Bisphosphonates (BPs) are clinically used for the treatment of bone metabolic abnormalities because they are powerful inhibitors of bone resorption. Osteonecrosis of the jaw has been observed after tooth extraction in a considerable number of BP-treated cancer patients, but the reason for this is not known. We studied the effects of BP on extraction socket healing in rats that were pretreated with BP prior to tooth extraction. Male Wistar rats (approximately 5 weeks old) were divided into experimental (BP) and control groups. In both groups, maxillary right second molars were extracted under general anesthesia. BP group rats were injected with 50 microl (1.0 mg/kg) alendronate into the right buccal alveolar bone every 4 days for 14 days, starting 2 days before tooth extraction. Control group rats were injected with physiological saline instead of alendronate. Rats were euthanized 3, 7, 10 or 14 days after tooth extraction, and maxillary bones were collected. Bone morphometric analysis using microfocus X-ray CT images and calculation of bone-resorption parameters based on hematoxylin and eosin or TRAP-stained pathological sections of the molar region showed that new bone formation in the extraction socket was delayed in the BP group relative to the control group during the first 7 days after extraction. A subsequent increase in new bone formation showed that bone resorption in the BP rats was eventually inhibited. This delay in initial healing may explain the jaw osteonecrosis observed in some BP-treated cancer patients.
This study examined the effect of photofunctionalization on bioactivity and osteoconductivity of titanium alloy Ti6Al4V. We also tested a hypothesis that the effect of photofunctionalization is as substantial as the one of surface roughening. Two different surface morphology, a roughened surface (sandblasted and acid-etched surface) and relatively smooth surface (machined surface), was tested. Ti6Al4V samples were photofunctionalized with UV light for 15 min using a photo device. Photofunctionalization converted Ti6Al4V surfaces from hydrophobic to superhydrophilic. The attachment, spread, proliferation, and the expression of functional phenotype of bone marrow-derived osteoblasts were promoted on photofunctionalized Ti6Al4V surfaces. The strength of bone-implant integration examined using a biomechanical push-in test in a rat femur model was at least 100% greater for photofunctionalized implants than for untreated implants. These effects were seen on both surface types. The strength of bone-implant integration for photofunctionalized machined implants was greater than that for untreated roughened implants, indicating that the impact of photofunctionalization may be greater than that of surface roughening. Newly prepared Ti alloy was hydrophilic, whereas the hydrophilic status degraded with time and was converted to hydrophobic in 4 weeks. This finding uncovered biological aging of Ti alloy and allowed us to consider photofunctionalization as a countermeasure for aging. These results suggest that photofunctionalization accelerates and enhances bone-implant integration of Ti6Al4V regardless of smooth and roughened surface features, supporting photofunctionalization as an effective and viable measure for improving efficacy of a wide range of Ti6Al4V-based materials used in dental and orthopedic medicine.
C-reactive protein (CRP) is one of the strongest independent predictors of cardiovascular disease. We have previously reported that oxidized LDL (oxLDL) interacts with b2-glycoprotein I (b2GPI), implicating oxLDL/b2GPI complexes as putative autoantigens in autoimmune-mediated atherosclerotic vascular disease. In this study, we investigated the interaction of CRP with oxLDL/b2GPI complexes and its association with atherosclerosis in patients with diabetes mellitus (DM). CRP/oxLDL/b2GPI complexes were predominantly found in sera of DM patients with atherosclerosis. In contrast, noncomplexed CRP isoforms were present in sera of patients with acute/chronic inflammation, i.e., various pyrogenic diseases, rheumatoid arthritis (RA), and DM. Immunohistochemistry staining colocalized CRP and b2GPI together with oxLDL in carotid artery plaques but not in synovial tissue from RA patients, strongly suggesting that complex formation occurs during the development of atherosclerosis. Serum levels of CRP correlated with soluble forms of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and oxLDL/b2GPI complexes correlated with total cholesterol and hemoglobin A1c. Thus, the generation of CRP/oxLDL/b2GPI complexes seems to be associated with arterial inflammation, hyperglycemia, and hypercholesterolemia. CRP/oxLDL/b2GPI complexes can be distinguished from pyrogenic noncomplexed CRP isoforms and may represent a more specific and predictive marker for atherosclerosis.-Tabuchi, M., K.
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