09/26/2011 07:49 pm ET | Updated Nov 26, 2011

Time to Bone Up on Osteoporosis Treatment Controversies

With federal regulators scrutinizing the safety and labeling of medications taken by as many as five million Americans for the health of their bones, it's a perfect time to talk about the prevalent condition for which doctors prescribe these drugs: osteoporosis.

This condition leaves people with low bone mass and increased bone fragility. It's the most common bone disease and the major cause of fractures of the spine, hips and forearms occurring with minimal trauma. It affects an estimated 10 million Americans; 33.6 million more people have low bone density or osteopenia.

Although osteoporosis primarily afflicts women after menopause, older men are not immune. Multiple lifestyle factors contribute to osteoporosis and fractures. These include low calcium intake; vitamin D insufficiency; high caffeine, salt, and alcohol intake; smoking; physical inactivity; and a thin body frame. Numerous diseases as well as a genetic predisposition also can lead to weakened bones.

Patients learn they're afflicted with osteopenia and osteoporosis when they suffer fractures or the condition may be detected through a bone mineral density test, recommended for those who have fractured a hip or spine, women older than 65 and men 70 or older.

For most people without osteoporotic fractures or a diagnosis via bone mineral density testing, bone health best can be sustained with: adequate calcium (at least 1,200 mg per day for individuals older than 50) and appropriate levels of vitamin D (800-1,000 units per day, unless there is an increased risk of vitamin D deficiency, in which case the daily requirement rises to 1,500-2,000 units per day). Physicians also recommend that those at risk do regular weight-bearing exercises and avoid smoking and drinking more than three alcoholic drinks per day.

For those who have suffered osteoporotic fractures or who have osteoporosis, doctors usually prescribe drugs. The available, FDA-approved medications for osteoporosis prevention or treatment include: bisphosphonates, calcitonin, estrogens, parathyroid hormone, raloxifene and denosumab.

Bisphosphonates are the most commonly prescribed medications. These include alendronate (Fosamax), risedronate (Actonel), ibandronate (Boniva), and zoledronic acid (Reclast).

These drugs reduce the breaking down of bone, allowing the right kinds of cells to lay down new bone. All bisphosphonates have been shown to increase bone mineral density and to decrease fractures of the spine and hips.

Medications Under Scrutiny

But these medications have drawn increasing criticism because of possible serious side effects. This led to an FDA advisory panel review of this class of drugs in September. Experts reviewed data on the medications' safety and effectiveness and recommended some label changes. They declined to limit their use. The major concerns that prompted the review included:

Instances of osteonecrosis (bone death) of the jaw: This rare problem primarily has been seen in patients receiving frequent, high doses of intravenous bisphosphonates for cancer involving bone. It crops up only in exceedingly rare cases in those taking oral bisphosphonates for osteoporosis; most reported cases involved patients who took the drugs for four or more years. The major predisposing factors for this problem are dental infections or major dental procedures. Many oral surgeons urge their patients to stop taking bisphosphonates for months before undergoing elective, major dental surgery.

Atypical hip fractures: These fractures occur with minimal or no trauma and have an unusual appearance on X-rays. Unfortunately, studies on this condition have used inconsistent definitions making it difficult to get an accurate picture of the risk. Although a strong association has been made between bisphosphonates use and atypical fractures, a cause-and- effect relationship remains unproven. The risk of this unusual fracture is minuscule compared with the numbers of hip fractures prevented by these drugs.

Esophageal cancer: Oral bisphosphonates can irritate the esophagus, which can lead to full-blown esophagitis and esophageal ulcers. This is why the directions say to take the pills first thing in the morning, with a full glass of water and while upright. A few cases of esophageal cancer have been noted in those taking these drugs, prompting concerns about the bisphosphonates' role. After extensive review, the FDA concluded that the "available evidence regarding the possible association between oral bisphosphonate and esophageal cancer is inconclusive."

Patients and physicians also have expressed concern about just how long bisphosphonates might be taken. Studies show continued increases in bone mineral-density for a decade or so of bisphosphonate use. Patients who stop taking these drugs after three to five years continue to show a slight increase in spine density and a slight decrease in the hips over the next three to five years. Data also indicate that the fracture-prevention benefit persists in patients taking bisphosphonates for 10 years. But some studies show a similar benefit occurs for up to five years after stopping the drugs following three to five years' use.

This has led more physicians to urge patients to go on "drug holidays" after taking bisphosphonates for four or five years; in patients with severe osteoporosis associated with fractures, many physicians continue to recommend they take the drugs for five to 10 years.

Alternative Therapies

As for other approaches, estrogens no longer are recommended as a first-line therapy for osteoporosis because of risks associated with the hormone's use and the availability of other effective medications.

Calcitonin (Miacalcin or Fortical), a hormone given as a nasal spray or by injection, is not as effective as the bisphosphonates.

Raloxifene (Evista) resembles estrogen as far as the bone is concerned, but has an anti-estrogen effect on the breast. It reduces the risk of spine fractures by about 30 percent in patients with a prior spinal fracture and over half in patients without vertebral fractures. It also has the advantage of reducing the risk of invasive breast cancer in postmenopausal women. Hot flashes and an increased risk of blood clots are the major side effects of this drug.

Parathyroid hormone (Forteo), given by daily injections, is a potent stimulator of new bone formation. It can be used for up to two years and is generally indicated for patients with established osteoporosis who have had or are at high risk for developing fractures.

The newest drug on the scene is denosumab (Prolia), which works very much like the bisphosphonates but through a different mechanism. The net result is that it turns off cells responsible for bone break down. It is indicated for postmenopausal osteoporosis and is given by injection every six months. In some studies, it promoted a greater increase in bone density than found with bisphosphonates. Its main side effects are gastrointestinal and musculoskeletal. A few cases of jaw bone death also have been noted in patients using this drug.

What's the bottom line, then? The best therapy is preventive. Be sure you're getting adequate amounts of calcium in your diet. Take care that you're generating enough vitamin D through sun exposure or by taking supplements. (Click here to see my prior blog on this topic.) And, of course, exercise. If you develop osteoporosis, your first line therapy may be a bisphosphonate or denosumab. As with all drugs, please discuss their pros and cons with your physician so you will be fully informed about the risks and benefits and what and how you need to monitor to optimize your bone density and strength.