Nutritional and genetic factors influencing perimenopausal bone loss - a longitudinal study in 3,800 British women (N05026)

Study Duration: February 2000 to July 2001

Contractor: University of Aberdeen

Osteoporosis is a major public health problem affecting one in three women over the age of 50. The bones become so fragile that they fracture easily; and in the case of hip fracture this leads to rapid deterioration in health, and often death. We know that our genetic make-up affects how strong our bones will be but there are other factors that can affect our bone health, such as physical activity, diet and smoking. However, there are few data on which nutrients might influence the bone loss around the time of the menopause, a time of rapid bone turnover because of changes in hormone levels, particularly estrogen.

Rationale and Objectives
To explore the influence of nutrients on bone mineral density and recent bone loss around the time of the menopause. We intend to find out the nutrients that might help protect bone at this particularly vulnerable time, which maybe especially important for those women who are not taking hormone replacement therapy (HRT). In addition to calcium and vitamin D there are other nutrients such as zinc, magnesium, copper and vitamin C that may play a role in bone health. It is assumed that sunlight exposure during the summer months is the most important source of vitamin D and that diet plays a less important role. Previous work has suggested that bone density might be affected by having a particular gene at the vitamin D receptor site. By examining whether this is the case in our population of Scottish women, and whether the effect is influenced by diet or sunlight, we would gain valuable information that we could use to define strategies for targeting appropriate preventative therapy at those most at risk of this debilitating disease.

A total of 3,883 women who had a bone scan in 1990-4 and again in 1997-2000 were asked to complete our validated food frequency questionnaire (FFQ). This asks questions regarding consumption of 98 foods eaten regularly in this area of Scotland, from which we were able to calculate the average nutrient intake for each woman in our study. We also asked questions on sunlight exposure, medication (including HRT) and, using blood samples the women provided, we were able to genotype the women for the vitamin D receptor site gene (VDR). A total of 3,241 women completed our FFQ (response rate 83.5%).

The most important factor affecting bone loss was menopausal status and HRT use. Some relationships were observed between certain nutrients and bone mineral density. These relationships are tentative and require further investigation before the likely extent of these benefits can be ascertained.

Regardless of menopausal status, calcium helped reduce bone loss at the hip. Also, women who had higher intakes of magnesium had greater bone mineral density (BMD) at the hip at the start and the end of the study.

What it means and why it's important

This is currently the largest study of diet and bone health in the world. Whatever the vitamin D receptor site genotype, calcium and magnesium are important for bone health at the hip around the time of the menopause. An interesting finding is that vitamin D and sunshine score affect bone health. Dietary vitamin D (with fish oil supplements) appears to be particularly important for postmenopausal women who are not taking HRT, for whom bone loss is rapid. This finding may have public health implications as it is assumed that women of this age obtain sufficient vitamin D through sunlight exposure. It is possible that, especially in the north of Scotland, the diet may play a more important role than previously thought and it is recommended that further work be carried out in this area. Zinc also appears to be important for postmenopausal and premenopausal women.

Again, alcohol comes out as having a protective effect on bone, particularly the spine. But it should be emphasised that this population are moderate drinkers (generally 3 or 4 units of alcohol per week).

Just before the menopause, during the late premenopausal and perimenopausal period, when women are in their mid to late forties, nutrients obtained from fruit and vegetables appear to be beneficial. This finding fits in with the theory that bone is a source of alkaline salts that are released to buffer acidic metabolites that are produced by eating a mixed diet. Fruit and vegetables provide alkaline metabolites so that less bone needs to be broken down to release the alkaline salts. However, the nutrients found in fruit and vegetables – magnesium, vitamin C – may also have a direct role in bone metabolism. It is possible in the future to use our database to examine the effect of another nutrient, vitamin K, which is found in dark green vegetables and has been implicated as being important for bone health.

From the present work we cannot report a strong gene nutrient effect on bone density between calcium and the vitamin D receptor (VDR) gene. This may be because there is adequate intake of calcium intake in this population to compensate for any negative effect of the gene. Alternatively, this gene may be more important earlier on in life, when bones are growing. There are other genes for which there could be nutrient interaction that could be examined in the future.

As this is an observational study, we can only report associations. However, the work suggests that there is now a need to carry out a controlled trial, to fully evaluate the importance of micronutrients or of fruit and vegetables for bone health. The study shows that a large number of women take HRT, for menopausal symptoms and to protect their bones. We know that with long-term use there is an increased risk in breast cancer which means many women will stop taking HRT after 5-10 years. It is apparent that much of the benefit of HRT is lost when therapy is stopped. Although there may be new drugs coming on the market these are only prescribed to women who have been scanned to show they have very low bone density, or who have already suffered a fracture when irreparable damage to the bone has already been done. This highlights the importance of preventative lifestyle advice that is easy to follow for most women.

For women who had not gone through the menopause, nutrients found in fruit and vegetables (fibre, vitamin C, potassium and magnesium) and zinc were associated with greater BMD at the hip; and fibre and potassium were associated with greater BMD at the spine at the beginning and end of the study. The intake of these nutrients did not alter the rates of loss of bone density in the entire population probably because any such changes were overwhelmed by the loss of BMD related to the menopause and the effects of HRT. Nutrients found in fruit and vegetables did however have mild beneficial effect on bone turnover rates analysed after the end of the study.

The research shows that there was a difference in bone mineral density between groups who reported a high or low fruit and vegetable intake. Therefore, for women who are unwilling or unable to take HRT, the possibility that fruit and vegetable intake may help reduce postmenopausal bone loss should be investigated in a prospective controlled study.

There appeared to be no influence of the vitamin D receptor site gene on BMD or bone loss. Sunshine score and dietary vitamin D do appear to influence BMD but there was no interactive effect with the gene. For postmenopausal women who did not take HRT, vitamin D and zinc help protect against bone loss at the hip. For the whole group, alcohol again appears to have a protective effect on bone loss at the spine, but closer examination shows that this is more beneficial for present and past HRT users. There is no obvious explanation as to why this should be but it is possible that the postmenopausal women are too heterogeneous a group to pick up an effect on alcohol.

Contact: Dr Alison Tedstone
Tel: 020 276 8929
Email: alison.tedstone@foodstandards.gsi.gov.uk