How osteoporosis medicines work: an overview of the main classes

If a doctor has mentioned medicine for osteoporosis, the names alone can be bewildering, and the warnings you may have read online can be alarming. This overview explains in general terms how the main classes of osteoporosis medicines work, and what authoritative sources say about benefits and risks. It does not recommend any medicine, and it says nothing about whether you should start, stop or change anything. Those decisions belong to you and your own doctor or specialist. For the wider context, see our guide to osteoporosis and bone health.

Two ways medicines act on bone

Bone is constantly renewed through a cycle of breakdown and rebuilding. The Bone Health and Osteoporosis Foundation (BHOF) describes the cycle as two distinct stages, resorption and formation, and sorts osteoporosis medicines by which stage they affect.

Antiresorptive drugs work by slowing the breakdown part of the cycle. Anabolic drugs work by stimulating the formation part. That single distinction explains most of the differences in how the classes are used and described. The sections below follow the groups named by the BHOF, the U.S. National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and the Endocrine Society.

Bisphosphonates

Bisphosphonates are antiresorptives. NIAMS describes them as drugs that slow bone loss, which can lower fracture risk. The Endocrine Society says they slow the natural breakdown of bone, and also lists situations in which they are not recommended, such as for premenopausal women who may become pregnant and for people with severely impaired kidney function.

The same source mentions two uncommon concerns: osteonecrosis (damage) of the jaw bone, with the risk greatest after dental operations, and fractures through the shaft of the thigh bone with little or no trauma after long-term treatment. The next section on risks puts these in perspective.

Denosumab

Denosumab is an antiresorptive that works through a different pathway, a protein called RANK ligand. NIAMS groups it as a RANKL inhibitor that slows bone loss, and says it is approved for high-risk postmenopausal women or men, for men and women with bone loss from prostate or breast cancer treatment, and for those who do not respond to other treatments. The Endocrine Society says it is commonly used when other medicines cannot be tolerated or are not working well.

The Endocrine Society also notes that denosumab has been linked to jaw osteonecrosis and atypical thigh fractures, and links stopping treatment to multiple spinal fractures if treatment is discontinued. The BHOF notes that, unlike bisphosphonates, other drugs must be taken continuously, so planning any change with the prescribing clinician is an important part of treatment. This page cannot say what that plan should look like for anyone.

Anabolic agents

Anabolic medicines build new bone instead of only slowing loss. The BHOF names teriparatide (a parathyroid hormone analog), abaloparatide (a parathyroid hormone-related protein analog) and romosozumab (a sclerostin inhibitor) in this group. NIAMS says the parathyroid hormone analog increases bone mass, and the sclerostin inhibitor blocks a protein so that new bone formation increases and bone loss slows.

The Endocrine Society describes limits on how long some of these are used. Teriparatide and abaloparatide are described as limited to no more than two years, and romosozumab is given for twelve months, with another medicine typically following to maintain gains. It also states safety points: a rat bone cancer concern for the first two, and a warning that romosozumab may increase the risk of heart attack or stroke and should not be given to women who had one in the past year. The Endocrine Society says teriparatide is limited to severe osteoporosis, and NIAMS describes the parathyroid hormone-related protein analog as usually for postmenopausal women with severe osteoporosis and multiple fractures.

Hormone-related options

Several options in the hormone family exist, and they act differently from each other. Our guide to menopause and bone health covers the hormonal background.

• Estrogen and hormone therapy. NIAMS says it is approved to prevent osteoporosis and fractures in postmenopausal women, with researchers recommending the lowest dose for the shortest time when other medications are not helping. The Endocrine Society adds that risks, including heart attack, stroke, blood clots and breast cancer, may outweigh benefits in many older women depending on dose and preparation, and that estrogen therapy is not usually prescribed solely for fracture prevention.
• Raloxifene (a selective estrogen receptor modulator). NIAMS says it has estrogen-like effects on some tissues and estrogen-blocking effects on others. The Endocrine Society says it increases bone density and reduces spine fracture risk but has not been shown to reduce non-spinal fractures, with possible side effects including hot flashes, leg cramps and blood clots.
• Calcitonin. NIAMS describes it as made from a thyroid gland hormone and approved for postmenopausal women who cannot take or tolerate other osteoporosis medications.

Rare risks, as the sources describe them

Two risks draw most attention: atypical femur fractures, which are sudden fractures of the thigh bone, and osteonecrosis of the jaw, a non-healing area of exposed jawbone. The BHOF calls atypical femur fracture a rare side effect, linked to bisphosphonates and denosumab. For jaw osteonecrosis, it states that it is almost always seen in people treated with high doses of these medicines for cancer, and that at the doses used for osteoporosis, both atypical femur fracture and osteonecrosis of the jaw are very rare. It gives no specific percentage.

The BHOF also says good dental care is a reasonable precaution for anyone taking an antiresorptive medicine. Questions about new symptoms or planned dental work are worth raising with the prescribing clinician, since only they can judge what applies. Other medicines in this overview carry their own listed risks, as noted above, and NIAMS advises asking a doctor or pharmacist about the side effects of any specific medicine.

Why duration and drug holidays are clinician decisions

Osteoporosis treatment is usually long term, and how long depends on the drug and the person. The BHOF describes a drug holiday as a temporary break from bisphosphonate treatment, "like a vacation, not permanent, like retirement." It says many providers consider one after five years of treatment if bone density is stable and no fractures have occurred. It adds that only bisphosphonates remain in the body long enough for a holiday to work, that other drugs must be taken continuously, and that holidays must be closely monitored so treatment can restart if needed.

Notice how much depends on the individual drug, the individual patient and their level of fracture risk. Monitoring often involves repeat bone density scans, which are explained in the bone density test (DXA) explained. Nutrition and activity continue alongside any medicine, as described in calcium and vitamin D basics. It is a good idea to bring written questions to appointments, and questions to ask an endocrinologist offers a starting list.

The short version

Osteoporosis medicines either slow bone breakdown or stimulate bone formation, and each class comes with its own benefits, listed risks and conditions of use. The best-known rare risks, atypical thigh fractures and jaw problems, are described by the BHOF as very rare at osteoporosis doses. How long a medicine is used and whether a break is appropriate are individual decisions that sit with a clinician.