No abstract

Inflammation and oxidative stress are important factors in the pathogenesis of diabetes and contribute to the pathogenesis of diabetic complications. Periodontitis is an inflammatory disease that is characterized by increased oxidative stress, and the risk for periodontitis is increased significantly in diabetic subjects. In this study, we examined the superoxide (O 2 − )-generating reduced nicotinamide adenine dinucleotide phosphate-oxidase complex and protein kinase C (PKC) activity in neutrophils. Fifty diabetic patients were grouped according to glycemic control and the severity of periodontitis. Neutrophils from diabetic patients with moderate [amount of glycated hemoglobin (HbA 1c ) between 7.0% and 8.0%] or poor (HbA 1c >8.0%) glycemic control released significantly more O 2 − than neutrophils from diabetic patients with good glycemic control (HbA 1c <7.0%) and neutrophils from nondiabetic, healthy individuals upon stimulation with 4β-phorbol 12-myristate 13-acetate or N-formyl-Met-Leu-Phe. Depending on glycemic status, neutrophils from these patients also exhibited increased activity of the soluble-and membrane-bound forms of PKC, elevated amounts of diglyceride, and enhanced phosphorylation of p47-phox during cell stimulation. In addition, we report a significant correlation between glycemic control (HbA 1c levels) and the severity of periodontitis in diabetic patients, suggesting that enhanced oxidative stress and increased inflammation exacerbate both diseases. Thus, hyperglycemia can lead to a novel form of neutrophil priming, where elevated PKC activity results in increased phosphorylation of p47-phox and O 2 − release.

More than three quarters of this sample of patients in a MMT program had low BMD. Treatable conditions associated with low BMD were commonplace. Efforts to increase awareness of low BMD in MMT patients should be considered so that effective treatment may be employed to lower future fracture risk.

SummaryOBJECTIVE-Testosterone therapy for osteoporosis has not been studied extensively in women because of its potential to cause virilization. Female-to-male transsexuals are genetic females who suffer from gender dysphoria and thus take supra-physiologic doses of testosterone to change from the female to male phenotype. The aim of this study is to examine the effects of testosterone treatment on the genetic female skeleton.PATIENTS AND DESIGN-A group of 15 female-to-male transsexuals was prospectively enrolled for observation over a 2-year period. The subjects had a mean age of 37·0 ± 3·0 years. All of the subjects self-administered testosterone esters intramuscularly at a mean dose of 70·7 ± 4·5 mg weekly. MEASUREMENTS-The subjects had measurements of bone mineral density (BMD) by dual X-ray absorptiometry (DXA) of the femoral neck and spine (L2-L4) at 12-month intervals. They had determinations of serum oestradiol, testosterone, soluble RANKL (sRANKL), osteoprotegerin (OPG) and urine N-telopeptide (NTX) at the date of enrolment and at the end of 2 years.RESULTS-There was a significant positive increase in mean BMD of 7·8% at the femoral neck and a nonsignificant increase in mean BMD of 3·1% at the spine over 2 years. The levels of testosterone reached the upper normal range for males and the levels of oestradiol declined to near the postmenopausal range. sRANKL levels decreased significantly in female-to-male transsexuals who newly initiated testosterone therapy. There was no significant change in urine NTX or serum OPG during the study.CONCLUSIONS-We conclude that supra-physiologic testosterone therapy increases BMD at the hip while maintaining BMD at the spine in female-to-male transsexuals. The effects of testosterone may be the result of testosterone hormone directly acting on the bone or indirectly through aromatization to oestradiol. Lower RANKL levels coupled with unchanged OPG levels results in an increased OPG/RANKL ratio, which may be beneficial to the bone by inhibiting osteoclastogenesis. Oestrogen is regarded as the dominant sex steroid hormone in maintaining bone mineral density (BMD) in males and females. Oestrogen therapy in postmenopausal women prevents bone loss (Wells et al., 2002), increases BMD (Lindsay & Thome, 1990) and prevents fractures (Women's Health Initiative, 2002). Oestradiol rather than testosterone in men correlates more strongly with BMD (Greendale et al., 1997;Khosla et al., 1998;Amin et al., 2000;Szulc et al., 2003) and is a stronger determinant of peak bone mass (Khosla et al., 2001). Men who have either defective aromatase (Bilezikian et al., 1998) or oestrogen receptor (Smith et al., 1994) develop severe osteoporosis, which further supports the notion that oestradiol is the more dominant sex steroid in preserving bone density.Previously, testosterone was considered the more dominant sex steroid in men. With ageing, men experience declining levels of testosterone (Morley et al., 1997) and decreasing BMD (Meier et al., 1984;Jones et al., 1994;Fatayerji et al., 1999;Melto...

Bone disease with osteoporosis and osteomalacia are common in sickle cell disease (SCD). Some patients have vitamin D deficiency and low bone mineral density (BMD). The role of vitamin D and calcium supplementation to restore bone health in SCD has not been well studied. In 14 adults with SCD, we measured 25(OH)D (25-hydroxyvitamin D) and BMD at the femoral neck, lumbar spine, and distal third of the ulna plus radius, along with markers of bone resorption (CTx; C-terminal component of pro-collagen type I) and bone formation (osteocalcin) before and after 12 months of vitamin D 2 and calcium carbonate treatment. Pretreatment, all patients were vitamin D deficient with a mean 25(OH)D level of 10.7 ± 4.7 ng/ml, had low BMD at the lumbar spine (L-spine), 0.87 ± 0.11 g/cm 2 (mean Z-score of -2.6 3 ± 0.71 SD and T score of -2.31 ± 0.75 SD), femoral neck, 0.8 ± 0.18 g/cm 2 (mean Z-score -1.36 ± 0.84, T-score -1.14 ± 0.75), and the distal radius and ulna, 0.6 ± 0.17 g/cm 2 (mean Z-score -1.18 ± 0.79, T-score -1.01 ± 0.74) and had elevated CTx (0.87 ± 0.5 ng/ml) and osteocalcin levels (12.3 ± 3.7 ng/ll). After treatment, all patients corrected their 25(OH)D level (38.8 ± 13.9 ng/ml) (P < 0.001) with a 3.6% ± 3.9% increase in BMD at the L-spine (P 5 0.009), 4.6% ± 8.5% increase at the femoral neck (P 5 0.05) and 6.5% ± 12.6% increase at the distal radius plus ulna (P 5 0.09). CTx, osteocalcin, and PTH(i) levels were unchanged. Treatment of adult SCD with vitamin D and calcium can restore 25(OH)D levels to normal and improve BMD, but, markers of bone resorption remained unchanged. Screening for vitamin D deficiency and BMD in SCD patients seems warranted. Am. J. Hematol. 83:271-274, 2008. V