How effective are the medications used to prevent bone fractures?

Your doctor can help you to estimate your personal risk of breaking (fracturing) a bone. Risk calculators can be useful here: These tools usually tell you how likely you are to break a bone within the next ten years. They generally differentiate between hip fractures and other types of fractures. Hip fractures can have particularly serious health consequences.

One widely used risk calculator, developed at the University of Sheffield, is known as the FRAX tool. The umbrella organization of German osteology-related societies (Dachverband Osteologie, DVO) has developed another risk calculator that is also used in Germany.

Doctors can calculate someone's risk of breaking a bone by entering information about the following risk factors into the FRAX tool:

• Older age
• Being a female
• Low body weight (compared to height)
• Previous bone fracture
• Very early menopause
• Low bone density
• Hip fractures in one or both parents
• Smoking (now and in the past)
• Drinking a lot of alcohol
• Daily use of steroids for more than three months, either now or in the past
• Other illnesses, such as rheumatoid arthritis or an untreated overactive thyroid

The influence of risk factors may best be shown using an example. The following table contains information about the risk of bone fractures in three different groups of women. All of them are of normal weight, 60 years old and have osteoporosis (T-score: -2.5). The women in the first group don't have any other risk factors. Those in the second group have 3 additional risk factors, and those in the third group have 5 additional risk factors (see the left column of the table). The types of fractures included here are fractures of the hips, vertebrae, and bones in the forearm and upper arm.

The column on the right of the table shows that the more risk factors a woman has, the more likely she is to break a bone. But these figures are only statistical averages: it's not possible to know for sure whether a specific woman will break a bone.

Bisphosphonates have been proven to reduce the risk of bone fractures. Their effectiveness depends on the woman's bone density, age and other risk factors.

The following illustration shows what women can expect from treatment with these medications. The women in the examples are of normal weight, 60 years old and have osteoporosis (T-score: -2.5). The illustration shows how effective medication is in women with no additional risk factors, in women with 3 additional risk factors, and in women with 5 additional risk factors. The types of fractures included here are fractures of the hips, vertebrae, and bones in the forearm and upper arm.

Four bisphosphonates have been approved for the treatment of osteoporosis in Germany:

• Alendronate
• Ibandronate
• Risedronate
• Zoledronic acid

They can be taken as tablets or be given in the form of an infusion (an IV drip), where they enter the bloodstream directly through a vein. Most people who decide to have treatment with these medications use the tablets. It’s important to follow the instructions carefully:

• The tablets are taken first thing in the morning with a glass of water (200 mL, not mineral water with a lot of calcium in it). They shouldn’t be crushed or chewed and should be swallowed quite quickly.
• After taking the tablet, it’s important to wait for at least 30 minutes in an upright position before swallowing other medications, food or drinks.

This ensures that the drugs are absorbed properly by the bowel.

Some bisphosphonates have to be administered more frequently than others, depending on the exact drug, dose and form:

• Alendronate: once a day (10 mg) or once a week (70 mg) as a tablet or an effervescent (fizzy) tablet to be dissolved in water
• Ibandronate: once a month (150 mg) as a tablet or every three months as an infusion into a vein
• Risedronate: once a day (5 mg) or once a week (35 mg) as a tablet, or once a month (two 75 mg tablets taken two days in a row)
• Zoledronic acid: once a year as an infusion into a vein

If the tablets are taken on a weekly or monthly basis, it’s important to always take them on the same day – for instance, every Monday (weekly) or on the first day of each month (monthly).

There isn’t enough research to be able to say whether one of the bisphosphonates is better than others at preventing bone fractures. Ibandronate hasn’t been proven to reduce the risk of hip fractures. Alendronate is by far the most commonly used bisphosphonate.

Bisphosphonates are usually well tolerated. The potential side effects mainly depend on whether they are taken as tablets or given as an infusion (through a drip).

Tablets sometimes lead to gastrointestinal (stomach and bowel) problems such as heartburn, nausea, diarrhea or constipation. So infusions might be better for people who already have problems such as heartburn or reflux. People who have other health problems affecting their food pipe, stomach or bowel are generally advised not to take the tablets.

Bisphosphonate infusions can lead to flu-like symptoms in the first few days after they are given – especially the first time they are used. Fever-reducing medications such as acetaminophen (paracetamol) or ibuprofen can relieve these symptoms. They are taken for up to three days.

In very rare cases, bisphosphonates cause the jaw bone, or parts of the jaw bone, to die (necrosis). It is estimated that up to 3 out of 10,000 women could develop this side effect after many years of treatment. Necrosis of the jaw bone is thought to be more likely in women who have cancer or who are given the medication through an infusion.

Before starting treatment with bisphosphonates, the doctor checks a few things to make sure that the treatment is suitable. For instance, he or she may ask whether you have other health problems, whether you are taking any other medication, and whether your jaw and teeth are healthy. It’s sometimes a good idea to postpone treatment with bisphosphonates if you are planning to have major jaw or dental treatment. It’s always important to let your dentist know that you’re taking bisphosphonates.

Various blood tests are done to check your kidney function and calcium levels. It’s important to make sure you have enough calcium and vitamin D in your body before starting treatment with bisphosphonates. If your kidneys aren’t working properly, bisphosphonates aren’t an option.

It’s not clear whether routinely checking bone density during the treatment has any advantages. Experts disagree here. Bone density measurements involve exposure to low levels of radiation.

Other medications used in the treatment of osteoporosis include denosumab, raloxifene and teriparatide.

Denosumab is injected under the skin every six months. It has been proven to reduce the risk of bone fractures, and is also suitable for people who have renal insufficiency (kidney problems). But there are safety concerns about this drug. In some studies it was observed that when people stopped using denosumab their bone density decreased a lot, increasing the risk of fractures. And the drug is also associated with a small risk of jaw bone necrosis.

Raloxifene is very rarely used. It has only been proven to prevent vertebral fractures. And it increases the risk of thrombosis and fatal strokes. Because of this, some international groups of experts are very much against raloxifene being used.

Teriparatide is also very rarely used. It hasn’t been proven to prevent bone fractures of any kind, including hip fractures. And it has only been approved for up to two years of treatment.

Different medical societies give different recommendations concerning when to consider using medication. They agree that the advantages of medication outweigh the disadvantages if the person has already broken a bone due to osteoporosis. This is known as “established” osteoporosis. Medication can also be a good idea if a person’s bone density is below a certain value and they have other risk factors too.

Ultimately, though, it is up to each individual to decide whether or not they would like to take medication to prevent osteoporosis. Calculating your personal risk can help with the decision. It can also be a good idea to talk to your family doctor before starting a treatment because she or he may have a better overview of your general health situation.

The risk of bone fractures is particularly small in young women with only a slightly low bone density and few risk factors. So most of them wouldn’t benefit from taking preventive medication.

People are usually advised to use the medication over a period of five years. If they are at great risk of breaking a bone, this period may be extended.