Relationship Between Oxidative Stress in the Rotator Cuff and Transcutaneous Advanced Glycation End-Products Measurement in Diabetic Rats.

Diabetes mellitus increases oxidative stress due to hyperglycemia, resulting in the degeneration of rotator cuff tissue. Currently, there is no established method to non-invasively assess the extent of this oxidative stress. To address this, we aimed to investigate the relationship between the accumulation of advanced glycation end-products (AGEs), a marker of oxidative stress, and transcutaneous autofluorescence intensity in rotator cuff tissue harvested from diabetic rats. Ten control Sprague-Dawley (SD) rats and streptozotocin-induced diabetic rats (n = 10 per group) were used. The rats were euthanized eight and 16 weeks after the induction of diabetes, and rotator cuff attachment sites were collected and histologically analyzed. Prior to euthanasia, autofluorescence intensity was measured transcutaneously in the rotator cuff area. The expressions of AGEs and type I collagen were evaluated immunohistochemically with specific antibodies and the stained areas were quantified. All data were statistically analyzed using the Mann-Whitney U test. Correlation analysis was performed for skin autofluorescence intensity and the percentage of AGEs staining area using Spearman's rank correlation coefficient. The immunohistochemical expression of AGEs at the rotator cuff attachment sites and transcutaneous AGEs measurements were significantly higher in diabetic rats than in the control group at 16 weeks. There was no significant difference in the level of type 1 collagen between the two groups. This study reveals that the accumulation of AGEs in rotator cuff tissue increases due to prolonged hyperglycemia in diabetes. In addition, transcutaneous skin fluorescence intensity may be related to histological oxidative stress at the rotator cuff.

Weekly teriparatide treatment increases vertebral body strength by improving cortical shell architecture in ovariectomized cynomolgus monkeys.

Weekly teriparatide treatment is reported to reduce the incidence of osteoporotic vertebral fractures. However, the effect of weekly teriparatide on cortical bone has not been clarified. This study aimed to examine the effects of weekly teriparatide treatment on bone mass, intracortical structure, and remodeling of the lumbar vertebral cortical shell and its relation to mechanical properties in ovariectomized cynomolgus monkeys. Female monkeys, aged 9 to 15 years, were divided into four groups: (1) SHAM group, (2) ovariectomized group (OVX group), (3) OVX with 1.2 µg/kg once-weekly teriparatide group (LOW group), (4) OVX with 6.0 µg/kg once-weekly teriparatide group (HIGH group). After 18 months, all animals were double-labeled with calcein, and lumbar vertebrae were analyzed with histomorphometry and compressive mechanical tests. Following ovariectomy, we found reductions in the anterior cortical shell area of the vertebrae and reductions in nearly all of the tested vertebral mechanical properties. Weekly teriparatide significantly preserved the anterior cortical shell area and the energy absorption capacity of the lumbar vertebrae in a dose-dependent manner. Multiple regression analyses indicated that improved mechanical properties were more associated with the increased anterior cortical shell area rather than the cancellous bone volume. The intracortical structure of the Haversian canals was also preserved following teriparatide treatment after ovariectomy. These findings suggest the importance of the cortical shell as a therapeutic target in the treatment of osteoporosis. Weekly teriparatide treatment increases the compressive mechanical strength of the lumbar vertebrae by thickening the anterior cortical shell.

Once-Weekly Teriparatide Treatment Prevents Microdamage Accumulation in the Lumbar Vertebral Trabecular Bone of Ovariectomized Cynomolgus Monkeys.

The effect of teriparatide treatment on microdamage accumulation has yet to be examined in animal studies. The purpose of this study was to investigate the effect of once-weekly teriparatide treatment on bone microdamage accumulation and the relationship between microdamage parameters and bone mass, architecture, turnover, and collagen cross-linking in the lumbar vertebral trabecular bone of ovariectomized (OVX) cynomolgus monkeys. Female monkeys were divided into four groups (n = 18-20 per group): (1) SHAM group, (2) OVX group, (3) OVX with 1.2 µg/kg once-weekly teriparatide group (LOW group), (4) OVX with 6.0 µg/kg once-weekly teriparatide group (HIGH group). After 18 months, all animals were double-labeled with calcein for histomorphometry. L3 and L7 lumbar vertebrae were harvested and analyzed for differences in histomorphometry, microdamage, and collagen cross-linking. The iliac crest was also analyzed for differences in bone turnover. In the OVX group, cancellous bone mass was reduced and microdamage accumulation was increased as compared with the SHAM control. Once-weekly teriparatide at both doses prevented the decrease in bone mass and increase in microdamage accumulation, and improved the distribution of collagen cross-linkage types. Regression analyses indicated that decreased microdamage accumulation was associated with reduced non-enzymatic cross-link pentosidine rather than increased cancellous bone mass or enzymatic cross-links. These findings suggest that once-weekly teriparatide treatment decreases microdamage accumulation by recovering the balance in collagen cross-links.