Bone Health

Healthy bones provide our bodies with a structure that protects our internal organs. The skull protects the brain, the spine protects the spinal cord, the ribcage protects the heart, liver and lungs, and so on. Our bones also store minerals. In addition, healthy bones allow us to move and engage in physical activity.

People living with HIV are at higher risk for osteoporosis and osteopenia—conditions characterized by low bone density—as well as a much rarer condition called avascular necrosis. Thankfully, though, there are many things you can do to promote your bone health—to prevent problems down the road or to help strengthen already weakened bones.

To understand how we can protect our bones, it helps to have a picture of how they work. Bone is a living tissue that is constantly rebuilding itself—old bone cells are continually being replaced with new bone cells. To do this, our bones need two key components: collagen and minerals. Collagen provides a flexible framework, which is important because bones need to have some “give”; without it, they can become too brittle and can break more easily. Minerals harden the collagen framework to give bones the strength they need to provide your body’s structure. To have healthy bones, we need to strike a balance between strength and flexibility.

Two types of cells work to keep our bones healthy: osteoclasts and osteoblasts. Osteoclasts remove old or damaged bone, leaving behind cavities where osteoblasts then build healthy new bone with collagen and minerals. As children and teenagers, we generally form more bone than we lose. Later, as adults, the bone loss can start to outpace bone growth. In particular, among HIV-negative adults, bone loss can accelerate when they begin menopause. Although it is norma l for our bones to become less dense as we age, we want to keep that bone loss to a minimum so that our bones stay strong throughout our lives.

Studies indicate that thinning bones are relatively common among HIV-positive people, affecting even some young adults. Although bone fractures are generally extremely uncommon (most people living with HIV never break a bone), people with HIV are at higher risk of fracture than HIV-negative people. A Danish study found that the fracture risk for people living with HIV was almost three times higher.

Many people think of osteoporosis as a disease of older women; however, everyone living with HIV will benefit from working with their healthcare providers to put together a program for their long-term bone health.

In general, it appears that cisgender men with HIV develop bone problems at an earlier-than-usual age, and postmenopausal cisgender women with HIV have a higher risk of developing osteopenia and osteoporosis than HIV- negative cisgender women.

What are osteopenia and osteoporosis?

Osteopenia is characterized by a slight thinning of the bones that can occur naturally with aging. It may or may not ever progress to osteoporosis. 

Osteoporosis is characterized by the gradual loss of bone tissue, resulting in thinning and weaker bones that may become brittle. With osteoporosis, there is both decreased bone mass and structural deterioration of the remaining bone tissue. The combination means that when a bone is stressed, it is more likely to fracture.

Risk factors for osteoporosis

The causes of bone disease in people living with HIV are not fully understood, but it appears that a combination of factors can increase a person’s risk. These include:

• HIV infection
• various medications, including some antiretroviral drugs
• hepatitis co-infection
• smoking
• low levels of sex hormones, such as testosterone and estrogen
• a family history of osteoporosis
• being 50 years or older
• early menopause (before age 45)
• excessive alcohol consumption
• a previous fragility fracture (a broken bone that results from minor trauma, for example, a fall from standing height or less)
• abnormally low body weight
• a lifestyle that does not include regular weight- bearing exercise
• malnutrition or any deficiency of the nutrients required for healthy bones (such as calcium, vitamin D, vitamin K and protein)
• health conditions that affect a person’s capacity to absorb nutrients, such as chronic diarrhea, celiac disease, irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD)
• hyperthyroidism (overactive thyroid)
• lipodystrophy (changes in body shape and metabolism that can result from taking antiretroviral medications)

Medications that can increase a person’s risk of osteoporosis include corticosteroids, proton pump inhibitors, Depo-Provera (birth control shot), excessive thyroid hormones (these hormones are appropriately prescribed to restore normal thyroid hormone levels in people with hypothyroidism but taking too much thyroid hormone can cause bone problems), heparin, antacids that contain aluminum, anticonvulsants, pentamidine, ketoconazole and cholestyramine.

In terms of antiretroviral medications, some protease inhibitors and some nukes (especially tenofovir disoproxil fumarate or TDF) may increase the risk for osteoporosis. Of course, stopping your drugs is not the answer. You need meds to keep HIV under control. Moreover, a large study recently found that people with HIV on treatment had a fracture risk that was about 36 percent lower than that of people with HIV not on antiretroviral therapy.

Although you may lose two to six percent of your bone density within two years of starting HIV treatment, the long-term use of antiretrovirals does not appear to cause continuing bone loss. If you have other serious risk factors for osteoporosis, the one drug that might be problematic is TDF (Viread; also in Truvada and generic formulations, Atripla, Stribild, Delstrigo and Complera). Some studies report higher rates of both osteoporosis and osteopenia among those using this drug, as well as increased rates of wrist, back and hip fractures. Although not all studies have shown this risk, if you have other risk factors or have already been diagnosed with osteoporosis, you might want to talk to your healthcare provider about this.

If you are taking TDF and tests show a significant loss of bone density, your physician may assess the possibility of low levels of phosphate in your blood, which can sometimes result from TDF use. Phosphate is crucial for providing mineral strength to bone; if your phosphate levels are low, you may need to take phosphate supplements.

A new version of tenofovir called TAF (tenofovir alafenamide) is now available. It is found in Odefsey, Biktarvy and Descovy. Clinical trials of TAF-based regimens indicate that this formulation of tenofovir has less potential for reducing bone density than a TDF-based regimen.

An important risk factor for osteoporosis is low testosterone. Because testosterone is often low in people with HIV and because it is essential for bone health as well as many other aspects of your health and well-being, it is important to have your levels checked periodically. If they are less than optimal, your healthcare provider may recommend testosterone replacement therapy. (For more on testosterone and HIV, see “Hormone Changes,” 

HIV infection itself may also contribute to the development of osteoporosis. It is thought that the ongoing inflammation caused by HIV as well as the constant activation of CD4 cells may contribute to accelerated bone loss. It is therefore important to counter chronic inflammation.

If you are diagnosed with osteopenia, this does not mean that you will definitely go on to develop osteoporosis. In fact, only a fraction of people with osteopenia will eventually progress to osteoporosis. However, a diagnosis of osteopenia should provide strong motivation to strengthen your bones and take steps to prevent bone loss. With proper care and/or treatment, bone loss can be reversed.

Bone density tests

Tests used to assess a person’s risk for osteoporosis and monitor bone density are called bone mineral density (BMD) tests. They measure the amount of calcium and other minerals in your bones.

A DEXA scan is the best way to accurately measure the loss of bone density. This scan measures the BMD of the spine, hip or total body. It is a type of X-ray but it emits approximately a tenth of the radiation of a chest X-ray. For this non-invasive test, you lie on a table while a mechanical arm moves over your body. A total body scan lasts approximately 20 minutes.

A baseline scan (ideally done before starting antiretroviral therapy) can eventually be compared with later readings. Current guidelines recommend that people living with HIV over the age of 50 obtain DEXA scans. This is particularly important for individuals who have any other risk factors for osteoporosis.

The results of a bone density test are shown as a T-score, which indicates how far from “normal” your BMD is. “Normal” is defined as the average BMD of a healthy young person, based on sex.

Normal healthy bone will result in a T-score greater than −1. Osteopenia is indicated by a T-score between

−1 and −2.5. Osteoporosis is indicated by a T-score of less than −2.5.

After a bone density test, you will also be given a Z-score. This score compares your BMD with the average BMD of people of your same age and sex. For diagnosing osteoporosis, the T-score is more important.

Preventing bone loss

Until all of the causes of osteoporosis in people living with HIV are well understood, advice on specific preventive measures will be incomplete. In the meantime, what we know about preventing or reversing osteoporosis in general can certainly help.

Do weight-bearing exercise

One of the most important things you can do to build and maintain healthy bones is to regularly combine strength training and aerobic exercise that puts weight on your bones. Activities such as walking or jogging (either outside or on a treadmill) are excellent weight-bearing exercises. Before you start an exercise program, speak to your healthcare provider to find out what exercises are safe for you.

Quit smoking

Smoking is strongly tied to an increased risk for osteoporosis, so if you can quit smoking you’ll be doing your bones a big favour.

Eat a nutrient-rich diet and make sure you get enough minerals and vitamins

Bones are made up of a matrix of minerals—including calcium, phosphorus, manganese, potassium, zinc, copper, boron and chromium. A diet with plenty of protein and a wide variety of vegetables, legumes, fruit, whole grains, nuts and seeds can supply an important base of the nutrients you need to form and maintain healthy bones.

You’ll want to make sure that you get enough calcium. Foods rich in calcium include dairy products, dark green leafy vegetables, fish (sardines and salmon with bones in, mackerel and herring), broccoli, almonds and legumes such as chickpeas and pinto beans.

Though it is best to get your calcium and other key nutrients from food, this is not always possible. If you do not get enough calcium from your diet and are considering supplements, talk to your healthcare provider or pharmacist first, as calcium supplements can interact with some prescription medications.

Want some help calculating your calcium intake? Osteoporosis Canada has a handy calcium calculator that can help you do the math at www.osteoporosis.ca.

Because your body needs vitamin D to absorb calcium and phosphorus, and many people with HIV have a vitamin D deficiency, talk to your healthcare provider about how to make sure you’re getting enough of it. Your healthcare provider can order a blood test to check your vitamin D levels to help determine the proper supplement dose for you. 

The other nutrient that is key for bone health is vitamin K, required for synthesizing osteocalcin, a bone protein needed for bone formation. Although vitamin K1 is plentiful in leafy green vegetables, vitamin K2, the nutrient that is most important for bone health, is found in only small amounts in a few foods, such as egg yolks, cottage cheese, fermented cheeses and the fermented soy product natto. For people concerned about osteoporosis, regular vitamin K2 supplementation can help ensure you get the right amount of this vitamin for your bones. Experts recommend supplements containing vitamin K2 (in the form of menaquinone-7, or MK-7) in a daily dose of 100 to 200 micrograms (mcg). Check the small print on labels of any supplements you are considering because many only contain vitamin K1, which is not the form you need to prevent osteoporosis. If you take a blood thinner, such as warfarin (Coumadin), speak to your healthcare provider and pharmacist before increasing your vitamin K intake, as it could potentially interfere with the effects of the medication.

Last but not least, you’ll want to make sure you’re getting enough vitamin B12. Several studies have shown that a vitamin B12 deficiency is associated with a higher risk for osteoporosis. Because many people with HIV have a vitamin B12 deficiency, supplementation may be important for your bone health as well as for its many other benefits.

Treating osteoporosis

Medications are often prescribed to treat osteoporosis but research on the effects of these drugs on people with HIV is extremely limited. Many of these medications have serious side effects, so you and your healthcare provider will want to weigh the possible benefits against the risks.

Most of the drugs work by stopping osteoclasts from doing their job of breaking down old or damaged bone tissue. Bisphosphonates—such as alendronate (Fosamax), risedronate (Actonel) and etidronate (Didronel or Didrocal)—work in this way. The result is an increase in bone mass and bone density, but some researchers fear that long-term use of these drugs may cause problems. The concern is that when the old bone tissue is not removed, the remaining bone tissue may become weaker and more brittle.

Studies have shown an accumulation of microscopic bone damage with bisphosphonate use and there have been some reports in recent years of osteonecrosis (death of bone tissue) of the jaw in small numbers of bisphosphonate users as well as a specific type of leg fracture following long-term use.

Some healthcare providers now recommend using bisphosphonates in a more limited way. They may prescribe one of these drugs for up to five years to increase a person’s bone density to within the normal range. After the drug is stopped, they order bone scans to track the bone density and resume bisphosphonate use if the bone density falls below normal. Other side effects of bisphosphonate can include nausea, abdominal pain and acid reflux, diarrhea, inflammation of the esophagus and esophageal ulcers. Some people may experience serious bone, joint and/or muscle pain. If you experience pain or difficulty swallowing while taking one of these medications, stop taking the medication and talk to your healthcare provider as soon as possible.

Hormone therapies—including testosterone, raloxifene (Evista) and teriparatide (Forteo)—are also used to prevent and treat osteoporosis.

As mentioned, countering testosterone deficiency is important for men at risk of osteoporosis (see Hormone Changes).

• Raloxifene (Evista), which belongs to a class of drugs known as SERMs (selective estrogen receptor modulators), was designed to have estrogen-like effects but without the risk of cancer. It is prescribed for the prevention and treatment of osteoporosis post-menopause; however, its effects on postmenopausal women with HIV have not yet been studied. Because this drug can potentially cause blood clots, it should not be taken by anyone with a history of blood clots.
• Teriparatide (Forteo) is a synthetic form of a human hormone that occurs naturally, called parathyroid hormone, which stimulates new bone growth. It is approved for the treatment of osteoporosis post-menopause, and for anyone at higher risk for a fracture. It is given as a daily injection under the skin on the thigh or stomach. Relatively short-term studies have shown that it reduces fracture risk. Because the long-term effects are not yet known, it is generally recommended that people take it for no more than two years.

Estrogen was once widely recommended for the treatment of osteoporosis in postmenopausal cisgender women. However, because of the risks of long-term use, including increased risk of cancer, heart attack and stroke, it is no longer recommended.

Calcitonin, a naturally occurring thyroid hormone that helps regulate calcium levels in the body, used to be prescribed to treat osteoporosis. However, because calcitonin use is associated with an increased risk of cancer, Health Canada has taken the drug off the market for this purpose.

Denosumab (Prolia) inhibits the formation of fully functional osteoclasts, the cells that remove old or damaged bone. Similar to bisphosphonates, it decreases the removal of old or damaged bone tissue. Denosumab is administered by injection twice a year. The most common side effects include respiratory infections, urinary tract infections and skin infections, as well as cataracts, constipation, rash, itchy dry skin, joint pain and eczema. A small study also reported a small increased risk of cancer and severe infections; although this finding was not statistically significant, there is concern that there might be a greater risk of these in people living with HIV who have low CD4 counts. In rare cases, osteonecrosis of the jaw has been reported in patients taking denosumab. This medication is not recommended for people with low calcium or vitamin D levels. If you are considering taking this drug, ask your healthcare provider to test your calcium and vitamin D levels first. There are no studies showing the results of long-term use of this drug.

Whether or not you take any of these treatments, you’ll want to make sure you get enough calcium and vitamin D on a daily basis to help your bones stay healthy.

It’s also a good idea to take steps to reduce your risk of falling. Here are some ways that you can fall-proof your environment:

• Clear away things you could trip over, such as electrical cords and objects on the floor.
• Secure area rugs to avoid slipping.
• Make sure your bathtub and shower aren’t slippery.
• Beware of medications that could make you drowsy or dizzy (such as sleeping pills, some antidepressants and pain medications).
• In the winter months, be sure to clear snow and ice from your porch and/or walkway, and sprinkle salt or sand.
• Have your eyes checked regularly, as poor vision can make it hard to see things you could trip over.
• Wear shoes that have a good tread.

An occupational therapist can help you fall-proof your home. 

Avascular necrosis

In addition to osteoporosis and osteopenia, people living with HIV are also at higher risk for a condition—although it occurs only rarely—called avascular necrosis. Avascular necrosis (also known as AVN, or osteonecrosis) is a disease in which a lack of blood flow causes the death of bone tissue, most commonly at the top end of the thigh bone (the femur), the section that creates part of your hip. Studies suggest that high cholesterol and triglyceride levels, which may be related to the use of protease inhibitors, may contribute to such bone problems.

The following are additional risk factors for AVN because each can contribute to decreased blood supply to the bone:

• long-term use of corticosteroid drugs
• excessive alcohol use
• smoking
• bone injury (such as a fracture)
• bone infection
• scuba diving
• certain medical conditions, such as diabetes, lupus, sickle cell anemia and Addison’s disease (Addison’s disease affects the adrenal gland and results in reduced production of the steroid hormone cortisol. It is usually treated with low doses of hydrocortisone, which are not thought to cause AVN but might contribute in a way similar to long-term corticosteroid use.)

AVN most commonly affects the hip, but it can also develop in the shoulder, knee or hand. Common early symptoms include:

• pain in the hip joint or groin area, which can radiate down the leg to the knee and may in some cases be very painful
• stiffness in the hip area, often particularly noticeable upon waking
• occasional aching, especially after long periods of walking or standing
• a decreased range of motion

With any such symptoms, a comprehensive physical exam is a must, followed if appropriate by an MRI scan of the bone.

Tips for managing avascular necrosis

Treatment is aimed at correcting the cause of AVN, if possible. This may include anti-inflammatory drugs or medications to treat blood clots. Pain medication and limiting movement of the joint may be helpful. If AVN is detected early, small holes can sometimes be drilled in the bone to increase blood flow and allow new blood vessels to grow, a process called core decompression surgery. However, there are no known cures for AVN. If it has progressed too far in the hip bone, a hip replacement or bone graft may be needed. For people with HIV who are concerned about AVN, it may be helpful to avoid activities that could increase the pressure on the hip joint, such as certain weight- lifting exercises, squats, running on concrete and carrying heavy weight on the shoulders.