Smoking, Antioxidant Vitamins, and the Risk of Hip Fracture

Abstract

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 B 6 . 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 adequeate intake seems to be protective.(J Bone Miner Res 1999;14:129-135)

Bone and nutrition in elderly women: protein, energy, and calcium as main determinants of bone mineral density

“…Our study, although much smaller and of a cross-sectional nature, is pointing in the same direction. Vitamin C is required for collagen crosslinking (Combs, 1998) and along with other antioxidant vitamins may serve to protect the skeleton from oxidative stress, especially from smoking (Melhus et al, 1999). Two recent population-based studies showed that use of long-term vitamin C supplements was beneficial for BMD in various skeletal sites (Leveille et al, 1997) and the effect was augmented by estrogen and Ca supplements use (Morton et al, 2001) in postmenopausal women.…”

Oxidative stress and bone mineral density in elderly men: Antioxidant activity of alpha-tocopherol

“…Trolox, a water-soluble vitamin E analogue, prevents osteoclast formation and bone loss by inhibiting both RANKL induction in osteoblasts and c-Fos expression in osteoclast precursors [42]. In an earlier study we established that an inadequate dietary intake of antioxidants increases considerably the risk of hip fracture in current smokers, whereas current smokers with a more adequate intake of antioxidants appear to have a fracture risk similar to that observed among never smokers [43], supporting the theory that oxidative stress has important effects on bone in man. A low intake of antioxidants has also recently been associated with an increased hip fracture risk in women [44,45].…”

Nuclear Factor-E2-related Factor-1 Mediates Ascorbic Acid Induction of Osterix Expression via Interaction with Antioxidant-Responsive Element in Bone Cells

“…Similarly, epidemiological studies have provided evidence for the increased risk of bone fractures in patients with vitamin C deficiency as well as in smokers with insufficient intake of other antioxidants, such as vitamin E and selenium (6,8). The severity of antioxidant depletion and its relevance to the pathogenesis of multiple cell types and the ability of AA to induce differentiation of multipotent progenitor cells to osteoblasts, chondrocytes, cardiac myocytes, and dopaminergic neurons suggested that AA must be acting via other novel mechanisms to regulate cell differentiation at early stages and subsequent bone formation besides its well studied action to promote collagen synthesis/maturation and matrix protein interaction (14,15,31).…”