Effective Medications for Treating Bone Loss With Osteoporosis

A Comprehensive Look at Osteoporosis Treatment Options

Woman with backache, massaging her back.
What medications are available to treat bone loss with osteoporosis and reduce your chance of fractures?. Peter Dazeley/Getty Images

Effective medications for treating bone loss increase bone density and lower the risk of fractures in people with osteoporosis and other conditions. What do you need to know about these treatments?

Understanding Osteoporosis

Osteoporosis is common condition which involves bones that have become weakened and brittle. Sometimes referred to as "brittle bone disease," osteoporosis weakens bones so that fractures can occur much more easily.

These fractures not only lead to disability and a reduced quality of life, but are a leading cause of illness and death as people age.

Osteopenia is not considered a disease, but is on the spectrum of bone loss. This is easier to describe in relation to T scores on a bone density test, in which your bone density is compared to a healthy young adult. On this test, a T score of -1.0 or higher is considered normal. A T score of -2.5 or lower indicates osteoporosis. Osteopenia is present if the T score is higher than -2.5 but lower than -1.0. (For those who are interested, each number refers to a change of one standard deviation).

For those who have osteoporosis, we are fortunate to have several categories of medications which may improve bone density and reduce fracture risk. While osteopenia is not considered a disease, people with osteopenia who are at an increased risk of developing osteoporosis or fractures may wish to consider medications as well.

When used to treat osteopenia, the doses of some of these medications (but not all) are lower than those used for osteoporosis.

Testing for Osteopenia and/or Osteoporosis

Some people learn that they have osteoporosis after experiencing a fracture. Anyone may experience a fracture, but fractures which occur in bones affected by osteoporosis often occur with less trauma.

For example, a healthy teenage boy may sustain a hip fracture in a serious motor vehicle accident. An elderly man with osteoporosis may instead suffer the same fracture from a mild fall.

Another way to determine if you have suffered bone loss is to have a bone density test. The test which is done most often is a dual-energy x-ray absortiometry test or DEXA scan. It's now recommended that all women over the age of 65 and all men over the age of 70 be tested. Other people who have risk factors for osteoporosis should be tested earlier.

Classes of Medications for Osteoporosis

There are several different types of medications which may be used for osteoporosis depending on the cause of your bone loss and other factors. These drugs work in different ways to build bone or prevent bone loss. Those used in cancer may even prevent bone metastases (the spread of cancer to bone) for some people. These classes of medications include:

  • Bisphosphonates
  • Selective estrogen receptor modulators (SERMS)
  • Hormone replacement therapy (estrogen)
  • Calcitonin
  • Parathyroid hormone
  • Bone modifying drugs for people with cancer

Let's begin with a brief review of bone anatomy and function so that the explanation about how these drugs work is clearer.

Bone Function

Many people do not think of bones as being "alive" but our bones are a busy place. Bone is constantly being broken down and rebuilt. If you have ever had a fracture this is more evident. Bone fractures are able to heal by both the actions of new bone formation and the removal of damaged bone.

There are two major types of bone cells. One is osteoblasts, the cells which build bone. The other is osteoclasts, the cells which break down and remove bone. Most of the time there is a balance between these two processes so that bones (after childhood) stay roughly the same size and density over time.

Parathyroid hormone (PTH) is a hormone produced in our bodies which regulates the balance between the osteoblasts and osteoclasts to maintain strong bones and repair any damage. Both vitamin D and calcium are important in the building and repair of healthy bones.

Let's look at the different classes of bone loss medications and how they work in building bones and/or preventing loss.

Bisphosphonates

Bisphosphonates are a category of osteoporosis medications which first became available in the 1990s. These drugs reduce the activity of osteoclasts (stops the destruction of bone) to reduce bone loss. This results in a net increase in bone density.

Over 95 percent of patients treated with bisphosphonates increase their scores on bone density testing. The specific drugs, however, differ in their likelihood of preventing specific fractures, how they are used, and some of the common side effects.

Once prescribed, you may not need to take bisphosphonates for the rest of your life. After three to five years of rebuilding your bones, physicians may recommend that patients with a low risk of fracture can stop taking it, according to a review from the U.S. Food and Drug Administration.

Medications in the bisphosphonate class include:

  • Actonel (risedronate): Actonel has been demonstrated to signifcantly reduce the risk of hip fractures in women with osteoporosis (by 60 percent in three years) and spinal fractures in people taking steroids (by 70 percent in 12 months).
  • Fosomax (alendronate): Fosomax has also been shown to increase bone density and reduce the risk of spine fractures.
  • Boniva (ibandronate): Boniva is a bisphosphonate which can be taken orally and is also available by injection. Boniva reduces the risk of spine fractures but has not been shown to reduce the risk of hip fractures, so may not be as good a choice for those who have hip or other non-spine fractures.
  • Reclast or Zometa (zoledronic acid): Reclast or Zometa is given only one time per year (for osteoporosis) or by injection.

Side effects of bisphosphonates depend on the particular drug as well as how it is given. With oral medications, indigestion, heartburn, and esophageal inflammation may occur. People are instructed to take these drugs with water (orange juice and coffee can interfere with absorption) and remain upright for at least 30 to 60 minutes. Muscle pain and headaches may also occur.

An uncommon side effect especially with Reclast or Zometa is osteonecrosis of the jaw. Other uncommon side effects may include femur fractures and atrial fibrillation.

Selective Estrogen Receptor Modulators (SERM)

Selective estrogen receptor modulators (SERMS) are interesting drugs in that they have estrogen-like effects on some tissues (such as the bones) and anti-estrogen effects in others (such as the breast tissue). Via their estrogen-like effects, they may strengthen bones similar to what estrogen (hormone replacement therapy) has accomplished in the past.

SERMS are only effective for osteoporosis in women. They slow bone loss and reduce the risk of spine fractures (but not hip fractures).

Medications include:

Since estrogen replacement therapy has been linked with breast cancer, Evista provides the benefit of estrogen to the bones without the risk of breast cancer or uterine bleeding found with hormone replacement therapy.

In addition to building bone, Evista may reduce the risk of developing hormone receptor positive breast cancer in postmenopausal women. The drug can perform double duty for women who have both osteoporosis or osteopenia and an increased chance of developing breast cancer.

Side effects include hot flashes, joint pain, increased sweating, and headaches. The medication should not be used for those who have had blood clots in their legs (deep vein thrombosis), lungs (pulmonary emboli), or eyes (retinal vein thrombosis).

Hormone Replacement Therapy

Once touted for its ability to reduce the risk of osteoporosis, hormone replacement therapy with estrogen has fallen out of favor due to an increased risk of breast cancer, strokes, heart attacks, and blood clots. That said, some women continue to use hormone replacement therapy to control menopausal symptoms and it has clearly been shown to improve quality of life for some people. For those who use HRT for this reason, an added benefit is a reduction in bone loss.

Calcitonin

Calcitonin is a hormone naturally present in our bodies which works to regulate calcium and bone metabolism.

Calcitonin is approved for the treatment of osteoporosis in women who are at least five years beyond menoopause. It increases bone density, particularly in the spine and appears to reduce the risk of spine fractures. It may also reduce pain for people who have fractures. The effect is greatest in the first year of treatment and falls off rapidly after that time. Doctors often recommend using a vitamin D and calcium supplement along with these medications, but talk to your doctor.

Medications include:

  • Miacalcin nasal spray (calcitonin) is available as both a nasal spray and an injection (see below). It is approved for Paget's disease, hypercalcemia (elevated calcium level in the blood), and postmenopausal osteoporosis in women.
  • Fortical (calcitonin): While the same main ingredient, Fortical is available only in a nasal spray and is approved only for the treatment of postmenopausal osteoporosis in women.
  • Calcimar (calcitonin): Calcimar is available as an injection and is approved for the treatment of Paget's disease, hypercalcemia, and postmenopausal osteoporosis in women.

Side effects of the nasal spray may include nasal irritation but is otherwise well tolerated. The injectable form of calcitonin can cause skin flushing, a rash, nausea, and urinary frequency.

Parathyroid Hormone (PTH) Therapies

Parathyroid hormone is a hormone naturally produced in the body. It stimulates bone formation by increasing the activity and number of osteoblasts, the bone-forming cells, and by minimizing the function of osteoclasts, reducing bone resorption. In other words, unlike bisphosphonates which reduce bone destruction, parathyroid hormone may actually work to build better and stronger bones.

Parathyroid hormone is most commonly prescribed for people who have been diagnosed with osteoporosis and who have a high risk of fractures, have failed to respond to other medications, or have experienced side effects with other osteoporosis drugs.

In studies, parathyroid hormone was found to reduce the risk of spinal fractures in postmenopausal women. Studies on Tymlos also found a reduction in non-spinal fractures.

Medications include:

  • Forteo (teriparatide): Forteo is a synthetic version of parathyroid hormone which is given as a daily injection. It was approved in 2002.
  • Tymlos (abaloparatide): Tymlos is actually a man-made version of only part of the PTH protein that acts like PTS at the PTH receptors in bone. It was approved in 2017 for the treatment of severe osteoporosis defined as a history of fractures, having multiple risk fractures, and/or having exhausted other osteoporosis treatment options.

The most common side effects of Forteo are dizziness and leg cramps. Tymlos has been associated with kidney stones due to the increased calcium in urine. 

It's recommended that use of parathyroid hormone be limited to two years. Parathyroid hormone should not be used for those who have Paget's disease (a disease of the bone), bone cancer, high blood calcium levels (hypercalcemia), or who have had radiation treatment to their bones. In clinical trials, there appeared to be an increase in bone cancer (osteosarcoma) and these drugs carry a black box warning for that reason.

Both Forteo and Tymlos are very expensive relative to other treatments, and may add up to $20,000 per year for treatment.

Following treatment (up to two years) it's recommended that use of a bisphoshonate be started to maintain the increase in bone density.

Monoclonal Antibody Therapy

The category of monoclonal antibody therapy includes two medications with the same structure but with different indications. Denosumab is a monoclonal antibody (man made antibody) that prevents osteoclasts, the bone dissolving cells from forming. These drugs work by slowing the break down of bone and bone remodeling.

The most common side effects include back back, joint aches, muscle pain, and increased cholesterol level and urinary tract infections. Adverse effects may include osteonecrosis of the jaw (as with bisphosphoates), an increased risk of infections (especially infections of the heart muscle), the potential for atypical fractures, and slow wound healing.

Medications include:

  • Prolia (denosumab): Prolia is available as an injection given once every 6 months. Prolia, unlike Xgeva, has several indications. It may be prescribed for men and postmenopausal women with osteoporosis who have a high risk of fractures. As a preventive measure, Prolia may be used for both women who are receiving aromatase inhibitor therapy for breast cancer and men with non-metastatic prostate cancer who are receiving androgen deprivation therapy.
  • Xgeva (denosumab): Xgeva is available as an injection given once every 4 weeks. Xgeva is approved for people with advanced breast cancer to reduce the risk of fractures related to bone metastases (spread of breast cancer to bone), to treat pain, and to reduce the risk of further fractures. It may also be used (but with different dosing) for people who have hypercalcemia of malignancy, and for people (again with different dosing) with giant cell tumors of the bone.

Similar to bisphosphonates, denosumab may increase the risk of osteonecrosis of the jaw.  Prolia and Xgeva appear to have anti-cancer properties in addition to reducing fracture risk.

Bone Modifying Medications

Bone modifying medications have been used to reduce the risk of fractures in people who have cancer which has spread to their bones. A common use is for breast cancer with bone metastases,or lung cancer with bone metastases.

Treatment options include Zometa (zoledronic acid), a bisphosphonate discussed above, and Xgeva (denosumab), a drug which has been found to reduce fractures in people who have breast cancer which has spread to their bones. Both Zometa and Xgeva (or Prolia) also appear to have anti-cancer properties.

Combination and Sequential Use of Osteoporosis Drugs

Since there are so many categories of osteoporosis drugs, all which work in different ways, you may wonder if a few of these drugs could be used together to reduce fracture risk. While that is a good thought, there is little evidence that combining more than one class of these drugs is of benefit.

An exception might be starting a bisphosphonate when discontinuing the use of either Prolia/Xgeva or Forteo, in which an overlap of 6 to 12 months may be beneficial to maintain improvements in bone density.

Calcium and Vitamin D in Osteoporosis Prevention

With many of these medications it's recommended that people get adequate amounts of calcium and vitamin D. A good diet often provides adequate calcium, but talk to your doctor. Vitamin D, however, is harder to get in a healthy diet (think: several glasses of milk and salmon each day), and not everyone everywhere is able to get an adequate amount via sunlight outdoors. Talk to your doctor about checking your vitamin D level (it's a simple blood test) and recommending a vitamin D3 supplement if needed. While an adequate amount of calcium and vitamin D are required for proper bone formation they are not a substitute for the use of osteoporosis medications.

A Word From Verywell on Medications for Bone Loss With Osteoporosis

As noted above, there are several different classes of medications for people with bone loss. Your doctor can discuss with you the reasons why one class may be better than another for your particular circumstances, as well as which drug within some of these classes may be best. There are many variables in choosing the right drug including a history of fractures, menopausal status, and potential side effects.

While these medications may increase bone density, the goal of treatment is to reduce the risk of fractures. Increasing bone density alone does not always mean a reduction in fractures. For example, fluoride can increase bone density but does not reduce fracture risk (and may actually increase risk as the bone which is formed is inferior).

It is also important to consider lifestyle factors which can reduce your risk of fractures if you have osteoporosis. Falls are a leading cause of illness and death in the United States due to the fractures they cause and subsequent complications. Regardless of the medication you choose, spend a moment of time reviewing some common sensical, as well as little known ways to reduce your risk of slips and falls.

Sources:

Ensrud, K., and C. Crandall. Osteoporosis. Annals of Internal Medicine. 2017. 167(3):ITC17-ITC32.

Khosla, S., and L. Hofbauer. Osteoporosis Treatment: Recent Developments and Ongoing Challenges. Lancet. Diabetes and Endocrinology. 2017 July 6. (Epub ahead of print).

McClung, M. Using Osteoporosis Therapies in Combination. Current Osteoporosis Reports. 2017. 15(4):343-352.

Continue Reading