Osteoporosis medications: what they do and what the risks actually are

Osteoporosis medications are among the most effective treatments in preventive medicine. They reduce fracture risk by 40 to 70% at the spine and 20 to 40% at the hip. Their safety profile is well established across decades of use and millions of patients. And yet fewer than a third of Australians who fracture receive treatment afterwards.

The main reason is fear. Fear of side effects, particularly osteonecrosis of the jaw (ONJ) and atypical femoral fractures. That fear is understandable, but it's based on a misunderstanding. The rates of these complications at osteoporosis treatment doses are vastly different from the rates seen in cancer treatment, where much higher doses are used. Most patients never learn that distinction.

This article explains how the main osteoporosis medications work, what the actual evidence says about their risks, and why for most people the risk of not treating is far greater than the risk of treatment.

How osteoporosis medications work

Bone is constantly being remodelled. Cells called osteoclasts break down old bone, and cells called osteoblasts build new bone. In osteoporosis, breakdown outpaces rebuilding. Medications address this imbalance in one of two ways.

Antiresorptive medications slow down the cells that break bone. This allows existing bone-building to catch up, stabilising or increasing density over time. Bisphosphonates and denosumab both work this way.

Anabolic medications stimulate the cells that build new bone. These are newer, typically reserved for people at very high fracture risk, and produce larger gains in bone density. These are typically reserved for people at very high fracture risk.

Both approaches reduce fractures. The choice depends on your individual situation: your fracture risk, your bone density, whether you have already fractured, and your other medical conditions.

Bisphosphonates

Bisphosphonates are the most widely used and longest-studied class of osteoporosis medication. They bind to bone surfaces and are absorbed by osteoclasts (the bone-removing cells), which disrupts those cells and slows bone breakdown. In practical terms, they act as a protective shield on the bone surface.

There are oral options (taken weekly or monthly) and an intravenous option (given as an infusion once a year). All are PBS-listed and can be prescribed by your GP.

Fracture reduction

The evidence for bisphosphonates is strong. Landmark trials have shown:

In patients who had already had a hip fracture, annual IV bisphosphonate reduced the risk of another fracture by 35% and, notably, reduced mortality by 28%.

Duration and drug holidays

Oral bisphosphonates are typically reviewed after 5 years of use, and the IV form after 3 years (three annual infusions). At that point, your GP and specialist will assess whether a "drug holiday" is appropriate. Bisphosphonates bind to bone and remain active for years after you stop taking them, so the protective effect doesn't disappear immediately.

Drug holidays are reasonable for people at moderate fracture risk. For people at high or very high risk, continued treatment is usually recommended. Your bone density and fracture risk are reassessed during the holiday, and treatment can be restarted if needed.

Common side effects

Oral bisphosphonates can cause upper GI symptoms: heartburn, reflux, or nausea. These are largely avoidable with correct dosing: take the tablet first thing in the morning on an empty stomach, with a full glass of water, and stay upright for 30 minutes afterwards.

The IV form can cause a flu-like reaction (fever, muscle aches, bone pain) after the first infusion, affecting up to 30% of patients. This is usually mild, settles within 1 to 3 days, and is much less common with subsequent infusions. Paracetamol before and after the infusion helps.

Denosumab

Denosumab is a targeted injection given every 6 months. It blocks a protein called RANKL, which is the signal that activates osteoclasts. Without that signal, bone breakdown slows dramatically.

Fracture reduction

The FREEDOM trial followed nearly 8,000 women over 3 years. Denosumab reduced vertebral fractures by 68%, hip fractures by 40%, and non-vertebral fractures by 20%. Long-term extension data out to 10 years showed fracture rates remained low and bone density continued to increase.

The important difference: you cannot just stop

Unlike bisphosphonates, which bind to bone for years, denosumab's effect wears off within about 6 months of the last injection. When it wears off, bone turnover doesn't just return to where it was before treatment. It rebounds above pre-treatment levels. This can lead to rapid bone loss and, in some patients, multiple vertebral fractures.

This means denosumab is a commitment. If you and your doctor decide to stop it, there must be a planned transition to an alternative medication (typically a bisphosphonate) timed to coincide with when your next injection would have been due. Denosumab should never be stopped without a transition plan in place.

This isn't a reason to avoid denosumab. It's an effective, well-tolerated medication. It just requires understanding upfront that it's not a "try it and see" treatment.

Bone-building medications

For patients at very high fracture risk, there are newer medications that actively build new bone rather than just slowing breakdown. These are called anabolic agents, and they represent the most significant advance in osteoporosis treatment in the past decade.

One works by stimulating bone-building cells directly, typically for 18 months. The other has a dual action: it increases bone formation and decreases bone breakdown simultaneously, given for 12 months. Both produce larger gains in bone density than antiresorptive medications alone.

In head-to-head trials, patients who received a bone-building medication first, followed by an antiresorptive, had substantially fewer fractures than those who started with an antiresorptive alone. The results included a 48% reduction in vertebral fractures and a 38% reduction in hip fractures compared with an active comparator (not placebo).

After completing a course of anabolic treatment, you transition to an antiresorptive medication to maintain the gains. This sequential approach (build first, then protect) is now the recommended strategy for people at highest risk.

ONJ and atypical fractures: the fear vs the reality

These are the two side effects that drive the most fear and the most treatment refusal. Both are real. Both are serious when they occur. And both are extremely rare at the doses used for osteoporosis.

Osteonecrosis of the jaw (ONJ)

ONJ is a condition where a small area of jawbone loses its blood supply and doesn't heal properly, usually after a dental procedure like a tooth extraction. It occurs most commonly in cancer patients receiving high-dose bone-targeting medications at frequent intervals (monthly or more often).

The incidence of ONJ in cancer patients receiving high-dose treatment is 1% to 15%. In patients receiving the much lower doses used for osteoporosis, the incidence is estimated at 1 in 10,000 to 1 in 100,000 per year. Over 90% of ONJ cases occur in the cancer treatment population.

For context: the dose of IV bisphosphonate used in cancer treatment is typically given monthly. The dose used for osteoporosis is given once a year. These are fundamentally different treatment regimens, and the risk profiles are not comparable.

Atypical femoral fractures (AFF)

Atypical femoral fractures are unusual breaks in the thighbone that can occur with prolonged antiresorptive use. The risk increases with duration of treatment, which is one reason why drug holidays are considered after 3 to 5 years. The estimated incidence is approximately 3 to 50 per 100,000 person-years of bisphosphonate use. The risk declines after stopping treatment.

Risk factors include treatment duration beyond 4 years, certain co-existing conditions, and glucocorticoid use. If you develop thigh or groin pain while on treatment, mention it to your GP, as this can occasionally be a warning sign.

What about dental work?

In March 2026, Healthy Bones Australia, the Australian Dental Association, and several specialist societies released an updated consensus statement on dental procedures and bone medication. The key points: routine dental care (fillings, cleaning, check-ups) is safe. A dental assessment before starting bone medication is ideal. For higher-risk procedures like extractions or implants, your dentist and GP can assess your individual risk together. Only a small group of patients fall into a higher-risk category, and they can be managed once identified.

The take-home message: being on bone medication does not mean you can't have dental work. It means your dentist should know about your medication, and for more invasive procedures, a brief risk assessment is sensible.

The treatment gap

Despite strong evidence, fewer than one-third of Australians who have a minimal trauma fracture receive bone medication afterwards. Of those who start treatment, only about 75% are still taking it at one year, and 45% at five years.

The consequences are real. Mortality in the first year after a hip fracture is up to three times higher than in people of the same age who haven't fractured. The risk of another fracture is highest in the first two years after the first one. Starting treatment in those early months is when it makes the biggest difference.

The most common reasons people don't start or don't continue medication are: fear of side effects (often based on the cancer-dose confusion described above), feeling well (osteoporosis has no symptoms until a fracture), not understanding their own risk, and the complexity of oral dosing instructions.

If you've been prescribed bone medication and you're hesitant, the most useful thing you can do is talk to your GP about the specific numbers for your situation. Understanding your actual fracture risk alongside the actual incidence of side effects usually changes the picture considerably.

Exercise and medication: better together

Medication and exercise are not competing strategies. They are complementary. Medication addresses bone density directly through pharmacology. Exercise also builds bone density (as the LIFTMOR trial demonstrated), and it reduces falls risk, builds muscle strength, improves balance, and supports quality of life. Combining both provides protection that neither achieves alone.

An Australian trial (MEDEX-OP) found that combining high-intensity resistance training with antiresorptive medication produced greater improvements in hip bone density and bone geometry than exercise alone. Further research is underway testing the combination of bone-building medication with targeted exercise.

Regardless of which medication you're on, exercise should be part of your plan. An exercise physiologist with experience in bone health can design a safe, supervised programme alongside your medical treatment.

Clinical information in this article is informed by the 2024 RACGP/Healthy Bones Australia guideline, the HBA position statement on osteoporosis management (2025), the FIT, HORIZON, FREEDOM, ARCH, and FRAME trials, the ECTS position statement on denosumab discontinuation (Tsourdi et al. 2021), and the HBA/ANZBMS/ADA consensus statement on dental procedures and bone medication (2026). This is general information only. Your GP can advise on what is relevant for your individual situation.

Written by

Dr David Nguyen

MBBS · FRACGP

Medication adherence is one of the biggest challenges I see in osteoporosis management. I wrote this guide because the evidence is clear, the treatments work, and the fears that keep people from taking them are almost always based on a misunderstanding of the actual risk.

Learn more about Dr David Nguyen → First published: 3 June 2026 · Last reviewed: 3 June 2026