Treatment and Prevention of Osteoporosis in women with breast cancer

Women who have had breast cancer may be at higher risk for osteoporosis than other women. First, they are more likely to undergo early menopause, due to chemotherapyinduced ovarian failure or oopherectomy. In addition, chemotherapy may have a direct adverse effect on bone minerai density (BMD), and osteoclastic activity may increase from the breast cancer itself. While estrogen therapy is considered standard for the prevention and treatment of osteoporosis, use of estrogen in women with a history of breast cancer is usually contraindicated. The approach to osteoporosis in women with breast cancer is also affected by the use of tamoxifen in many, as this drug appears to have opposite effects on BMD in premenopausal and postmenopausal women. We have reviewed therapeutic alternatives for the prevention and treatment of osteoporosis, focusing on patients with a history of breast cancer. Alendronate and raloxifene are currently approved in the United States for the prevention of osteoporosis; alendronate, raloxifene, and calcitonin are approved for treatment. Alendronate has the greatest positive effect on BMD and reduces the incidence of vertebral and nonvertebral fractures. Raloxifene and calcitonin appear to reduce the incidence of vertebral fractures; their effects on the incidence of nonvertebral fractures are not yet proven. 

Although no published studies specifically address the use of these approved agents for osteoporosis in women with breast cancer, understanding their relative effects on BMD in postmenopausal women in general will facilitate therapy selection in this population. Postmenopausal women with a history of breast cancer should undergo bone mineral analysis. Normal results and absence of other risk factors ensure that calcium and vitamin D intake are adequate. If osteopenia or other risk factors are present, preventive therapy with alendronate or raloxifene should be considered. For osteoporosis, treatment with alendronate should be strongly considered. Raloxifene and calcitonin are alternatives when alendronate is contraindicated. Further studies are needed to evaluate the optimal timing of initial bone mineral analysis in premenopausal women after breast cancer diagnosis and to determine the value of preventive treatment in women scheduled to undergo chemotherapy.

What is osteoporosis?

Osteoporosis is a condition where your bones lose their strength and thickness (density). This leads to bones becoming weaker and more likely to break (fracture).

Bones have a thick outer shell and a strong inner mesh filled with collagen (protein), calcium salts and other minerals. The inside looks like a honeycomb, with blood vessels and bone marrow in the spaces between.

Osteoporosis means some of the outside and inside of the bone become thin. Sometimes the structure starts to break down causing wider spaces, and bones can fracture easily with little or no force.

Generally, osteoporosis causes no pain or symptoms, so often a person will not realise they have the condition until a fracture happens. The most common sites for a fracture are the wrist, hip and back (spine).

Although osteoporosis cannot be cured, treatments are available to try to keep the bones strong and less likely to fracture.

What causes osteoporosis?

Your risk of getting osteoporosis is increased by:

  • Getting older
  • Lower oestrogen levels
  • Other factors such as your family and medical history

Age

Our bones increase in density and strength until we reach our late 20s. Around the age of 35 we start to lose bone density as part of the natural ageing process. This happens gradually over time but is much more significant after the menopause.

Low oestrogen levels

The hormone oestrogen protects against bone loss and helps to keep bones strong. Women who have gone through the menopause are at increased risk of osteoporosis and fractures because their ovaries no longer produce oestrogen, although small amounts of oestrogen are still produced by fat cells.

Women may also have low levels of oestrogen because of:

  • An early natural menopause (before the age of 45)
  • Eating disorders such as anorexia nervosa or bulimia
  • An oophorectomy (surgical removal of the ovaries)
  • Treatment for cancer (such as chemotherapy, hormone therapy or ovarian suppression)

Other risk factors

Other risk factors for osteoporosis and fractures include:

  • A family history of osteoporosis or hip fractures
  • Low body weight
  • Previous wrist, back (spine) or hip fracture that was not caused by injury
  • Conditions that leave you immobile for a long time
  • Previous fracture after a fall from standing height or less (this may be a sign that the bones are weaker)
  • Some antidepressants
  • Medical conditions such as Crohn’s disease, coeliac disease, ulcerative colitis, overactive thyroid (hyperthyroidism) and diabetes
  • Medication (usually long-term use) including corticosteroid tablets (for conditions such as arthritis and asthma) and anticonvulsants (for conditions such as epilepsy)

Breast cancer treatments and bone health

Some breast cancer treatments can lower bone density and increase the risk of osteoporosis and fractures in both premenopausal women (women who have not gone through the menopause) and postmenopausal women (women who have gone through the menopause).

The likelihood of developing osteoporosis and having fractures will also depend on how healthy your bones were before your breast cancer treatment.

Treatments include:

  • Chemotherapy
  • Tamoxifen
  • Aromatase inhibitors (anastrozole, exemestane and letrozole)
  • Ovarian suppression

Chemotherapy

Chemotherapy can affect the ovaries, causing an early menopause in some women. This means less oestrogen is produced, which can reduce bone density.

Women aged 45 or under whose periods have stopped for at least a year as a result of treatment may also be at risk of osteoporosis, even if their periods restart.

Some research has shown that postmenopausal women who have chemotherapy may have greater loss of bone density than they would have had without chemotherapy.

Ovarian suppression

Ovarian suppression is when the ovaries are stopped from working (suppressed), either temporarily or permanently. This means there is less oestrogen in the body to help the cancer to grow. However, having less oestrogen in the body can also reduce bone density.

Tamoxifen

Tamoxifen blocks the effect of oestrogen on cancer cells.

Tamoxifen may slightly increase the risk of osteoporosis for premenopausal women. This is unlikely to lead to osteoporosis, unless ovarian suppression is given as well. However, your risk may be higher if you’re 45 or under and your periods have stopped for at least a year.

In postmenopausal women, taking tamoxifen slows down bone loss and can reduce the risk of osteoporosis.

Aromatase inhibitors

Aromatase inhibitors (such as anastrozole, exemestane and letrozole) reduce the amount of oestrogen made in the body, which can reduce bone density and cause fractures.

They are usually used to treat breast cancer in postmenopausal women, but some premenopausal women take an aromatase inhibitor at the same time as having ovarian suppression. Having these two treatments together can reduce bone density.

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Can osteoporosis be prevented or treated?

There are a range of ways to prevent and reduce further bone loss:

  • Teriparatide
  • Lifestyle changes to look after your bones
  • Raloxifene
  • Supplements
  • Denosumab
  • Bisphosphonates

Although osteoporosis cannot be cured, treatments are available to try to stop the bones losing more bone density and to make them less likely to fracture. You will be advised about any appropriate drug treatment and its possible side effects. 

Supplements

Your GP may recommend a calcium and vitamin D supplement. You may be prescribed a tablet that contains both, such as Adcal D3.

Bisphosphonates

Bisphosphonates are usually given to people who have had breast cancer to treat osteoporosis. This includes alendronate, zoledronic acid, risedronate and ibandronate.

Bisphosphonates help strengthen your bones and reduce your risk of fractures. They can be given as a tablet or as an injection into the vein. They may also be prescribed to protect your bones if you’re taking an aromatase inhibitor (such as exemestane, letrozole or anastrozole). Bisphosphonates may be used as a treatment to reduce the risk of primary breast cancer spreading. They are also sometimes given as a treatment for secondary breast cancer in the bone. This is not the same as having osteoporosis.

Denosumab

Denosumab is a drug that may be recommended to reduce the risk of fractures. It is given as an injection twice a year and slows down bone loss in osteoporosis. It’s a treatment for postmenopausal women who are unable to take certain bisphosphonates.

Raloxifene

Raloxifene is given for the prevention and treatment of osteoporosis in postmenopausal women. Raloxifene is only prescribed for women who have had breast cancer after they have completed their breast cancer treatment.

Teriparatide

Teriparatide is also prescribed for osteoporosis but is usually only recommended if you are unable have bisphosphonates or denosumab. It may be suggested if you have a very high risk of fracture, particularly of the spine.

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