Identification of osteoprotegerin and osteoprotegerin-ligand in calcified atherosclerosic lesions

Abstract

s-Posters IBMS/ECTS 2001-First Joint Meeting S118 metabolism in uremic patients. Thus circulating OPG may be an uremic toxin to develop uremic bone and parathyroid diseases through increasing skeletal resistance to PTH. Ji Shui Tan Hospital Objectives: To observe change of the serum TNF-alpha concentration when patients with osteodystrophy have been treated by 1-alpha(OH)D3. Methods: Twelve patients with chronic renal failure and renal osteodystrophy treated with 1-alpha(OH)D 3 , 0.5µg /day for 2 weeks and 4 weeks individually. Results: The serum TNF-alpha concentration descended obviously after 1-alpha(OH)D3 treatment. Conclusions: 1-alpha(OH)D3 may regulate TNF-alpha producting and secreting in mononuclear leukocyte. Objective To investigate the characteristic of bone metabolism in type 2 diabetes mellitus. Methods The levels of serum 25OHD, IBGP and urine HOP, Crosslaps were determined in 64 type 2 diabetes mellitus patient. Results (1) The levels of serum 25OHD in type 2 diabetes mellitus group were lower than that in normal controls (Male and premenopause women vs controls P<0.01; postmenopause women vs controls P<0.05). (2) The levels of serum IBGP in the whole type 2 diabetes mellitus group were lower than that in normal controls (P<0.01). (3) The levels of urine HOP in men group were higher than that in normal (P<0.05). The levels of urine Crosslaps in the whole diabetic group were higher than that in normal (premenopause women vs controls P<0.05; Male and postmenopause women vs controls P<0.01). Conclusion The data suggest that the abnormal bone metabolism in type 2 diabetes mellitus are the lack of Vitamin D, low bone formation and turnover, heighten bone resorption. The serum IBGP and the urine Crosslaps are sensitive biochemical markers of bone metabolism. Objective: To investigate the relationship between type 2 diabetes and osteoporosis(op). Methods: Bone mineral density (BMD) of lumbar 2-4 and Ward's triangle was measured between diabetic group and two control groups (healthy young and elder using DXA, Norland-X236). The correlation between the parameters of glucose metabolism and bone metabolism parameters was observed. Results: The BMD(L2-4) of young group was obviously higher than that of the elder groups (p<0.05). In the diabetic group, the BMD of L2-4 and Ward's were higher than that in elder group (p>0.05). The relevant analysis suggests there was no significant relativity among age | duration of diabetes and the BMD | serum BGP | ALK-B | Pyr-D | calcium | phosphorus and urine calcium in diabetic group. There were obvious positive relations between bodyweight index and serum phosphorus and BMD (P<0.05 and P<0.01). Conclusions: Low body weight is a risk for diabetic patients to get OP. BMD in diabetic patients is a bit higher than in normal elder, but no significant difference. The nature of ectopic bone and depositions of amorpheous calcifications in advanced atherosclerosic lesions is not well understood. Accumulating evidence suggests that atherosclerotic calcification shares features with bone calcification. We studied the presence of osteoprotegerin (OPG) and osteoprotegerin ligand (OPGL) in ectopic bone and amorpheous calcifications of type Vb human atherosclerotic lesions derived from the abdominal aorta. The localization of OPG and OPGL was determined by immunohistochemistry in 5 patients with ectopic bone formation (Group 1) and in 7 patients with amorpheous calcified depositions without bone structure (Group 2). In group 1, areas of lamellar bone were found containing lining cells, osteoblasts, osteoid, trabecular bone with cement lines, osteocytes and osteoclasts. In some areas cartilage structures were found containing matrix, lacunas and chondrocytes. In group 2, amorphous calcium deposits were found. OPGL was absent in and around the bone matrix in group 1. Faint OPGL depositions were close to areas of inflammation, which included T cells. In the lesions with cartilage structure, no OPG or OPGL could be identified. In group 2, deposition of OPGL was found in areas immediately around amorphous calcium depositions. OPG was found in the lining cells and in some of the smooth muscle cells in group 1 but could not be detected in group 2. These results indicate that OPG and OPGL are involved in ectopic bone formation and in the deposition of amorpheous calcium in atherosclerosis. This could provide a base for the study of the effect of bone-specific agents on the progression of atherosclerosis. Inflammatory Bowel Disease (IBD) is often followed by a loss of bone mass and bone quality. The resulting metabolic osteopathy should be characterized using laboratory and bone histomorphometric parameters. We investigated 19 patients (9 men, 10 women, age 23-68 years) suffering from Crohn's disease (16) or ulcerative colitis (3). The mean duration of the disease was 5,2 years (0,5-23). At the time of investigation, 16 patients were treated with corticosteroids (for a mean of 1,9 ys.). As serologic parameters we determined ESR, CRP, calcium, 25-OH-vitamin-D3, PTH and osteocalcin. After tetracycline labelling, bone biopsies were taken from the right anterior iliac crest applying a vertical technique. The samples were embedded in methylmetacrylate, sectioned on a heavy-duty microtome and stained (Masson-Goldner, Gomori, Giemsa). The following histomorphometric parameters were obtained using a Merz grid: bone volume (BV, in % of total bone volume), osteoid surface (OS), eroded surface (ES), osteoblast-(ObS) and osteoclast-covered surface (OcS), mineralized surface (MS, each in % of bone surface) and mineral apposition rate (MAR in microm). Patients with IBD showed increased CRP-levels (30,2±39,1 mg/l) and normal levels of calcium (2,32±0,21 mmol/l), 25-OH-vitamin-D3 (20,0±10,3 ng/ml) and PTH (25,6±10,9 ng/l), with a tendency towards low osteocalcin-levels (5,7±3,1 ng/ ml, reference 5-12). Histomorphometric parameters of IBD-patients were as follows (reference value of healthy young adults in parenthesis): 0,73±0,29microm (0,75). Osteopathy in IBD may be caused by a reduced calcium and vitamin-D resorption, the systemic action of inflammatory cytokines and the effect of corticosteriod treatment on bone. The normal levels of calcium, vitamin D and PTH in our patients do not support the hypothesis of a calcium deficiency as a main pathogenetic aspect. Small osteoid surface and low osteocalcin levels reflect a reduced bone formation, which is likely to be caused by the effects of corticosteriods on bone. In contrast, both the elevation of eroded surface and osteoclast-covered bone surface point to an increased bone resorption. According to our histomorphometric parameters, reduced bone formation and increased bone resorption seem to be characteristic features of osteopathy in patients with IBD.