Common Bone Disease Research Articles

Enfermedad ósea de Paget: aproximación a sus orígenes históricos

Paget's disease of bone is the second most common bone disease after osteoporosis. It is characterized by focal regions of highly exaggerated bone remodeling, with abnormalities in all phases of the remodeling process. This study aims to investigate the hypothesis of a possible British origin of Paget's disease of bone by studying the worldwide geographic distribution of cases identified in ancient skeletons excavated from archaeological sites. The methodology consists in reviewing cases of Paget's disease of bone described in the literature.

The application of FRAX values to determine the distribution of risk factors for Osteoporosis in Postmenopausal women

Background: Osteoporosis is the most common bone disease in humans that causes a bone fracture occurring without trauma or after a minimum trauma as complication. Aim: This study was to apply FRAX values to investigate the distribution of risk factors of osteoporosis in menopause in Palembang community.Methods: Cross sectional approach was applied in this study in order to know the distribution of risk factors for osteoporosis in postmenopausal women at Sub District in Palembang, Sumatera selatan, Indonesia. The study population was women who reside in Sub District of Palembang. Samples are all postmenopausal women in that sub district of Palembang with ages between 50-79 years. The sub district was randomly selected based on the completeness of population data to facilitate the conduct of research, and then carried out questionnaires to women after that the data on risk factors will be incorporated into the FRAX score to earn the percentage Major Osteoporotic and hip fracture for the next 10 years.Results: The value of major FRAX osteoporotic most often found in the percentage of 20% (108 people), while the value of FRAX hip fracture most often found in the percentage of 3% (90 people).Conclusions: women will have a risk to get possibility fracture that can be occurred in the next 10 years. It is required counseling and provision of basic knowledge to the public about the various risk factors associated with the incidence of osteoporosis. This includes lifestyle, physical activity and sport Key words: Osteoporosis, FRAX, Postmenopausal Women

Identification of crucial genes related to postmenopausal osteoporosis using gene expression profiling.

Postmenopausal osteoporosis is a common bone disease and characterized by low bone mineral density. This study aimed to reveal key genes associated with postmenopausal osteoporosis (PMO), and provide a theoretical basis for subsequent experiments. The dataset GSE7429 was obtained from Gene Expression Omnibus. A total of 20 B cell samples (ten ones, respectively from postmenopausal women with low or high bone mineral density (BMD) were included in this dataset. Following screening of differentially expressed genes (DEGs), coexpression analysis of all genes was performed, and key genes in the coexpression network were screened using the random walk algorithm. Afterwards, functional and pathway analyses were conducted. Additionally, protein-protein interactions (PPIs) between DEGs and key genes were analyzed. A set of 308 DEGs (170 up-regulated ones and 138 down-regulated ones) between low BMD and high BMD samples were identified, and 101 key genes in the coexpression network were screened out. In the coexpression network, some genes had a higher score and degree, such as CSTA. The key genes in the coexpression network were mainly enriched in GO terms of the defense response (e.g., SERPINA1 and CST3), immune response (e.g., IL32 and CLEC7A); while, the DEGs were mainly enriched in structural constituent of cytoskeleton (e.g., CYLC2 and TUBA1B) and membrane-enclosed lumen (e.g., CCNE1 and INTS5). In the PPI network, CCNE1 interacted with REL; and TUBA1B interacted with ESR1. A series of interactions, such as CSTA/TYROBP, CCNE1/REL and TUBA1B/ESR1 might play pivotal roles in the occurrence and development of PMO.

Neuroprotective Effects of Etidronate and 2,3,3-Trisphosphonate Against Glutamate-Induced Toxicity in PC12 Cells.

Etidronate is one of the best known bisphosphonates (BP) derivatives. It is often used as a reference drug in research related to hypercalcaemia and other common bone diseases. 2,3,3-trisphosphonate (TrisPP) is brand new analogue of BP, that also contains a 'germinal bisphosphonate' unit with an additional phosphoryl group attached in proximity to the BP unit. It is known that BPs bind to calcium by chemisorptions to form Ca-BP complexes through (O)P-C-P(O) moiety and hydrogen coordinations, and so they suppress calcium flow by interfering with Ca(2+) channel operations. The mechanistic actions of BP, involving interactions and regulations of Ca(2+), are somewhat similar to the pathogenesis of well-known neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease and Huntington's disease. To investigate if neuroprotective effects are exhibited by the compounds of interests, we used a rat adrenal pheochromocytoma cell line (PC12) as our in vitro model to observe any occurrence of neuron inter-reflection. We pre-treated these PC12 cells with etidronate and TrisPP before challenging the cells with a high concentration of the neurotoxin, glutamate. Our data showed that pre-treatment with 100 μM etidronate partially ameliorated the glutamate-induced decrease in cell viability (47 %), whereas pre-treating cells with 10-100 μM TrisPP showed remarkable cell protection (78-86 %). Moreover, pre-treatments of the cells with etidronate or TrisPP attenuated cell apoptosis, reactive oxygen species generation, Ca(2+) overloading and caspase-3 protein expression, which were associated with a remarkable increase in superoxide dismutase activity in our glutamate-injured PC12 cells. Therefore, this study supports the notion that etidronate and TrisPP may be promising neuroprotective agents.

Upper gastrointestinal safety and tolerability of oral alendronate: A meta-analysis.

Osteoporosis (OP), which is a common bone disease associated with reduced bone mineral density and disordered bone microstructure, may result in an increased risk of bone fracture. The present study aimed to investigate the frequency of alendronate (Aln)-associated upper gastrointestinal tract adverse events (GIAEs) in postmenopausal women with OP. The following databases were searched in order to identify relevant studies: Medline (using PubMed as the search engine), Embase, the Web of Science and the Cochrane Central Register of Controlled Trials (up to December 2014). Studies were selected for inclusion if they were randomized, double-blind, placebo-controlled trials, which had investigated the safety of Aln versus a placebo for the treatment of postmenopausal women with OP. The primary outcomes of the included studies were total adverse events (AEs) and upper GIAEs, whereas individual upper GIAEs were considered as secondary outcomes. The general characteristics and outcomes of each study were abstracted by two independent researchers, and Review Manager 5.3 software was used for data syntheses and the meta-analysis. A total of nine studies, including 15,192 randomized patients, met the inclusion criteria and contributed to some or all of the meta-analysis outcomes. The Mantel-Haenszel method was used to calculate risk ratios, and their 95% confidence intervals (CI) were determined using either the fixed or random effects model, depending on the level of heterogeneity. The relative risk (95% CI) of AEs associated with Aln treatment, as compared with the placebo group, was 1.01 (0.97-1.06), and the relative risk (95% CI) of discontinued Aln treatment due to AEs was 1.04 (0.91-1.19). In addition, the relative risk (95% CI) of upper GIAEs was 1.02 (0.99-1.06), and the relative risk (95% CI) of discontinued Aln treatment due to upper GIAEs was 1.23 (0.97-56). In addition, these results remained robust to sensitivity analyses. The results of the present study suggested that Aln has a good GI tract tolerability, and that daily treatment with 10 mg Aln sodium does not increase the risk of GIAEs in postmenopausal women with OP.

PMS128 - Prevention of Fragility Fractures in Osteoporotic Patients: Can the Secondary Therapy Help Contain Costs for Admissions? A Retrospective, Observational Case Control Study Based on Asl Pavia’s Administrative Databases

Osteoporosis is one of the commonest bone diseases in which bone fragility is increased. There are several possibilities for the prevention of primary, secondary and tertiary osteoporosis but until now they have not been promoted enough and bone fragility is thought about only after the onset of a fracture (tertiary prevention). Preventative strategies against osteoporosis can be aimed at either optimizing the peak bone mass obtained, or reducing the rate of bone loss. Optimization of peak bone mass may be more amenable to public health strategies. A group of patients over 50 year old that has been treated with medicines included in the AIFA Note 79 during a period of 5 years is studied in comparison with a similar group that has not been treated with medicines included in the AIFA Note 79 for the same period time. For both groups are also extracted inpatient and outpatient medical records and medicine prescriptions. Only patients treated for at least three years are considered significant. To avoid confounding the resulting data were standardized and stratified. The total expenditure for patients compliant with therapy who have had access to the hospital is less than twenty-eight percent compared to the total expenditure for patients not receiving therapy or not compliant. Osteoporosis is the most common bone disease and its incidence is rapidly increasing with the aging population. Even if curable, it is often left untreated causing a moderate use of economic resources that could be avoided.

Characterization of trabecular bone plate-rod microarchitecture using multirow detector CT and the tensor scale: Algorithms, validation, and applications to pilot human studies.

Osteoporosis is a common bone disease associated with increased risk of low-trauma fractures leading to substantial morbidity, mortality, and financial costs. Clinically, osteoporosis is defined by low bone mineral density (BMD); however, increasing evidence suggests that trabecular bone (TB) microarchitectural quality is an important determinant of bone strength and fracture risk. A tensor scale based algorithm for in vivo characterization of TB plate-rod microarchitecture at the distal tibia using multirow detector CT (MD-CT) imaging is presented and its performance and applications are examined. The tensor scale characterizes individual TB on the continuum between a perfect plate and a perfect rod and computes their orientation using optimal ellipsoidal representation of local structures. The accuracy of the method was evaluated using computer-generated phantom images at a resolution and signal-to-noise ratio achievable in vivo. The robustness of the method was examined in terms of stability across a wide range of voxel sizes, repeat scan reproducibility, and correlation between TB measures derived by imaging human ankle specimens under ex vivo and in vivo conditions. Finally, the application of the method was evaluated in pilot human studies involving healthy young-adult volunteers (age: 19 to 21 yr; 51 females and 46 males) and patients treated with selective serotonin reuptake inhibitors (SSRIs) (age: 19 to 21 yr; six males and six females). An error of (3.2% ± 2.0%) (mean ± SD), computed as deviation from known measures of TB plate-width, was observed for computer-generated phantoms. An intraclass correlation coefficient of 0.95 was observed for tensor scale TB measures in repeat MD-CT scans where the measures were averaged over a small volume of interest of 1.05 mm diameter with limited smoothing effects. The method was found to be highly stable at different voxel sizes with an error of (2.29% ± 1.56%) at an in vivo voxel size as compared to the original ex vivo voxel size. Tensor scale measures derived from imaging under in vivo and ex vivo conditions with significantly different modulation transfer function, i.e., difference in "true resolution," showed strong linear correlation (r = 0.92). The study of healthy volunteers shows that, after adjustment for height and weight, males have a 14% higher mean TB plate-width as compared to females (p < 0.05). SSRI-treated patients have 12.5% lower mean TB plate-width (p = 0.052) as compared to age-similar and sex-, height-, and weight-matched healthy controls. In contrast, the observed group difference in dual-energy x-ray absorptiometry (DXA)-derived hip BMD was 10.5% between males and females and only 5.04% between healthy controls and patients on SSRIs. Tensor scale analysis of MD-CT images yields accurate and reproducible characterization of TB plate-rod microarchitecture that may be more sensitive than DXA-derived BMD to sex differences and to the skeletal changes associated with medical conditions or their treatments.

TNF Induction of NF-κB RelB Enhances RANKL-Induced Osteoclastogenesis by Promoting Inflammatory Macrophage Differentiation but also Limits It through Suppression of NFATc1 Expression.

TNF induces bone loss in common bone diseases by promoting osteoclast formation directly and indirectly, but it also limits osteoclast formation by inducing expression of NF-κB p100. Osteoclast precursors (OCPs) are derived from M1 (inflammatory) and M2 (resident) macrophages. However, it is not known if TNF stimulates or limits osteoclast formation through regulation of M1 or M2 differentiation or if RelB, a partner of p100, is involved. To investigate these questions, we treated bone marrow cells (BMCs) with M-CSF alone or in combination with TNF to enrich for OCPs, which we called M-OCPs and T-OCPs, respectively. We found that TNF switched CD11b+F4/80+ M-OCPs from Ly6C-Gr1- M2 to Ly6C+Gr1-CD11c+ and Ly6C-Gr1-CD11c+ M1 cells. RANKL induced osteoclast formation from both Ly6C+Gr1- and Ly6C-Gr1- T-OCPs, but only from Ly6C+Gr1- M-OCPs, which formed significantly fewer osteoclasts than T-OCPs. Importantly, Ly6C+Gr1- cells from both M- and T-OCPs have increased expression of the M1 marker genes, iNOS, TNF, IL-1β and TGFβ1, compared to Ly6C-Gr1- cells, and Ly6C-Gr1- cells from T-OCPs also have increased expression of iNOS and TGFβ1 compared to cells from M-OCPs. Both RANKL and TNF increased RelB mRNA expression. TNF significantly increased RelB protein levels, but RANKL did not because it also induced RelB proteasomal degradation. TNF inhibited RANKL-induced NFATc1 mRNA expression and osteoclast formation from M-OCPs, but not from T-OCPs, and it did not induce Ly6C+Gr1-CD11c+ or Ly6C-Gr1-CD11c+ M1 macrophages from RelB-/- BMCs. Furthermore, overexpression of RelB in M-OCPs reduced RANKL-induced osteoclast formation and NFATc1 mRNA expression, but it increased TNF-induced OC formation without affecting NFATc1 levels. Thus, TNF induction of RelB directly mediates terminal osteoclast differentiation independent of NFATc1 and limits RANKL-induced osteoclastogenesis by inhibiting NFATc1 activation. However, the dominant role of TNF is to expand the OCP pool by switching the differentiation of M-CSF-induced M2 to M1 macrophages with enhanced osteoclast forming potential. Strategies to degrade RelB could prevent TNF-induced M2/M1 switching and reduce osteoclast formation.

Anti-osteoporotic activity of puerarin 6″-O-xyloside on ovariectomized mice and its potential mechanism

Context: Osteoporosis is one of the most common bone diseases, and radix of Pueraria lobata (Willd.) Ohwi possesses an obvious therapeutical effect on postmenopausal osteoporosis.Objective: This study investigates the anti-osteoporotic activity of the puerarin 6″-O-xyloside (PXY) on ovariectomized mice and its related mechanism.Materials and methods: Osteoporotic mice model was established by ovariectomy (OVX). A total of 50 mice were divided into five groups (n = 10): sham, OVX group, PXY treatment groups (20, 40, and 60 mg/kg/d, i.p.). After 12 weeks’ treatment, body weights were recorded. Then, mice were sacrificed, and serum samples were collected to determine the blood calcium, blood phosphorus, alkaline phosphatase (ALP), and osteoprotegerin (OPG) concentrations and uterine index was assayed. The thigh-bones of mice were collected to evaluate histopathological changes. In the in vitro experiment, the effect of PXY on osteoblasts’ proliferation was evaluated and western blotting was performed to determine expressions of OPG and the receptor activators of NF-κB ligand (RANKL), as well as the ratio of OPG/RANKL.Results: PXY (40 and 60 mg/kg/d, i.p.) obviously decreased body weights and increased uterine index of OVX (p < 0.05), and improved osteoporotic syndromes of OVX mice; PXY also significantly increased the concentrations of blood calcium, blood phosphorus, ALP, and OPG of OVX mice (p < 0.05); moreover, PXY obviously up-regulated the ratio of OPG/RANKL (p < 0.05).Conclusion: Our results demonstrated that the puerarin 6″-O-xyloside possesses significant anti-osteoporotic activity on ovariectomy mice.

Mechanistic and therapeutic insights into skeletal biology learned from the study of rare bone diseases

To date, nearly 500 unique rare bone diseases have been described,which in the aggregate affect 1 in 5000 live births and comprise 5% of all birth defects. Currently, the overwhelming majority of these disorders have no cure. Studying rare bone diseases has helped elucidate biological pathways and reveal valuable therapeutic targets that also benefit patients with common bone diseases. In an effort to engage scientists, clinicians, young investigators, advocacy groups and representatives of the pharmaceutical industry in fruitful discussion of how the study and treatment of rare bone diseases has helped, and will continue to help, expand our understanding of bone health, The National Bone Health Alliance and Rare Bone Disease Patient Network sponsored this workshop in partnership with the American Society for Bone and Mineral Research and the United States Bone and Joint Initiative.

Protein Phosphatase 2A Mediates Oxidative Stress Induced Apoptosis in Osteoblasts.

Osteoporosis is one of the most common bone diseases, which is characterized by a systemic impairment of bone mass and fragility fractures. Age-related oxidative stress is highly associated with impaired osteoblastic dysfunctions and subsequent osteoporosis. In osteoblasts (bone formation cells), reactive oxygen species (ROS) are continuously generated and further cause lipid peroxidation, protein damage, and DNA lesions, leading to osteoblastic dysfunctions, dysdifferentiations, and apoptosis. Although much progress has been made, the mechanism responsible for oxidative stress induced cellular alternations and osteoblastic toxicity is still not fully elucidated. Here, we demonstrate that protein phosphatase 2A (PP2A), a major protein phosphatase in mammalian cells, mediates oxidative stress induced apoptosis in osteoblasts. Our results showed that lipid peroxidation products (4-HNE) may induce dramatic oxidative stress, inflammatory reactions, and apoptosis in osteoblasts. These oxidative stress responses may ectopically activate PP2A phosphatase activity, which may be mediated by inactivation of AKT/mTOR pathway. Moreover, inhibition of PP2A activity by okadaic acid might partly prevent osteoblastic apoptosis under oxidative conditions. These findings may reveal a novel mechanism to clarify the role of oxidative stress for osteoblastic apoptosis and provide new possibilities for the treatment of related bone diseases, such as osteoporosis.

Anti-osteoporosis activity of red yeast rice extract on ovariectomy-induced bone loss in rats.

Osteoporosis is the most common bone disease, affecting millions of people worldwide and leading to significant morbidity and high costs. Monacolin K, an extract of red yeast rice (RYR, Hongqu), plays important roles in the management of dyslipidemia, coronary heart disease, and diabetes. Our study aimed to investigate the protective effect of monacolin K on ovariectomy-induced bone loss in rats. Fifty female Sprague-Dawley rats were randomly divided into a sham-operated and five ovariectomized (OVX) groups: OVX with vehicle, OVX with fluvastatin, and OVX with RYR extract of three graded doses. Bone mineral density (BMD), biochemical markers, and cell viability were analyzed by dual energy X-ray absorptiometry, enzyme-linked immunosorbent assay, and 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays. Gene expression was evaluated by real-time polymerase chain reaction amplification and western blot. Our results showed that administration of RYR extract markedly increased the bone mineral density in OVX rats. Moreover, RYR extract decreased the levels of bone turnover markers, including osteocalcin and tartrate resistant acid phosphatase activity. The MMT assay revealed that RYR extract treatment significantly improved the osteoblast viabilities in a dose-dependent manner (P < 0.05). At the molecular level, we further demonstrated that RYR extract enhanced the expression of Bmp2 and Bmp4 both at the mRNA and protein levels. Collectively, these data suggested RYR extract could protect against osteoporosis in ovariectomized rats, most likely through activation of BMP2/4 expression.

Antioxidant Effect of Eugenol in Human Periodontal Ligament Fibroblasts

Periodontal disease (PD) is the most common osteolytic disease of alveolar bone, oral infection seen in humans worldwide. PD is a common, chronic immunoinflammatory disease initiated by a complex subgingival bacterial and results in the inflammatory destruction of periodontal tissues, including the alveolar bone periodontal ligament, and gingivae. The effects of eugenol on periodontal ligament fibroblasts (PDLF) cell under oxidative injury have not been fully studied. Despite many studies in regard to the antioxidant effect of eugenol, the protective effect of eugenol against oxidative damage to PDLF cell, as well as the relationship between eugenol and apoptosis, has not been investigated so far. The aim of this study was to assess the protective effect of eugenol against H₂O₂-induced oxidative stress in PDLF cell. Cell lines were separately grown as monolayers at 5% CO₂ and 37℃ humidified atmosphere using appropriate media supplemented with 10% fetal bovine serum, 2 mM glutamine and 100 μg/mL penicillin-streptomycin. DMEM/F12 was used as the culture medium for periodontal ligament fibroblast cells. The viability of the PDLF cells which induced by the different concentrations of H₂O₂ (control, 50, 100, 200, 400 μM) for 24 h was detected by MTT assay. Cell viability was significantly reduced in a H₂O₂-concentration dose-dependent manner. The mitochondria-dependent pathway of apoptosis is regulated by Bcl-xl family, such as the anti-apoptotic protein Bcl-xl, pro-apoptotic protein Bak. With H₂O₂ injury, the protein level of Bak was upregulated while the protein level of Bcl-xl was down-regulated. In group treated H₂O₂ and eugenol, the ratio was reduced and the expression of Bak decreased at the same time, indicating that eugenol can attenuate apoptosis through mitochondrial related pathway in PDLF cells. Therefore, although the findings of this study are limited to an in vitro interpretation, we suggest that eugenol preconditioning may have a beneficial effect in the recovery of periodontal ligament from oxidative stress.

The Importance of a Correct Diet in Preventing Osteoporosis

Osteoporosis is a very common bone disease characterized by low bone mass and micro architectural deterioration of bone tissue. It may result in high risk of bone fractures with impaired quality of life. The prevention of this disorder is based on an appropriate lifestyle and a proper diet. The correct supply of Vitamins D and K, protein, fatty acids and dietary components are notable factors that help maintain healthy bone structure. The effects of these elements have been briefly discussed and they have been shown to correlate to bone health.

Smith-McCort variant syndrome: A rare case with associated enamel hypoplasia

The Smith-McCort syndrome (SMC), which was first described by Smith and McCort in 1958, is a rare form of osteochondrodysplasia, specifically a spondyloepimetaphyseal dysplasia. It is one of the rare syndromes that can present with skeletal dysplasia and mimic some of the common bone diseases. Enamel hypoplasia is a part of this disorder. Literature that describes the orofacial characteristics of this syndrome is lacking. Here we report a case of a 23-year-old female, who presented with characteristic orofacial features, along with skeletal abnormalities.

Bisphosphonate Therapy of Osteoporosis Predisposes Epithelial Breakdown in Osteonecrosis of the Jaws, with Calcium Ion Constraint

Osteoporosis is a common bone disease prevalent in aging in humans deriving from all ethnic backgrounds. Bisphosphonates (BPs) influence the metabolism of soft tissues, including direct toxicity on oral mucosae. This contributes to mucosal ulceration and exposure of underlying bone (1) The ulcerative necrosis is prevalent on sites when thin mucosa covers bony protuberances, prominences or exostoses. BONJ cases are often preceded by dento-alveolar therapy. Dental treatment procedures, like deep root-planing, extractions and surgical placement of osseo- integrated implants are acknowledged as predisposing practices which precipitate BONJ. The increased demand for calcium ions necessary for bone regeneration and repair, exceeds the dysfunctional osseous reserve, and results in epithelial break down and localized osseous necrosis. Oral biofilm is highly infectious, and without intact epithelium and resilient bone, BONJ develops. Consequently because oral surgical procedures are central in developing BONJ, not only should all dentists must be aware of this and be ultra-vigilant about all patients being treated with bisphosphonates, but all dental treatments should be concluded before starting the bisphosphonate therapy. When the normally very low (10-8 M) intra-cellular calcium levels rise, the gap junctions undergo conformation changes that close the gap junctions channel, inhibiting transfer of other metabolites (2).

Signaling Pathways in Craniofacial Development: Insights from Rare Skeletal Disorders.

In the developing embryo, signaling pathways define how the mesenchymal precursors of bone form individual skeletal elements with the proper size, shape, orientation, and integration. Disruptions to these signaling processes lead to a large variety of congenital conditions categorized as skeletal dysplasias. While individually these skeletal disorders are rare, collectively they represent a significant cause of disability in the United States. Here, we discuss how the study of these rare events in human development reveal novel and unexpected insights into signaling mechanisms that regulate normal skeletal development and, in the process, advance novel molecular-based therapies for treatment of rare and common bone diseases alike.

Anti-catabolic effect of caffeic acid phenethyl ester, an active component of honeybee propolis on bone loss in ovariectomized mice: a micro-computed tomography study and histological analysis

Background Osteoporosis (OP) is a common bone disease, which adversely affects life quality. Effective treatments are necessary to combat both the loss and fracture of bone. Recent studies indicated that caffeic acid phenethyl ester (CAPE) is a natural chemical compound from honeybee propolis which is capable of attenuating osteoclastogenesis and bone resorption. Therefore, this study aimed to investigate the effect of CAPE on bone loss in OP mice using micro-computed tomography (CT) and histology. Methods Eighteen mice were prepared and evenly divided into three groups. The six mice in the sham+PBS group did not undergo ovariectomy and were intraperitoneally injected with PBS during the curing period. Twelve mice were ovariectomized (OVX) to induce OP. Six of them in the OVX+CAPE group were intraperitoneally injected with 0.5 mg/kg CAPE twice per week for 4 weeks after ovariectomy. The other six OVX mice in OVX+PBS group were treated with PBS. All the mice were sacrificed 4 weeks after ovariectomy. The tibias were bilaterally excised for micro-CT scan and histological analysis. The Mann-Whitney U test was used to test the statistical differences among groups. Results Bone loss occurred in OVX mice. Compared with the sham+PBS group, mice in the OVX+PBS group exhibited a significant decrease in bone mineral density (BMD, P &lt;0.05), bone volume fraction (BV/TV, P &lt;0.01), trabecular thickness (Tb.Th, P &lt;0.05), and trabecular number (Tb.N, P &lt;0.01), as well as a non-insignificant increase in the number of osteoclasts (N.Oc/B.Pm). With CAPE treatment, the microarchitecture of the tibial metaphyses was significantly improved with a reduction of osteoclast formation. Compared with the OVX+PBS group, BV/TV in the OVX+CAPE group was significantly increased by 33.9% (P &lt;0.05). Conclusion CAPE therapy results in the protection of bone loss induced by OVX.

Controlled-release naringin nanoscaffold for osteoporotic bone healing

ObjectivesOsteoporosis is one of the most common bone diseases in the world and results from an imbalance of bone cell functions. In the process of guided bone regeneration, osteoporosis weakens the bonding strength between scaffold and bone. Naringin is evidenced to be effective for the treatment of osteoporosis and bone resorption and the aim was to explore methods and benefits of its incorporation. MethodsIn this study, naringin was incorporated in the electrospun nanoscaffold containing poly(ɛ-caprolactone) (PCL) and poly(ethylene glycol)-block-poly(ɛ-caprolactone) (PEG-b-PCL). ResultsThe nanoscaffold demonstrated unchanged chemical structure, improved hydrophilicity, thinner and more uniform nanofibers by Fourier-transform infrared spectroscopy, contact angle measurement and scanning electron microscopy. The nanoscaffold also showed faster degradation rate and controlled-release of naringin. Osteoblast-nanoscaffold interactions were studied by the evaluation of adhesion, proliferation, differentiation of MC3T3-E1 osteoblasts and mineralization of ECM on the nanoscaffolds. Meanwhile, the response of osteoclasts to nanoscaffolds was evaluated in a mouse calvarial critical size defect organ culture model. The osteoclasts around the bone defect were shown by tartrate resistant acid phosphatase staining. SignificanceThe results demonstrated that controlled-release naringin nanoscaffolds supported greater osteoblast adhesion, proliferation, differentiation, and mineralization and suppressed osteoclast formation.

Modifications to nano- and microstructural quality and the effects on mechanical integrity in Paget's disease of bone.

Paget's disease of bone (PDB) is the second most common bone disease mostly developing after 50 years of age at one or more localized skeletal sites; it is associated with severely high bone turnover, bone enlargement, bowing/deformity, cracking, and pain. Here, to specifically address the origins of the deteriorated mechanical integrity, we use a cohort of control and PDB human biopsies to investigate multiscale architectural and compositional modifications to the bone structure (ie, bone quality) and relate these changes to mechanical property measurements to provide further insight into the clinical manifestations (ie, deformities and bowing) and fracture risk caused by PDB. Here, at the level of the collagen and mineral (ie, nanometer-length scale), we find a 19% lower mineral content and lower carbonate-to-phosphate ratio in PDB, which accounts for the 14% lower stiffness and 19% lower hardness promoting plastic deformation in pathological bone. At the microstructural scale, trabecular regions are known to become densified, whereas cortical bone loses its characteristic parallel-aligned osteonal pattern, which is replaced with a mosaic of lamellar and woven bone. Although we find this loss of anisotropic alignment produces a straighter crack path in mechanically-loaded PDB cases, cortical fracture toughness appears to be maintained due to increased plastic deformation. Clearly, the altered quality of the bone structure in PDB affects the mechanical integrity leading to complications such as bowing, deformities, and stable cracks called fissure fractures associated with this disease. Although the lower mineralization and loss of aligned Haversian structures do produce a lower modulus tissue, which is susceptible to deformities, our results indicate that the higher levels of plasticity may compensate for the lost microstructural features and maintain the resistance to crack growth.