Canadian Urological Association best practice report: Bone health in prostate cancer Flashcards
What has led to men diagnosed with prostate cancer living longer?
Advances in treatment.
What has become a growing concern due to extended survival of prostate cancer patients?
Increased attention to cancer treatment-induced bone loss and optimizing care of men with castrate-resistant prostate cancer (CRPC) and bony metastases.
How does Androgen deprivation therapy (ADT) affect bone health?
ADT with gonadotropin-releasing hormone agonists, antagonists, or orchiectomy decreases bone mineral density (BMD) and increases the risk of fracture.
List some risk factors for low BMD in men with prostate cancer.
Advanced age, smoking, low protein intake, family history of osteoporosis, glucocorticoid use, and a prior history of fall or fracture.
What significant morbidity is associated with fractures in Canadian men?
One-third of Canadian men who experience a hip fracture die within one year, and hip fracture is an independent risk factor for mortality.
What do previous reports suggest about men on ADT in terms of osteoporosis management?
Men on ADT have low rates of osteoporosis screening and infrequently receive interventions to reduce bone loss.
Why has the cumulative impact of systemic prostate cancer treatments on bone health become crucial?
It’s an important aspect of patient-centered, comprehensive prostate cancer care.
Describe the function and process of bone remodeling.
Bone remodeling is a continuous physiological process whose function is to maintain bone integrity. It involves osteoclast-induced bone breakdown (resorption) and osteoblast-performed bone synthesis (ossification).
How do androgens influence osteoblasts and bone density?
Osteoblasts express the androgen receptor. Androgens improve bone density by stimulating osteoblast proliferation and by getting converted peripherally to estrogens, which downregulate osteoclast activity via the RANK pathway.
Explain the role of the RANKL/RANK pathway in bone resorption.
When RANKL binds to RANK, osteoclast differentiation, activation, and survival increase. Estrogens inhibit the RANKL/RANK pathway, which reduces osteoclast activity, thus decreasing bone resorption.
How does a decrease in androgen levels affect bone density?
When androgen levels are decreased, bone density is reduced through downregulation of osteoblasts and upregulation of osteoclasts.
What is the impact of ADT on bone mineral density (BMD)?
ADT reduces testosterone, disrupting bone homeostasis and promoting net bone resorption, thereby reducing BMD. BMD decreases at an accelerated rate in men on ADT compared to healthy controls, especially in the first year of therapy.
After 10 years of ADT, what percentage of men might have osteoporosis? And what fracture risk do they face in the first five years?
Up to 85% of men may have osteoporosis after 10 years of ADT, with up to 20% experiencing a fracture within the first five years.
How do glucocorticoids affect bone loss?
Glucocorticoids increase bone loss by inducing osteoblast apoptosis and increasing osteoclast survival.
What risk is associated with ARAT therapies regarding osteoporotic fracture?
ARAT therapies, such as abiraterone, enzalutamide, apalutamide, and darolutamide, may be associated with an increased risk of osteoporotic fracture. Use of ARATs is linked with a 1.6-fold increased risk of fracture and a 1.8-fold increased risk of falls compared to men not receiving ARATs.
Compare the fracture risk in patients receiving abiraterone acetate to those on placebo.
There’s a similar increase in fracture risk in patients receiving abiraterone acetate compared to placebo, with rates being 5.9% vs. 2.3%.
Why should physicians managing men with prostate cancer on ADT assess bone health?
With treatment advances leading to longer survival for men with advanced prostate cancer, many patients have prolonged exposure to medications that accelerate bone loss. Assessing bone health can help prevent treatment-induced bone loss.
What should men on ADT be evaluated for?
Men on ADT should be evaluated for fracture risk.
Name the tools used for estimating fracture risk in men on ADT.
FRAX, CAROC risk assessment tools, and BMD assessment with a DXA scan.
What does the FRAX algorithm provide an estimate of?
An individual’s 10-year fracture risk.
What factors does the FRAX algorithm incorporate for fracture risk assessment?
Femoral neck T-score from a DXA scan, age, BMI, glucocorticoid use, prior fracture history, rheumatoid arthritis, smoking, alcohol consumption, parental hip fracture history, and ADT as a secondary cause of osteoporosis.
What parameters does the CAROC tool require to estimate fracture risk?
Age, sex, fragility fracture history, glucocorticoid use, and femoral neck T-score from a DXA scan.
What areas are BMD measurements taken at, and how are they reported?
Measurements are taken at the lumbar spine and hip, reported as T-scores, which describe the number of standard deviations below or above the mean value for a healthy 30-year-old of similar sex.
How is osteoporosis defined based on T-score values?
Osteoporosis is defined as a T-score value 2.5 standard deviations or more below the mean (T≤ - 2.5).
How is osteopenia defined based on T-score values?
Osteopenia is defined as a T-score between 1 and 2.5 standard deviations below the mean (T -1 to -2.5).
Why might relying solely on BMD scores be problematic in assessing fracture risk?
BMD scores alone may underestimate fracture risk, as many men with fractures have BMD scores that are not in the osteoporotic range. It’s recommended to incorporate BMD scores and other patient risk factors in a validated calculator for the best assessment.
What is the significance of a previous fracture in assessing the risk for osteoporotic related fracture?
It indicates spontaneous fractures or those induced by minimal trauma that wouldn’t normally cause a fracture. This category also includes asymptomatic vertebral fractures.
How is glucocorticoid use defined as a risk factor for osteoporotic related fracture?
It refers to the oral intake of glucocorticoids equivalent to ≥5 mg/day of prednisone (FRAX) or ≥7.5 mg of prednisone (CAROC) for more than 3 months.
It refers to the oral intake of glucocorticoids equivalent to ≥5 mg/day of prednisone (FRAX) or ≥7.5 mg of prednisone (CAROC) for more than 3 months.
If a mother or father had a history of hip fracture at age less than 80 years, it’s considered a risk factor.
How do FRAX and CAROC differ in age as a risk factor for osteoporotic related fractures?
FRAX includes ages 40–90 years, while CAROC focuses on ages 50–85.
How does BMI influence the risk of osteoporotic related fracture?
A low BMI is associated with a higher risk of fracture.
Describe the association between tobacco use and osteoporotic related fractures.
Men who are currently smoking are at an increased risk.
What level of alcohol consumption is considered a risk factor for osteoporotic related fractures?
Consumption of 3 or more alcoholic beverages per day.
Between rheumatoid arthritis and osteoarthritis, which is a risk factor for osteoporotic related fractures?
Rheumatoid arthritis is a risk factor, while osteoarthritis is not.
Fig. 1. Assessment and management of bone health in men on ADT. §Baseline DXA is useful to assess fracture risk. If DXA cannot be performed, fracture risk can be assessed using FRAX or CAROC without DXA. *Non-pharmacological strategies include smoking cessation, moderation of alcohol consumption, exercise, and fall prevention. ¶The Canadian Osteoporosis Society recommends bone targeted agents may be considered in men on ADT with moderate risk of 10-year major osteoporotic fracture (10–20% risk). A shared decision-making approach is appropriate. May consider referral to an osteoporosis expert for patients wishing to discuss further. ‡Evidence to guide the optimal interval to repeat a DXA scan and BMD assessment is limited. The panel recommends clinicians consider repeat DXA every 2–3 years in low-risk patients and every 1–2 years for moderate-risk patients who are not on treatment or when new clinical factors/treatments arise that may impact bone health. Men on bone-targeted therapy may consider a repeat DXA scan to confirm effectiveness of therapy. †Recommend baseline serum calcium and creatinine. ADT: androgen deprivation therapy; BMD: bone mineral density; CAROC: The Canadian Association of Radiologists and Osteoporosis Canada fracture risk assessment; DXA: dual energy X-ray absorptiometry; FRAX: The World Health Organization fracture risk assessment algorithm.
What is the recommendation for initiating treatment to prevent bone loss in patients on ADT?
Treatment should be initiated in patients with osteoporosis (T-score ≤ -2.5), a prior fragility fracture, or a 10-year major osteoporotic fracture risk of >20%.
Define a fragility fracture.
It’s a fracture from minimal mechanical force (e.g., fall from standing height) that wouldn’t ordinarily cause a fracture. It predicts future fractures, independent of FRAX or CAROC score.
How often does Osteoporosis Canada recommend BMD surveillance for men on ADT?
Every 1-3 years.
In men on ADT at low risk of fracture, how often should a repeat BMD be done?
Every 2-3 years.
How often should men on ADT at moderate or high risk of fracture, who aren’t receiving pharmacological treatment for bone loss, have a repeat BMD?
Every 1-2 years.
For men receiving pharmacological treatment, how soon should a repeat BMD be done to assess treatment efficacy?
Within the first two years.
When is it reasonable to stop a bisphosphonate in men on ADT?
After a period of treatment if a repeat risk assessment with FRAX or CAROC shows they’re no longer at elevated risk of fracture.
When might a patient consider a one-year bisphosphonate holiday?
After three years of intravenous or five years of oral bisphosphonate therapy, provided they don’t have a history of fragility hip or vertebral fracture, have no more than one fragility fracture, hip BMD T-scores > -2.5, and aren’t high risk for fracture as per FRAX.
Why should denosumab not be discontinued abruptly?
It can lead to rapid bone loss and a risk of rebound fracture. Discontinuation should be done in conjunction with an osteoporosis expert.
What is the main purpose of educating patients initiating ADT about cancer treatment-induced bone loss?
To inform them about the potential bone loss due to cancer treatments, its consequences, and prevention strategies. This education empowers patients, increases their autonomy, and improves health outcomes.
How does education impact prostate cancer patients in terms of health outcomes?
Education empowers patients, increases their autonomy, and leads to improved health outcomes.
