Muscle and bone effects of androgen deprivation therapy: current and emerging therapies. By Lee et al. 2014
Key sentence from the paper: “An audit of 236 men (mean age 70 years) newly commencing ADT showed that 11% had osteoporosis and 40% osteopenia. 61% of the men with osteoporosis were unaware of the diagnosis (Cheung et al. 2013).”
For the full abstract, see: http://www.ncbi.nlm.nih.gov/pubmed/25056176
Commentary: This is an extensive review of the musculoskeletal impact of ADT. It covers the same ground as most of the papers summarized below and is also another study from Australia. The paper revisits the fact that the X-ray analysis for osteoporosis (i.e., the DEXA test) is not a particularly good predictor of a fracture risk. The authors point out that “in a cohort of men [with advanced prostate cancer] receiving ADT for over 6 months, vertebral fractures were diagnosed in 37%, however only 7% were classified with osteoporosis by DEXA.”
Unlike the formal Australian review just listed, the authors here do comment on estradiol as a possible bone-protective agent and a possible agent for reducing some of the other side effects of androgen suppression in patients on ADT. They state that “estradiol (E2) derived from aromatization of testosterone, is largely responsible for regulating bone resorption[l1] and some of the key consequences of male hypogonadism.” However, they go on to say that “further research is needed to elucidate whether manipulation of E2 in men undergoing ADT in the setting of low testosterone will have benefit on bone or other side effects related to hypogonadism [=low testosterone] as well as a favourable safety profile.”
Cheung AS, Zajac JD, Grossmann M. 2014. Muscle and bone effects of androgen deprivation therapy: current and emerging therapies. Endocr Relat Cancer 21(5):R371-394.
Development and validation of a prognostic index for fracture risk in older men undergoing prostate cancer treatment. By Graham-Steed et al. 2014.
Key sentence from the paper: “…clinicians prescribing ADT or initiating radiation should use risk factors such as concurrent use of central nervous system-active medications, increasing age, and history of anxiety or Parkinson’s to guide decision making.”
For the full abstract, see: http://www.ncbi.nlm.nih.gov/pubmed/25240918
Commentary: Based on the findings of the four papers summarized here, prolonged use of ADT is bad news for bone integrity. Furthermore, the interventions to maintain bone strength for patients on ADT have not been shown to significantly reduce the fracture risk, even though they help maintain bone density. So what should patients do to avoid fractures while on ADT?
This paper is insightful in looking at factors other than ADT, that can increase the fracture risk. Knowledge about those risks can help physicians decide when to limit the use of ADT if patients have an exceptionally high chance of breaking a bone. Those risk factors include: a prior history of a fracture, taking certain drugs that affects the central nervous system (e.g. , anti-depressants and anti-anxiety medications), {C}[l1] overall age [older age = more risk of fractures], and a history of certain neuromotor disability (e.g., Parkinson’s disease). Of course, some fractures have more impact than others (e.g. breaking a finger, vs. breaking a hip). Simply stated, patients with a high risk of falling down and breaking a hip should be prescribed ADT with caution.
Graham-Steed TR, Soulos PR, Dearing N, Concato J, Tinetti ME, Gross CP. 2014. Development and validation of a prognostic index for fracture risk in older men undergoing prostate cancer treatment. Journal of Geriatric Oncology. 18 September 2014 [Epub ahead of print].
Bone complications among prostate cancer survivors: long-term follow-up from the prostate cancer outcomes study. By Morgans et al. 2014.
Key sentence from the paper: “Men receiving prolonged ADT had higher odds of fracture...”
“The risk of death at 1 year after hip fracture is 31-35% for men…”
For the full abstract, see: http://www.ncbi.nlm.nih.gov/pubmed/25134939
Commentary: This paper makes a key point that differentiates between experiencing osteoporosis vs. breaking a bone. Simply stated, the danger lies in experiencing a fracture, and not osteoporosis per se. The authors point out that “men with prolonged ADT had significantly higher odds of fracture over a 15-year period after diagnosis than men not treated with ADT.” The good news is that short-term use (i.e. less than 1 year) of ADT does not elevate the risk of bone fracture. Patients on ADT for less than 1 year, do show signs of increased osteoporosis. Those two statements may seem contradictory, but it’s pointed out that, as other recent authors have noted, the X-ray assessment of osteoporosis is not a very precise estimate of fracture risk (see commentary on Skolarus et al. paper below).
Morgans AK, Fan KH, Koyama T, Albertsen PC, Goodman M, Hamilton AS, Hoffman RM, Stanford JL, Stroup AM, Penson DF. 2014. Bone complications among prostate cancer survivors: long-term follow-up from the prostate cancer outcomes study. Prostate Cancer and Prostatic Diseases. 19 August 2014 [Epub ahead of print].
Androgen-deprivation-associated bone disease. By Skolarus et al. 2014.
Key sentence from the paper: “Most interventions used bone mineral density as a surrogate outcome, despite compelling evidence that it inadequately captures fracture risk.”
For the full abstract, see: http://www.ncbi.nlm.nih.gov/pubmed/25144145
Commentary: Lastly we have here a brief, but intense, look at the osteological side effects of ADT. The senior author Dr. Vahakn Shahinian has published many insightful papers on the impact of ADT on patients. In this paper, he and his coauthors point out that some of the more potent drugs used to maintain bone strength for patients on ADT, such as the bisphosphonates [e.g., Zometa, Fosamax, Actonel] and denosumab [Prolia, Xgeva] have not been demonstrated to reduce “clinically relevant fracture outcomes in the nonmetastatic setting in men on ADT…”. They also flag the adverse effects of these bone-protecting agents, such as a risk of osteonecrosis of the jaw and low calcium. In addition, they point out that calcium and vitamin D alone are not sufficient to prevent bone loss on men on ADT. They further state that even with exercise it is hard to prevent bone loss with ADT.
The overall message is that it is very hard to prevent bone loss in patients on long term ADT , therefore they encourage “restricting the use of ADT to settings in which its benefits are clearly established in order to limit unnecessary complications.”
Skolarus TA, Caram MV, Shahinian VB. 2014. Androgen-deprivation-associated bone disease. Current Opinion in Urology 24(6):601-607.