Medications that prevent bone loss and breakdown
Currently, the most effective medications for osteoporosis that are approved by the FDA are antiresorptive agents, which decrease the removal of calcium from bones. The bone is a living dynamic structure; it is constantly being built and removed (resorbed). This process is an essential part of maintaining the normal calcium level in the blood and serves to repair tiny cracks in the bones that occur with normal daily activity and to remodel bone based on the physical stresses placed on the bone. Osteoporosis results when the rate of bone resorption exceeds the rate of bone rebuilding. Antiresorptive medications inhibit removal of bone (resorption), thus tipping the balance in favor of bone rebuilding and increasing bone density. HRT is one example of an antiresorptive agent. Others include alendronate (Fosamax), risedronate (Actonel), raloxifene (Evista), ibandronate (Boniva), calcitonin (Calcimar), zoledronate (Reclast), and denosumab (Prolia).
Bisphosphonates decrease the risk of hip fracture, wrist fracture, and spine fracture in people with osteoporosis and can improve the T-score. Alendronate (Fosamax), risedronate (Actonel, Atelvia), ibandronate (Boniva), and zoledronate (Reclast) are bisphosphonates.
To reduce side effects and to enhance absorption of the medicine, all bisphosphonates taken by mouth (orally) should be taken in the morning, on an empty stomach, 30 minutes before breakfast, and with at least 8 ounces (240 ml) of water (not juice). This improves the absorption of the bisphosphonate. Taking the pill sitting or standing (as well as drinking adequate amounts of liquids) minimizes the chances of the pill being lodged in the esophagus, where it can cause ulceration and scarring. Patients should also remain upright for at least 30 minutes after taking the pill to avoid reflux of the pill into the esophagus. Newer intravenous bisphosphonates, such as ibandronate (Boniva) and zoledronate (Reclast), bypass the potential esophagus and stomach problems.
Food, calcium, iron supplements, vitamins with minerals, or antacids containing calcium, magnesium, or aluminum can reduce the absorption of oral bisphosphonates, thereby resulting in loss of effectiveness. Therefore, oral bisphosphonates should be taken with plain water only in the morning before breakfast. Also, no food or drink should be taken for at least 30 minutes afterward.
Alendronate (Fosamax) is a bisphosphonate antiresorptive medication. Alendronate is approved for the prevention and treatment of postmenopausal osteoporosis as well as for osteoporosis that is caused by cortisone-related medications (glucocorticoid-induced osteoporosis). Alendronate has been shown to increase bone density and reduce fractures in the spine, hips, and arms. Fosamax is taken by mouth once a week to prevent and treat postmenopausal osteoporosis. Alendronate is the first osteoporosis medication also approved for increasing bone density in men with osteoporosis, either in a daily or a weekly dosing schedule.
Fosamax generally is well tolerated with few side effects. One side effect of alendronate is irritation of the esophagus (the food pipe connecting the mouth to the stomach). Inflammation of the esophagus (esophagitis) and ulcers of the esophagus have been reported infrequently with alendronate use.
Risedronate (Actonel, Atelvia) is another bisphosphonate antiresorptive medication. Like alendronate, this drug is approved for the prevention and treatment of postmenopausal osteoporosis as well as for osteoporosis that is caused by cortisone-related medications (glucocorticoid-induced osteoporosis). Risedronate is chemically different from alendronate and has less likelihood of causing esophageal irritation. Risedronate also is more potent in preventing the resorption of bone than alendronate.
Ibandronate (Boniva) is a bisphosphonate for prevention and treatment of postmenopausal osteoporosis. It is available in formulations for both daily and monthly oral use as well as for intravenous use every three months.
Zoledronate (Reclast) is a unique intravenous bisphosphonate antiresorptive medication that is given once every year. This formulation seems to have very good ability to strengthen bones and prevent fractures of both spinal and nonspinal bones. The convenience of once-a-year dosing is obvious. As with all bisphosphonates, patients taking Reclast must be taking adequate calcium and vitamin D prior to and after infusion of the medication for optimal results. Generally, patients are given acetaminophen (Tylenol) the day of the infusion and for several days afterward to prevent occasional minor muscle and joint aches. The infusion lasts approximately 20-30 minutes. Reclast is used to treat and prevent osteoporosis in postmenopausal women and increases bone mass in men with osteoporosis. Reclast is also used to treat and prevent steroid-induced osteoporosis (glucocorticoid-induced osteoporosis). Reclast reduces risk of fractures after a low-trauma hip fracture. Reclast should not be used in patients who have had avascular necrosis or during/prior to pregnancy.
Selective estrogen receptor modulators (SERMs)
Raloxifene (Evista) belongs to a class of drugs called selective estrogen receptor modulators (SERMs). SERMs work like estrogen in some tissues but as an antiestrogen in other tissues. The SERMs were developed to reap the benefits of estrogen while avoiding the potential side effects of estrogen. Thus, raloxifene can act like estrogen on bone but as an antiestrogen on the lining of the uterus where the effects of estrogen can promote cancer.
The first SERM to reach the market was tamoxifen (Nolvadex), which blocks the stimulative effect of estrogen on breast tissue. Tamoxifen has proven valuable in women who have had cancer in one breast for preventing cancer in the second breast. Raloxifene is the second SERM to be approved by the FDA. Evista has been approved for the prevention and treatment of osteoporosis in postmenopausal women. In a three-year study involving some 600 postmenopausal women, raloxifene was found to increase bone density (and lower LDL cholesterol) while having no detrimental effect on the uterine lining (which means that it is unlikely to cause uterine cancer).
Because of its antiestrogen effects, the most common side effects with Evista are hot flashes. Conversely, because of its estrogenic effects, Evista increases the risk of blood clots, including deep vein thrombosis (DVT) and pulmonary embolism (blood clots in the lung). The greatest increase in risk occurs during the first four months of use. Patients taking raloxifene should avoid prolonged periods of immobility during travel, when blood clots are more prone to occur. The risk of deep vein thrombosis with raloxifene is probably comparable to that of estrogen, about two to three times higher than the usual low rate of occurrence. Evista decreases the risk of spinal fractures in postmenopausal women with osteoporosis, but it is not known if there is a similar benefit in decreasing the risk of hip fracture. (The only agents that are definitely proven to decrease the risk of hip fracture are bisphosphonates and denosumab.)
Calcitonin (Calcimar, Miacalcin)
Calcitonin (Calcimar, Miacalcin) is a hormone that has been approved by the FDA in the U.S. for treating osteoporosis. Calcitonins come from several animal species, but salmon calcitonin is the one most widely used. Calcitonin can be administered as a shot under the skin (subcutaneously), into the muscle (intramuscularly), or inhaled nasally (intranasally). Intranasal calcitonin is the most convenient of the three methods of administration.
Calcitonin has been shown to prevent bone loss in postmenopausal women. In women with established osteoporosis, calcitonin has been shown to increase bone density and strength in the spine only.
Calcitonin is a weaker antiresorptive medication than bisphosphonates. Calcitonin is not as effective in increasing bone density and strengthening bone as estrogen and the other antiresorptive agents, particularly bisphosphonates. In addition, it is not as effective as bisphosphonates in reducing the risk of spinal fractures and has not been proven effective in reducing hip fracture risk. Therefore, calcitonin is not the first choice of treatment in women with established osteoporosis. Nevertheless, calcitonin is a helpful alternative treatment for patients who cannot tolerate other medications.
Common side effects of either injected or nasal spray calcitonin are nausea and flushing. Patients using Miacalcin Nasal Spray can develop nasal irritation, a runny nose, or nosebleeds. Injectable calcitonin can cause local skin redness at the site of injection, skin rash, and flushing.
Teriparatide (Forteo) is a synthetic version of the human hormone, parathyroid hormone, which helps to regulate calcium metabolism. Unlike other medications for osteoporosis that reduce the resorption of bone, teriparatide very effectively promotes the growth of new bone. Forteo is self-injected into the skin. Because long-term safety is not yet established, it is only FDA-approved for 24 months of use. It reduces spinal fractures in women with known osteoporosis, but it is not known if there is a similar reduction in the risk for hip fracture. Generally, after a two-year course of teriparatide the patient is switched to bisphosphonate therapy to maintain bone density.
The latest treatment approved for osteoporosis is denosumab (Prolia), an injectable antibody that blocks a chemical messenger that plays a role in promoting bone thinning by the bone cells that are responsible for bone resorption. Prolia strengthens bone by increasing its density and reduces fractures. Prolia is administered by twice yearly injections under the skin. Denosumab is used for the treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy. Denosumab can cause increased risk of infections and low blood calcium levels (hypocalcemia).