Epidemiological investigations of biomarker and dietary relationships with osteoporosis and fracture risk

Diet may aid osteoporosis and fracture prevention as it is modifiable, but limited evidence for a role of vitamin K1, vitamin C and iron exists, despite suggestions of potential underlying mechanisms. Positive associations between these nutrients and bone health have been reported in population studies; however, evidence is scarce in men, in British populations, for nutrient status and for fracture risk. Combining measures of dietary intake with biomarkers may limit errors associated with establishing population intakes, but no such studies exist in bone health. Therefore, this thesis aimed to investigate micronutrient intakes and blood measures and i) their cross-sectional associations with heel ultrasound and ii) their prospective associations with fracture risk in a sub-set of EPIC-Norfolk participants. An additional aim was to explore means of limiting the impact of measurement errors on the association between vitamin C and bone health. The main results showed significant associations between higher intakes of vitamin K1 and C and 0.6-5.5% higher heel ultrasound in both sexes, and additionally with total and plant-based iron intakes in women (0.4-5.8%). Moreover, upper versus lower quintiles of plasma vitamin C concentrations in men showed significant associations with reduced fracture risk at the hip (HR:0.35, 95%CI:0.16-0.80) and spine (HR:0.26, 95%CI:0.10-0.69). In women, upper versus lower quintiles of vitamin K1 intake (HR:0.47, 95%CI:0.24-0.91), total iron intake (HR:0.41, 95%CI:0.21-0.79), animal-based iron intake (HR:0.44, 95%CI:0.24-0.82) and serum ferritin concentrations (HR:0.30, 95%CI:0.14-0.64) were significantly inversely associated with spine fracture risk. In contrast, upper versus lower quintiles of animal iron intake in men was significantly associated with higher hip fracture risk (HR:2.29, 95%CI:1.11-4.73). . In further investigations, combining vitamin C intake and plasma status strengthened the associations with bone health in men, but not in women. In conclusion, this thesis provides novel insights into the role of diet in osteoporosis and fracture prevention

Is there a role for vitamin C in preventing osteoporosis and fractures?:A review of the potential underlying mechanisms and current epidemiological evidence

Osteoporosis and related fractures are a major global health issue, but there are few preventative strategies. Previously reported associations between higher intakes of fruits and vegetables and skeletal health have been suggested to be partly attributable to vitamin C. To date, there is some evidence for a potential role of vitamin C in osteoporosis and fracture prevention but an overall consensus of published studies has not yet been drawn. The present review aims to provide a summary of the proposed underlying mechanisms of vitamin C on bone and reviews the current evidence in the literature, examining a potential link between vitamin C intake and status with osteoporosis and fractures. The Bradford Hill criteria were used to assess reported associations. Recent animal studies have provided insights into the involvement of vitamin C in osteoclastogenesis and osteoblastogenesis, and its role as a mediator of bone matrix deposition, affecting both the quantity and quality of bone collagen. Observational studies have provided some evidence for this in the general population, showing positive associations between dietary vitamin C intake and supplements and higher bone mineral density or reduced fracture risk. However, previous intervention studies were not sufficiently well designed to evaluate these associations. Epidemiological data are particularly limited for vitamin C status and for fracture risk and good-quality randomised controlled trials are needed to confirm previous epidemiological findings. The present review also highlights that associations between vitamin C and bone health may be non-linear and further research is needed to ascertain optimal intakes for osteoporosis and fracture prevention

Cross-sectional and prospective associations between dietary and plasma vitamin C, heel bone ultrasound, and fracture risk in men and women in the European Prospective Investigation into Cancer in Norfolk cohort

Background: Vitamin C sufficiency may help prevent osteoporosis and fractures by mediating osteoclastogenesis, osteoblastogenesis, and bone collagen synthesis. Objective: We determined whether dietary intakes and plasma concentrations of vitamin C were associated with a heel ultrasound and hip and spine fracture risks in older men and women. Design: Participants were recruited from the European Prospective Investigation into Cancer in Norfolk study with 7-d diet diary estimates of vitamin C intake and plasma concentrations. A random subset (4000 of 25,639 subjects) was available for the cross-sectional (ultrasound) study of broadband ultrasound attenuation (BUA) and velocity of sound (VOS), which were determined during the second health examination. The prospective (fracture) study was a case-cohort sample of all participants with a fracture up to March 2009 and the random subset (n = 5319). ANCOVA-determined associations between quintiles of vitamin C intake and plasma status with adjusted BUA and VOS and adjusted Prenticeweighted Cox proportional HRs were calculated for fracture risk. Results: Women were 58% of the population (39–79 y old), and the median follow-up was 12.6 y (range: 0–16 y). Positive associations across all quintiles of vitamin C intake but not plasma status were significant for VOS in men (b = 2.47 m/s, P = 0.008) and BUA in women (b = 0.82 dB/MHz, P = 0.004). Vitamin C intake was not associated with fracture risk, but there was an inverse association with plasma concentrations in men, with quintile 4 having significantly lower risks of hip fractures (HR: 0.35; 95% CI: 0.16, 0.80) and spine fractures (HR: 0.26; 95% CI: 0.10, 0.69) than quintile 1. Conclusions: Higher vitamin C intake was significantly associated with higher heel ultrasound measures in men and women, and higher plasma vitamin C concentrations were significantly associated with reduced fracture risk in men only. Our findings that vitamin C intake and status were inconsistently associated with bone health variables suggest that additional research is warranted