Tamoxifen for bone mets

Interesting question. This is the kind of thing that profs would write as a bonus questions on a pathophys exam lol .

Spitballing here but I think the answer for how it works might have something to do with bone physiology. Because yes, in other tissues tamoxifen is an estrogen antagonist, but in bone it is an estrogen agonist.

So, bone is living tissue, and in healthy bone, we have two types of cells: osteoblasts which build new bone, and osteoclasts which destroy bone (supposed to chew up old bone but under certain conditions osteoclasts get carried away).

Each of these cell types has numerous cell signalling pathways that are unique to its type, plus they communicate with each other. RANK/RANK-L pathway is the most commonly mentioned as some of the osteoporosis drugs target it.

Now, osteoblasts are sensitive and respond to estrogen. During menopause, it's the slowing of osteoblast activity that can cause osteoporosis. So of course you can always treat it in at least two different ways: try to slow down osteoclasts, or try to speed up osteoblasts. (plus you can mess with signalling and communication between both)

In metastatic bone tumors, part of the issue will be which types of cells is the cancer invading? Is the cancer making hard bone tumors or is it eating away at the bone? In breast cancer I've read that the cancer cells tend to cause more osteoclast activity (but in other cancers it can be other cells affected)

So for breast cancer bone mets, this might be one reason why an agent which promotes osteoblast activity would be helpful. Healthy bone would crowd out the lytic lesions caused by the malignant osteoclasts.

All of this btw is also why bone mets are difficult to image and difficult to measure progression -it's a big blob and hard to tell what is happening.

the cancer cells that are metastasizing to the bone are still breast cancer cells, therefore they have breast estrogen receptors. The tamoxifen blocks the estrogen receptors in those cells causing them to stop growing or die. It doesn't have anything to do with bone regeneration.

My Ophthalmologist told me she only saw retinal lesions and macular edema with patients receiving high dose Tamoxifen. I was worried about my eyes. Talk to your Ophthalmologist and see what the side effects "might be" and what to watch out for. Some complain about cataracts forming. As we age we all will have cataracts. Fish oil helps me with the side effect of dry eyes.