Medications:

Two types of drugs are used to prevent and treat osteoporosis:

• Antiresorptive Drugs. Antiresorptives include bisphosphonates, hormone replacement therapy, selective estrogen-receptor modulators (SERMs), and calcitonin. Bisphosphonates are the standard drugs used for osteoporosis. These drugs block resorption (preventing bone break down), which slows the rate of bone remodeling, but they cannot rebuild bone. Because resorption and reformation occur naturally as a continuous process, blocking resorption may eventually also reduce bone formation.
• Anabolic (Bone-Forming) Drugs. Drugs that rebuild bone are known as anabolics. The primary anabolic drug is low-dose parathyroid hormone (PTH), which is administered through injections. This drug may help restore bone and prevent fractures. PTH is still relatively new, and long-term effects are still unknown. Fluoride is another bone-building drug, but it has limitations and is not commonly used.

Both types of drugs are effective in preventing bone loss and fractures, although they may cause different types of side effects.

Bisphosphonates

Bisphosphonates are the primary drugs for preventing and treating osteoporosis. They can help reduce the risk of both spinal and hip fractures, including among patients with prior bone breaks.

Studies indicate that these drugs are effective and safe for at least 10 years. Eventually, however, bone loss continues with bisphosphonates. This may be due to the fact that bone breakdown is one of two phases in a continuous process of rebuilding bone. Over time, blocking resorption interrupts this process and impairs the second half of the process -- bone formation. Some, but not all, patients who are at low risk for fracture may be able to stop using the drug after 5 years. Other patients need to continue taking this type of drug on a continuous basis.

Candidates. National Osteoporosis Foundation guidelines recommend that the following people should take or consider bisphosphonates:

• Women with a below-normal bone density of 2.5 standard deviation or greater and no history of fractures
• Women with below-normal bone density 1 standard deviation or more and a history of fractures

Brands. Bisphosphonates are available in different forms:

• Oral bisphosphonates. These pills include alendronate (Fosamax, generic), risedronate (Actonel), and ibandronate (Boniva). Alendronate and risedronate are taken once a week. In 2005, ibandronate was approved as the first once-monthly pill. Risedronate is also available in a pill that contains calcium, and is available as a once-a-month pill. Alendronate is also available in a formulation that has vitamin D . Risedronate and alendronate are approved for both men and women.
• Injectable bisphosphonates. In 2007, zoledronic acid (Reclast) was approved as the first once-yearly injection treatment for postmenopausal osteoporosis, and in 2008 was approved to prevent new fractures in patients who have had a hip fracture. The injectable form of ibandronate (Boniva), approved in 2006, requires injections 4 times a year. Injectable bisphosphonates are an alternative for patients who may have difficulty swallowing pills or sitting upright after oral bisphosphonate treatment.

Side Effects. The most distressing side effects of bisphosphonates are gastrointestinal problems, particularly stomach cramps and heartburn. These symptoms are very common and occur in nearly half of all patients. Other side effects may include irritation of the esophagus (the tube that connects the mouth to the stomach) and ulcers in the esophagus or stomach. Some patients may have muscle and joint pain. To avoid stomach problems, doctors recommend:

• Take the pill on an empty stomach in the morning with 6 - 8 ounces of water (not juice or carbonated or mineral water).
• After taking the pill, remain in an upright position. Do not eat or drink for at least 30 - 60 minutes. (Check your drugâ ' s dosing instructions for exact time.)
• If you develop chest pain, heartburn, or difficulty swallowing, stop taking the drug and see your doctor.

Other Concerns. Osteonecrosis (bone death) of the jaw is a rare side effect that has occurred mainly in patients who received intravenous bisphosphonates for cancer treatment (not osteoporosis). Many of these patients had major dental procedures before developing osteonecrosis. However, this bone decay condition has also been reported in some patients who have taken bisphosphonates by mouth (mainly alendronate). Symptoms may include jaw pain or swelling, gum infections, and poor healing of the gums. Talk to your doctor or dentist if you experience any jaw or gum discomfort while taking a bisphosphonate drug.

There have also been concerns raised that bisphosphonates may increase the risk for atrial fibrillation, a heart rhythm disorder common in elderly patients. The FDA is monitoring reports of atrial fibrillation among patients who use bisphophonates but at this time does not recommend any changes to prescribing practices. As of late 2008, the FDA had evaluated almost 20,000 patients who had received bisphosphonates without identifying a clear link between these drugs and the risk of atrial fibrillation.

SERMs

Raloxifene (Evista) belongs to a class of drugs called selective estrogen-receptor modulators (SERMs). These drugs are similar, but not identical, to estrogen. Raloxifene provides the bone benefits of estrogen without increasing the risks for estrogen-related breast and uterine cancers. Raloxifene was approved in 1997 to prevent osteoporosis in postmenopausal women, and in 1999 for the treatment of osteoporosis in postmenopausal women. In 2007, the Food and Drug Administration approved raloxifene for prevention of breast cancer in postmenopausal women with osteoporosis, as well as postmenopausal women at high risk for invasive breast cancer.

While there are many SERM drugs, raloxifene is the only one approved for both treatment and prevention of osteoporosis. Only postmenopausal women who have or are at risk for osteoporosis should take this drug. Studies indicate that raloxifene can stop the thinning of bone and help build better quality and stronger bone.

A thrombus is a blood clot that forms in a vessel and remains there. An embolism is a clot that travels from the site where it formed to another location in the body. Thrombi or emboli can lodge in a blood vessel and block the flow of blood in that location, depriving tissues of normal blood flow and oxygen. This can result in damage, destruction (infarction), or even death of the tissues (necrosis) in that area.

Side Effects. Raloxifene increases the risk for blood clots in the veins. Because of this side effect, raloxifene also increases the risk for stroke (but not other types of heart disease). These side effects, though rare, are very serious. Women should not take this drug if they have a history of blood clots, or if they have certain risk factors for stroke and heart disease. More common mild side effects include hot flashes and leg cramps.

Calcitonin

Produced by the thyroid gland, natural calcitonin regulates calcium levels by inhibiting the osteoclastic activity, the breakdown of bone. The drug version is derived from salmon and is available as a nasal spray (Miacalcin) and an injected form (Calcimar). Calcitonin is not used to prevent osteoporosis. It treats osteoporosis. It may be effective for spinal protection (but not hip) in both men and women. Calcitonin may be an alternative for patients who cannot take a bisphosphonate or SERM. It also appears to help relieve bone pain associated with established osteoporosis and fracture.

Side Effects. Side effects include headache, dizziness, anorexia, diarrhea, skin rashes, and edema (swelling). The most common adverse effect experienced with the injection is nausea, with or without vomiting. This occurs less often with the nasal spray. The nasal spray may cause nosebleeds, sinusitis, and inflammation of the membranes in the nose. Also, many people who take calcitonin develop resistance or allergic reactions after long-term use.

Parathyroid Hormone

Teriparatide (Forteo), an injectable drug made from selected amino acids found in parathyroid hormone, can help reduce the risks for spinal and non-spinal fractures. Although high persistent levels of parathyroid hormone (PTH) can cause osteoporosis, daily injections of low and intermittent doses of this hormone actually stimulate bone production and increase bone mineral density.

Side effects of PTH are generally mild and include nausea, dizziness, and leg cramps. No significant complications have been reported to date. A nasal spray version of PTH is currently in clinical trials.

Early animal studies did report bone tumors in mice that were given parathyroid long-term. Such effects have not been observed in humans to date. However, people with Paget disease, (a disorder in which bone thickens but also, oddly, weakens), should not take parathyroid hormone, since they are at higher than normal risk for bone tumors.

Hormone Replacement Therapy

Hormone replacement therapy (HRT) was formerly used to prevent osteoporosis, but is rarely used for this purpose today. Studies have shown that estrogen increases the risk for breast cancer, blood clots, strokes, and heart attacks. For this reason, women need to balance the benefits that HRT has on bone-loss protection, with the risks it carries for other serious health conditions. The FDA recommends that women first try other medications for prevention of osteoporosis.

[For more information on HRT, see In-Depth Report #40: Menopause.]

Investigational Drugs

• New SERMs. Bazedoxifene (Viviant) and lasofoxifene (Fablyn) are two new selective estrogen receptor modulators (SERMs) that are currently being considered for approval by the FDA. The FDA is weighing the potential benefits of these drugs against their risks, which include stroke. If approved, the FDA may limit these drugs to certain groups of women, such as those at significantly high risk for fractures.
• Biologic Drugs. Denosumab is a humanized monoclonal antibody injectable drug currently in phase III studies. It targets the RANK ligand, a protein involved with cells that break down bone (osteoclasts). Odanacatib is another biologic drug currently being investigated. Odanacatib inhibits cathepsin K, a protein that also plays a role in osteoclast activity.