Oxidative stress modulates osteoblastic differentiation of vascular and bone cells.

Atherosclerotic calcification and osteoporosis often coexist in patients, yielding formation of bone mineral in vascular walls and its simultaneous loss from bone. To assess the potential role of lipoproteins in both processes, we examined the effects of minimally oxidized low-density lipoprotein (MM-LDL) and several other lipid oxidation products on calcifying vascular cells (CVCs) and bone-derived preosteoblasts MC3T3-E1. In CVCs, MM-LDL but not native LDL inhibited proliferation, caused a dose-dependent increase in alkaline phosphatase activity, which is a marker of osteoblastic differentiation, and induced the formation of extensive areas of calcification. Similar to MM-LDL, oxidized 1-palmitoyl-2-arachidonoyl- sn -glycero-3-phosphorylcholine (ox-PAPC) and the isoprostane 8-iso prostaglandin E2 but not PAPC or isoprostane 8-iso prostaglandin F2α induced alkaline phosphatase activity and differentiation of CVCs. In contrast, MM-LDL and the above oxidized lipids inhibited differentiation of the MC3T3-E1 bone cells, as evidenced by their stimulatory effect on proliferation and their inhibitory effect on the induction of alkaline phosphatase and calcium uptake. These results suggest that specific oxidized lipids may be the common factors underlying the pathogenesis of both atherosclerotic calcification and osteoporosis.

Lipid Oxidation Products Have Opposite Effects on Calcifying Vascular Cell and Bone Cell Differentiation A Possible Explanation for the Paradox of Arterial Calcification in Osteoporotic Patients

Role of nutrients in skeletal metabolism and pathology in fish — An overview

The epidemiological correlation between osteoporosis and cardiovascular disease is independent of age, but the basis for this correlation is unknown. We previously found that atherogenic oxidized lipids inhibit osteoblastic differentiation in vitro and ex vivo, suggesting that an atherogenic diet may contribute to both diseases. In this study, effects of an atherogenic high-fat diet versus control chow diet on bone were tested in two strains of mice with genetically different susceptibility to atherosclerosis and lipid oxidation. After 4 months and 7 months on the diets, mineral content and density were measured in excised femurs and lumbar vertebrae using peripheral quantitative computed tomographic (pQCT) scanning. In addition, expression of osteocalcin in marrow isolated from the mice after 4 months on the diets was examined. After 7 months, femoral mineral content in C57BL/6 atherosclerosis-susceptible mice on the high-fat diet was 43% lower (0.73 ± 0.09 mg vs. 1.28 ± 0.42 mg; p = 0.008), and mineral density was 15% lower compared with mice on the chow diet. Smaller deficits were observed after 4 months. Vertebral mineral content also was lower in the fat-fed C57BL/6 mice. These changes in the atherosclerosis-resistant, C3H/HeJ mice were smaller and mostly not significant. Osteocalcin expression was reduced in the marrow of high fat-fed C57BL/6 mice. These findings suggest that an atherogenic diet inhibits bone formation by blocking differentiation of osteoblast progenitor cells.

Atherogenic High-Fat Diet Reduces Bone Mineralization in Mice

Smoking increases the concentrations of free radicals, which have been suggested to be involved in bone resorption. We examined whether the dietary intake of antioxidant vitamins may modify the increased hip fracture risk associated with smoking. We prospectively studied 66,651 women who were 40-76 years of age. Forty-four of the cohort members who sustained a first hip fracture within 2-64 months of follow-up (n = 247) and 93 out of 873 age-matched controls were current smokers. Information on diet was obtained by a validated food-frequency questionnaire. The relative risk of hip fracture for current versus never smokers was analyzed in relation to the dietary intake of antioxidant vitamins stratified into two categories (low/high), where median intakes among the controls were used as cut-off points. After adjustment for major osteoporosis risk factors, the odds ratio (OR) for hip fracture among current smokers with a low intake of vitamin E was 3.0 (95% confidence interval 1.6-5.4) and of vitamin C 3.0 (1.6-5.6). In contrast, the OR decreased to 1.1 (0.5-2.4) and 1.4 (0.7-3.0) with high intakes of vitamin E and C, respectively. This effect was not seen for beta-carotene, selenium, calcium, or vitamin B6. In current smokers with a low intake of both vitamins E and C, the OR increased to 4.9 (2.2-11.0). The influence of the intake of these two antioxidant vitamins on hip fracture risk was less pronounced in former smokers. Our results suggest a role for oxidant stress in the adverse effects on the skeleton of smoking, and that an insufficient dietary intake of vitamin E and C may substantially increase the risk of hip fracture in current smokers, whereas a more adequate intake seems to be protective.

https://asbmr.onlinelibrary.wiley.com/doi/pdf/10.1359/jbmr.1999.14.1.129

Smoking, Antioxidant Vitamins, and the Risk of Hip Fracture

The effects of dietary vitamin E (VIT E) and lipids on tissue lipid peroxidation and fatty acid composition, epiphyseal growth plate cartilage development, and trabecular bone formation were evaluated in chicks. A 2×2 factorial design was followed using two levels (30 and 90 IU/kg of diet) of dl-α-tocopheryl acetate and two different dietary lipids. The basal semipurified diet contained one of the following lipid treatments: anhydrous butter oil (40 g/kg)+ soybean oil (60 g/kg), [BSO], or soybean oil (100 g/kg), [SBO]. After 14 days of feeding, the level of α-tocopherol in plasma was higher and thiobarbituric acid reactive substances (TBARS) were less in plasma and liver of chicks supplemented with 90 IU of VIT E compared with those given 30 IU of VIT E. Body weights and tibiotarsal bone lengths were not affected by the dietary treatments Saturated fatty acids (14:0, 15:0, 16:0, 17:0, and 18:0) were increased in tibiotarsal bone of chicks fed the BSO diet. In contrast, total polyunsaturated fatty acids and the ratio of unsaturated fatty acids/saturated fatty acids were higher in plasma of chicks fed SBO compared with the values from chicks fed BSO. The thickness of the entire growth plate cartilage and the lower hypertrophic chondrocyte zone was significantly greater in chicks fed 90 IU/kg of VIT E. Kinetic parameters on bone histomorphometry indicated that mineral apposition rate was higher in chicks fed 90 IU/kg of VIT E. The interaction effect between the VIT E and BSO treatments led to the highest trabecular bone formation rate among the groups. These data suggest that VIT E protects against cellular lipid peroxidation in cartilage to sustain normal bone growth and modeling.

M. F. Seifert

Papers

Vitamin E stimulates trabecular bone formation and alters epiphyseal cartilage morphometry.