Two types of drugs are used to prevent and treat osteoporosis:
Antiresorptive Drugs. Antiresorptives include bisphosphonates, selective estrogen-receptor modulators (SERMs), and calcitonin. Bisphosphonates are the standard drugs used for osteoporosis. Denosumab (Prolia) is a newer type of antiresorptive. 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. The United States Preventive Services Task Force (USPSTF) recommends that these drugs should be prescribed only to patients who have been diagnosed with osteoporosis.
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 up to 5 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.
Candidates. Clinical guidelines recommend that the following people should take or consider taking bisphosphonates:
- Any woman who has a T score of -2.5 or lower on a DXA scan
- Women who have a T score between -1 and -2.5 (indicates low bone density [osteopenia]) and a history of fractures
Brands. Bisphosphonates for osteoporosis prevention and treatment are available in different forms:
- Oral bisphosphonates. These pills include alendronate (Fosamax, generic), risedronate (Actonel, generic), and ibandronate (Boniva, generic). Alendronate and risedronate are taken once a week. Ibandronate is available as a once-monthly pill. Risedronate is also available as a once-a-month pill and in a pill that contains calcium. Alendronate is available in a formulation that has vitamin D. Risedronate and alendronate are approved for both men and women.
- Injectable bisphosphonates. Zoledronic acid (Reclast) is approved for treatment and prevention of osteoporosis in postmenopausal women. It is given as a once-yearly injection. The injectable form of ibandronate (Boniva) 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 drug’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. The FDA is currently reviewing whether long-term (more than 3 - 5 years) use of bisphosphonate drugs provides any benefits for fracture prevention. Possible concerns for long-term use of bisphosphonates are increased risks for thigh bone (femoral fractures), esophageal cancer, and osteonecrosis (bone death) of the jaw. The FDA recommends that doctors periodically reevaluate patients who have been on bisphosphonates for more than 5 years. Patients should inform their doctors if they experience any new thigh or groin pain, swallowing difficulties, or jaw or gum discomfort. Do not stop taking your medication unless your doctor tells you to do so.
For the injectable drug zoledronic acid (Reclast), kidney failure is a rare but serious side effect. Zoledronic acid should not be used by patients with risk factors for kidney failure.
Denosumab (Prolia) is a newer drug approved for treatment of osteoporosis in postmenopausal women who are at high risk for fracture. Denosumab is the first “biological therapy” drug approved for osteoporosis. It is considered an antiresorptive drug, but it works in a different way than bisphosphonates. It is a monoclonal antibody that works by targeting RANKL, a chemical factor involved with bone resorption.
Denosumab slows down the bone-breakdown process. However, because it also slows down the bone build-up and remodeling process, it is unclear what its long-term effects may be. Possible concerns are that denosumab may slow the healing time for broken bones or cause unusual fractures. For now, denosumab is recommended for women who cannot tolerate or who have not been helped by other osteoporosis treatments.
Denosumab is given as an injection in a doctor’s office twice a year (once every 6 months). Common side effects include back pain, pain in the arms and legs, high cholesterol levels, muscle pain, and bladder infection. Denosumab can lower calcium levels and should not be taken by women who have low blood calcium levels (hypocalcemia) until this condition is corrected.
Because denosumab is a biologic drug, it can affect or weaken the immune system and may increase the risk for serious infections. Other potential adverse effects include inflammation of the skin (dermatitis, rash, eczema) and inflammation of the inner lining of the heart (endocarditis). Denosumab may increase the risk of jaw bone problems such as osteonecrosis.
Selective estrogen-receptor modulators (SERMs) are a class of drugs that are similar, but not identical, to estrogen. They can provide the bone benefits of estrogen without increasing the risks for estrogen-related breast and uterine cancers.
Raloxifene (Evista). Raloxifene (Evista) is the only SERM approved for both treatment and prevention of osteoporosis in postmenopausal women. Raloxifene is recommended for postmenopausal women with low bone mass or younger postmenopausal women with osteoporosis. It may help prevent bone loss and reduce the risk of vertebral (spine) fractures. It is less clear how effective it is for preventing other types of fractures. Raloxifene is taken as a pill once a day. Common mild side effects include hot flashes, joint pain, and swelling of legs, feet, and ankles.
Bazedoxifene and Conjugated Estrogens (Duavee). In 2013, the FDA approved Duavee, a drug that combines the SERM bazedoxifene with the conjugated estrogens used in hormone replacement therapy for menopause. The medication is approved both to treat moderate-to-severe menopausal symptoms such as hot flashes, and to prevent post-menopausal osteoporosis. When Duavee is used solely for the prevention of osteoporosis, the FDA recommends that it should be reserved for high-risk women, and that other, non-estrogen drugs should be tried first. Common side effects include muscle spasms, nausea, diarrhea, and upset stomach.
Serious Side Effects. All SERMs increase the risk for blood clots in the veins. Because of this side effect, these drugs also increase the risk for stroke (but not other types of cardiovascular disease). These side effects, though rare, are very serious. Women should not take a SERM drug if they have a history of blood clots, or if they have certain risk factors for stroke and heart disease.
Teriparatide (Forteo), an injectable drug made from selected amino acids found in parathyroid hormone, may 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 doses of this hormone actually stimulate bone production and increase bone mineral density. Teriparatide is usually recommended for patients with osteoporosis who are at high risk of fracture.
Side effects of PTH are generally mild and include nausea, dizziness, and leg cramps. No significant complications have been reported to date.
Early animal studies reported 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 weakens), should not take parathyroid hormone, because they are at higher than normal risk for bone tumors.
Produced by the thyroid gland, natural calcitonin regulates calcium levels by inhibiting the osteoclastic activity, the breakdown of bone. The drug version, calcitonin salmon, is derived from salmon and is available as a nasal spray (Miacalcin, Fortical, generic) and an injected form (Miacalcin, generic). Calcitonin is used to treat, not prevent, osteoporosis. In 2013, an FDA advisory committee recommended against the use of calcitonin products for osteoporosis due to concerns that the drug may increase the risk for cancer. According to the advisors, the risks for cancer outweigh any possible benefits. The FDA is currently considering the committee’s recommendations and will make a final decision by 2014.
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. The nasal spray may cause nosebleeds, sinusitis, and inflammation of the membranes in the nose. Many people who take calcitonin develop resistance or allergic reactions after long-term use. As noted above, cancer risks are a concern.
Hormone Replacement Therapy
Hormone replacement therapy (HRT) was formerly used to prevent osteoporosis, but is rarely used for this purpose today. Studies show 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. HRT is now mainly used for short-term treatment of symptoms of menopause. The United States Preventive Services Task Force (USPSTF) recommends against the use of HRT for prevention of osteoporosis or other chronic health conditions.