Medications for Osteoporosis

Osteoporosis is a disease of low bone strength that increases the risk of fractures occurring with little or no trauma. Fractures may result in pain, disability, loss of independence, and sometimes death. Osteoporosis is caused by an imbalance in the activity of osteoclasts (cells that dissolve, or resorb, bone) and osteoblasts (cells that form new bone). When old bone is being dissolved faster than new bone is being formed, osteoporosis may be the ultimate result. We are fortunate to have medications that can restore the balance of bone resorption and formation, causing bone density to stabilize or increase, making bones stronger and less likely to break. Medications that primarily reduce bone resorption are called antiresorptives, and those that primarily increase bone formation are called osteo-anabolic.

The effectiveness and safety of medications for the treatment of osteoporosis are evaluated through clinical trials conducted at research facilities such as New Mexico Clinical Research & Osteoporosis Center. Medications are approved when there is strong evidence that the benefit of treatment outweighs the potential risk of side effects. This is a summary of current treatment options, their benefits and potential risks. For more detailed information, read the package insert that comes with each medication, and discuss your expectations and concerns with your healthcare provider.

All patients with osteoporosis should take care to have an adequate daily intake of calcium (at least 1200 mg per day with diet plus supplements, if needed) and vitamin D (at least 800-1000 IU per day, with many patients needing more). Regular physical activity, avoidance of smoking, and moderation of alcohol intake is recommended as well. When medication is prescribed, it must be taken regularly and correctly in order to achieve the desired effect of reducing fracture risk.

Bisphosphonates
Oral: alendronate (generic, Fosamax), risedronate (Actonel, Atelvia), ibandronate (Boniva); Intravenous (IV): ibandronate (Boniva), zoledronate (Reclast)

Bisphosphonates are antiresorptive synthetic compounds similar to pyrophosphate, a naturally occurring substance that regulates mineralization of bone and soft tissue. In 1995, alendronate became the first bisphosphonate approved for the treatment of osteoporosis. Since then, others have come along, with a trend toward longer intervals between doses and more recently the use of IV preparations. When taken by mouth, these drugs are very poorly absorbed, with less than 1% of the medication ending up in the bloodstream. For this reason, they must be taken with a glass of plain water on a totally empty stomach when first arising in the morning; no other liquid, food, or pills should be taken for at least 30 minutes after Fosamax and Actonel or 60 minutes after Boniva. If any food or drink gets into the stomach too soon after taking the pill, it will not be absorbed and will not work. Atelvia is a sustained release form of Actonel that is taken immediately after breakfast. To minimize the risk of the pill irritating the stomach or esophagus, it is recommended that you remain upright for the 30-60 minutes as well. Liquid Fosamax is available for those who cannot swallow pills. Oral bisphosphonates are available in doses that are taken daily (Fosamax, Actonel), weekly (Fosamax, Actonel, Atelvia), or monthly (Boniva, Actonel), while IV bisphosphonates are given every 3 months (Boniva) or every 12 months (Reclast). IV bisphosphonates are typically used when oral bisphosphonates cannot be used due to side effects, malabsorption, or poor response to therapy.

Oral bisphosphonates should not be taken by anyone with a blockage or ulceration in the esophagus. Bisphosphonates are not recommended for anyone with severe kidney disease. The most common side effect with oral bisphosphonates is upset stomach or heartburn. With IV bisphosphonates, the most common side effects are flu-like symptoms that occur in about 15-20% of patients not previously exposed to bisphosphonates who have received the first dose of an IV bisphosphonate. When this occurs, the symptoms are usually mild and self-limited, with resolution in several days. There have been reports of very rare occurrences of osteonecrosis of the jaw, atypical femur fractures, and chronic musculoskeletal pain in patients taking bisphosphonates for osteoporosis. Bisphosphonates are retained in bone for a long time, so that after taking them for 5-10 years, if the risk of fracture is no longer high, sometimes a “drug holiday” of about 1 year is considered. The medication that remains in the bone after stopping medication will continue to work for a while; however, sooner or later, the effect will wear off and treatment must be restarted.

Denosumab (Prolia)

Prolia is an antiresorptive medication that is given as a subcutaneous injection by a healthcare professional once every 6 months. It is most often used in patients who are unable to take an oral bisphosphonate due to side effects, malabsorption, or poor response to therapy.

Prolia is generally well tolerated with few side effects. There have been reports of a slightly increased risk of eczema and skin infections in patients taking Prolia.

Teriparatide (Forteo)

Forteo is an osteo-analbolic medication that is composed of a portion of a naturally occurring hormone molecule called PTH (parathyroid hormone). It is the only approved medication that is able to form new bone where bone has been lost. It is given as a daily self-administered subcutaneous injection into the thigh or abdominal wall with a “pen,” similar to the ones used by diabetics use to inject insulin. It should not be used for longer than 2 years in a lifetime. Forteo is used to treat patients at very high risk for fracture.

IIn large doses, Forteo has caused osteosarcoma (bone cancer) in rats. Although this is not known to be a problem in humans treated for 2 years or less with relatively lower doses, it is not recommended for patients at high risk for osteosarcoma, such as those with Paget’s disease of bone, unexplained elevation of a blood test called alkaline phosphatase, bone cancer of any type or cancer that has spread to the bones, open epiphyses or prior radiation therapy to the skeleton.

Salmon Calcitonin (Miacalcin Nasal Spray, Fortical Nasal Spray)

This antiresorptive medication is given as a daily nasal spray that is approved for the treatment of postmenopausal osteoporosis in women more than five years postmenopausal. It is given as one spray in the nose each day, alternating nostrils. Salmon calcitonin does not interact with other medications, and can be taken lying down with disregard to meals. It is the weakest of all available treatments for osteoporosis, but has been shown to reduce the risk of vertebral fractures in a large clinical trial. It may have a pain relieving effect in patients with recent painful vertebral fractures.

Some people develop mild irritation of the nose or nose bleeding when taking calcitonin nasal spray.

Raloxifene (Evista)

Raloxifene is an antiresorptive medication classified as a selective estrogen receptor modulator (SERM), also called an estrogen agonist/antagonist. It is not a hormone, but it does some of the good things that estrogen does, without some of the bad things. Evista is taken as a daily pill at any time of day, with or without food. It reduces the risk of estrogen receptor positive invasive breast cancer, making it an attractive consideration for women at high risk for breast cancer.

Evista increases the risk of blood clots similar to what is seen with taking estrogen or birth control pills, and may cause a small increase in the chance of fatal strokes in women at high risk for cardiovascular disease. It should not be taken by women with a history of blood clots or high risk of stroke. It may cause hot flashes or leg cramps.

Estrogen (many brands)

Estrogen is antiresorptive medication that is approved for the prevention, but not treatment, of postmenopausal osteoporosis. It comes in many forms, combinations, and brands. It should not be taken by women with a history of breast cancer, uterus cancer, or ovarian cancer, or by women with a history of blood clots, unless specifically approved by your doctor. While estrogen can stabilize or increase bone density and reduce fracture risk in postmenopausal women, its use in the management of osteoporosis has been limited due to concern over possible side effects. Estrogen is the best treatment for menopausal symptoms and may be helpful for some patients with osteoporosis. For most women with osteoporosis, other treatments are probably more effective with less risk.

A study called the Women’s Health Initiative (WHI) showed that a combination of estrogen and progesterone increased the risk of heart attacks, strokes, breast cancer, and blood clots. Another arm of the same study showed that estrogen alone reduced increased the risk of strokes. For these reasons, estrogen alone or in combination with progesterone is not recommended as a primary treatment of osteoporosis.