Raloxifene for Osteoporosis: Benefits, Blood Clot and Stroke Risks, and Who It Suits

Raloxifene is a daily tablet for women after the menopause that lowers the risk of spine fractures by acting like oestrogen on bone. It does not have proven protection for the hip, and it carries a small but real risk of blood clots and of fatal stroke. In the UK it is usually an alternative when bisphosphonates are unsuitable, rather than the first choice.

What is raloxifene and how does it work?

Raloxifene is a selective oestrogen receptor modulator (SERM): a medicine that copies some of oestrogen's helpful effects on bone while blocking oestrogen's effects in breast tissue. After the menopause, falling oestrogen speeds up bone loss, which is why menopause is such a turning point for bone health. Raloxifene slows that loss without being hormone replacement therapy.

The UK product information describes it as a treatment to "treat and prevent osteoporosis in post-menopausal women" emc patient leaflet. It is only for postmenopausal women. It is not licensed for men, and it must not be used by women who could still become pregnant emc SmPC.

How well does raloxifene prevent fractures?

Raloxifene clearly reduces spine (vertebral) fractures, but it has not been shown to reduce hip or other non-spine fractures. In the main osteoporosis trial described in the product information, after 3 years raloxifene "reduced the incidence of vertebral fractures by 47%" in women with osteoporosis without an existing spine fracture (and by 31% in those who already had one) emc SmPC.

The same document is equally clear about the limit: "An effect on non-vertebral fractures has not been demonstrated." The UK National Osteoporosis Guideline Group (NOGG) agrees that raloxifene reduces vertebral fracture risk, but "reduction in non-vertebral and hip fractures has not been demonstrated" NOGG, section 6.

This matters because hip fractures are the most serious kind. For a woman whose main worry is the hip, other medicines usually make more sense. Our osteoporosis treatment guide compares the options.

Is raloxifene a first-line osteoporosis treatment in the UK?

No. For most people, UK guidance starts with a bisphosphonate, and raloxifene is an alternative if those are unsuitable or not tolerated. NOGG recommends offering "oral bisphosphonates (alendronate or risedronate) or intravenous zoledronate" first, or HRT in postmenopausal women aged 60 or under. It then advises considering alternatives, including raloxifene, "if these first-line bisphosphonates are unsuitable or not tolerated" NOGG summary.

In practice, raloxifene may be discussed for a postmenopausal woman who:

• cannot take or tolerate bisphosphonate tablets such as alendronic acid, for example because of stomach problems;
• is mainly at risk of spine rather than hip fractures;
• has no history of blood clots and no major stroke risk;
• may also benefit from lower breast cancer risk.

It is not a substitute for HRT if you need help with menopause symptoms. If that is your situation, see our guide to oestrogen, HRT and bone density.

What are the blood clot and stroke risks with raloxifene?

Raloxifene raises the risk of blood clots in the veins, a risk similar in size to HRT, and slightly increases the risk of dying from a stroke. The product information states that raloxifene "is associated with an increased risk for venous thromboembolic events" similar to that seen with HRT emc SmPC. NOGG adds that the increase is small and happens "mostly within the first few months of treatment" NOGG, section 6.

An NHS breast-cancer leaflet puts this in everyday numbers: about 2 in 1,000 women in the general population develop a blood clot each year, and if all of them took raloxifene, about 4 in 1,000 would Greater Manchester Cancer leaflet.

On stroke, the product information reports that a large trial (RUTH) found no rise in the number of strokes overall, but there was "an increase in death due to stroke" with raloxifene: 2.2 per 1,000 women per year, compared with 1.5 on placebo emc SmPC.

Who should not take raloxifene?

Raloxifene is not suitable if you have had a blood clot, could still become pregnant, are breastfeeding, have liver disease or severe kidney problems, or have unexplained vaginal bleeding or womb cancer. These are the contraindications listed in the UK patient leaflet emc patient leaflet.

You should also tell your doctor if you have had a stroke or mini-stroke, or have risk factors such as atrial fibrillation, high blood pressure or smoking. NOGG advises caution in women with a history of stroke or stroke risk factors NOGG, section 6.

What are the common side effects of raloxifene?

The most common side effects are hot flushes, flu-like symptoms, stomach upset and leg cramps. The UK patient leaflet lists these as very common or common emc patient leaflet:

• Very common (more than 1 in 10): hot flushes, flu-like symptoms, raised blood pressure, nausea, vomiting, tummy pain or indigestion.
• Common (up to 1 in 10): headache including migraine, leg cramps, swelling of the hands, feet or legs, gallstones, rash and mild breast tenderness.

The leaflet is clear that raloxifene "does not treat post-menopausal symptoms, such as hot flushes". NOGG also lists leg cramps, swelling (oedema) and vasomotor symptoms among its side effects NOGG, section 6. An NHS breast-cancer leaflet notes that menopausal-type side effects such as hot flushes commonly settle after the first few months Greater Manchester Cancer leaflet.

Does raloxifene reduce breast cancer risk?

Yes. Raloxifene lowers the risk of oestrogen-sensitive breast cancer, which is why it is used for two different reasons. In the 4-year osteoporosis trial, raloxifene "reduced the risk of total breast cancer by 62%" compared with placebo emc SmPC. NOGG also notes that women treated with raloxifene had "a significantly decreased risk of developing breast cancer" NOGG, section 6.

Separately, NHS breast clinics may offer raloxifene to postmenopausal women with a higher-than-average risk because of family history. One NHS leaflet describes a 60mg tablet once a day for five years, lowering breast cancer risk by about a quarter. For example, a woman with an 8% ten-year risk might drop to around 6% Greater Manchester Cancer leaflet. Breast screening continues as normal whether or not you take it.

How do you take raloxifene?

The usual dose is one 60mg tablet once a day, swallowed whole with water, with or without food. It does not matter what time of day you take it, but the same time each day helps you remember. Do not crush or break the tablet emc patient leaflet.

Your doctor may also suggest calcium and vitamin D supplements if your diet is short of them. Our guide to vitamin D, calcium and protein explains how much you need. The leaflet stresses that you should keep taking raloxifene "for as long as your doctor prescribes the medicine" and should not stop without talking to your doctor first.

How is raloxifene treatment monitored?

Your GP or specialist will review whether raloxifene is still the right choice, usually alongside a repeat fracture-risk assessment and, where needed, a bone density scan. Because raloxifene protects the spine more than the hip, it helps to know where your bone density stands at each site. The FRAX and NOGG treatment thresholds are what UK doctors use to decide whether treatment needs to change.

If you would like a picture of your bone health between NHS reviews, a radiation-free REMS bone health assessment from Screen My Bones assesses the spine and hip and can be repeated safely over time. It is a screening and monitoring option, not a replacement for a DXA scan when your doctor needs a formal diagnosis. Read more about how REMS works.

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This article is for general information and does not replace advice from your GP, pharmacist or specialist. Do not start, stop or change any medicine without talking to your doctor. See also our guides to denosumab (Prolia) and romosozumab (Evenity).