25; 95% CI, 1.15–1.36) with the highest risk observed for hip fracture

(RR = 1.84; 95% CI, 1.52–2.22). The risk ratio was adjusted downward when account was taken of BMD, but remained significant AZD5582 (RR = 1.15 and 1.60 for any fracture and hip fracture, respectively); low BMD accounted for only 23% of the increased risk for hip fracture associated with current smoking. The fracture risk was also adjusted downward when accounting for a lower BMI in smokers, but risk ratios for any fracture and hip fracture remained above unity and significant when adjusting for either BMI or both BMI and BMD. Risk ratios associated with smoking where selleck higher in men compared with women for any fracture and osteoporotic fracture, but not for hip fracture. Risk ratio increased with age for any fracture and osteoporotic fracture, but decreased with advancing age for hip fracture. Subjects with a history of smoking had a significantly higher fracture risk than never smokers, but a lower risk than current smokers [97]. The mechanisms of the BMD-independent increased fracture risk associated with smoking are unknown, but might hypothetically involve altered bone geometry or material property

not captured by DXA evaluation [96], relative physical inactivity and co-morbidity such as chronic lung disease resulting in frailty and increased risk for falls. In most countries, in particular in mid- and southern Europe, the diet provides only a minor part of the vitamin D requirement. A major source of vitamin D3 is

synthesis in Epigenetics inhibitor the skin under influence of UV light, as is illustrated by the marked seasonal variations in serum 25-hydroxyvitamin D levels [98]. The reported very high prevalence of vitamin D inadequacy in particular, but not exclusively, in elderly subjects [98–100] indicates that a low dietary intake of vitamin D is not compensated by sufficient synthesis in the skin. This might in turn result from insufficient skin exposure Anacetrapib to the sunlight and a lesser efficacy of vitamin D synthesis in de skin of elderly persons [98]. In urban areas, pollution may contribute to the limitation of effective exposure to UV from sunlight [101]. The fact that sun exposure tend to be generally low in elderly subject is illustrated by the paradoxical finding in a multi-country study in European elderly subjects of a positive association between mean serum 25-hydroxyvitamin D levels and degree of northern latitude [94]. This is most likely explained by a generally low sun exposure, also in southern European countries, and higher vitamin D availability in the diet and/or as supplements in Northern European countries. The low sun exposure in elderly persons is related to an indoor style of living and/or clothing leaving little skin exposed.