Risk factors for bone fragility and fracture in postmenopausal women

University dissertation from Clinical and Molecular Osteoporosis Research Unit

Abstract: The aim of this thesis was to evaluate risk factors for bone fragility and fractures in postmenopausal women in a long-term perspective. The study period spanned from the age of 48 to age 82 and is thus unique in its length. The studied sample was homogeneous and consisted of 390 north European women from a population-based cohort. At the start of the study, general health and lifestyle parameters were noted and bone measurements of the distal forearm were done by single-photon absorptiometry. The women who were still premenopausal were invited to enter a prospective perimenopausal study, and were followed through their natural menopausal transition by continuous endocrinological and bone measurements. Age at menopause could thus be determined exactly according to the criteria established by the World Health Organization (WHO). Bone measurements were done on average every second year during the first twenty years. At age 72, all women still remaining from the original cohort were invited to participate in a follow-up measurement, which was repeated at age 77. During the entire follow-up period, incident fractures were registered through repeated searches in hospital archives and databases, and mortality was registered through correspondence with the national population registers. Our studies found that menopause before age 47 is a risk factor for osteoporosis, fragility fracture and mortality also in a long-term perspective. When the 390 women were dichotomised into categories of women with menopause before and after the age of 47, we found that the risk was significantly increased in the women with early menopause. When a list of other known risk factors were taken into account, menopause before age 47 remained an independent risk factor for mortality, but not for fracture. Only low BMD predicted fracture risk independently, indicating that the predictability of early menopause is mediated by other factors, chiefly low BMD. As regards mortality risk, early menopause could either be the causal factor itself, or a result of complex underlying circumstances that lead to both early menopause and mortality. We therefore recommend women with early menopause to obtain advice on lifestyle and consider having their bone mass measured during the first decade after menopause. The effects of physical activity were studied in 112 women who were followed through their menopause with repeated SPA measurements for 25 years on. The women reported their level of everyday general moderate physical activity during the follow-up period in questionnaires, and were dichotomised according to a cut-off value of 30 minutes per day. The physically active women had a significantly lower rate of annual bone loss than the inactive women, and higher bone mineral content at study end (age 77). The results remained after adjustment for age at menopause and postmenopausal oestrogen levels, and there were no significant group differences in lifestyle, diseases or medication. These results suggest that physical activity could be a useful strategy for postmenopausal women to reduce the risk of bone fragility. In 81 women who were followed through their menopause and participated in the repeated bone measurements, changes in bone mass and bone structure were evaluated in different time phases after menopause. During the first eight years after menopause, there was an oestrogen-related annual bone loss of 2%, followed by an age-dependent bone loss of 1% per year until study end (on average 24 years post-menopause). This was partially compensated by an annual increase in periosteal width of 1% during the first eight years, whereas during the rest of the study period, no periosteal expansion was found. These results could not be associated with fracture risk, but indicate that bone strength is partially preserved in the early postmenopausal period, by the increased bone width which counteracts the rapid bone loss.

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