Osteoporosis is a progressive disease where bone catabolism increases faster than its formation decreasing the density of bones which results in a great bone weakness. Osteoporosis is associated with a great level of calcium loss making the bones very porous and fragile. Osteoporosis is a disease that affects 1 in 3 women and 1 in 12 men and can cause death in a severely fractured hip. Osteoporosis treatments targets bone cells to prevent bone weakening. Additionally, it also significantly reduces menopausal symptoms but increase the risk of breast cancer development. However, other treatments and specific inhibition factors can prevent or delay the formation of breast cancer in women.
Bones hold 99% of the body’s calcium which is involved in the daily turnover of the bones. Two essential cells are involved in the daily turnover of the bones. Osteoblasts, cells responsible for the bone formation taking place by producing a matrix of collagen which becomes mineralised. Osteoclasts cells functions in the breakdown and resorption of the bone tissue. Skeletal homeostasis is maintained through a balance between the activity of osteoblasts and osteoclasts.
The leading cause for osteoporosis is the lack of certain hormones and particularly oestrogen in women. This is because bone loss takes place as a result of oestrogen deficiency. In post-menopausal women an excessive resorption takes place causing bone weakness (osteopenia) and over time osteoporosis.6 During menopause osteoblasts fail to function properly and bone weakening rapidly occurs due to oestrogen levels significantly dropping. Therefore, the risk of osteoporosis in post-menopausal women increases due to a decline in oestrogen levels. Oestrogen regulates the activity of osteoclasts cells which results in slowing the dissolving of the bones.
Treatments
Hormones are the most crucial modulators of bone formation as it has a direct effect on the bones by interacting with receptors. Treatments such as hormone replacements therapy (HRT) are widely used to entirely restore the rate of post-menopausal loss.1 HRT protects against thinning of the bones by increasing the availability of oestrogen levels in the body. It has a direct effect on cells by interacting with receptors at the surface of the cell. Its effect is mediated through a receptor called oestrogen receptor ?. The hormone binds to the receptor and is transported to the nucleus where receptor hormone acts as a switch to turn on the gene. However, many severe side effects are associated with this type of treatments such as breast cancer.
Other treatments such as selective oestrogen receptor modulator (SERM) also target oestrogen receptors in the body. SERM’s act as agonist or antagonist depending on different tissues in the body, it blocks oestrogen functioning in various parts of the body in order to increase the availability of the hormone in receptors located inside the bones for increased bone formation. Raloxifene is a selective oestrogen receptor modulator that has oestrogenic actions on the bone and anti-oestrogenic actions on other tissues such as the breast and the uterus. However, both treatments HRT and SERM are highly effective in alleviating menopausal symptoms. 4
Activation of RANK-ligand leads to breast cancer
Receptor activator nuclear factor (RANK) is a protein that is involved in the activation of bone formation and regulation of osteoclastic bone resorption. It acts primarily as a signal pathway to increase bone removal. Bone resorption is dependent on a cytokine known as RANK-L. RANK binds to its receptor RANK-L when expressed by the osteoclasts to activate and stimulate the osteoclastic formation which leads to bone resorption.
HRT triggers the RANK-L protein in breast cells which allows it to multiply causing a tumour. Studies and researches have shown that the activation of RANK is responsible for causing cancer in patients with osteoporosis.3 Therefore, blocking the RANK pathway with a drug can prevent breast cancer and also stop normal bone destruction.
Studies showed that women taking HRT had a higher rate of developing breast cancer. After 5 years of follow up, women taking these hormones had a 20% increase in breast cancer risk compared with placebo group. Therefore, the longer HRT medication is taken for, the greater the risk of breast cancer. In the fourth year and thereafter, breast cancer rates were higher in the oestrogen group with a significant trend of increasing breast cancer over time.
Raloxifene shows a reduced incidence of breast cancer by 27% compared to HRT. A statistically significant reduction in the incidence of breast cancer is shown among women taking raloxifene compared with the placebo group.5 According to the graph above raloxifene appeared to be most effective in reducing the incidence of breast cancer compared to HRT.
HRT aims to reduce the level of bones affected by increasing oestrogen in the body. However, it is one of the leading causes for breast cancer in women. Raloxifene is an alternative treatment used for patients with osteoporosis to reduce the level of bone dissolving and preventing severe side effects such as breast cancer. A separate study has shown that women who have abandoned HRT treatment had reduced breast cancer rates by 6%.2A study contradicting, based on several years of clinical trials shows that HRT is not the direct cause for breast cancer as women are at an elevated risk of developing breast cancer with age. Lifestyle also plays a great role in breast cancer development, the study reported that standard way of living such as smoking, fish intake, working on a night shift and birth weight increases the relative risk of breast cancer development and not synthetic hormones alone.1 Therefore if women were to abandon HRT drugs, normal daily life routine should also be considered in order to reduce the risk of breast cancer.
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