) and 13 items of molecular function (CC). KEGG pathway enrichment screened 85 signaling pathways (P<0.05), including the IL-17 signaling pathway, TNF signaling pathway, advanced glycation end products and their receptors signaling pathway and cAMP signaling pathway. The active ingredients of NZZ. exert their anti-OP effects through multi-components, multi-targets and multi-pathways, which can provide new evidence for further study of their anti-OP mechanism.

Análisis descriptivo de un modelo de osteoporosis inducida en ratas (Rattus norvegicus) / Descriptive analysis of an induced osteoporosis model in rats (Rattus norvegicus)

RESUMEN: El objetivo del presente estudio fue realizar un análisis histopatológico de un modelo animal en ratas, que simule las características observables en huesos de pacientes con osteoporosis. Para ello, se utilizaron 10 ratas hembras (Rattus norvegicus) Sprague Dawley de 12 semanas de desarrollo y aproximadamente 200-250 g. De las cuales, a 5 se le realizó ovariectomía (OVX) bilateral, mientras que las 5 restantes fueron utilizadas como control. Posterior a 12 semanas de realizadas las ovariectomías en el grupo experimental, se realizó la eutanasia de los animales y la obtención de ambos fémur, los cuales fueron posteriormente seccionados para procesar su porción distal para su procesamiento histológico de rutina. Todos los animales sobrevivieron al final del estudio sin ninguna complicación postoperatoria, las imágenes histológicas evidenciaron en el grupo experimental (OVX), una disminución del grosor del hueso cortical, mayor cantidad de hueso esponjoso, pérdida de la continuidad de periostio y endostio alrededor de la matriz ósea además de mayor cantidad de tejido adiposo en la médula ósea, al ser comparados con el grupo control. Se puede concluir que a las 12 semanas post ovariectomía se observa un fenotipo histopatológico compatible con características oseteoporóticas en ratas adultas.

SUMMARY: The aim of the present study was to conduct a histopathological analysis of an animal model in rats, which simulates the characteristics observable in bones of patients with osteoporosis. To this end, 10 female rats (Rattus norvegicus) Sprague Dawley of 12 weeks of development and approximately 200-250 g were used. Of these, 5 underwent bilateral ovariectomy (OVX), whereas the remaining 5 were used as control. After 12 weeks of ovariectomy in the experimental group, the animals were euthanized and the two femurs were collected, which were then sectioned to process their distal portion. All the animals survived at the end of the study without any signs of postoperative complications. In the experimental group (OVX), the histological images showed a decrease in the thickness of the cortical bone, a greater amount of cancellous bone, loss of the continuity of the periosteum and endostium around the bone matrix in addition to a greater amount of adipose tissue in the bone marrow, when compared with the control group. It can therefore be inferred that a histopathological phenotype can be found at 12 weeks post- ovariectomy that would be consistent with osteoporotic characteristics in adult rats.

Low Body Mass Index as a Risk Factor for the Onset of Porosity of the Mandibular Bone in the Elderly

ABSTRACT Objective: To investigate whether a low body mass index (BMI) has a significant relationship with mandibular bone porosity progression by conducting a mandibular inferior cortex (MIC) classification in elderly Japanese people. Material and Methods: A total of 266 study subjects, aged 70 at baseline, were recruited for this study, conducted from 1998 to 2007. The subjects were divided into two groups according to changes in the MIC on serial panoramic radiographs during this nine-year study period: a no change group (MIC-NC) and a change group (MIC-C). All subjects in the MIC-C showed changes trending toward greater fragility. We evaluated the BMI at baseline. Logistic regression analysis was performed to assess the relationship between the MIC condition during the nine-year period (0: MIC-NC, 1: MIC-C) and BMI (kg/m2) adjusted for gender, current health status (CHS), and smoking habit (SH) at baseline. Results: The mean and standard deviations of the BMI at baseline in the MIC-NC and MIC-C were 22.8 ± 2.1 and 21.8 ± 2.5 kg/m2 for males and 23.1 ± 2.9 and 21.9 ± 2.4 kg/m2 for females. There was a significant relationship between the MIC condition and the BMI in both males (p=0.04) and females (p=0.01). The logistic regression analysis revealed a significant association between the MIC condition over the nine-year period and the BMI (OR=0.84, p=0.003), which was adjusted depending on the gender (OR=5.18, p=0.000), CHS (OR=0.53, p=0.015), and SH (OR=4.15, p=0.002) at baseline. Conclusion: A low BMI carries a risk of developing mandibular bone porosity by measuring the MIC condition in panoramic radiographs.

Influence of green tea extract with different concentrations of epigallocatechin gallate on calvaria bone repair of ovariectomized rats / Influencia del extracto de té verde con diferentes concentraciones de galato de epigalocatequina sobre la reparación ósea de calvaria de ratas ovariectomizadas

Impairing osteoporosis progression is a challenge, and recently the role of antioxidants has been associated to bone metabolism. Green tea extract is rich in catechins, especially epigallocatechin gallate (EGCG), which may help control osteoporosis damage in bone tissue. This investigation evaluated the efficacy of green tea ingestion containing different concentrations of EGCG in calvaria bone repair of ovariectomized rats. Wistar rats (n=15) were ovariectomized and divided into 3 groups: ovariectomized (OVX), ovariectomized + GTE 15 % EGCG (OVX/GTE15), and ovariectomized + GTE 94 % EGCG (OVX/GTE94). Green tea extract was administered by gavage in the concentration of 50 mg/kg and sham group (n=5) received water. Bone defects were performed in the calvaria 60 days after ovariectomy followed by 4 weeks until euthanasia. Bone samples were collected to perform qualitative and quantitative histological analysis of bone formation. Data obtained were submitted to normality and ANOVA statistical test for p<0.05. The mean values of neoformed bone for Sham, OVX, OVX/GTE15 and OVX/GTE94 were respectively: 21.11 ± 3.91; 19.92 ± 2.20; 33.05 ± 1.26 e 34.75 ± 0.54 (p<0.05). Results show that continuous ingestion of green tea extract immediately after ovariectomy shows positive effects in the prevention of bone loss in osteoporosis, even with low concentrations of EGCG.

La disminución en la progresión de la osteoporosis es un desafío, y recientemente el papel de los antioxidantes se ha asociado al metabolismo óseo. El extracto de té verde es rico en catequinas, especialmente el galato de epigalocatequina (EGCG), lo que puede ayudar a controlar el daño de la osteoporosis en el tejido óseo. Esta investigación evaluó la eficacia de la ingesta de té verde con diferentes concentraciones de EGCG en la reparación ósea de calvaria de ratas ovariectomizadas. Las ratas Wistar (n = 15) fueron ovariectomizadas y divididas en 3 grupos: ovariectomizadas (OVX), ovariectomizadas + GTE 15 % EGCG (OVX / GTE15), y ovariectomizadas + GTE 94 % EGCG (OVX / GTE94). El extracto de té verde se administró por sonda en una concentración de 50 mg/kg y el grupo simulado (n = 5) recibió agua. Los defectos óseos se realizaron en la calvaria 60 días después de la ovariectomía, seguido de 4 semanas hasta la eutanasia. Se obtuvieron muestras de hueso para realizar un análisis histológico cualitativo y cuantitativo de la formación ósea. Los datos obtenidos se sometieron a normalidad y prueba estadística ANOVA (p<0,05). Los valores medios de hueso neoformado para Sham, OVX, OVX / GTE15 y OVX / GTE94 fueron: 21,11 ± 3,91; 19,92 ± 2,20; 33,05 ± 1,26 y 34,75 ± 0,54 (p <0,05), respectivamente. Los resultados muestran que la ingesta continua de extracto de té verde, inmediatamente después de la ovariectomía, muestra efectos positivos en la prevención de la pérdida ósea ocurrida en la osteoporosis, incluso con concentraciones bajas de EGCG.

A SERM increasing the expression of the osteoblastogenesis and mineralization-related proteins and improving quality of bone tissue in an experimental model of osteoporosis

Abstract Raloxifene is an antiresorptive drug, selective estrogen receptor modulator (SERM) used in the treatment of osteoporosis. Objective To evaluate proteins related to bone repair at the peri-implant bone in a rat model of osteoporosis treated with raloxifene. Material and Methods 72 rats were divided into three groups: SHAM (healthy animals), OVX (ovariectomized animals), and RLX (ovariectomized animals treated with raloxifene). Raloxifene was administered by gavage (1 mg/kg/day). Tibial implantation was performed 30 days after ovariectomy, and animals were euthanized at 14, 42, and 60 days postoperatively. Samples were collected and analyzed by immunohistochemical reactions, molecular analysis, and microtomographic parameters. Results RLX showed intense staining of all investigated proteins at both time points except for RUNX2. These results were similar to SHAM and opposite to OVX, showing mild staining. The PCR gene expression of OC and ALP values for RLX (P<0.05) followed by SHAM and OVX groups. For BSP data, the highest expression was observed in the RLX groups and the lowest expression was observed in the OVX groups (P<0.05). For RUNX2 data, RLX and SHAM groups showed greater values compared to OVX (P<0.05). At 60 days postoperatively, microtomography parameters, related to closed porosity, showed higher values for (Po.N), (Po.V), and (Po) in RLX and SHAM groups, whereas OVX groups showed lower results (P<0.05); (BV) values (P=0.009); regarding total porosity (Po.tot), RLX group had statistically significant lower values than OVX and SHAM groups (P=0.009). Regarding the open porosity (Po.V and Po), the SHAM group presented the highest values, followed by OVX and RLX groups (P<0.05). The Structural Model Index (SMI), RLX group showed a value closer to zero than SHAM group (P<0.05). Conclusions Raloxifene had a positive effect on the expression of osteoblastogenesis/mineralization-related proteins and on micro-CT parameters related to peri-implant bone healing.

Effects of continual intermittent administration of parathyroid hormone on implant stability in the presence of osteoporosis: an in vivo study using resonance frequency analysis in a rabbit model

Abstract Objective: This study aimed to evaluate the effects of continual intermittent administration of parathyroid hormone (PTH) on implant stability in the presence of osteoporosis, using rabbit models. Material and Methods: Fifteen female New Zealand white rabbits underwent ovariectomy and were administered glucocorticoids to induce osteoporosis, following which they were divided into three groups. The first group received intermittent subcutaneous PTH for 4 weeks until implant placement (PTH1), while the second and third groups received PTH (PTH2) and saline (control), respectively, for 4 weeks before and after implant placement. After intermittent administration of PTH or saline, titanium implants were inserted into the left femoral epiphyses of all animals, and the implant stability quotient (ISQ) was measured immediately after placement to assess the primary stability and at 2 and 4 weeks after implant placement to assess osseointegration. At 4 weeks after implant placement, histological and histomorphometric evaluations were conducted and the bone area around the implant socket was measured as a ratio of the total bone area to the total tissue area. Results: Regarding primary stability, the ISQ values for the PTH1 and PTH2 groups were significantly higher than those for the control group (p<0.05). Concerning osseointegration, the ISQ values at 2 and 4 weeks were significantly higher for the PTH2 group than for the PTH1 and control (p<0.05) groups. Histological assessments showed a thicker and more trabecular bone around the implant sockets in the PTH2 specimens than in the PTH1 and control specimens. The bone area around the implant socket was significantly greater in the PTH2 group than in the PTH1 and control groups (p<0.05). Conclusions: Our results suggest that continual intermittent PTH administration before and after dental implant placement is effective for the achievement of favorable stability and osseointegration in the presence of osteoporosis.

Compromiso óseo en mastocitosis sistémica: una asociación frecuente, pero muchas veces inadvertida / Bone involvement in systemic mastocytosis: report of two cases

Systemic mastocytosis (SM) is characterized by pathologic expansion and activation of mast cells. The main clinical manifestations of SM include skin involvement, gastrointestinal symptoms and anaphylaxis due to the release of its mediators. Thirty percent of pat ients with SM have a low bone mass and 20% fractures. At the same time, SM affects 10% of male patients with idiopathic osteoporosis. Measuring serum tryptase is essential for the screening of MS. We report two cases of SM with bone involvement. A 25-year- old woman with prior diagnosis of SM, based on skin involvement, flushing, high serum tryptase and compatible bone marrow (BM) biopsy and genetic study. Low bone mass was diagnosed and treatment was started with calcium and vitamin D plus oral bisphosphona tes with adequate response. A 47 years old man who presented with multiple osteoporotic vertebral fractures and low bone mass. Treatment with vitamin D and alendronate was started, but the patient developed new vertebral fractures. The study was extended w ith measurement of serum tryptase that was elevated. Diagnosis of SM was confirmed with BM biopsy and the patient was referred to hematology for specific care. These cases emphasize the importance of bone assessment in SM, as well as the need to rule out S M in patients with osteoporosis and no evident cause.

Effects of physical exercise on the cartilage of ovariectomized rats submitted to immobilization / Efeitos do exercício físico sobre a cartilagem de ratas ooforectomizadas submetidas à imobilização

ABSTRACT Objective To analyze the effects of physical exercise on cartilage histomorphometry in osteoporosis-induced rats subjected to immobilization. Methods We used 36 Wistar rats that were separated into six groups: G1, G2 and G3 submitted to pseudo-oophorectomy, and G4, G5 and G6 submitted to oophorectomy. After 60 days at rest, G2, G3, G5 and G6 had the right hind limbs immobilized for 15 days, followed by the same period in remobilization, being free in the box to G2 and G5, and climb ladder to G3 and G6. At the end of the experiment, the rats were euthanized, their tibias bilaterally removed and submitted to histological routine. Results There was significant increase in thickness of the articular cartilage (F(5;29)=13.88; p<0.0001) and epiphyseal plate (F(5;29)=14.72; p<0.0001) as the number of chondrocytes (F(5;29)=5.11; p=0.0021) in ovariectomized rats, immobilized and submitted to exercise. In the morphological analysis, degeneration of articular cartilage with subchondral bone exposure, loss of cellular organization, discontinuity of tidemark, presence of cracks and flocculation in ovariectomized, immobilized and free remobilization rats were found. In ovariectomized and immobilized remobilization ladder rats, signs of repair of the cartilaginous structures in the presence of clones, pannus, subcortical blood vessel invasion in the calcified zone, increasing the amount of isogenous groups and thickness of the calcified zone were observed. Conclusion Exercise climb ladder was effective in cartilaginous tissue recovery process damaged by immobilization, in model of osteoporosis by ovariectomy in rats.

RESUMO Objetivo Analisar os efeitos do exercício físico sobre a histomorfometria da cartilagem de ratas induzidas à osteoporose e submetidas à imobilização. Métodos Foram utilizadas 36 ratas Wistar separadas em seis grupos: G1, G2 e G3 submetidas à pseudo-ooforectomia e G4, G5 e G6, à ooforectomia. Após 60 dias em repouso, G2, G3, G5 e G6 tiveram o membro posterior direito imobilizado por 15 dias, seguido pelo mesmo período em remobilização, sendo livres na caixa para G2 e G5, e de subida em escada para G3 e G6. Ao final do experimento, as ratas foram eutanasiadas, e suas tíbias foram retiradas bilateralmente e submetidas à rotina histológica. Resultados Houve aumento significativo de espessura da cartilagem articular (F(5;29)=13,88; p<0,0001) e da placa epifisária (F(5;29)=14,72; p<0,0001), bem como do número de condrócitos (F(5;29)=5,11; p<0,0021) em ratas ooforectomizadas, imobilizadas e submetidas ao exercício em escada. Nas análises morfológicas, verificaram-se degeneração da cartilagem articular com exposição de osso subcondral, perda da organização celular, descontinuidade da tidemark, presença de fissuras e floculações em ratas ooforectomizadas, imobilizadas e com remobilização livre. Nas ratas ooforectomizadas, imobilizadas e com remobilização em escada, observaram-se sinais de reparação das estruturas cartilaginosas com presença de clones, pannus, invasão de vasos sanguíneos subcorticais na zona calcificada, aumento da quantidade de grupos isógenos e espessura da zona calcificada. Conclusão O exercício físico de subida em escada mostrou-se efetivo no processo de recuperação do tecido cartilaginoso danificado pela imobilização, em modelo de osteoporose por ooforectomia em ratas.

Practical Use of Bone Scan in Patients with an Osteoporotic Vertebral Compression Fracture

Rib fractures are one of main causes of chest or flank pain when related to an osteoporotic vertebral compression fracture (OVCF). The authors investigated the incidence and risk factors of rib fracture in 284 patients with OVCF using bone scans and evaluated the feasibility as to whether bone scans could be utilized as a useful screening tool. Hot uptake lesions on ribs were found in 122 cases (43.0%). The factors analyzed were age, sex, number and locations of fractured vertebrae, BMD, and compression rates as determined using initial radiography. However, no statistical significances were found. In 16 cases (5.6%), there were concurrent multiple fractures of both the thoracic and lumbar spines not detected by single site MRI. Sixty cases (21.1%) of OVCF with the a compression rate of less than 15% could not be identified definitely by initial plain radiography, but were confirmed by bone scans. It is concluded that a bone scan has outstanding ability for the screening of rib fractures associated with OVCF. Non-adjacent multiple fractures in both thoracic and lumbar spines and fractures not identified definitely by plain radiography were detected on bone scans, which provided a means for determining management strategies and predicting prognosis.

Practical Use of Bone Scan in Patients with an Osteoporotic Vertebral Compression Fracture

Rib fractures are one of main causes of chest or flank pain when related to an osteoporotic vertebral compression fracture (OVCF). The authors investigated the incidence and risk factors of rib fracture in 284 patients with OVCF using bone scans and evaluated the feasibility as to whether bone scans could be utilized as a useful screening tool. Hot uptake lesions on ribs were found in 122 cases (43.0%). The factors analyzed were age, sex, number and locations of fractured vertebrae, BMD, and compression rates as determined using initial radiography. However, no statistical significances were found. In 16 cases (5.6%), there were concurrent multiple fractures of both the thoracic and lumbar spines not detected by single site MRI. Sixty cases (21.1%) of OVCF with the a compression rate of less than 15% could not be identified definitely by initial plain radiography, but were confirmed by bone scans. It is concluded that a bone scan has outstanding ability for the screening of rib fractures associated with OVCF. Non-adjacent multiple fractures in both thoracic and lumbar spines and fractures not identified definitely by plain radiography were detected on bone scans, which provided a means for determining management strategies and predicting prognosis.

Relación de la aterosclerosis carotídea con la osteoporosis de columna lumbar y caderas en el infarto agudo de miocardio / Relationship between carotid atherosclerosis and lumbar spine and hip osteoporosis in acute myocardial infarction

OBJETIVO: determinar en pacientes con infarto agudo del miocardio, la existencia de asociación entre la aterosclerosis carotídea y la osteoporosis de la columna lumbar y caderas. MÉTODOS: se exploraron 104 pacientes con diagnóstico clínico y de laboratorio de infarto agudo del miocardio. A cada paciente se les realizó ultrasonido doppler carotídeo, en el que se describió grosor íntima-media, localización y tipo de placas ateromatosas, grado de estenosis e índice aterogénico; seguido de densitometría de columna lumbar y caderas. Se clasificaron los niveles de densidad mineral ósea en normal, osteopenia y osteoporosis, según T score. RESULTADOS: no se encontró correlación entre el valor de la densidad mineral ósea y la magnitud del daño aterosclerótico del sector carotídeo. La mayoría de los factores de riesgo se asociaron con valores normales de grosor íntima-media, índice aterogénico aumentado y baja prevalencia de estenosis significativa, así como de osteopenia densitométrica; el envejecimiento y la hipertensión resultaron los predominantes. CONCLUSIONES: más allá de la existencia de factores de riesgo en común, no hubo asociación entre la osteoporosis y la aterosclerosis carotídea en los pacientes con infarto agudo del miocardio.

OBJECTIVE: determine the relationship between carotid atherosclerosis and lumbar spine and hip osteoporosis in patients with acute myocardial infarction. METHODS: a study was conducted of 104 patients with a clinical and laboratory diagnosis of acute myocardial infarction. All patients underwent carotid Doppler ultrasonography for intima media thickness, location and type of atheromatous plaques, stenosis degree and atherogenic index, followed by lumbar spine and hip densitometry. Bone mineral density levels were classified as normal, osteopenia or osteoporosis, according to the T-score. RESULTS: no correlation was found between bone mineral density values and the extent of atherosclerotic damage to the carotid sector. Most risk factors were associated with normal intima media thickness values, an increased atherogenic index, a low prevalence of significant stenosis, and densitometric osteopenia. Aging and hypertension were the predominant risk factors. CONCLUSIONS: except for the existence of common risk factors, no association was found between osteoporosis and carotid atherosclerosis in patients with acute myocardial infarction.

Role of Triticum aestivum aqueous extract in glucocorticoid induced osteoporosis in rats.

Administration of aqueous extract of T. aestivum (200 and 400 mg/kg/day, po, for 30 days) and risedronate (20 mg/kg, sc, five times a week for 30 days) following methyl prednisolone sodium succinate (10 mg/kg, sc, thrice a week for 4 weeks) induced osteoporosis in Wistar rats showed an increase in the serum levels of bone mineral content markers, decrease in the serum and urinary levels of bone resorption markers. An incline in strength of femur and tibia was seen particularly with 400 mg/kg of T. aestivum. Maintenance of calcium homeostasis, formation of collagen and scavenging of free radicals can plausibly be the mode of action of aqueous extract of T. aestivum thereby combating osteoporosis induced by glucocorticoids.

Levothyroxine Dose and Fracture Risk According to the Osteoporosis Status in Elderly Women / 예방의학회지

OBJECTIVES: To evaluate the association between fracture risk and levothyroxine use in elderly women with hypothyroidism, according to previous osteoporosis history. METHODS: We conducted a cohort study from the Korean Health Insurance Review and Assessment Service claims database from January 2005 to June 2006. The study population comprised women aged > or =65 years who had been diagnosed with hypothyroidism and prescribed levothyroxine monotherapy. We excluded patients who met any of the following criteria: previous fracture history, hyperthyroidism, thyroid cancer, or pituitary disorder; low levothyroxine adherence; or a follow-up period 150 microg/d. The hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with the Cox proportional hazard model, and subgroup analyses were performed according to the osteoporosis history and osteoporosis-specific drug prescription status. RESULTS: Among 11 155 cohort participants, 35.6% had previous histories of osteoporosis. The adjusted HR of fracture for the >150 microg/d group, compared with the 51 to 100 microg/d group, was 1.56 (95% CI, 1.03 to 2.37) in osteoporosis subgroup. In the highly probable osteoporosis subgroup, restricted to patients who were concurrently prescribed osteoporosis-specific drugs, the adjusted HR of fracture for the >150 microg/d group, compared with the 51 to 100 microg/d group, was 1.93 (95% CI, 1.14 to 3.26). CONCLUSIONS: While further studies are needed, physicians should be concerned about potential levothyroxine overtreatment in elderly osteoporosis patients.

Caracterización de la asociación aterosclerosis-osteoporosis en hombres y mujeres: estudio en fallecidos / Caracterization of the aterosclerosis-osteoporosis asociation in men and women: patient death study

Objetivos: Caracterizar la asociación entre las lesiones ateroscleróticas de las arterias coronarias con la osteoporosis de la columna lumbar y de fémur proximal en hombres y mujeres. Métodos: Se estudiaron 79 necropsias, realizando densitometría postmorten de columna lumbar y fémur proximal, clasificando los niveles de densidad mineral ósea (DMO) según T score en: normal, osteopenia y osteoporosis; seguido del examen patomorfológico y morfométrico de las tres coronarias epicárdicas principales aplicando el sistema aterométrico, clasificando las lesiones ateroscleróticas como: estría adiposa, placa fibrosa y placa grave. Resultados: La asociación aterosclerosis-osteoporosis mostró características especiales para cada sexo, con predominio significativo de osteoporosis en hombres y de osteopenia en mujeres. Tras remover el efecto del tabaquismo, las diferencias entre los géneros se modificaron, observándose que los fumadores, de ambos sexos, presentaron una DMO y una asociación aterosclerosis-osteoporosis similares. Conclusiones: La interferencia ejercida por sexo sobre la asociación aterosclerosis-osteoporosis resultó despreciable

Objective: characterize the association between coronary atherosclerotic lesions and osteoporosis of lumbar spine and hip in men and women. Methods: We study 79 necropsies, doing lumbar spine and hip bone densitometry, classifying bone mineral density (BMD) by T score in: normal, osteopenia and osteoporosis. Then we carry out morphological and morphometric characterization of the three principal coronary arteries using the atherometric system, classifying atherosclerotic lesions like: fatty streak, fibrous plaques and severe plaques. Results: The atherosclerosis-osteoporosis association show special characteristics for each sex, with significantly predominance of osteoporosis in men and osteopenia in women. After smoking adjustment, the differences between sexes were modified, finding similar BMD and atherosclerosis-osteoporosis association between smoker patients of both sexes. Conclusions: The sex interference about atherosclerosis-osteoporosis association resulting contemptible

Efeito in vitro da triiodotironina sob o potencial osteogênico reduzido de células-tronco mesenquimais do tecido adiposo de ratas ovariectomizadas e com osteoporose / In vitro effects of triiodothyronine on the reduced osteogenic potential of adipose tissue derived mesenchymal stem cells from of ovariectomized rats and with osteoporosis

OBJETIVO: Avaliar se a triiodotironina (T3) aumenta a diferenciação osteogênica das células-tronco mesenquimais do tecido adiposo (CTM-TA) de ratas adultas ovariectomizadas e com osteoporose e compará-lo ao de ratas adultas e jovens sem osteoporose. MATERIAIS E MÉTODOS: CTM-TA foram cultivadas em meio osteogênico e distribuídas em sete grupos: 1) CTM-TA de ratas jovens sem osteoporose; 2) CTM-TA de ratas adultas sem osteoporose; 3) CTM-TA de ratas adultas com osteoporose e 4, 5, 6 e 7) CTM-TA de ratas adultas com osteoporose tratadas com T3 (0,01 nM, 1 nM, 100 nM e 1.000 nM). AVALIARAM-SE: atividade da fosfatase alcalina, conversão do dimetiltiazol (MTT), porcentagem de nódulos de mineralização, celularidade e quantificação de transcriptos gênicos para colágeno I, osteocalcina, osteopontina e Bmp-2. RESULTADOS: Independente da dose, T3 reduziu a conversão do MTT, a atividade da fosfatase, a porcentagem de células e a expressão de colágeno I em pelo menos uma das doses e dos períodos estudados (p < 0,05). Mas o tratamento com T3 não alterou o número de nódulos de mineralização e a expressão de osteopontina e Bmp-2 em culturas de CTM-TA de ratas adultas com osteoporose (p > 0,05). CONCLUSÃO: T3 apresenta efeitos negativos sobre alguns fatores envolvidos na diferenciação osteogênica de CTM-TA, sem, no entanto, reduzir a formação de nódulos de mineralização e a expressão de proteínas ósseas.

OBJECTIVE: To examine if triiodothyronine (T3) increases osteogenic differentiation adipose tissue derived stem cells (ASCs) from ovariectomized adult rats with osteoporosis compared with young rats and adult rats without osteoporosis. MATERIALS AND METHODS: The ASCs were cultured in osteogenic medium and distributed into seven groups: 1) ASCs of young rats without osteoporosis; 2) ASCs of adult rats without osteoporosis; 3) ASCs of adult rats with osteoporosis and 4, 5, 6 and 7) ASCs of adult rats with osteoporosis treated with T3 (0.01 nM, 1 nM, 100 nM and 1,000 nM). We analyzed alkaline phosphatase activity, dimethylthiazol (MTT) conversion, percentage of mineralized nodules, cellularity and quantification of gene transcripts for collagen I, osteocalcin, osteopontin and Bmp-2. RESULTS: Regardless of the dose, T3 reduced the MTT conversion, alkaline phosphatase activity, percentage of cells and the expression of collagen I in at least one of the doses and periods studied (p < 0.05). But, the treatment with T3 does not modify the number of mineralized nodules and the expression of osteopontin and Bmp-2 in culture of ASCs from adult rats with osteoporosis (p > 0.05). CONCLUSION: T3 has a negative effect on some factors involved in osteogenic differentiation of ASCs from adult rats with osteoporosis, without; however, reduce the formation of mineralized nodules and the expression of bone proteins.

Usefulness of Prone Cross-Table Lateral Radiographs in Vertebral Compression Fractures

BACKGROUND: Dynamic radiographs are recommended to investigate non-healing evidence such as the dynamic mobility or intravertebral clefts in osteoporotic vertebral compression fractures (VCFs). However, it is difficult to examine standing flexion and extension lateral radiographs due to severe pain. The use of prone cross-table lateral radiographs (PrLRs) as a diagnostic tool has never been proposed to our knowledge. The purpose of this study is to clarify the usefulness of PrLRs in diagnosis and treatment of VCFs. METHODS: We reviewed 62 VCF patients examined with PrLRs between January 1, 2008 and June 30, 2011. To compare the degree of pain provoked between standing extension lateral radiographs (StLRs) and PrLRs, numeric rating scale (NRS) scores were assessed and compared by a paired t-test. Vertebroplasty was done for 40 patients and kyphoplasty was done for 9 patients with routine manners. To assess the degree of postural reduction, vertebral wedge angles (VWA) and vertebral height ratios (VHR) were calculated by using preoperative StLRs, PrLRs, and postoperative lateral radiographs. Two variables derived from changes in VWA and VHR between preoperative and postoperative radiographs were compared by a paired t-test. RESULTS: The average NRS scores were 6.23 +/- 1.67 in StLRs and 5.18 +/- 1.47 in PrLRs. The degree of pain provocation was lower in using PrLRs than StLRs (p < 0.001). The average changes of VWA between preoperative and postoperative status were 5.24degrees +/- 6.16degrees with PrLRs and 3.46degrees +/- 3.47degrees with StLRs. The average changes of VHR were 0.248 +/- 0.178 with PrLRs and 0.148 +/- 0.161 with StLRs. The comparisons by two variables showed significant differences for both parameters (p = 0.021 and p < 0.001, respectively). The postoperative radiological status was reflected more precisely when using PrLRs than StLRs. CONCLUSIONS: In comparison with StLR, the PrLR was more accurate in predicting the degree of restoration of postoperative vertebral heights and wedge angles, and provoked less pain during examination. The PrLR could be a useful diagnostic tool to detect intravertebral cleft or intravertebral dynamic instability.

Estudo radiomorfométrico como indicador de risco de osteoporose / Radiomorphometric study as an osteoporosis risk indicator

Objetivo: Avaliar a existência de diferenças nas imagens de radiografias panorâmicas por meio de um estudo radiomorfométrico. Método: Foi realizado um estudo observacional, sendo a amostra composta por radiografias panorâmicas de 60 pacientes de ambos os sexos, dividida em três grupos etários (n=20): G1: 20-30, G2: 30-45 e G3: 45-60. As radiografias foram digitalizadas e analisadas. O Índice panorâmico mandibular, a Altura original da mandíbula e a Porcentagem do osso reabsorvido foram calculados e comparados por meio dos resultados da média, do desvio padrão e do coeficiente de variação de cada medida. Resultados: Na comparação entre os gêneros, as alterações foram mais evidentes nas medidas de Forame mentual - crista óssea (FC) e na Porcentagem de reabsorção óssea alveolar (%AO). Foi observada uma pequena diferença numérica entre os lados direito e esquerdo nas avaliações das estruturas ósseas mandibulares (Altura total da mandíbula e na Proporção AM/AF). Conclusões: Como as variações entre as medidas não foram muito discrepantes, sugere-se que as medidas da Altura total da mandíbula (AM), da Altura do forame mentual-crista óssea (FC) e da Porcentagem de reabsorção óssea (%AO), devam ser consideradas como um seguimento que inclua os períodos de ganho ou perda de cálcio, identificados como um fator de risco de osteoporose.

Objective: Evaluation of the existence of differences in images of panoramic radiographs through a radiomorfometric study. Method: An observational study was conducted using 60 panoramic radiograph images of 60 different patients of both sex, divided in three age groups (n= 20): G1: 20-30, G2: 30-45 and G3: 45 - 60. The radiographs were digitized and analyzed. The Panoramic mandibular index, the original height of the mandible and the percentage of bone reabsorbed were calculated and compared through the mean, standard deviation and coefficient of variation results. Results: The results were most evident considering the distance between mentual foramen and alveolar ridge, and the percentage of alveolar bone loss, when the genders were compared. A small numerical difference was observed between right and left sides in the evaluations of mandibular bone structures. Conclusions: As the variations between the measures were not very discrepant, it is suggested that measures of Total Mandibular Height, Mentual Foramen Alveolar Bone Ridge in the Percentage of Bone Resorption should be considered in the follow-up periods which includes calcium gains or loss, identified as a risk factor of osteoporosis.

Bone histomorphometry: a concise review for endocrinologists and clinicians / Histomorfometria óssea: uma revisão concisa para endocrinologistas e clínicos

Bone histomorphometry is a quantitative histological examination of an undecalcified bone biopsy performed to obtain quantitative information on bone remodeling and structure. Labeling agents taken before the procedure deposit at sites of bone formation allowing a dynamic analysis. Biopsy is indicated to make the diagnosis of subclinical osteomalacia, to characterize the different forms of renal osteodystrophy and to elucidate cases of unexplained skeletal fragility. Bone histomorphometric parameters are divided into structural and remodeling subgroups, with the latter being subdivided into static and dynamic categories. Metabolic bone disorders such as osteomalacia, hyperparathyroidism, hypothyroidism, osteoporosis and renal osteodystrophy display different histomorphometric profiles. Antiresorptive and anabolic drugs used for the treatment of osteoporosis also induce characteristic changes in the bone biopsy. Bone histomorphometry is an important research tool in the field of bone metabolism and provides information that is not available by any other investigative approach.

Histomorfometria óssea é uma avaliação histológica quantitativa de uma biópsia óssea calcificada realizada para obter informação sobre a remodelação e a estrutura óssea. Uma análise dinâmica é possível quando substâncias que fazem a marcação do osso são tomadas antes do procedimento e se depositam no local de formação óssea. A biópsia é indicada para diagnóstico de osteomalácia, diferentes formas de osteodistrofia renal e nos casos não explicados de fragilidade esquelética. O preparo e a análise das amostras necessitam de um laboratório especializado. A histomorfometria avalia parâmetros estruturais e de remodelação óssea, sendo o último subdividido em estático e dinâmico. Doenças osteometabólicas como osteomalácia, hiperparatireoidismo, hipoparatireoidismo, osteoporose e osteodistrofia renal apresentam parâmetros histomorfométricos distintos. Medicações antirreabsortivas e anabólicas usadas no tratamento da osteoporose também induzem alterações características na biópsia óssea. A histomorfometria óssea é uma ferramenta importante no metabolismo ósseo e oferece informação que não é possível por nenhum outro método diagnóstico.

Asociación de la Infección por el Virus de Inmunodeficiencia Humana con Osteopenia y Osteoporosis / Association of Infection with Human Immunodeficiency Virus Osteopenia and Osteoporosis

La infección por el Virus de Inmunodeficiencia Humana (SIDA) es una pandemia, que con el advenimiento de la terapia antirretroviral de alta eficacia (TARAE), ha presentado un marcado control de la morbimortalidad; sin embargo, surgen problemáticas asociadas a dicho tratamiento, como los trastornos de la densidad mineral ósea. Encontrar la posible relación entre la infección por el VIH con la presencia de osteopenia y osteoporosis, en pacientes que reciben o no TARAE y su relación con la carga viral ARN para VIH, contaje linfocitario T CD4 y el empleo de TARAE. Se estudiaron tres grupos, Grupo 1: 28 pacientes SIDA en TARAE; Grupo 2: 22 pacientes VIH-positivo sin TARAE y Grupo 3: 30 pacientes seronegativos controles. Se analizaron 80 individuos. De los 50 pacientes VIH-positivos, 34 presentaron alteración de la densidad mineral ósea, 16 (32%) con osteopenia y 18 (36%) osteoporosis, en comparación con 4 (13.3%) y 2 (6,7%) del grupo control que presentaron osteopenia y osteoporosis respectivamente; observándose una relación estadísticamente significativa (p= 0.001) entre la infección por VIH y la alteración de la densidad mineral ósea. No hubo asociación significativa con el empleo o tipo de TARAE, carga viral o nivel de T CD4. Existe relación estadísticamente significativa entre la infección por VIH y el riesgo de padecer osteopenia y osteoporosis (p=0,001) independiente del empleo de TARAE...

HIV infection is a pandemic, but the morbidity and mortality have been controlled with the arrival of HAART. This treatment has brought other problems, like changes in bone density. To find a possible relationship between HIV infection, osteoporosis and osteopenia in patients under HAART, and the relation with CD4+ and viral load. The sample was divided in three groups: 1. 28 HIV patients treated with HAART; group 2: 22 patients HIV+ without treatment and group 3: 30 HIV negative, subjects. The total were 80 subjects. In the group with AIDS, 34 had an abnormal bone density: 16 (32%) osteopenic and 18 (36%) osteoporosis, compared with only 4 (13,3%) and 2 (7,7% ) of the control subjects. This was statistically significant (p= 0,001), but we found no association when HAART, viral load or CD4+. There is a significant association of the risk for low bone density ant AIDS...

Changes in bone histology due to capacitive electric field stimulation of ovariectomized rat.

Background & objectives: Postmenopausal osteoporosis leads to a significant decline in bone mass. That complicates the treatment outcome. The objective of the present study was to find out the effects of pulsed modulated low level electric field capacitively coupled on bone histology of induced osteoporotic rats, for screening the potential therapy for osteoporosis. Methods: Osteopororosis was induced by performed by bilateral ovariectomy of female Wistar rats. After one month of surgery electric field stimulation was delivered to one leg of experimatal rats while the other was sham exposed. After 60 days of exposure treated rats were sacrificed and femur and tibia bones were segregated into (i) control (CON), (ii) ovariectomized (OVX) and (iii) ovariectomized + electrical stimulation (OVX+ES). Results: Histopathological analyses showed that capacitively coupled pulsed electric field exposure treatment augmented and restored the bone marrow cell population. Immunohistological localization of alkaline phosphatase (ALP) showed the increased activity of this enzyme after electrostimulation, which showed an enhanced osteoblast differentiation. Collagen histochemistry showed high amount of collagen fiber in exposed rats bones than that of osteoporotic bones. Electron microscopic study revealed the enhancement of microstructural composition and compactness in cortical and trabecular part of treated bones. Interpretation & conclusions: Our results suggest that capacitively coupled pulsed electric field exposure treatment of specified parameters is efficacious in attenuating the effects of ovariectomy induced osteoporosis and restore the bone loss.