What are the effects of medicines used to prevent fractures in men?

Key messages

• It is unclear if medicines used to prevent bone loss (bisphosphonates) lower the risk of breaking a hip, backbone (spine), or other bones in men.

• These medicines probably do not cause more unwanted effects or serious health problems than dummy treatment (placebo) in men.

• Other medicines (parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) analogues, denosumab, and romosozumab) appear to show similar results, except we are very uncertain about the effects of PTH/PTHrP analogues on unwanted effects.

What is osteoporosis, and how is it related to fractures in men?

Bone loss (osteoporosis) is when bones become thin, fragile, and break (fracture) easily. Fractures commonly occur in the hip, backbone (spine), and other bones. These fractures often happen in older people after a fall from a standing height or less. Such fractures can lead to long-lasting pain, loss of independence, disability, and in some cases even death. Osteoporosis in men usually starts later in life and progresses more slowly than in women. Other risk factors for fractures such as balance, muscle strength, co-existing conditions, medications, and fall direction may also differ between men and women.

Doctors often use bone-strengthening medicines to help prevent fractures caused by minor falls or injuries. Common medicines include bisphosphonates (zoledronic acid, alendronate, risedronate, ibandronate), parathyroid hormone (PTH) or parathyroid hormone-related protein (PTHrP) analogues, denosumab, or romosozumab. Most research on these medicines has been done in women, especially after menopause. Much less is known about the effects of these treatments in men who are at risk of fracture.

What did we want to find out?

We wanted to find out if these medicines reduce fractures of the hip, spine, or other bones, and if they cause unwanted effects in men at risk of fracture.

What did we do?

We searched for studies where men at risk of fracture were given bisphosphonates, PTH/PTHrP analogues, denosumab, or romosozumab compared with dummy treatment (placebo) or other treatments. We compared and summarised the results of the studies and rated our confidence in the evidence based on factors such as study methods and sizes.

What did we find?

We found 17 studies (4132 participants). The average age of participants ranged from 52 to 73 years. Two studies were conducted in Germany, four in the USA, one in Turkey, one in Taiwan, and nine studies were multinational.

Main results

Compared with placebo, at up to two years:

• 0.1% less people had a hip fracture when taking bisphosphonates, but the evidence is very uncertain (4 studies, 1635 people):

  • 0.2% of people had a hip fracture with bisphosphonate;

  • 0.3% of people had a hip fracture with placebo.

• 0.4% less people had symptomatic spine fractures when taking bisphosphonates, but the evidence is very uncertain (5 studies, 1876 people):

  • 0.4% of people had a symptomatic spine fracture with bisphosphonate;

  • 0.8% of people had a symptomatic spine fracture with placebo.

• 0.5% less people had other (not hip or spine) fractures when taking bisphosphonates, but the evidence is very uncertain (6 studies, 2043 people):

  • 1.6% of people had other fractures with bisphosphonate;

  • 2.1% of people had other fractures with placebo.

Bisphosphonates probably do not increase the risk of unwanted effects. 4.2% more people experienced unwanted effects with bisphosphonates compared to those taking a placebo (7 studies, 2548 people):

• 74.6% of people experienced unwanted effects with bisphosphonate;

• 70.4% of people experienced unwanted effects with placebo.

1.2% less people withdrew from the study because of unwanted effects with bisphosphonate compared to those taking a placebo, but the evidence is very uncertain (7 studies, 2548 people):

• 2.5% of people withdrew from the study because of unwanted effects with bisphosphonate;

• 3.7% of people withdrew from the study because of unwanted effects with placebo.

Bisphosphonates probably do not increase the risk of serious unwanted effects (6 studies, 2457 people). 1.4% less people experienced serious unwanted events with bisphosphonates compared to those taking a placebo:

• 27.2% of people experienced serious unwanted effects with bisphosphonate;

• 28.6% of people experienced serious unwanted effects with placebo.

Disability was not measured in any trial.

We found similar results for PTH or PTHrP analogues (4 studies, 569 people), denosumab (1 study, 240 people), and romosozumab (1 study, 244 people) compared with placebo.

What are the limitations of the evidence?

We have very low confidence in the effect of bisphosphonates on preventing fractures as there were few trials; the follow-up time was usually short (mostly two years or less); and there were few people with fractures in both study groups.

We have only moderate confidence in the effect of bisphosphonates on unwanted effects or serious unwanted effects because it was not clear if all studies had fully reported every event. We have very low confidence in the effect of bisphosphonates on study withdrawals due to unwanted effects, because in some studies it was not clear whether people withdrew because of unwanted effects or for other reasons.

How up to date is this evidence?

The evidence is current to October 2025.