Treatment of osteoporosis starts with the same three-pronged plan used for prevention: exercise, nutrition, and medication.

Medications approved for treating osteoporosis fall into the following general categories: bisphosphonates, selective estrogen receptor modulators, hormone and hormone-like preparations, and anabolic agents.

Bisphosphonates

The bisphosphonates are the drugs most often prescribed to treat and prevent osteoporosis. Bisphosphonates help to preserve bone mass by slowing down bone resorption. Clinical studies of these drugs have focused on their effect on BMD and fracture risk.

Members of this drug class include Fosamax, ibandronate (Boniva), Actonel, and Reclast. Fosamax and Actonel are indicated for the treatment of postmenopausal osteoporosis in women, for corticosteroid-induced osteoporosis in both women and men, and for other types of osteoporosis in men. Boniva and Reclast are indicated for the treatment of osteoporosis in postmenopausal women. Both Fosamax and Actonel are also approved for the prevention of osteoporosis.

Although not approved for treating osteoporosis, three other bisphosphonates—etidronate (Didronel), pamidronate (Aredia), and tiludronate (Skelid)—are, nonetheless, used for this purpose.

Combined estrogen replacement and bisphosphonate therapies have a modest additive effect in boosting bone mass. Several trials have shown that women with existing osteoporosis have a greater increase in BMD when treated with combination therapy than with either drug therapy alone.

Oral bisphosphonates are not easily absorbed, and they may lead to gastrointestinal side effects such as indigestion, diarrhea, stomach pain, heartburn, nausea, and peptic ulcers (nonhealing defects in the stomach or small intestine) as well as muscle cramps. Some people may experience side effects with one bisphosphonate, but they are able to tolerate another.

Generally, less frequent dosing may lead to fewer gastrointestinal side effects. In addition, to improve the absorption of oral bisphosphonates and to reduce the risk of gastrointestinal and esophageal side effects, it is important to follow the directions for use. First, the drug should be taken immediately after getting up in the morning, at least half an hour before eating or drinking anything besides water (even tea, coffee, fruit juice, or mineral water can interfere with absorption), and before taking any other medication. It is important to drink at least 8 oz of water when taking the tablet and to sit or stand upright for at least 30 minutes afterward.

Changing your dosing regimen or switching to another formulation are additional strategies that can help reduce the risk of experiencing side effects.

Recent reports have linked bisphosphonates to osteonecrosis of the jaw (ONJ), a condition that is manifest by exposed areas of jaw-bone in the mouth. Invasive procedures, such as dental extraction, can increase the risk of ONJ. This condition is very rare (about 1 in 100,000 for oral bisphosphonate users), and most reported cases have been in people taking I.V. bisphosphonates in high doses for the prevention and treatment of bone metastases.

Some dentists recommend discontinuing use of bisphosphonates for several months before and after having a tooth extraction or implant surgery. Evidence to support this advice is limited but studies are ongoing. For now, it’s wise to get regular dental checkups and to inform the dentist if you’re taking a bisphosphonate.

Selective estrogen receptor modulators

Raloxifene (Evista) is a member of a class of drugs called selective estrogen receptor modulators (SERMs). SERMs mimic some, but not all, of the actions of estrogen while apparently providing the benefits of estrogen without some of its negative effects.

Although Evista appears to increase bone density in the spine and the hip, studies have found significant fracture reduction only in the spine. Thus, if you have osteoporosis in the hip, Evista may not be the ideal medication for you.

The FDA approved Evista for the prevention of breast cancer in postmenopausal women with osteoporosis who are at high risk for invasive breast cancer.

Approval was based on findings from three studies that compared Evista with placebo and a fourth that compared it with tamoxifen, which was the first drug approved by the FDA for the chemoprevention of breast cancer.

In the first three trials, Evista reduced the risk of invasive breast cancer by 44 ti 71 percent compared with placebo. In the Study of Tamoxifen and Raloxifene (STAR) trial, Evista was as effective as tamoxifen for preventing breast cancer in postmenopausal women who were at high risk for it. Both drugs reduced the risk of invasive breast cancer by about 50 percent.

Because of its lack of estrogen-like action on breast and uterine tissue, Evista does not cause the breast tenderness and vaginal bleeding frequently seen with estrogen therapy. In addition, Evista does not increase the risk of uterine cancer when given without progesterone. An additional benefit is its estrogen-like effect of lowering “bad” low-density lipoprotein (LDL) cholesterol. Furthermore, there appears to be no increased risk of heart attack. Although studies have not shown an increased risk of stroke, the number of serious strokes associated with Evista use was greater than the number reported with placebo.

As with estrogen therapy, Evista is associated with an increased risk of serious venous thromboembolic events (the blocking of a blood vessel by a particle that has broken away from a blood clot), particularly in the first four months of therapy. Unlike estrogen, however, Evista does not relieve menopausal symptoms, and, it may increase the occurrence of hot flashes.

Studies of a new SERM, lasofoxifene, are under way.

Hormonal preparations

Estrogen and calcitonin are hormonal preparations currently used to treat osteoporosis.

Estrogen. Used alone or with progesterone, estrogen continues to play a role in osteoporosis treatment, despite concern about its side effects. If you take estrogen for osteoporosis, use the lowest possible dose that can prevent bone loss effectively.

Calcitonin. Given by injection or nasal spray, calcitonin (Fortical, Miacalcin) is a synthetic version of a hormone produced by the human thyroid gland. It improves bone density and may slow bone loss in the spine. There appears to be a modest reduction in fracture risk in the spine; however, calcitonin does not appear to protect against hip fracture. Overall, it is not as effective as the bisphosphonates, though it does have the particular benefit of relieving the pain of recent vertebral fractures.

The usual dosage of calcitonin is an injection every day or every other day, or one puff of nasal spray daily. Although most people tolerate the nasal spray fairly well, some may develop rhinitis (nasal inflammation).

Anabolic therapy

The only “anabolic” therapy for osteoporosis is teriparatide (Forteo), a synthetic version of human parathyroid hormone. A daily subcutaneous injection of Forteo has been shown to dramatically increase BMD and to reduce fracture in the spine and hip. Forteo works differently from antiresorptive medications in that it stimulates bone formation rather than preventing bone resorption.

One troubling potential side effect of Forteo is that it increased the risk of bone cancer in rats that were injected with high doses of the medication. Although an increase in this type of cancer has not been observed in humans treated with the medication, people at increased risk for bone cancer should not use Forteo. This includes people with Paget’s disease or an unexplained rise in alkaline phos- phatase levels, which would show up on a standard blood test. In addition, individuals who have undergone radiation therapy targeting bone or cancer that has spread to bone should not use Forteo.

Forteo may also raise blood calcium levels, so anyone with high levels of calcium in the blood should not use it. A transdermal patch formulation under investigation does not appear to cause this side effect. Forteo should not be used for more than two years, and another osteoporosis medication must be used after Forteo treatment to maintain the gain in bone density.

RANK ligand inhibitor

Denosumab (Prolia) was approved by the FDA in 2010 for the treatment of osteoporosis in women; it is the only monoclonal antibody approved for that purpose.

The drug inhibits the receptor activator of nuclear factor-kappa B (RANK) ligand protein responsible for the maturation of osteoclasts (the cells that break down bone). It is administered every six months by injection in the upper arm, upper thigh, or abdomen.

Prolia was tested on 7,808 women between the ages of 60 and 90 in a randomized, placebo-controlled study. The results, which were published in The New England Journal of Medicine, showed that Prolia significantly reduced the risk of vertebral, nonvertebral, and hip fractures during the three-year study.

It is not clear whether Prolia works better than older medications for osteoporosis because there have been few head-to-head comparisons. As such, Prolia may be a good option for people who cannot tolerate bisphosphonates or other osteoporosis medications.

Prolia may lower levels of calcium in the blood. Therefore, if you have hypocalcemia, it needs to be treated before beginning therapy with Prolia. As with bisphosphonates, Prolia may increase the risk of osteonecrosis of the jaw.

Publication Review By: Lee H. Riley III, M.D., and Suzanne M. Jan de Beur, M.D.

Published: 18 Nov 2011

Last Modified: 05 Feb 2015