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An in-depth report on the causes, diagnosis, treatment, and prevention of osteoporosis.


Major drug therapies now exist for treating osteoporosis. Unfortunately, studies continue to report that physicians are failing to evaluate and treat both men and women adequately for this condition, even after a fracture. In a 2002 study of Caucasian women over 60, fewer than 2% were evaluated for osteoporosis or spinal fracture by their physicians. And among those who were diagnosed, only 36% received appropriate medication. Two studies in 2003 further reported that among adults who had sustained fractures, less than 5% of men and fewer than half of women were evaluated and treated according to recommended guidelines. In one of studies, only 24% of women were given treatments for osteoporosis after a fracture. In both studies, the older a woman was the less likely she was to have adequate evaluation or treatment.

Agents Used to Treatment Osteoporosis. The following are the two types of agents now available for treating osteoporosis.

  • Antiresorptive Agents. Antiresorptives include bisphosphonates, hormone replacement therapy, SERMs, and calcitonin. The bisphosphonates are the current standard drugs used for osteoporosis. These agents block resorption (bone break down) and so slow the rate of bone remodeling, but they cannot rebuild bone. In fact, because resorption and reformation occur naturally as a continuous process, blocking resorption may eventually also reduce bone formation.
  • Anabolic, or Bone-Forming, Agents. Agents that rebuild bone are known as anabolics. The primary anabolic agent is low-dose parathyroid hormone (PHT), which is administered as injections. It is proving to be very effective in restoring bone and preventing fractions. PHT is still relatively new and long-term effects are still unknown. Fluoride is another bone-building agent, but it has limitations and is not commonly used.

Both types of agents are effective in preventing bone loss and fractures, although they vary in their effectiveness and safety.

The anti-resorptive bisphosphonates are the current standard agents used for osteoporosis. The older agents, alendronate (Fosamax) and risedronate (Actonel), are proven to be safe and effective for up to 10 years. Some evidence suggests, however, that the anti-resorptive process employed by bisphosphonates eventually results in impaired bone formation--the body's bone-building process. Overtime, then bone density might decline.

Experts have hoped that a combination of anabolic agents, notably PHT, with a bisphosphonate will stabilize and perhaps increase bone mass. Unfortunately, two major studies reported that adding a bisphosphonate actually reduces the effectiveness of PHT. Some experts now believe that using the agents in sequence (for example taking PHT for a couple of years and switching to a bisphosphonate) may provide a solution.

Bone-Protective Drugs with Other Health Effects after Menopause



Parathyroid Hormone


Forms and Brands

Oral agents: Alendronate (Fosamax), risedronate (Actonel) ibandronate (Boniva). Injected agents (at this time in cancer patients only): pamidronate (Aredia), zoledronate (Zometa). Injected Zometa and Boniva under investigation for osteoporosis.

Raloxifene (Evista) is only SERM approved for osteoporosis. Others under investigation.

Teriparatide (Forteo).

Calcitonin available as nasal spray (Miacalcin) and injection (Calcimar).

Osteoporosis and Fracture

The first choice for most women. Best proven agents to date for preventing fractures, including hip and spine. Good option for people on corticosteroids and for men with osteoporosis.

Increase bone density; reduce spinal fractures after three years of use. Does not appear to prevent hip fractures and not as effective as bisphosphonates.

The only agent that actually stimulates bone growth. Lowers risk for fracture. May be good option for people with severe osteoporosis at high risk for fracture.

Appears to protect the spine, but not hips. Protection, if any, takes five years. May relieve bone pain associated with osteoporosis. Possible alternative for men or anyone who cannot take bisphosphonates or SERMS.


Injected agents may have anti-tumor properties. Some evidence suggests that it may slow metastasis to the bone in cancer patients.

Tamoxifen and raloxifene reduce breast cancer risk. Tamoxifen, but not raloxifene, increase risk for uterine cancer.

Animal studies report higher risk for bone tumors. Not known if this applies to people.


Heart Disease

No known effects.

Possible protection, according to a 2002 study, in women with existing heart disease.



Other Positive Effects

In patients with insulin-dependent diabetes, may reduce the need for insulin.

No vaginal bleeding. Fewer side effects than HRT or alendronate.



Other Negative Effects

Increased risk for heartburn and other gastric problems. Possible long-term risk for ulcers, particularly in combination with NSAIDs.

Increased risk in blood clots. Side effects include menopausal symptoms (hot flashes, leg cramps, etc). Swelling in the legs.

Must be injected.

Gastrointestinal effects (more with injected form). Sinus problems with inhaler. Allergic reactions fairly common.


The bisphosphonates are anti-resorptive agents; that is, they prevent bone breakdown. They are now the primary drugs against osteoporosis in postmenopausal women and in people taking corticosteroids or hormonal agents that suppress estrogen. They are proving to reduce the risk of both spinal and hip fractures, including in women who have had prior bone breaks.

Studies to date have reported that these drugs are effective and safe for at least 10 years. Eventually, however, bone loss progresses with bisphosphonates. This may be due to the fact that bone breakdown (resorption) is one of two phases in a continuous process of bone resorption and reformation. Over time, then, just blocking resorption will interrupt this process and impair the second half--bone build-up. Some experts are hoping that this problem may be overcome by building bone for a couple of years with parathyroid hormone (PHT) and then following this with bisphosphonates to prevent breakdown. (Administering the two agents simultaneously is not effective because the bisphosphonates interfere with PHT.)

Brands. A number of bisphosphonates in different forms are available or under investigation.

  • Oral bisphosphonates include alendronate (Fosamax), risedronate (Actonel), and ibandronate (Boniva). Studies suggest these agents reduce spinal and hip fracture in people with osteoporosis. They also prevent osteoporosis in people taking corticosteroids. All are taken orally and can taken daily. Fosamax and Actonel are also available in weekly doses. Boniva is taken daily but is being investigated in weekly doses.
  • Intravenous bisphosphonates, such as pamidronate (Aredia) and zoledronate (Zometa), are very powerful agents used to treat cancer patients. Zoledronate and injected forms of oral bisphosphonates, notably ibandronate (Boniva), are also showing promise for preventing bone loss in postmenopausal women. In one study, for example, ibandronate was administered every three months for a year. At the end of the study, bone density in the spine and hip was higher than those on placebo. An annual injection of zoledronate is being investigated. Presumably, injected form would have fewer gastrointestinal side effects. General aching is the most common reported side effect.

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

  • Women with a below-normal bone density of 2.5 SD or greater and who have no history of fractures should take bisphosphonates.
  • Women with below-normal bone density 1 SD or more and have a history of fractures should consider bisphosphonates.

Alendronate has also now been approved for men with osteoporosis. Both alendronate and risedronate are approved for both men and women who take corticosteroids.

Side Effects. The most distressing side effects are gastrointestinal problems, particularly stomach cramps and heartburn, which are very common, occurring in nearly half of patients. Patients should strictly adhere to instructions for taking the drug (although gastrointestinal problems may still occur).

  • It is generally recommended that alendronate and risedronate be taken on an empty stomach in the morning with 6 to 8 ounces of water (not juice or carbonated or mineral water).
  • The patient should remain upright and not eat for 30 minutes after taking the pill.
  • Anyone taking the drug who develops chest pain, heartburn, or difficulty swallowing should stop taking the drug and see the physician. (It should be noted, however, that patients who stop taking the drug because of GI symptoms may be able to safely resume taking a bisphosphonate.)

Long-Term Risk for Ulcers. Studies to date suggest that agents do not harm the upper GI tract (the esophagus and throat). Of concern, however, is the possibility for long-term injury to the lower gastrointestinal tract, including the development of stomach ulcers, particularly when people regularly take both bisphosphonates and NSAIDs, common pain relievers used for many conditions. NSAIDs include aspirin and ibuprofen (Motrin IB, Advil, Nuprin, Rufen), naproxen (Aleve), ketoprofen (Actron, Orudis KT). Long-term use of NSAIDs is known to increase the risk of ulcers, so both agents may have a double effect on the stomach lining. A 2002 study, in fact, reported a far higher risk for ulcers (38%) from taking both Fosamax and naproxen compared to either drug alone. (The risk for ulcers was 8% with Fosamax alone and 12% with naproxen alone.) It is not known yet if the risks for these adverse actions are as high with other combinations. For example, ibuprofen may have a lower risk for ulcers than naproxen, and Actonel may have fewer adverse effects on the stomach than Fosamax does. Because so many older people take NSAIDs, regularly clarifying these effects is very important.

SERMs and Other Designer Hormones

A number of drugs known as selective estrogen-receptor modulator (SERM) have been designed with the goal of producing the same benefits that estrogen has on the bones and cholesterol levels without increasing the risk for hormone-related cancers. Some studies have been performed with SERMs in men, but benefits to date are not strong. More studies are needed.


  • Raloxifene (Evista). Raloxifene (Evista) is the first SERM to be approved for preventing spinal fractures. (It does not appear to have any protective effect on other fractures, including those in the hip.) Raloxifene also appears to reduce the risk of breast cancer. A 2002 study further reported possible heart protection in women with existing heart disease, although the findings could have been due to chance. Longer studies are needed on possible risks and benefits. Raloxifene does not effect ovulation and may be an option for women at risk for osteoporosis who are still menstruating, but it should not be used in pregnant or breast-feeding women. Raloxifene also increases risk for deep vein thrombosis, in which clots form in the large veins of the legs. Such clots can travel to the lungs, causing an embolism that may lead to complications, including death. It also causes menopausal symptoms, which can be distressing.
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.
  • Tamoxifen (Nolvadex). Tamoxifen (Nolvadex) is the best-studied SERM. Low-dose tamoxifen may reduce the risk for fractures, but it has not been approved for this purpose. Tamoxifen has some beneficial effects on cholesterol levels (although not as strong as estrogens) and does not increase the risk of uterine or breast cancer, as estrogen does. Taking tamoxifen for five years may lower breast cancer risk, at least in high-risk women, although protective benefits after that appear to be weak. Tamoxifen, like estrogen, however, increases the risk for uterine cancer and blood clots.
  • Tibolone (Livial). Tibolone (Livial) is SERM-like but has different effects on estrogen. It is showing promise for improving bone mineral density, most effectively in the lower spine. It has minimal side effects and does not appear to pose any added risk for blood clots. Patient compliance in clinical trials has been high. At this time, it is used outside the US.
  • Investigative SERMs. Investigative SERMs showing promise for osteoporosis include ospemifene, lasofoxifene, and arzoxifene.

Common Side Effects. Most SERMs do not relieve menopausal symptoms, and some exacerbate them. It should be noted that any beneficial effects of the SERMs on the heart (as with estrogen) are still unclear. Long-term studies are also still needed to confirm or refute any effect on breast cancer for any of these agents. Because of the common risks for blood clots, anyone taking these agents should stop three days before any prolonged immobilization, such as long air flights or surgery.


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 in injected form (Calcimar). Calcitonin is not used to prevent osteoporosis; it is used to treat 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, because calcitonin is a protein, a large number of people taking the drug develop resistance or allergic reactions after long-term use.

Parathyroid Hormone (PTH)

Although high persistent levels of parathyroid hormone can cause osteoporosis, daily injections of low and intermittent doses of this hormone actually stimulate bone production and increase bone mineral density. Teriparatide (Forteo), an agent made from selected amino acids found in parathyroid hormone, has reduced the risk for spinal and non-spinal fractures by 50% to 65%. It may prove to be a very useful agent for men with osteoporosis. Unlike most treatments for osteoporosis, including bisphosphonates, the benefits may persist even after the injections have been stopped.

Although the treatment requires injections, experts believe that patients will get used to them, just as people with diabetes grow accustomed to insulin shots. Side effects are mild and include nausea, dizziness, and leg cramps. No significant complications have been reported to date.

Of concern are early studies reporting bone tumors in mice that were given parathyroid long-term. Such effects have not been observed in humans to date. (Of note in this regard, persons 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.)

Researchers are investigating a genetically designed parathyroid hormone (ALX1-11). Results to date are promising.

Hormone Replacement Therapy

Hormone replacement therapy (HRT) contains estrogen with or without progesterone and is available in many brands and forms. HRT increases bone density. It also appears to improve balance and protects against falling. However, evidence of higher risks for other serious health conditions, notably breast cancer and heart problems, now outweigh the bone-loss protection in most postmenopausal women.

It should be noted that women who stop taking HRT begin to lose bone density, and after five years all protection is lost. HRT. They must then seek alternative options, which, fortunately, are effective. In one study, although women experienced bone loss for the first year or so after they stopped taking HRT, switching to a bisphosphonate such as alendronate (Fosamax) increased or maintained both spinal and hip bone density.

Low doses of HRT or those that use different progestins might still help prevent bone breakdown and pose fewer health risks than the regimens used in previous studies. More work is needed in these areas. HRT may still be useful and probably safe for reducing menopausal symptoms because it is not taken for as long periods as it is for preventing heart disease or osteoporosis. [For more information,see Well-Connected Report #40 Menopause, Estrogen Loss, and Their Treatments.]

Other Investigative Medications

All of the following are drugs under investigation for osteoporosis:

  • Diuretics. Diuretics are used to treat high blood pressure. They have different effects on osteoporosis depending on the type, with loop diuretics associated with bone loss. Thiazide diuretics, on the other hand, confer protection against fracture, and may prove to be particularly useful for men at risk for osteoporosis. Protection against fracture lasts only during the time they are used. There are many thiazides and thiazide-related drugs; some common ones are chlorothiazide (Diuril), chlorthalidone (Hygroton), indapamide (Lozol), and hydrochlorothiazide (Esidrix, HydroDiuril).
  • Osteoprotegerin. Osteoprotegerin is a unique agent that prevents bone breakdown by regulating osteoclasts. It currently under investigation and showing promise in early trials. It may also be useful in conjunction with PTH, parathyroid hormone.
  • Male Hormones. There is some evidence that testosterone replacement therapy may be helpful for men with osteoporosis. Dehydroepiandrosterone is a weak male hormone that also may protect against osteoporosis. However, more studies are needed to confirm their benefits. These agents may lower levels of HDL (good cholesterol) and they may have adverse effects on the heart and pose a risk for certain cancers.
  • Strontium. Strontium, a chemical element found in bone, may help to increase bone formation and decrease bone resorption.

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