Bone health and fracture risk during ADT for prostate cancer

Dr Omondi Ogude highlights bone health and fracture risk for prostate cancer patients who are on androgen deprivation therapy.

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When treatment affects more than the cancer

If you’re receiving hormone treatment for prostate cancer, you’ve probably heard about hot flushes and fatigue. But one important consequence often receives less attention: what androgen deprivation therapy (ADT) does to your bones.

This isn’t a reason to avoid treatment. ADT remains one of the most effective therapies for prostate cancer. But bone health is a real and manageable consequence of treatment, and men who understand the risks early are often better able to prevent long-term complications.

Why ADT affects your bones

ADT works by lowering testosterone to very low levels, depriving prostate cancer cells of the hormone they need to grow. What’s less well known is that testosterone also plays an important role in maintaining bone strength. When testosterone levels fall, bone is lost faster than it’s replaced, and this process can begin within months of starting treatment.

Over time, this may lead to osteoporosis, where bones become brittle and prone to fracture. A landmark study involving more than 50 000 men demonstrated that ADT significantly increases fracture risk across all age groups,¹ while more recent real-world data confirmed approximately a 1.6-fold increase in fracture risk compared with men not receiving hormonal therapy.²

Fractures, particularly of the spine and hip, can significantly affect mobility, independence, and quality of life.

Recently, I saw a gentleman in his late sixties who had been on ADT for about eighteen months. He felt well and remained active, but a routine DEXA scan showed  early osteoporosis despite the absence of symptoms. Identifying it early allowed us to intervene before a fracture occurred. That’s exactly why screening matters.

Who’s at higher risk?

Risk increases with longer ADT duration, age over 65, low body weight, smoking, excess alcohol intake, previous fractures, and a family history of osteoporosis.

Despite this, fewer than 5% of men on ADT undergo baseline bone density assessment in routine practice.² A DEXA scan, a simple low-dose X-ray that measures bone density, is the standard starting point. Your doctor may also use a FRAX® score, which estimates your 10-year fracture risk using clinical risk factors.

Most major oncology and multi-disciplinary guidelines recommend a baseline DEXA scan when long-term ADT is started, with repeat scans generally every one to two years depending on initial results and overall risk.³^,6

Protecting your bones

Bone protection starts with lifestyle and nutritional measures.

Vitamin D is particularly important because many men are deficient before treatment even begins. Without adequate vitamin D levels, calcium supplementation alone is often far less effective. Most guidelines recommend at least 800 to 1 000IU daily, although some men may require higher replacement doses depending on blood levels.

Calcium intake also matters, with most men requiring approximately 1 000 to 1 200mg daily through diet and supplementation combined.

Exercise is equally important, but the type of exercise matters. Resistance training and weight-bearing exercise appear especially beneficial for maintaining bone strength and muscle mass during ADT. Light weights, resistance bands, stair climbing, and supervised strength training are generally more relevant for bone protection than walking alone, although walking still provides cardiovascular and general health benefits.

Smoking cessation, moderation of alcohol intake, and reducing fall risks at home remain important parts of prevention.

When medication is needed

For men with osteoporosis or high fracture risk, lifestyle measures alone are often insufficient.

The two most used medication approaches are zoledronic acid and denosumab.

Zoledronic acid is an intravenous bisphosphonate that strengthens bone and reduces ongoing bone breakdown. 

For ADT-related osteoporosis prevention, it may be administered as a 5mg infusion once yearly. 

In men with bone metastases, lower doses are often given more frequently, typically every three to four weeks, to reduce skeletal complications from metastatic disease.

Denosumab works differently by blocking a protein called RANKL, which drives bone breakdown. In men receiving ADT, it significantly reduced vertebral fracture risk in a pivotal randomised trial.⁴

The schedule depends on why treatment is being used. One brand of denosumab is mainly used for osteoporosis prevention and is typically given every six months, while another denosumab brand is more commonly used in metastatic bone disease and is usually administered every four weeks. 

This distinction is important because many prostate cancer patients know someone else receiving these medications on a completely different schedule. The reason often relates to whether treatment is aimed at osteoporosis prevention or protection against complications from bone metastases.

Both treatments require adequate calcium and vitamin D supplementation and appropriate monitoring.

Bone-protecting therapy becomes especially important in men receiving  radium-223 alongside ADT, as the ERA 223 trial demonstrated substantially higher fracture risk in this setting when bone-protecting therapy wasn’t used.⁵

Staying well: the bigger picture 

Bone health during ADT works best as a team effort involving your oncologist, GP, and allied healthcare professionals, such as physiotherapists or biokineticists.

Speak up if you develop new back pain, loss of height, worsening posture, or increasing frailty. Vertebral fractures are sometimes missed until they become advanced.

The men who maintain the best quality of life during ADT are usually the ones who stay informed, remain physically active, monitor    their bone health proactively, and communicate openly with their care team.

Bone loss during ADT is common, predictable, and often preventable with the right approach. You don’t have to accept fragility as part of the deal.

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REFERENCES

1. Shahinian VB, Kuo YF, Freeman JL, Goodwin JS. Risk of fracture after androgen deprivation for prostate cancer. N Engl J Med. 2005;352(2):154–164. PMID 15647578
2. Matsushima H, Taguchi T, Kodama S, et al. Androgen deprivation therapy-related fracture risk in prostate cancer: an insurance claims database study in Japan. J Bone Miner Metab. 2024;42(2):223–232. PMID 38493435
3. Casado E, Borque-Fernando A, Caamaño M, et al. Multidisciplinary consensus on the prevention and treatment of osteoporosis and fragility fractures in patients with prostate cancer receiving androgen-deprivation therapy. World J Mens Health. 2022;40(1):74–86. PMID 34983087
4. Smith MR, Egerdie B, Hernández Toriz N, et al. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. 
5. N Engl J Med. 2009;361(8):745–755. PMID 19671656
6. Smith M, Parker C, Saad F, et al. Addition of radium-223 to abiraterone acetate and prednisone or prednisolone in patients with castration-resistant prostate cancer and bone metastases (ERA 223). Lancet Oncol. 2019;20(3):408–419. PMID 30738780
7. Saylor PJ, Rumble RB, Tagawa S, et al. Bone health and bone-targeted therapies for prostate cancer: ASCO endorsement of a Cancer Care Ontario guideline. J Clin Oncol. 2020;38(15):1736–1743. PMID 31990618

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