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Early Changes in Cement-Bone Fixation Using a Novel Rat Knee Replacement Model.

Trabecular resorption from interdigitated regions between cement and bone has been found in postmortem-retrieved knee replacements, but the … on, when it did occur, started at the cement border with medullary-adjacent bone in the presence of osteoclasts. There was substantial loss of viable bone (~80% empty osteocyte lacunae) in the interdigitated regions. Pre-surgical fluorochrome labels remained in the interdigitated regions, and did not diminish with time, indicating that the bone was not remode …

Antibody Response to Paramyxoviruses in Paget's Disease of Bone.

Paget's disease of bone (PDB) is a common skeletal disorder characterised by focal abnormalities of increased and disorganised bone turnover. Genetic factors play a central role in the pathogenesis of PDB but environmental factors also contribute. Measles virus (MV), respiratory syncytial virus (RSV) and canine distemper virus (CDV) have all been implicated as potential disease triggers but the data are conflicting. Since chronic paramyxovirus infection with measles is known to be accompanied by increased production of antiviral antibodies, we have analysed circulating concentrations of antibo

Mechanical regulation of signaling pathways in bone.

A wide range of cell types depend on mechanically induced signals to enable appropriate physiological responses. The skeleton is particularl … s those cells within the skeleton that are responsive to mechanical signals, including osteoblasts, osteoclasts, osteocytes and osteoprogenitors. This is discussed in light of a range of experimental approaches that can vary parameters such as strain, fluid shear stress, and pressure. The identity of mechanoreceptor candidates is approached, with consideratio …

Anti-tumor necrosis factor therapies in immune-mediated rheumatic diseases. Other observations from the clinic.

To date, over 2 million patients worldwide have been treated with anti-tumor necrosis factor (TNF) therapies, dramatically improving the treatment outcomes of immune-mediated inflammatory diseases (IMID). Observations from clinicians have identified some curious disconnects between clinical and radiographic outcomes, and the paradoxical occurrence of anti-TNF therapy-induced IMID such as psoriasis or reactivation of uveitis and Crohn's disease. These observations point to the need for a better understanding of the mechanisms underlying the ability of anti-TNF therapies to reduce inflammation a

Root resorption and the OPG/RANKL/RANK system: a mini review.

Odontoclastic root resorption is a significant clinical issue in relation to orthodontic tooth movement, and resorption of the roots of primary teeth is an intriguing biological phenomenon. The functional coordination of the OPG/RANKL/RANK system seems to contribute not only to alveolar remodeling, but also to resorption during orthodontic tooth movement and physiological root resorption. Serum OPG and s-RANKL are related to regulation of bone homeostasis by the OPG/RANKL/RANK system, and determination of their concentrations might be useful for predicting the rate of bone remodeling during or

Effect of orthodontic forces on root resorption in molars submitted to experimental periodontitis.

The present experimental study addresses the issue of the development and size of root resorption areas in molars of rats submitted to orthodontic forces of 51 or 75 g and the induction of periodontal disease by placing a cotton ligature around the cervix of the first upper molars for 48 hours. Immediately on removal of the ligature or 48 hs later we put an orthodontic device in place. The device comprised two steel bands. The arms of a helicoidal spring that exerted force towards palatine passed through the palatine tubes welded to the bands. The number of odontoclasts and the percentage of r

Ultrastructural study of the root dentine surface resuming resorption on human deciduous teeth.

Resorption of deciduous teeth is not continuous, but alternates with periods of repair or rest. Dentine surfaces in periods of rest or repair resume resorption by odontoclasts during physiological root resorption of the deciduous teeth. However, no observations of such dentine surfaces have been shown. The characteristic feature of the dentine surfaces resuming resorption remains unknown. Tartrate-resistant acid phosphatase activity (TRAP) was detected on human deciduous teeth. The root resorbing surfaces on these teeth were photographed with a whole-mount light microscope, and the photographe

Risk factors for odontoclastic resorptive lesions in cats.

A cross-sectional study evaluating potential risk factors for odontoclastic resorptive lesions (ORL) in feline teeth was conducted. Owners of 32 cats with ORL and 27 cats without ORL were interviewed regarding their respective cat's demographic characteristics, diet, and medical and dental histories. Four factors were identified as significantly associated with ORL using unconditional logistic regression. A history of dental disease (gingivitis, calculus, or periodontal disease; odds ratio [OR], 4.5); city residence (OR, 4.4); and being an exclusively indoor cat (OR, 4.5) were associated with

Growth of the vomero-premaxillary suture in children with bilateral cleft lip and palate. A histological and roentgencephalometric study.

The significance of the vomero-premaxillary suture (VPS) in mid-facial development in patients with complete bilateral cleft lip and palate (C-BCLP) was evaluated. Histological analysis of the VPS in eight specimens, ranging in age from full term to 22 months, revealed evidence of growth at both sutural borders. Various theories to explain the consistent presence of secondary cartilage, localized mainly to the posterior end of the suture, were assessed. It was considered most likely that the formation of cartilage was promoted by mechanical stresses, set up during a period of rapid growth. Roe

Chrysanthemum lavandulifolium Essential Oil Attenuates Periodontitis via Antibacterial and Anti-Inflammatory Effects.

Periodontitis, driven by Porphyromonas gingivalis (P. gingivalis) biofilms, is a global health burden with limited treatment options due to … nificantly reduced gingival inflammation, alveolar bone resorption, and the number of TRAP-positive osteoclasts compared with the vehicle-treated periodontitis group (all p < 0.05). Furthermore, CLEO treatment dose-dependently lowered serum MMP-9 levels (from 24.15 ± 0.24 pg/mL in the model group to 12.36 ± 0.54 pg/mL in the high-dose group) and COX-2 levels …

Treg cells mitigate inflammatory responses and symptoms via β2-AR/β-Arr2/ERK signaling in an experimental rheumatoid arthritis.

BACKGROUND: β2-adrenergic receptor (β2-AR) is widely expressed on immune cells, including T cells and it has a non-canonical signaling pathway, which is β2-AR-β-arrestin 2 (β-Arr2)-extracellular signal-regulated kinase 1/2 (ERK1/2). Our previous studies have shown that the β2-AR agonist terbutaline (Terb) can activate β2-AR and significantly inhibit helper T (Th) 17 cell function in collagen-induced arthritis (CIA). However, the effects of β2-AR on regulatory T (Treg) cells in CIA have not been consistently determined. The aim of our research was to explore whether β2-AR-β-Arr2-ERK1/2 signalin

Bortezomib-releasing silica-collagen xerogels for local treatment of osteolytic bone- and minimal residual disease in multiple myeloma.

BACKGROUND: Accumulation of malignant plasma cells in the bone marrow causes lytic bone lesions in 80% of multiple myeloma patients. Frequently fracturing, they are challenging to treat surgically. Myeloma cells surviving treatment in the presumably protective environment of bone lesions impede their healing by continued impact on bone turnover and can explain regular progression of patients without detectable minimal residual disease (MRD). Locally applicable biomaterials could stabilize and foster healing of bone defects, simultaneously delivering anti-cancer compounds at systemically intole

Multi-Targeting DKK1 and LRP6 Prevents Bone Loss and Improves Fracture Resistance in Multiple Myeloma.

An imbalance between bone resorption and bone formation underlies the devastating osteolytic lesions and subsequent fractures seen in more than 90% of multiple myeloma (MM) patients. Currently, Wnt-targeted therapeutic agents that prevent soluble antagonists of the Wnt signaling pathway, sclerostin (SOST) and dickkopf-1 (DKK1), have been shown to prevent bone loss and improve bone strength in preclinical models of MM. In this study, we show increasing Wnt signaling via a novel anti-low-density lipoprotein receptor-related protein 6 (LRP6) antibody, which potentiates Wnt1-class ligand signaling

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… To identify osteoclasts, paraffin femur sections were stained for tartrate‐resistant acid phosphatase (TRAP), and staining was performed as described. ( 24 , 27 ) The number of TRAP‐positive osteoclasts sitting on the bone surface (N.Oc/BS.Pm) were counted, and osteoclast surface (Oc.S/BS.Pm) was calculated … as a percentage of bone surface covered by multinucleated TRAP‐positive osteoclasts. …

Calcium phosphate hybrid micelles inhibit orthotopic bone metastasis from triple negative breast cancer by simultaneously killing cancer cells and reprogramming the microenvironment of bone resorption and immunosuppression.

Triple negative breast cancer (TNBC) is prone to develop drug resistance and metastasis. Bone is the most common distant metastasis site of … o-loaded calcium phosphate hybrid micelles (DZ@CPH) were prepared. DZ@CPH reduced the activation of osteoclasts and inhibited bone resorption. At the same time, DZ@CPH inhibited the invasion of bone metastatic TNBC cells by regulating the expression of apoptosis and invasion related protein in bone metastasis tissue. Moreover, the ratio between M1 type macrop …

Intermittent parathyroid hormone enhances the healing of medication-related osteonecrosis of the jaw lesions in rice rats.

Medication-related osteonecrosis of the jaw (MRONJ) is a potentially severe adverse event in patients treated with antiresorptives. Manageme … t surface (p < 0.001), more osteoblasts (p < 0.001), higher osteoclast surface (p < 0.001) and more osteoclasts (p = 0.002) at alveolar bone surfaces than ZOL/VEH rats. Greater gingival epithelial thickness and epithelial cell proliferation rate was found in the oral mucosa and gingiva of ZOL/PTH rats than in ZOL/VEH rats (p < 0.001). Our data suggest that iP …

Nonclinical and clinical pharmacological characterization of the potent and selective cathepsin K inhibitor MIV-711.

BACKGROUND: Cathepsin K is an attractive therapeutic target for diseases in which bone resorption is excessive such as osteoporosis and osteoarthritis (OA). The current paper characterized the pharmacological profile of the potent and selective cathepsin K inhibitor, MIV-711, in vitro and in cynomolgus monkeys, and assessed translation to human based on a single dose clinical study in man. METHODS: The potency and selectivity of MIV-711 were assessed in vitro using recombinant enzyme assays and differentiated human osteoclasts. MIV-711 was administered to healthy cynomolgus monkeys (3-30 µmol…

Effect of Intravenous Zoledronic Acid on Histopathology and Recurrence after Extended Curettage in Giant Cell Tumors of Bone: A Comparative Prospective Study.

BACKGROUND: Giant cell tumor (GCT) of the bone is known for its locally aggressive behavior and tendency to recur. It is an admixture of rounded or spindle-shaped mononuclear neoplastic stromal cells and multinucleated osteoclast-like giant cells with their proportionate dispersion among the former. Zoledronic acid (a bisphosphonate) is being used in various cancers such as myelomas and metastasis, for osteoporosis with an aim to reduce the resorption of bone, and as an adjuvant treatment for the management of GCT of bone for reduction of local recurrence. We have carried out a prospective com

Observational study of the bisphosphonate-related osteonecrosis of jaws.

INTRODUCTION: The bisphosphonate-related osteonecrosis of the jaw was first referred to in 2003. Bisphosphonates action is focused on the osteoclasts. The drastic inhibition of the osteoclastic function is harmful for the jaws which are the only bones of the human skeleton in relative contact with the external environment. The adverse effects of the bisphosphonate-related therapy include the pathology for which they are prescribed, the atypical fractures in pathological bone. METHOD: The aim of this research was to analyze the risk factors and the treatment methods in case of osteonecrosis of…