About ten prescription drugs, some available as less-expensive generics, have been approved to prevent or treat osteoporosis. Experts are still debating about who should take the drugs besides people with osteoporosis. After some of the drugs were also approved for osteopenia two decades ago, many women (and some men) with the condition started taking them, raising concerns about overtreatment. But in recent years the treatment pendulum seems to have swung in the opposite direction, with more women with osteopenia hesitating to take the drugs, often because of concerns about their side effects.
Most of these drugs are “anti-resorptive,” meaning they slow the breakdown of bone; some also increase bone strength. There’s good evidence that they can improve BMD and other markers of bone health and reduce fracture risk in women with osteoporosis. However, research involving women with osteopenia, people over 75, and men is limited. It is not known whether one drug or one type of drug is better than another, since there’s little research comparing them.
Estimates of efficacy from research reviews vary considerably. One review estimated that in women who already had a fracture, 100 would have to be treated with bisphosphonates for three years to prevent one additional hip fracture. Of course, in people at lower risk, even more would likely have to be treated to prevent a single fracture.
All of these drugs can have side effects, which cause many people to stop taking them. We mention only some of the more common side effects here.
• Bisphosphonates are the first-line treatment for osteoporosis and are also FDA-approved for its prevention in women with osteopenia. They are alendronate (brand name Fosamax), ibandronate (Boniva), risedronate (Actonel), and zoledronic acid (Reclast, Zometa, Aclasta). Weekly or monthly dosing can be as effective as daily doses and is often better tolerated. Ibandronate can be administered intravenously every three months; zoledronic acid once a year to treat osteoporosis and once every two years to prevent it. Various bisphosphonates can have different clinical effects.
Optimal use of bisphosphonates requires adequate calcium and vitamin D intake before and during therapy. To improve absorption and prevent esophageal injury, you must take the drug after an overnight fast, and then you can’t lie down or consume anything except plain water for 30 to 60 minutes.
Side effects include heartburn, irritation of the esophagus, nausea, indigestion, leg and arm pain, flu-like symptoms, and fever. The most serious but rare side effect is a deterioration of the jawbone, known as osteonecrosis of the jaw—see Bisphosphonate Worries, below.
Optimal duration of bisphosphonate use is unclear. Experts advise most women to stop taking the drugs after five years—or to take a “drug holiday” of at least a year or two—because there is limited evidence of efficacy from longer use and good evidence of increased risk of side effects. This decision will depend on your medical history and risk factors for fractures such as changes in BMD and markers of bone turnover. Since the drugs are retained in bone, it’s expected that they will continue to have some anti-fracture efficacy after discontinuation.
• Raloxifene (Evista). Approved for the treatment and prevention of osteoporosis, this selective estrogen receptor modulator (SERM) mimics estrogen to keep bones strong. Also used to treat or prevent breast cancer, raloxifene provides the benefits of estrogen without many of its drawbacks. Side effects include hot flashes, leg cramps, and blood clots. Women at high risk for stroke (such as those with uncontrolled hypertension) should not take it.
• Conjugated estrogens/bazedoxifene (Duavee). Approved only for prevention of osteoporosis in women with an intact uterus, this combines estrogen with a SERM. It increases BMD and reduces fractures. Short-term studies show that it is safe, but long-term safety is not known.
• Estrogen/progestin therapy. Such hormone therapy was once widely prescribed to improve bone health, but because studies found that long-term use increases the risk of breast cancer, blood clots, and strokes, it is now recommended as an option only for women who are at high risk for fractures but cannot take other drugs, according to a 2017 review by the Cochrane Collaboration. A 2016 Swiss study found that women undergoing hormone therapy for menopausal symptoms had improvements not only in BMD but also in bone structure, and these effects persisted at least two years after treatment stopped.
• Teriparatide (Forteo). Approved for the treatment of osteoporosis, this parathyroid hormone stimulates bone formation. It comes as a self-administered daily injection and is approved only for two-year use. Side effects include leg cramps, nausea, and dizziness. It is expensive.
• Denosumab (Prolia). Approved only for the treatment of osteoporosis, this human monoclonal antibody inhibits bone loss. It is injected once every six months. It may be an option for women who haven’t responded to bisphosphonates or can’t tolerate them, though it is expensive.
• Calcitonin (Fortical, Miacalcin). Approved only for the treatment of osteoporosis, this is a hormone involved in calcium regulation and bone metabolism. It is given as a nasal spray or injection. Side effects include serious allergic reactions (anaphylaxis), nasal irritation (for the nasal spray), headache, flushing of the hands and face, and urinary frequency. Because of its side effects, its limited evidence of efficacy, and its high cost, many experts no longer recommend it, and it has been removed from the market in Canada and Europe, according to the Medical Letter.
• Testosterone. For older men with low testosterone levels, treatment with testosterone gel increases BMD and estimated bone strength, according to a large clinical trial in JAMA Internal Medicinein 2017. Because relatively few of the men in this study had osteopenia or osteoporosis, and because the balance of benefits and risks of testosterone therapy remains uncertain, it should be considered only by men who are at high risk for fractures but cannot take other drugs.
Worries about bisphosphonates
Many people may fear taking bisphosphonates because they’ve heard about two potential serious adverse effects: osteonecrosis of the jaw and atypical fractures.
Osteonecrosis (meaning bone death) of the jaw is characterized by pain, swelling, infection, loose teeth, and exposed bone inside the mouth. The condition is irreversible. Most cases have been reported in people with cancer who receive high doses of intravenous bisphosphonates for the prevention of skeletal complications of cancer.
Most research finds that this side effect is rare, occurring in fewer than one per 1,000 users per year. The risk seems to increase when oral bisphosphonates are taken for more than three to five years and when oral health is poor. Before starting drug therapy, you should have a thorough dental exam, along with any major dental work (especially implants and extractions) you require. If you are already taking bisphosphonates, be sure to tell your dentist before any procedure. Some dentists advise stopping the drug before undergoing dental surgery, though bisphosphonates remain in the body a long time, so it may not help to interrupt treatment.
Bisphosphonates are also associated with increased risk of atypical factures of the thigh bone (femur), though this is also rare and more likely with long-term use (more than five years).