Relationship of homocysteine levels with lumbar spine and femur neck BMD in postmenopausal women.

OBJECTIVE: The focus of several studies in recent years has been the association between increased plasma concentrations of homocysteine (Hcy), reduced bone mineral density and increased risk of bone fractures. Nevertheless, inconsistencies persist in the literature. Thus, the objective of this study was to investigate the possible relationship between serum Hcy and vitamin B12 status, and bone mineral density, on a group of post-menopausal women. MATERIALS AND METHODS: One hundred thirty-nine postmenopausal women were recruited to enter this cross-sectional study. Bone mineral density (BMD) of total hip, femoral neck and lumbar spine was measured by dual-energy X-ray absorptiometry (DXA) and serum Hcy, vitamin B12, parathyroid hormone (PTH), total calcium and magnesium levels were determined. In addition, we investigated the relationship of Hcy and vitamin B12 and BMD using a meta-analysis approach. RESULTS: Serum Hcy levels were significantly higher in osteoporotic women when compared to other BMD groups, and were inversely related to lumbar spine BMD and femur neck BMD. Body mass index and serum Hcy levels were shown to be significant predictors of BMD at lumbar spine, femur neck and total hip. The performed meta-analysis showed that serum Hcy levels were significantly higher in osteoporotic subjects compared to normal BMD subjects. CONCLUSION: This study shows that Hcy status, but not vitamin B12 status, is associated with BMD in this cohort of postmenopausal women. We therefore confirm that high Hcy levels are an independent risk factor for osteoporosis. BMD evaluation in women at post menopause with high Hcy levels may be helpful in advising precautionary measures.

The novel protease inhibitor SRD441 ointment is not effective in the treatment of adult subjects with atopic dermatitis: results of a randomized, vehicle-controlled study.

BACKGROUND: There is evidence that excessive protease activity in the skin is an important factor in the development of atopic dermatitis. SRD44 is a topically formulated novel protease inhibitor that selectively inhibits Staphylococcal-derived aureolysin and matrix metalloproteinases (MMPs). METHODS: This was a double-blind, vehicle-controlled randomized trial conducted in thirteen hospital dermatology outpatient clinics in Germany (9), Bulgaria (3) and Finland (1). Ninety-three out of 103 screened adult subjects with confirmed atopic dermatitis affecting ≤ 20% of body surface area, with an IGA score of 2 or 3 at randomization were randomized following a washout period to either SRD441 ointment or matching vehicle twice daily for 28 days. The primary efficacy endpoint was the clearance of Atopic dermatitis (AD score of 0 or 1 IGA) at Day 21. Secondary endpoints included measures of SCORing Atopic Dermatitis, pruritus self-assessment, rescue medication use and occurrence of new exacerbations. A range of safety and tolerance endpoints were included. RESULTS: There were no significant treatment differences in IGA success rates at Day 21 (SRD441 ointment, 11.1%; vehicle ointment, 12.5%; P = 1.000). Evaluation of secondary efficacy variables revealed no clinical or important statistical differences between treatment groups. Eighteen subjects (19.4%) discontinued the study drug because of an AE (seven subjects [15.6%] in the SRD441 group and 11 subjects [22.9%] in the vehicle group). Twenty-seven subjects (60.0%) in the SRD441 group and 34 subjects (70.8%) in the vehicle group reported an adverse event (AE). CONCLUSIONS: SRD441 ointment did not demonstrate efficacy in the treatment of atopic dermatitis raising questions on the effectiveness of MMPs as a target for the treatment of atopic dermatitis. NCT00882245.