Associations of vascular and bone status in arthritis patients.

Cardiovascular (CV) disease and osteoporosis (OP) have been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Bone and vascular biomarkers and parameters along with the effect of 1-year anti-TNF therapy on these markers were assessed in order to determine correlations between vascular pathophysiology and bone metabolism in RA and AS. Thirty-six patients treated with etanercept or certolizumab pegol and 17 AS patients treated with ETN were included in a 12-month follow-up study. Bone and vascular markers were previously assessed by ELISA. Bone density was measured by DXA and quantitative CT (QCT). Flow-mediated vasodilation (FMD), common carotid intima-media thickness (IMT) and pulse-wave velocity (PWV) were assessed by ultrasound. Multiple correlation analyses indicated associations between bone and vascular markers. Osteoprotegerin, sclerostin and cathepsin K were significantly associated with FMD, IMT and PWV, respectively (p < 0.05). Moreover, total and trabecular BMD determined by QCT inversely correlated with IMT (p < 0.05). On the other hand, among vascular parameters, platelet-derived growth factor BB and IMT correlated with DXA femoral and QCT total BMD, respectively (p < 0.05). In the RM-ANOVA analysis, anti-TNF treatment together with baseline osteocalcin, procollagen 1 N-terminal propeptide (P1NP) or vitamin D3 levels determined one-year changes in IMT (p < 0.05). In the MANOVA analysis, baseline disease activity indices (DAS28, BASDAI), the one-year changes in these indices, as well as CRP exerted effects on multiple correlations between bone and vascular markers (p < 0.05). As the pattern of interactions between bone and vascular biomarkers differed between baseline and after 12 months, anti-TNF therapy influenced these associations. We found a great number of correlations in our RA and AS patients undergoing anti-TNF therapy. Some of the bone markers have been associated with vascular pathophysiology, while some vascular markers correlated with bone status. In arthritis, systemic inflammation and disease activity may drive both vascular and bone disease.

BMSC seeding in different scaffold incorporation with hyperbaric oxygen treats seawater-immersed bony defect.

INTRODUCTION: The experiment was undertaken to estimate the effect of BMSC seeding in different scaffold incorporation with HBO on the repair of a seawater-immersed bone defect. And future compared n-HA/PLGA with ß-TCP/PLGA as a scaffold in treatment effect of the seawater-immersed bone defect. METHODS: Sixty New Zealand White rabbits with standard seawater defect in radius were randomly divided into group A (implant with nothing), group B (implanted with autogenous bone), group C (implanted with n-HA/PLGA/BMSCs), and group D (implanted with ß-TCP/PLGA/BMSCs). After the implant, each rabbit receives HBO treatment at 2.4 ATA 100% oxygen for 120 min/day for 2 weeks. Radiograph, histological, and biomechanical examinations were used to analyze osteogenesis. RESULT: X-ray analysis shows that n-HA/PLGA/BMSCs and ß-TCP/PLGA/BMSCs could accelerate the new bone formation, and the new bone formation in group C was larger than that in group D or group A and close to group B (P < 0.05). After 12 weeks, in group A, the defect without scaffold shows a loose connect tissue filled in the areas. The medullary canal in group B was recanalized. Defects in groups C and D show a larger number of woven bone formation. The new woven bone formation in defect areas in group C was larger than that in group D. The mechanical examination revealed ultimate strength at 12 weeks was group D > group C > group B > group A (P < 0.05). CONCLUSION: Scaffolds of n-HA/PLGA and ß-TCP/PLGA incorporation with HBO and BMSCs were effective to treat seawater-immersed bone defect, and n-HA/PLGA was more excellent than ß-TCP/PLGA.

Anacardic acid-mediated regulation of osteoblast differentiation involves mitigation of inflammasome activation pathways.

Disruption of the finely tuned osteoblast-osteoclast balance is the underlying basis of several inflammatory bone diseases, such as osteomyelitis, osteoporosis, and septic arthritis. Prolonged and unrestrained exposure to inflammatory environment results in reduction of bone mineral density by downregulating osteoblast differentiation. Earlier studies from our laboratory have identified that Anacardic acid (AA), a constituent of Cashew nut shell liquid that is used widely in traditional medicine, has potential inhibitory effect on gelatinases (MMP2 and MMP9) which are over-expressed in numerous inflammatory conditions (Omanakuttan et al. in Mol Pharmacol, 2012 and Nambiar et al. in Exp Cell Res, 2016). The study demonstrated for the first time that AA promotes osteoblast differentiation in lipopolysaccharide-treated osteosarcoma cells (MG63) by upregulating specific markers, like osteocalcin, receptor activator of NF-κB ligand, and alkaline phosphatase. Furthermore, expression of the negative regulators, such as nuclear factor-κB, matrix metalloproteinases (MMPs), namely MMP13, and MMP1, along with several inflammatory markers, such as Interleukin-1ß and Nod-like receptor protein 3 were downregulated by AA. Taken together, AA expounds as a novel template for development of potential pharmacological therapeutics for inflammatory bone diseases.

Layered Antimicrobial Selenium Nanoparticle-Calcium Phosphate Coating on 3D Printed Scaffolds Enhanced Bone Formation in Critical Size Defects.

Preventing bacterial colonization on scaffolds while supporting tissue formation is highly desirable in tissue engineering as bacterial infection remains a clinically significant risk to any implanted biomaterials. Elemental selenium (Se0) nanoparticles have emerged as a promising antimicrobial biomaterial without tissue cell toxicity, yet it remains unknown if their biological properties are from soluble Se ions or from direct cell-nanoparticle interactions. To answer this question, in this study, we developed a layered coating consisting of a Se nanoparticle layer underneath a micrometer-thick, biomimetic calcium phosphate (CaP) layer. We showed, for the first time, that the release of soluble HSe- ions from the Se nanoparticles strongly inhibited planktonic growth and biofilm formation of key bacteria, Staphylococcus aureus. The Se-CaP coating was found to support higher bone formation than the CaP-only coating in critical-size calvarial defects in rats; this finding could be directly attributed to the released soluble Se ions as the CaP layers in both groups had no detectable differences in the porous morphology, chemistry, and release of Ca or P. The Se-CaP coating was highly versatile and applicable to various surface chemistries as it formed through simple precipitation from aqueous solutions at room temperature and therefore could be promising in bone regeneration scaffolds or orthopedic implant applications.

Bioarchaeological reconstruction of physiological stress during social transition in Albania.

OBJECTIVE: We test the hypothesis that physiological stress increased in response to increasing social turmoil following waves of colonization and social transition. The ways local conditions, including variation in geography, environment, and levels of urbanization impact physiological stress are also explored. MATERIALS: In Albania, the historic period is a sequence of different waves of colonization. Skeletal data come from three Albanian archaeological sites: Apollonia (n = 231), Durrës (n = 246), and Lofkënd (n = 129). METHODS: Prevalence of cribra orbitalia, porotic hyperostosis, linear enamel hypoplasia, and periosteal new bone formation are analyzed using chi-square and logistic regression tests. RESULTS: We observe increased skeletal manifestations of physiological stress between prehistoric and historic groups, but physiological stress is generally consistent through time. CONCLUSIONS: General increase in skeletal pathology between prehistoric and historic periods corresponds to broad increases in political unrest associated with colonization spanning the entire historic period. However, little difference in physiological stress across colonization episodes (Greek, Roman, Byzantine, Bulgarian, Ottoman) suggests skeletal health is affected similarly by colonization, regardless of particularities in method and type of colonial control. SIGNIFICANCE: Examining human response to social change across broad time scales is useful in identifying broad patterns in the human experience. LIMITATIONS: Exploring variation across broad time scales and multiple sites is potentially problematic because confounding factors could impact results and interpretations. SUGGESTIONS FOR FURTHER RESEARCH: Environmental, social, and geographic differences, likely impacted the lives and lifestyles of individuals living in the past and should be explored further to understand the nuances in local response to colonization.

Black bone syndrome in broilers fed ethanolic extract of mango seeds.

This study aimed to evaluate the incidence of black bone syndrome (BBS) in broiler chickens fed with ethanolic extract of mango seed (EEMS). A total of 504 one-day-old male broilers were used in a completely randomised design assigned with 7 experimental diets and 6 replicates of 12 broilers per experimental plot. The experimental diets consisted of: diet without addition of synthetic antioxidant; diet with addition of synthetic antioxidant (200 ppm); and 5 levels of EEMS: 200 ppm, 400 ppm, 600 ppm, 800 ppm, and 1,000 ppm. Two methods of cooking (roasted and boiled) were used to prepare thigh samples. According to the results, the diets did not significantly influence the performance of the broilers. BBS incidence was higher in broilers fed a diet without antioxidants and was reduced with EEMS dietary inclusion, with the lowest incidence occurring with the inclusion of 1,000 ppm. The synthetic antioxidant butylated hydroxytoluene in the diet promoted a significantly higher BBS incidence than that obtained with 800 and 1,000 ppm EEMS and did not differ from the other diets. Of the cooking methods, a higher BBS incidence was observed for the boiled method. For the meat coloration and bone parameters, there were no significant interactions between the factors, diets and cooking methods. There was a linear reduction in the darkening score and linear increase in the luminosity (L∗) of the meat with increasing EEMS in the diet. With regard to the cooking method, the boiled thighs had lower luminosity (L∗), higher parameter a∗, and lower parameter b∗ values because of more pronounced meat darkening. The roasted bones were less heavy, dense, and flexible. A negative correlation was observed between the degree of darkening of the meat that characterizes the BBS with the luminosity (L∗) and intensity of yellow. We concluded that the addition of EEMS contributes to a reduced darkening of meat that characterises the BBS and recommend the dietary inclusion of 1,000-ppm EEMS.

Comorbidity and polypharmacy in patients with breast cancer.

BACKGROUND: Cancer sufferers are aged ≥ 65 years, but research has focused infrequently on elderly patients with the majority of cancer. We aimed not only to determine the frequency of comorbidity and polypharmacy, but also to present the discrepiancies in elderly versus non-elderly patients with breast cancer. METHODS: A total of 352 female patients aged over 18 years, 252 non-elderly and 100 elderly, followed-up in the oncology department of a tertiary hospital between January 2016 and September 2019 were retrospectively screened. Demographic data, comorbidity and medications of the patients were recorded hospital data processing system. Polypharmacy was defined as the use of ≥ 5 different medications. RESULTS: The most common four chronic diseases in both non-elderly and elderly groups were muscle-joint-bone disease, gastrointestinal diseases, diabetes mellitus and hypertension. The most common four prescribed drugs were NSAID, adjuvant endocrine therapy, PPI, and vitamin D or/and calcium in non-elderly group while those were ACEI-ARB, PPI, NSAID, and diuretics in elderly one. The frequency of polypharmacy was 50% (n = 126) in the non-elderly patients and 74% (n = 74) in the elderly ones. These were considered statistically significant (p < 0.001). The mean number of prescription medication categories reported was 5.02 (SD = 2.90; range 0-14) in non-elderly group whereas those was 6.83 (SD = 3.18; range 0-15) in elderly one (p < 0.001). The mean of ages were 47.9 years (without polypharmacy) and 51.3 years (with polypharmacy) in non-elderly patients while those are, respectively, 70.9 years and 74.7 years in elderly ones. These were considered statistically significant (respectively; p = 0.006, p = 0.009). CONCLUSIONS: We first gained to raise awareness in the literature of comorbidity and polypharmacy in patients with breast cancer and to compare between the elderly and non-elderly participants. For the effectiveness of cancer treatment, importance in geriatric population, attention to drug-drug interaction, such studies should be considered during clinical practice.

Disordered bone metabolism in hereditary spherocytosis patients.

Aim: This study was planned to evaluate bone health in patients with hereditary spherocytosis.Materials and methods: In this prospective study, a total of 30 hereditary spherocytosis patients which followed in the Pediatric Hematology and Oncology Department of KSU Medical Faculty and 30 patients for control group were included. Patient and control group were chosen equal in age and sex. Hemogram and biochemical tests (serum calcium, phosphorus, alkaline phosphatase, parathormone, vitamin D) and osteocalcin were studied from the patient and control groups. Also DXA examination was performed in the patient group.Results: There was a significant difference in hemogram parameters between the two groups due to hemolytic anemia in hereditary spherocytosis patients. In the patient group, osteocalcin was 6.88 ± 4.35 ng/ml, vitamin D was 17.74 ± 7.76 ng/ml and in the control group osteocalcin was 11.93 ± 8.92 ng/ml, vitamin D was 24.04 ± 11.70 ng/ml. There was a statistically significant difference between the vitamin D and osteocalcin levels of the two groups (p = 0.017 and 0.008, respectively). Bone density was assessed in the patient group. In patients DXA results showed lower Z-scores then the normal population according to age and sex.Conclusion: Hereditary spherocytosis patients should be followed closely in terms of development, puberty, bone health as they are in other hemolytic anemias. Nutritional recommendations, vitamin D supplementation, physical activity should be advised to protect bone health.

Patients with SMARCA4-deficient thoracic sarcoma and severe skeletal-related events.

OBJECTIVES: SMARCA4-deficient thoracic sarcoma(DTS) is a recently identified new entity of thoracic malignancies characterized by inactivation of SMARCA4. Patients with SMARCA4-DTS have a particulary aggresive clinical course and no effective treatments. However, the detailed clinical features of SMARCA4-DTS remain unclear. Here, we report the clinical courses and molecular profiles of two cases of SMARCA4-DTS. MATERIALS AND METHODS: We experienced strikingly similar two patients of SMARCA4-DTS. The clinicopathologic features were reviewed, and detailed immunohistochemical and comprehensive cancer panel analysis with next generation sequencing confirmed the diagnosis. RESULTS: Our cases had many clinical and radiological observations characteristic of SMARCA4-DTS in common. Immunohistochemical staing showed complete loss of SMARCA4 in tumor cells. Loss of function mutations were detected in SMARCA4. We found that severe SREs comprise a new significant clinical feature of SMARCA4-DTS. CONCLUSION: Integrated clinico-radiologic-pathologic-genetic diagnosis is essential for SMARCA4-DTS and physicians should pay attention to severe SREs during the clinical course of this disease.

Treatment with Vancomycin Loaded Calcium Sulphate and Autogenous Bone in an Improved Rabbit Model of Bone Infection.

Bone infection results from bacterial invasion, which is extremely difficult to treat in clinical, orthopedic, and traumatic surgery. The bone infection may result in sustained inflammation, osteomyelitis, and eventual bone non-union. Establishment of a feasible, reproducible animal model is important to bone infection research and antibiotic treatment. As an in vivo model, the rabbit model is widely used in bone infection research. However, previous studies on rabbit bone infection models showed that the infection status was inconsistent, as the amount of bacteria was variable. This study presents an improved surgical method for inducing bone infection on a rabbit, by blocking the bacteria in the bone marrow. Then, multi-level evaluations can be carried out to verify the modelling method. In general, debriding necrotic tissue and implantation of vancomycin-loaded calcium sulphate (VCS) are predominant in antibiotic treatment. Although calcium sulphate in VCS benefits osteocyte crawling and new bone growth, massive bone defects occur after debriding. Autogenous bone (AB) is an appealing strategy to overcome bone defects for the treatment of massive bone defects after debriding necrotic bone. In this study, we used the tail bone as an autogenous bone implanted in the bone defect. Bone repair was measured using micro-computed-tomography (micro-CT) and histological analysis after animal sacrifice. As a result, in the VCS group, bone non-union was consistently obtained. In contrast, the bone defect areas in the VCS-AB group were decreased significantly. The present modeling method described a reproducible, feasible, stable method to prepare a bone infection model. The VCS-AB treatment resulted in lower bone non-union rates after antibiotic treatment. The improved bone infection model and the combination treatment of VCS and autogenous bone could be helpful in studying the underlying mechanisms in bone infection and bone regeneration pertinent to traumatology orthopedic applications.

Beware of bone pain with bisphosphonates.

A 71-year-old woman who had been taking ibandronate for 10 years presented to an Endocrinology Department with persistent mid-thigh pain. Pelvic X-ray showed bilateral femoral cortical expansion, indicating impending atypical femoral fractures (AFFs). AFFs have been linked to long-term bisphosphonate therapy and have morbidity and mortality similar to that of hip fractures. Such fractures can be averted by regular reviews of bisphosphonate therapy and vigilance for prodromal symptoms. This patient's bisphosphonate therapy was stopped, and fractures were avoided by treatment with vitamin D and parathyroid hormone.

Biophysical stimulation of bone and cartilage: state of the art and future perspectives.

INTRODUCTION: Biophysical stimulation is a non-invasive therapy used in orthopaedic practice to increase and enhance reparative and anabolic activities of tissue. METHODS: A sistematic web-based search for papers was conducted using the following titles: (1) pulsed electromagnetic field (PEMF), capacitively coupled electrical field (CCEF), low intensity pulsed ultrasound system (LIPUS) and biophysical stimulation; (2) bone cells, bone tissue, fracture, non-union, prosthesis and vertebral fracture; and (3) chondrocyte, synoviocytes, joint chondroprotection, arthroscopy and knee arthroplasty. RESULTS: Pre-clinical studies have shown that the site of interaction of biophysical stimuli is the cell membrane. Its effect on bone tissue is to increase proliferation, synthesis and release of growth factors. On articular cells, it creates a strong A2A and A3 adenosine-agonist effect inducing an anti-inflammatory and chondroprotective result. In treated animals, it has been shown that the mineralisation rate of newly formed bone is almost doubled, the progression of the osteoarthritic cartilage degeneration is inhibited and quality of cartilage is preserved. Biophysical stimulation has been used in the clinical setting to promote the healing of fractures and non-unions. It has been successfully used on joint pathologies for its beneficial effect on improving function in early OA and after knee surgery to limit the inflammation of periarticular tissues. DISCUSSION: The pooled result of the studies in this review revealed the efficacy of biophysical stimulation for bone healing and joint chondroprotection based on proven methodological quality. CONCLUSION: The orthopaedic community has played a central role in the development and understanding of the importance of the physical stimuli. Biophysical stimulation requires care and precision in use if it is to ensure the success expected of it by physicians and patients.

Examining the osteological paradox: Skeletal stress in mass graves versus civilians at the Greek colony of Himera (Sicily).

OBJECTIVES: Bioarchaeologists interpret skeletal stress as evidence of resilience or frailty, where absence of lesions might result from lack of exposure to pathogens (i.e., good health) or extreme vulnerability (i.e., selection). We examine physiological stress in two skeletal series from Greek Himera: (1) nine mass graves from the battles of Himera (480 and 409 BCE) and (2) Himeran civilians (648-409 BCE). Civilians are assumed to have died from multiple causes, including ill health leading to their deaths. Individuals from the battles presumably died while in relatively good health, in battle. More skeletal stress among civilians than battle casualties would support the idea that skeletal stress is a sign of frailty at Himera. We compare variation in skeletal stress between and among civilians and battle casualties. MATERIALS AND METHODS: Cribra orbitalia, porotic hyperostosis, linear enamel hypoplasia (LEH), and sub-periosteal new bone formation, were examined in 474 individuals (mass graves n = 64; civilians n = 410). RESULTS: Chi-square tests showed significantly higher prevalence of LEH (p = 0.04) and sub-periosteal new bone formation (p = 0.05) among young and mid-aged adult male civilians than mass grave casualties. Skeletal stress was also lower in the earlier battle, and varied among civilians with burial style. DISCUSSION: Our findings generally support the hypothesis that skeletal stress is evidence of frailty (i.e., leading to greater risk of mortality). However, the relationship between stress and frailty is complicated by social factors, when considering historical context. In particular, a possible "soldier-class" may have experienced less stress than the overall civilian population.

A rat model of SHPT with bone abnormalities in CKD induced by adenine and a high phosphorus diet.

The study of parathyroid hyperplasia with bone disease as a critical manifestation of chronic kidney disease-mineral and bone disorders (CKD-MBDs) is challenging due to the lack of a suitable research model. Here, we established a rat model with secondary hyperparathyroidism (SHPT) and bone disease induced by adenine and a high phosphorous diet and analyzed the skeletal characteristics. We performed blood analysis, emission computed tomography (ECT), dual energy X-ray absorptiometry (DEXA), micro-computed tomography (micro-CT), bone histomorphometry, and bone mechanical tests. The CKD rats with SHPT induced by adenine and a high phosphorus diet showed severe abnormalities in calcium and phosphorus metabolism and exhibited parathyroid hyperplasia. The bone mineral density (BMD) of femurs and lumbar vertebrae was significantly lower in the CKD rats than in the control (CTL) rats. The cortical and trabecular bone parameters of femurs showed significant bone loss. In addition, we found decreases in ultimate force, work to failure, stiffness, and elastic modulus in the CKD rats. In conclusion, our findings demonstrated that the CKD rats with SHPT induced by adenine and a high phosphorus diet may serve as a useful model for skeletal analysis in CKD with SHPT.

Contrast enhanced µCT imaging of early articular changes in a pre-clinical model of osteoarthritis.

OBJECTIVE: The objective of this study was to characterize early osteoarthritis (OA) development in cartilage and bone tissues in the rat medial meniscus transection (MMT) model using non-destructive equilibrium partitioning of an ionic contrast agent micro-computed tomography (EPIC-µCT) imaging. Cartilage fibrillation, one of the first physiological developments in OA, was quantified in the rat tibial plateau as three-dimensional (3D) cartilage surface roughness using a custom surface-rendering algorithm. METHODS: Male Lewis rats underwent MMT or sham-operation in the left leg. At 1- and 3-weeks post-surgery, the animals (n = 7-8 per group) were euthanized and the left legs were scanned using EPIC-µCT imaging to quantify cartilage and bone parameters. In addition, a custom algorithm was developed to measure the roughness of 3D surfaces. This algorithm was validated and used to quantify cartilage surface roughness changes as a function of time post-surgery. RESULTS: MMT surgery resulted in significantly greater cartilage damage and subchondral bone sclerosis with the damage increasing in both severity and area from 1- to 3-weeks post-surgery. Analysis of rendered 3D surfaces could accurately distinguish early changes in joints developing OA, detecting significant increases of 45% and 124% in surface roughness at 1- and 3-weeks post-surgery respectively. CONCLUSION: Disease progression in the MMT model progresses sequentially through changes in the cartilage articular surface, extracellular matrix composition, and then osteophyte mineralization and subchondral bone sclerosis. Cartilage surface roughness is a quantitative, early indicator of degenerative joint disease in small animal OA models and can potentially be used to evaluate therapeutic strategies.

Bone remodeling and regulating biomarkers in women at the time of breast cancer diagnosis.

PURPOSE: The majority of breast cancer patients receive endocrine therapy, including aromatase inhibitors known to cause increased bone resorption. Bone-related biomarkers at the time of breast cancer diagnosis may predict future risk of osteoporosis and fracture after endocrine therapy. METHODS: In a large population of 2,401 female breast cancer patients who later underwent endocrine therapy, we measured two bone remodeling biomarkers, TRAP5b and BAP, and two bone regulating biomarkers, RANKL and OPG, in serum samples collected at the time of breast cancer diagnosis. We analyzed these biomarkers and their ratios with patients' demographic, lifestyle, clinical tumor characteristics, as well as bone health history. RESULTS: The presence of bone metastases, prior bisphosphonate (BP) treatment, and blood collection after chemotherapy had a significant impact on biomarker levels. After excluding these cases and controlling for blood collection time, several factors, including age, race/ethnicity, body mass index, physical activity, alcohol consumption, smoking, and hormonal replacement therapy, were significantly associated with bone biomarkers, while vitamin D or calcium supplements and tumor characteristics were not. When prior BP users were included in, recent history of osteoporosis and fracture was also associated. CONCLUSIONS: Our findings support further investigation of these biomarkers with bone health outcomes after endocrine therapy initiation in women with breast cancer.

Antineoplastic treatment effect on bone mineral density in Mexican breast cancer patients.

BACKGROUND: Breast cancer is the most deadly malignancy in Mexican women. Although treatment has improved, it may significantly affect bone mineral status in those who receive it. The aim of this study was to assess the impact of cancer treatment on bone mineral density (BMD) and bone mineral content (BMC), in patients with breast cancer and explore the interaction of menopausal status and clinical stage with cancer treatment on such changes. METHODS: A quasi-experimental design was applied with measurements before and after a chemotherapy treatment in 40 patients with primary diagnosis of invasive breast cancer. BMD and body composition measurements were taken by dual X-ray absorptiometry (DXA) and changes in these variables due to therapy were analyzed using mixed regression for repeated measurements. RESULTS: Significant loss was found in femoral neck and L2-L4 BMD (p < 0.001). Patients diagnosed with osteopenia or osteoporosis received calcium + vitamin D supplementation (600 mg/200 IU day). It showed a protective effect in the decrease of femoral neck BMD and total BMC. BMD loss in both femoral neck and L2-L4 BMD was higher in premenopausal women: 0.023 g/cm2 in femoral neck and 0.063 g/cm2 in L2-L4 (p < 0.001), while in postmenopausal women BMD loss was 0.015 g/cm2 in femoral neck and 0.035 g/cm2 in L2-L4 (p = 0.021 and p = 0.001 respectively). Change in lumbar spine BMD was prominent in premenopausal women with advanced clinical stage (IIB, IIIA, IIIB): 0.066 g/cm2 (p = 0.003). CONCLUSION: The antineoplastic breast cancer treatment with chemotherapy had a negative impact on BMD, in premenopausal women overall, although a differential effect was found according to clinical stage and calcium supplementation status.

Copper, iron, and selenium dietary deficiencies negatively impact skeletal integrity: A review.

Nutrients have been known to have a significant role in maintaining the health of the skeleton, both bone and cartilage. The nutrients that have received the majority of the attention are Vitamin D and calcium. However, limited attention has been directed toward three trace elements that may have mechanistic impact upon the skeletal tissues and could compromise skeletal health resulting from inadequate intakes of copper, iron, and selenium. The role of copper and selenium has been known, but the role of iron has only received recent attention. Copper deficiency is thought to impact bone health by a decrease in lysyl oxidase, a copper-containing enzyme, which facilitates collagen fibril crosslinking. Iron deficiency impact upon bone has only recently been discovered but the exact mechanism on how the deficient states enhance bone pathology is speculative. Selenium deficiency has an impact on cartilage thereby having an indirect impact on bone. However, several studies suggest that a mycotoxin when consumed by humans is the culprit in some cartilage disorders and the presence of selenium could attenuate the pathology. This review summarizes the current knowledge base with respect to skeletal integrity when each of these three trace elements are inadequate in diets of both animals and humans.

Bone and Celiac Disease.

More than 50% of untreated patients with celiac disease (CD) have bone loss detected by bone densitometry (dual-energy X-ray absorptiometry:DXA). Moreover, patients with CD are more likely to have osteoporosis and fragility fractures, especially of the distal radius. Although still controversial, we recommend DXA screening in all celiac disease patients, particularly in those with symptomatic CD at diagnosis and in those who present risk factors for fracture such as older age, menopausal status, previous fracture history, and familial hip fracture history. Bone microarchitecture, especially the trabecular network, may be deteriorated, explaining the higher fracture risk in these patients. Adequate calcium and vitamin D supplementation are also recommended to optimize bone recovery, especially during the first years of gluten free diet (GFD). If higher fracture risk persists after 1 or 2 years of GFD, specific osteoactive treatment may be necessary to improve bone health.

Effects of low level laser therapy on inflammatory and angiogenic gene expression during the process of bone healing: A microarray analysis.

The process of bone healing as well as the expression of inflammatory and angiogenic genes after low level laser therapy (LLLT) were investigated in an experimental model of bone defects. Sixty Wistar rats were distributed into control group and laser group (830nm, 30mW, 2,8J, 94seg). Histopathological analysis showed that LLLT was able to modulate the inflammatory process in the area of the bone defect and also to produce an earlier deposition of granulation tissue and newly formed bone tissue. Microarray analysis demonstrated that LLLT produced an up-regulation of the genes related to the inflammatory process (MMD, PTGIR, PTGS2, Ptger2, IL1, 1IL6, IL8, IL18) and the angiogenic genes (FGF14, FGF2, ANGPT2, ANGPT4 and PDGFD) at 36h and 3days, followed by the decrease of the gene expression on day 7. Immunohistochemical analysis revealed that the subjects that were treated presented a higher expression of COX-2 at 36h after surgery and an increased VEGF expression on days 3 and 7 after surgery. Our findings indicate that LLLT was efficient on accelerating the development of newly formed bone probably by modulating the inflammatory and angiogenic gene expression as well as COX2 and VEGF immunoexpression during the initial phase of bone healing.