Hormonal Regulators: Calcitonin, Estrogen and Glucocorticoids – Bone and Calcium Medications

00:01 The next thing that I wanna talk about is calcitonin.

00:04 What is calcitonin? Calcitonin is a peptide that is secreted by the thyroid gland.

00:11 It decreases serum calcium and serum phosphate levels.

00:15 It inhibits osteoclast activity or bone resorption, and it inhibits renal reabsorption of calcium and phosphate.

00:23 Calcitonin is used for the treatment of hypercalcemia.

00:28 It's also used sometimes in osteoporosis because of its actions on the bone.

00:33 Now, it has been used in mania. It was given as subcutaneous injections, but the research has essentially been abandoned to the best of my knowledge and I don't think that we're using it much anymore.

00:44 Calcitonin has also been shown to reduce spinal fractures and compression wedge fractures.

00:51 So, you can see here in the image, this person's spine has had what we call a wedge compression.

00:57 Now, the spinal column is slanting forward or hunching forward because the vertebral column has got a wedge in it instead of a nice, round cylinder.

01:09 This is a very common thing that we see in elderly patients and that's why elderly patients tend to have a bit of a stooped posture.

01:16 It's because somewhere in their spine, they have a wedge compression fracture.

01:20 We can prevent this through proper treatment of osteoporosis and osteopenia.

01:25 Now, we reduce spinal compression fractures with calcitonin, but it's not as effective as some other agents that I'm going to talk about later.

01:35 Calcitonin is often administered as salmon calcitonin.

01:41 So, it comes from the fish, the salmon. It is a nasal spray, so it's exceedingly easy to take.

01:48 Most patients can tolerate it quite nicely and it's a psychological benefit too because patients don't feel that it adds to their medication burden if they're given as a nasal spray.

02:00 They don't think of it as a pill or as a medication, so it's a nice drug that way.

02:06 Now, in terms of why -- where and when we would use salmon calcitonin and why we would use it, these are the indications.

02:15 Now, I wanna caution you that they're not all the same in all countries, but generally speaking, I'm going to be using the US experience.

02:22 We use it in Paget's disease of the bone, but be careful on your exam because it is not used in Paget's disease of the nipple which has absolutely no correlation with bone disease at all.

02:34 It's just that the same doctor discovered the two different diseases.

02:37 It's used in bone metastases and cancer.

02:40 We use it in postmenopausal osteoporosis.

02:44 We use it in phantom limb pain through an unknown mechanism.

02:48 We use it in hypercalcemia, which, you know, makes sense the way it works, and we use it in non-operative treatment of spinal stenosis.

02:58 So, patients who have narrowing of the spinal column due to another disease, we -- if they're unable to undergo operation to release the spinal column, we sometimes use calcitonin to help us in this regard.

03:12 The next category is estrogen.

03:15 Now, we know that estrogen has important interactions with bone mineral homeostasis.

03:19 We use estrogens and selective estrogen receptor modulators like raloxifene in the treatment of several diseases.

03:29 We may delay bone loss in patients who are postmenopausal.

03:34 We also inhibit parathyroid-stimulated bone resorption.

03:38 So, you can see here, there is a micrograph of a person's bony structure and trubeculations in a normal patient are nice and thick so the bones are very strong.

03:47 You can see on the other image, the trubeculations are narrower, the person has some wedge compression fractures of the spine, and they have increased risk of fracture of the large bones.

03:59 Glucocorticoids is another issue.

04:01 So, we don't use glucocorticoids to treat bone fractures, but I put it in here because it has a very important effect on bone mineral homeostasis.

04:11 Glucocorticoids, of course, are anti-inflammatory agents and I covered those drugs in another lecture.

04:18 But let's talk about how they affect bone mineral homeostasis.

04:21 It inhibits bone mineral maintenance.

04:26 The patients who are on chronic use end up developing osteoporosis in many, many, many cases.

04:33 And it can be used in short term treatment of hypercalcemia because it reduces calcium levels in the serum.

04:41 How do glucocorticoids work? Now, you can also have a look at my glucocorticoid lecture to see how these things interact with a corticosteroid binding units in the host cell DNA, but here's a little bit of a recap.

04:55 Now, we're going to do a slightly different diagram and mechanism just because we're focusing on bone minerals.

05:03 So, first of all, the CBG, that's the corticosteroid binding globulin, binds to the substrate or in this case, let's say a drug like prednisone.

05:13 The prednisone substrate enters into the cell.

05:17 It enters as a free molecule and it binds to the receptor inside the cell.

05:23 The receptor is represented by an R.

05:26 Now, there is another protein on their called the Hsp90 protein that is bound to the receptor.

05:33 When the drug binds to the receptor, the Hsp is discarded and now you have an active receptor represented by the R with a star beside it.

05:45 So, we have this steroid receptor that is an activated receptor.

05:49 That receptor steroid complex enters into the nucleus of the cell.

05:54 That's where all the DNA is, and the DNA has a GRE or a glucocorticoid response element in it which binds to the steroid receptor complex.

06:05 When these two get together, gene transcription is activated and you have the machinery responsible for bone resorption.