How Breast Cancer Treatment Causes Osteoporosis
By Dr. John Neustadt
The American Cancer Society estimates that one in eight women will be diagnosed with breast cancer in their lifetime, and this year alone there will be nearly 300,000 new cases.1 Many of those cancers will be estrogen receptor positive (ER+). Because in these cancers estrogen can worsen the condition, the standard of care is to prescribe a medication that suppresses estrogen production. This class of drugs is called aromatase inhibitors (AI). Some drugs in the category include anastrozole (Arimidex), exemestane (Aromasin), and letrozole (Femara).
The bone damaging effect of these medications is well documented. It’s so common that up to 80% of patients with breast cancer lose bone because of these drugs.2,3 The consequences are deadly because they increase the risk of osteoporosis and fractures. Patients with breast cancer who are hospitalized for a fracture have an 83% higher risk of dying compared to breast cancer patients who don’t fracture.4
The medications are powerful bone destroyers. AIs increase bone loss up to four times faster than naturally losing bone when a woman goes through menopause. It’s been estimated that 20% of women taking one of these drugs for five years will break a bone. This means that in 1 in every 5 women on long-term AI therapy will experience an AI-related fracture.5
How AIs Damage Bone
How AIs damage bone has been studied for years. Estrogen helps maintain strong bones, so when estrogen decreases, bone loss follows. AIs reduce estrogen levels even more than what happens during menopause, and that sets off a cascade of events that destroys bone and increases fracture risk.6-9
Low estrogen activates the immune system to increase inflammation and bone-damaging chemicals. Interleukin 7 (IL-7) is a chemical signal produced by your immune system. Low estrogen increases IL-7, which then activates a complex cascade that increases damaging free radicals and reactive oxygen species (ROS). In turn, this activates receptor activator of nuclear factor kappa-Β ligand (RANKL) and tumor necrosis factor alpha (TNFα).10 The net result is that estrogen deficiency not only increases osteoclasts, which are the cells in your bones that destroy bone, but it also increases how long osteoclasts live. This causes more and faster bone loss.11
Testing for Bone Loss
If you’re taking an AI, it’s important to get your bones tested. Most expert panels recommend a bone density test before starting an AI and every one to two years. Unfortunately, however, most patients are not getting this testing done. Only 34.5% of cancer patients taking AIs are screened with a baseline and follow up bone density scans.12 Therefore, it’s important to speak with your doctor and make sure you’re getting the recommended testing.
If you need to stay on the AI medication, there are many things you can do to reduce your fracture risk, which I discuss in my book, Fracture-Proof Your Bones. These include improving bone health through diet and exercise, such as the Stork exercise that can increase balance to reduce your risk for falls and fractures.
Identifying Other Dangerous Drugs
One important thing to look at is whether you’re taking other medications that destroy bone and increase your fracture risk. According to the data, it’s likely that you are. Medications are so common that 44% of men and 57% of women 65 years old or older are taking at least five medications, while 12% of people in this age group take 10 or more medications.13
Even lots of younger folks are taking meds. In the United States and Canada, where overall prescribing rates are similar, nearly 70% of adults 40-79 years old take at least one prescription drug, which increases to about 83% for people 60 years old or older.14
As I discuss in my book, there are lots of medications that damage bones and the bottom line is that people are taking a lot of drugs. Taking them along with an AI, can magnify the damage. You can talk to your doctor about this, but your local pharmacist is also an important person to speak with. It may be possible to switch to a safer medication, decrease the dose, or discontinue it altogether.
Prolia, a Good Option for You?
Conventionally, the osteoporosis medication denosumab (Prolia) has been studied in women taking aromatase inhibitors with favorable results. The clinical trial enrolled 3,425 postmenopausal women with hormone receptor positive (HR+) breast cancer who were taking an AI medication. The patients were given a Prolia injection every six months and followed the women for eight years. Not only did the women taking Prolia have a 20% decrease in bone metastasis and a 26% increase in overall survival.15 A second clinical trial with breast cancer patients taking Prolia for three years showed a 49% decrease in fractures.16
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1 Key Statistics for Breast Cancer. American Cancer Society. Accessed September 20, 2023. https://www.cancer.org/cancer/types/breast-cancer/about/how-common-is-breast-cancer.html.
2 Chen Z, Maricic M, Pettinger M, et al. Osteoporosis and rate of bone loss among postmenopausal survivors of breast cancer. Cancer. Oct 1 2005;104(7):1520-30. doi:10.1002/cncr.21335
3 Lindsey AM, Gross G, Twiss J, Waltman N, Ott C, Moore TE. Postmenopausal survivors of breast cancer at risk for osteoporosis: nutritional intake and body size. Cancer Nurs. Feb 2002;25(1):50-6. doi:10.1097/00002820-200202000-00010
4 Colzani E, Clements M, Johansson AL, et al. Risk of hospitalisation and death due to bone fractures after breast cancer: a registry-based cohort study. Br J Cancer. Nov 22 2016;115(11):1400-1407. doi:10.1038/bjc.2016.314
5 Hadji P, Aapro MS, Body JJ, et al. Management of Aromatase Inhibitor-Associated Bone Loss (AIBL) in postmenopausal women with hormone sensitive breast cancer: Joint position statement of the IOF, CABS, ECTS, IEG, ESCEO IMS, and SIOG. J Bone Oncol. Jun 2017;7:1-12. doi:10.1016/j.jbo.2017.03.001
6 Hadji P. Aromatase inhibitor-associated bone loss in breast cancer patients is distinct from postmenopausal osteoporosis. Critical reviews in oncology/hematology. 2009/01/01/ 2009;69(1):73-82. doi:https://doi.org/10.1016/j.critrevonc.2008.07.013
7 Hadji P. Cancer Treatment-Induced Bone Loss in women with breast cancer. Bonekey Rep. 2015;4:692. doi:10.1038/bonekey.2015.60
8 Hadji P, Asmar L, van Nes JG, et al. The effect of exemestane and tamoxifen on bone health within the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial: a meta-analysis of the US, German, Netherlands, and Belgium sub-studies. J Cancer Res Clin Oncol. Jun 2011;137(6):1015-25. doi:10.1007/s00432-010-0964-y
9 Lee SJ, Kim KM, Brown JK, et al. Negative Impact of Aromatase Inhibitors on Proximal Femoral Bone Mass and Geometry in Postmenopausal Women with Breast Cancer. Calcified Tissue International. 2015/12/01 2015;97(6):551-559. doi:10.1007/s00223-015-0046-x
10 Weitzmann MN, Pacifici R. T cells: unexpected players in the bone loss induced by estrogen deficiency and in basal bone homeostasis. Ann N Y Acad Sci. Nov 2007;1116:360-75. doi:10.1196/annals.1402.068
11Faienza MF, Ventura A, Marzano F, Cavallo L. Postmenopausal Osteoporosis: The Role of Immune System Cells. Clinical and Developmental Immunology. 2013/05/23 2013;2013:575936. doi:10.1155/2013/575936
12Stratton J, Hu X, Soulos PR, Davidoff AJ, Pusztai L, Gross CP, Mougalian SS. Bone Density Screening in Postmenopausal Women With Early-Stage Breast Cancer Treated With Aromatase Inhibitors. Journal of Oncology Practice. 2017;13(5):e505-e515. doi:10.1200/jop.2016.018341
13Woodruff K. Preventing polypharmacy in older adults. American Nurse Association. Accessed January 18, 2021. https://www.myamericannurse.com/preventing-polypharmacy-in-older-adults/
14Hales CM, Servais J, Martin CB, Kohen D. Prescription Drug Use Among Adults Aged 40-79 in the United States and Canada. NCHS Data Brief. Aug 2019;(347):1-8.
15Gnant M, Frantal S, Pfeiler G, et al. Long-term outcomes of adjuvant denosumab in breast cancer: Fracture reduction and survival results from 3,425 patients in the randomised, double-blind, placebo-controlled ABCSG-18 trial. Journal of Clinical Oncology. 2022;40(16_suppl):507-507. doi:10.1200/JCO.2022.40.16_suppl.507
16Gnant M, Pfeiler G, Dubsky PC, et al. Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. Aug 1 2015;386(9992):433-43. doi:10.1016/s0140-6736(15)60995-3
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