The first line treatment for osteoporosis is a class of drugs known as bisphosphonates. Bisphosphonates inhibit the action of osteoclasts, the cells that destroy bone. The bisphosphonates that are approved for the treatment of osteoporosis and low bone density are alendronate (Fosamax), risedronate (Actonel), ibandronate (Boniva), and zoledronic acid (Reclast). Alendronate and risedronate are oral medications. Ibandronate is available orally or as an injection while zoledronic acid is an injection-only medication.
Bisphosphonates are used for both prevention and treatment of osteoporosis, whether the disease occurs as a consequence of menopause or long-term steroid use. Alendronate and risedronate have been approved to treat osteoporosis in men and the others may be used "off label."
Selective estrogen receptor modulators or SERMs are drugs that can either stimulate or block the effects of estrogen, depending on the location of the estrogen receptor in the body. In bone, SERMs work like estrogen, by increasing the density of bone. The FDA has approved the selective estrogen receptor modulator, raloxifene (Evista), for the treatment of postmenopausal osteoporosis. The medication has been shown to increase bone density and decrease the incidence of spine fractures. Because it can affect estrogen receptors, this class of drugs is not used in premenopausal women. Scientists suspect SERMs increase the risk of blood clots, although evidence is unclear.
In addition to being a hormone, calcitonin can be given as a medication. Prescription calcitonin is available as an injection or a nasal spray. It is not a first line osteoporosis treatment because it has only been shown to reduce the risk of fractures in the spine but not in other bones. Also, calcitonin takes an average of five years to show a clinical benefit. Side effects of calcitonin include nausea, vomiting, and dry mouth. It can also cause a decrease in calcium in the bloodstream.
Antacids are used for gastrointestinal issues, but that can have both positive and negative effects on bone health. Some contain calcium carbonate or other calcium compounds and double as a calcium supplement in addition to their heartburn-soothing abilities. Other contain magnesium or aluminum and long-term use can result in a reduction of calcium levels in the body.
Parathyroid hormone is another naturally occurring hormone that is involved in how bone is formed and maintained. Teriparatide (Forteo) is an osteoporosis medication that is synthetic parathyroid hormone. Available in once-a-day injection form, this drug is usually self-administered by the patient or a home health care worker. Teriparatide is approved for postmenopausal women and men for the treatment of osteoporosis. It can increase bone mass density and reduce the risk of fractures; however it needs to be used for an average of 18 months to achieve optimal results.
In a sense, teriparatide works in a manner opposite to that of the bisphosphonates; it increases bone formation while bisphosphonates decrease bone resorption to the blood stream. Scientists had the idea that using them together would work better than either one alone. However, several trials found that a regimen of teriparatide plus alendonate did no better than teriparatide alone. More on osteoanabolics.
Teriparatide is very expensive and requires refrigeration, making it more difficult to manage and administer than bisphosphonates. Teriparatide is now recognized as the preferred treatment for glucocorticoid-induced osteoporosis. An experiment even attached a PTH molecule to a bisphosphonate and showed this was a method for getting the PTH into the bone tissue.
A new osteoporosis medication is denosumab, a monoclonal antibody that binds to the RANKL receptor. This medicine is sold under the names Prolia and Xgeva. This antibody binds to a receptor in cells that develop into osteoclasts, and prevents that development. With fewer osteoclasts, the natural bone desorption is slowed. In 2011 the FDA expanded the list of indications for denosumab, allowing it to be used for bone loss associated with breast cancer and prostate cancer treatment. In November 2012 Health Canada sent an alert sent an alert about denosumab being associated with small fractures in some users. Less than one in 10,000 users appear to get these fractures.
Odanacatib was an osteoporosis drug that worked by blocking the cathepsin-K enzyme in osteoclasts. There were very high hopes for it in the pharmaceutical market, and the developed, Merck, took it all the way to Phase III trials. But testing indicated an unacceptable risk of strokes. Odanacatib was never sold and further development on it was stopped.
|Drug Class||Generic Name||Brand Name||Dose/Route||Side Effects|
70 mg orally each week OR 10 mg orally each day
35 mg orally each week OR 5 mg orally each day
|Risedronate||Actonel||Treatment or prevention in women:
5 mg orally each day OR
35 mg orally each week OR
150 mg orally each month
Treatment in men:
35 mg orally each week
|Ibandronate||Boniva||150 mg orally each month OR
2.5 mg orally each day OR
3 mg intravenously every three months
|GI effects orally,
Rarely a kidney reaction
|Zoledronic acid||Reclast||5 mg intravenously once a year||When taken with some other treatments may cause bone loss in the jaw|
|SERMs||Raloxifene||Evista||60 mg orally each day||May increase the risk for blood clots, may lead to liver problems|
|Calcitonin||Calcitonin||Miacalcin, Calcimar, Cibacalcin||One puff once a day in alternating nostrils OR
One injection every other day
|Nasal administration can cause irritation in the nose,
Low blood calcium
|Parathyroid Hormone||Teriparatide||Forteo||20 microgram injection each day||Dizziness,
high blood calcium
Drugs work only if patients take them and getting patients to comply with their doctors’ instructions is a challenge for all sorts of drugs. One reason many pills are designed to be taken once a day is that this regimen is easy to remember. Osteoporosis drugs may see low adherence because of the odd schedule (once a week for some bisphosphonates), discomfort after swallowing the pill, and concerns about side effects.
German researchers report that adherence with bisphosphonates falls to "30-60% within 1 year". (http://www.ncbi.nlm.nih.gov/pubmed/20964548) A survey of raloxifene patients found similar numbers.
Some public health officials actually recommend zoledronic acid.over SERMs or alendronate because it can be administered once a year as an infusion.
Scientists at the University of Wisconsin-Madison http://www.ncbi.nlm.nih.gov/pubmed/15760582 looked at published research and clinical results and found that a regimen that added two antiresorbtion agents –the example used was estrogen plus bisphosphonates – resulted in higher gains in bone density than either one agent alone. The risk of using two antiresorbtion drugs is that bone turnover is reduced too much and can result in lower overall bone quality (despite the increase in density). They also found that a combination of an anabolic agent (teriparatide) with a conventional bisphosphonate doesn’t seem to help at all. They concluded that combination therapy for osteoporosis in general is not worth the cost and risk of adverse side effects.
A large meta-analysis by experts in 2003 looked at a bunch of potential combinations. They also concluded there was insufficient evidence to recommend combination therapy for osteoporosis.
See also our page on personalized treatment.
Other Bone Diseases: