Quality of care provided to prostate cancer (PC) patients for prevention and treatment of osteoporosis induced by androgen deprivation therapy (ADT): Beyond the Abstract

Nearly 24,000 men in Canada and 186,320 men in United States are diagnosed with prostate cancer each year.[1] The majority of prostate cancer occurs in men between the ages of 60 and 79, most of whom are already at risk for osteoporosis or fragility fracture primarily because of age-related bone loss. [2] The American Cancer Society states that the risk of prostate cancer diagnosed in men aged 65 or older is estimated to be 60%. 

Approximately half of these men will receive Androgen Deprivation Therapy (ADT) at some point after their diagnosis.[3] While ADT helps to treat prostate cancer and prolong survival for older men, it can lead to bone loss and increased risk of fracture. Hormones such as testosterone and estrogen are known to protect against bone loss. Therefore when these hormones are blocked, bones become less dense and can break more easily. This can cause osteoporotic or low trauma/fragility fractures, bone pain, and decline in mobility. In men with prostate cancer, fractures are also associated with increased mortality.[4] For such patients, effective screening and timely interventions are essential for reducing bone-related morbidity.
“The use of androgen deprivation therapy for prostate cancer in men is likely to result in accelerated bone loss; however there is still hope for an improved quality of life while minimizing negative bone effects, if timely managed bone health care services are provided for patients on ADT.”

Due to the age range in which prostate cancer develops, a significant proportion of men already have an important degree of bone loss before even starting treatment for prostate cancer. Up to 1 in 8 men age 65 or older have osteoporosis independent of prostate cancer .[5] Therefore Osteoporosis Canada recommends screening for osteoporosis with Bone Mineral Density (BMD) testing for all men older than 65 and for younger men with clinical risk factors for fracture.

However, BMD alone is only moderately predictive of fracture risk. Validated tools such as the FRAX, a Fracture Risk Assessment System from the World Health Organization (WHO) released in 2008, along with Canadian Association of Radiologists and Osteoporosis Canada (CAROC) tools incorporate additional risk factors such as age and prior fragility fracture to improve fracture predictions. In the United States, the National Osteoporosis Foundation (NOF) recommends a dual-energy x-ray absorptiometry (DXA) scan (to measure BMD) for men diagnosed with prostate cancer before initiation of ADT.[6] The results of this baseline (pre-ADT) test can help guide subsequent bone health care. However, it was discovered that when the more detailed FRAX tool is employed, a significant number of men are found to be at elevated risk for fracture, despite DXA T-scores that are within normal limits. 

With no validated guidelines present in the ADT population for fracture risk assessments, very few clinicians are ordering tests prior to starting ADT; which subsequently leads to a gap in the quality of bone health care.  In a recent province-wide study, it was estimated that BMD testing was not performed in up to 50% of patients starting ADT.[7] Among men with prior fragility fracture or a diagnosis of osteoporosis, both of whom would be at elevated risk of future fracture, the situation was not much better. Other studies have shown that during clinical encounters, relatively few patients are receiving recommendations about lifestyle changes which can prevent bone loss, such as smoking cessation, moderating alcohol intake, and regular weight-bearing exercises, as well as pharmacological interventions such as calcium, vitamin D, and antiresorptive therapy such as bisphosphonates and Denosumab.[8,9] Yet these interventions have been shown to improve BMD and reduce fracture risk.

Our study looked to identify the specific tests ordered, and the quality of services provided by a specialized osteoporosis clinic at the initial clinic visit, and whether the results of commonly ordered tests such as BMD, baseline blood counts with vitamin D levels, bone turnover markers, and Serum Protein Electrophoresis (SPEP), affected subsequent management for the patients on ADT. The goal was also to understand whether or not men on ADT had their fracture risk systematically assessed with any tool such as the CAROC/FRAX tool at baseline. Even though such tools are not specifically validated in men on ADT, they are widely recommended by experts in the field as the most appropriate option at the present time. We also continued to monitor if the recommended tests by the physicians for 100 study patients (median age 73) were implemented within the first 6 months of the initial clinic visit.

Prescribed pharmacological interventions were documented for all patients seen in the clinic, taking vitamin D, calcium (from all sources) and bone targeted medication for the patients who were diagnosed with osteopenia or osteoporosis before visiting the specialized clinic.

Some important findings were that 29% of the study population were taking more than 1200 mg daily calcium and 23% were taking <500 mg of calcium daily from all sources, while 30% of the patients were not taking the appropriate amount of vitamin D.

The main findings were that patients seen in the clinic had very high rates of adherence to published guidelines around lifestyle modification, appropriate doses of calcium and vitamin D being prescribed, and almost 100% use of systematic fracture risk assessment with the CAROC tool by the clinic.  No patients were inappropriately prescribed antiresorptive therapy (e.g. those at low fracture risk).

In summary, the single osteoporosis clinic we studied in Toronto performed a comprehensive assessment and recommended guideline-based bone health care for the vast majority of the men on ADT, suggesting a systemic approach to assessing bone health is associated with high rates of guideline-adherent care. We also noticed a few interesting trends. First, radiation oncologists were more inclined to refer a patient to the osteoporosis clinic compared to urologists. Second, a significant proportion of men were taking excessive amounts of calcium, which is associated with gastrointestinal upset, kidney stones, and possibly an increased risk of cardiovascular disease. Third, a number of men starting ADT did not undergo BMD testing until at least 6 months after starting ADT (in contrast to guideline-recommendations). An important limitation is that our study involved a single physician in a single specialized osteoporosis clinic. Little is known about the quality of care provided to men on ADT in other such clinics. Despite high knowledge about appropriate bone health care among prostate cancer specialists, there remain significant gaps in screening and monitoring of bone health, suggesting the need to develop innovative strategies to overcome barriers to implementation and prevent gaps in guidelines for those who can benefit. Since many urologists and radiation oncologists report feeling ill-equipped to manage bone health issues in the men they are initiating on ADT, one collaborative approach could involve referring these men to an osteoporosis clinic.[10]

Written by: Baig S, Chahin R, Breunis H, Alibhai SMH, University Health Network, Toronto, ON, Canada

References:

1. Jemal, A., Siegel, R., Ward, E., Hao, Y., Xu, J., Murray, T. and Thun, M. J. (2008), Cancer Statistics, 2008. CA: A Cancer Journal for Clinicians, 58: 71–96.

2. Ebeling PR: Clinical practice. Osteoporosis in men. N Engl J Med 2008, 358(14):1474-1482.


3. Alibhai S.M.H, Breunis H, Timilshina N, Johnston C, Tomlinson G, Tannok I, et al. Impact of Androgen deprivation therapy on physical function and quality of life in men with non-metastatic prostate cancer. Journal of Clinical Oncology. 2010; 28(34):5038-5045.

4. Oefelein MG, Ricchiuti V, Conrad W, Resnick MI: Skeletal fractures negatively correlate with overall survival in men with prostate cancer. J Urol, 2002; 168(3):1005-1007.


5.  Watts NB, Adler RA, Bilezikian JP, Drake MT, Eastell R, Orwoll ES, Finkelstein JS: Osteoporosis in men: an Endocrine Society clinical practice guideline. J Clin Endo Metab, 2012; 97(6):1802-1822.

6. Papaioannou A, Morin S, Cheung AM, et al. 2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary. CMAJ. 2010:182:1864-1873.

7. Alibhai S.M.H, Yun L, Cheung A.M and Paszat L. Screening for osteoporosis in men receiving Androgen deprivation therapy. JAMA, 2012; 18(3):255-256.

8. Tanvetyanon T: Physician practices of bone density testing and drug prescribing to prevent or treat osteoporosis during androgen deprivation therapy. Cancer 2005, 103(2):237-241.

9. Panju AH, Breunis H, Cheung AM, Leach M, Fleshner N, Warde P, Duff-Canning S, Krahn M, Naglie G, Tannock I et al: Management of decreased bone mineral density in men starting androgen-deprivation therapy for prostate cancer. BJU Int 2009, 103(6):753-757.

10. Damji AN, Bies K, Alibhai SM, Jones JM: Bone health management in men undergoing ADT: examining enablers and barriers to care. Osteoporos Int 2015, 26(3):951-959.


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