Bones. Far from static objects. In this podcast, Anne discusses aspects of bone physiology that made their way into THE SILVER SKULL.

 

PODCAST TRANSCRIPT: Elemental Bones

Hello. I’m Anne Renwick, steampunk romance author. Welcome into the laboratory. This is episode seven, Elemental Bones. Today I’m going to talk about the science in THE SILVER SKULL that revolves around bone physiology. I’m going to cover that anatomy lesson first, briefly, to bring us all to a common point before I leap off into the strange and curious.

Most of us, myself included, are used to thinking about bone is a static thing. Dinosaur bones in museums, a human skeleton on display for a medical exhibit or for a Halloween set up, or bones from a meal, chicken bones, beef bones, pork bones, et cetera. But that’s when bone is separated from life. Our bones and that of every other animal are very much alive.

They’re constantly being remodeled according to our age and our use – and perhaps various disease states that might exist. Bones have grown and changed over the course of our lifetimes. It all comes back down to cells.

I’m going to be referencing two basic varieties of bone cells today, while I’m talking about bone growth or remodeling of bone, and those two cells are osteoblasts and osteoclasts. But let me pause for a moment here and make a brief note of word roots. My favorite, right?

Osteo is the word root, meaning bone.

For example, you have osteology. That’s the study of bone. You can have osteogenesis – bone beginnings. How do you form a bone? We’re all, you know, used to the story of egg meets sperm. You grow a child, well, you have to grow bones. So where are they coming from? Osteogenesis. And we have osteocytes, which just mean bone cells, osteo (bone) cytes (cells). We’re going to talk about building bone and remodeling bone, and that means we’re going to talk a lot about osteoblasts.

Osteoblasts, which are the cells that build bone and osteoclasts, which are the cells that break it down.

You need both kinds of cells to have healthy bone, and they have to be working in a kind of equilibrium. You don’t want the cells breaking down too much bone and not building it back up and you don’t want cells building too much bone and not having it removed.

You have to have both to have healthy bone. 10% of your bone as an adult, and about 20% as a young adult, is replaced every single year. Bone remodeling. This replacing of the bone is not just something that occurs when you, say, break a bone and require it to be repaired to be healed. It’s also about how your body maintains a very precise calcium level and element that is critical for many physiological processes.

We’re all used to hearing that “drink a glass of milk”. It has calcium. It’s good for your bones. You’ve heard that.

Bone physiology is under the control of several hormones among them, parathyroid hormone, growth hormone, and a couple others. It also requires adequate levels of vitamin D. That’s why you see vitamin D fortified Milk. It goes together. The calcium and the vitamin D are both required to make strong bones.

Vitamin D also plays a key role in preventing rickets, which is the disease of vitamin D deficiency that prevents calcium from being deposited into the bones leading to weakened bones. So if you’ve seen pictures of someone with rickets, they often have bowed legs because the force of the body weight pushing down on the leg bones, the bone isn’t strong enough to resist those bending forces, and they start to bow outward.

You can get vitamin D from your diet, you can take a supplement. You can also make it by exposing skin to the sun. In fact, vitamin D is made in the skin and then it’s transported by your blood to the bones wherever else it’s needed and, whether or not you can make vitamin D, actually depends on where you live.

If you’re too far North or, correspondingly in the Southern hemisphere, too far South, you can only make vitamin D by sunlight certain times of the year. Those of you who live closer to the equator have a much easier time making vitamin D year-round.

Bones also require an adequate amount of vitamin C for the osteoblasts, the cells that make bones to be able to make collagen.

Collagen is sort of the biological framework into which calcium and phosphate will be deposited to make your bones stronger. A lack of vitamin C can lead to something known as scurvy. You’ve heard about that reference to pirate ships and so on, they’d pack citrus fruit for those trips across the ocean because scurvy will lead to a loss of bone mass, a loss of bone strength. And yes, those classic loose teeth, because the bone that holds the teeth in becomes less dense and so the teeth become loose.

Now, while bones are growing, as you go from being a child to an adult, they grow at the ends, at a location called the epiphyseal cartilage. That’s where the bones actually expand and get longer. So, if you break a bone as a child, they tend to get very worried if the break is close to this epiphyseal cartilage. Because, if you’ve damaged the cells there, it can stop growing. So, say if you just, you broke your bone at the epiphyseal cartilage of your right leg, then your right leg may end up shorter than your left leg.

There’s also sex differences that apply here. As your sex hormones rise at puberty, both males and female, those hormones are going to stimulate the osteoblasts to produce bone faster than the epiphyseal cartilage can expand. And that’s going to mean that that epiphyseal cartilage at the end eventually closes and the bones stop growing. Now. What’s the difference between males and females at this point? Well, estrogens will cause that closure to occur sooner than with androgens, the male hormone will. And that’s why women, when we average all our heights, are generally shorter than the average of all male heights.

So a critical thing in bone physiology us to maintain something called homeostasis. Homeostasis is a term applied to the biological processes that keep everything in balance. So think of it as sort of like a teeter-totter. We want that board to balance perfectly on the fulcrum. We can teeter-totter up and down a little, but we don’t want to swing too wide and have things become too unbalanced.

You’ll hear the term homeostasis applied to all sorts of physiological process, such as kidneys and digestive, but we’re applying it to bone in this case. So swing too wide, too high, too low, either depositing bone or removing bone, and you will find yourself in a disease state of some kind.

So where are these cells, osteoclasts and osteoblasts, located?  They’re located in a membrane known as the periosteum. Peri means “next to”, ostium “bone”. Periosteum “next to the bone”. Thus is a fibrous membrane that covers the surface of the bone and is attached to the bone itself via some fibrous fibers known as Sharpey’s fibers.

Holds them really tight to the bone. So if you’ve ever cooked or, and then peeled the meat away from the bone, you might have some sort of vague recollection of seeing that membrane for yourself. If not, maybe next time you’re in the kitchen and you have a knife and some fresh meat, you can kind of peel away a membrane from the surface of the bone and have a look for yourself.

Okay, so let’s look a little closer at these cell types. Osteoblasts, let’s start with them. Osteoblasts are the cells that are going to produce bone. Osteoblasts lay down something called bone matrix. Its formal name is osteoid and this bone matrix is the biological, the organic component, of bone.  It’s comprised of proteins and other organic components. The osteoblast will also sort of elevate the levels of calcium phosphate in the area that’s going to then promote the deposition of these calcium cells onto this fibrous material, and that is how we mineralize bones.

So what is this bone mineral? It’s called hydroxyapatite. It’s a calcium phosphate mineral that comprises 50% of the volume of the bone itself, and accounts for 70% of the weight of our bone. Now, these calcium phosphate crystals are hard, but they’re also inflexible and very brittle, which means they can withstand a lot of compression, but if you bend or twist them or hit them with a sudden impact that can make these crystals shatter.

And that is why you need the osteoid, the collagen fibers, which are really strong under tension that’s pulling and they’re very flexible. So if you twist, you know, your plant your foot, and you twist around to reach for something, you’re not going to just shatter your bone.

So this collagen, this osteoid matrix forms the framework upon which these hydroxyapatite crystals form and get locked into place. Between the hydroxy appetite and the college and framework, we have a really, really strong bone. In fact, bone is on par with steel reinforced concrete, except it’s even better because bone can repair itself.

Now, we can’t just be building bone. We need to have a way to remove bone in case we need to do some remodeling. This removing bone is the job of the osteoclasts. These cells are able to dissolve bone and resort the calcium and phosphate minerals back into body fluids into your blood and send them, perhaps, to other locations in your body where they’re needed. After all nerve signaling and muscle contraction, particularly your cardiac muscle, your heart muscle is very dependent upon calcium. So much so that if calcium levels dropped by 35%, your nerves will get really excitable – and that can end in convulsions. 50% lower and you’re going to die. Now if you raise calcium levels by 30% higher, then the neurons and those muscle cells can become relatively unresponsive. They’ll just sort of stop working. In fact, if you’re a murder mystery reader, you might’ve run into this in a plot here or there where someone will be injected with calcium, and that actually makes the heartbeat slow down until the body sort of spasms and the individual dies. Calcium is very important. We don’t want our body to have large fluctuations, and it will rarely fluctuate more than 10%.

in short, osteoclasts and osteoblasts will regulate the levels of calcium in your blood so that you don’t have too much or too little. So if there’s too much, it may deposit the calcium if it can, and if there’s not enough calcium in your blood, it will remove it from the bone itself to provide that for another physiological system.

Additionally, you can influence the strength of your bones by things like strength training. Even as adults, if you start lifting weights, you’re putting an increased amount of load on those bones so the cells will respond. The osteoblasts by increasing the mineral content and building stronger bone.

On the other hand, if you just sit around on the sofa like a couch potato and never do any weight bearing exercise at all, you’re going to start having a decrease in the strength of your bones.

German surgeon, Julius Wolff, who lived between 1836 and 1902. Developed something known as Wolff’s law, where he did all sorts of calculations and studies and showed how a bone will remodel to adapt to the forces placed upon it. Forces exerted upon a bone will actually stimulate osteo progenitor cells to differentiate and become osteoblasts, so you will actually make more osteoblasts in response to putting forces on the bones.

Now that we’ve covered all the basics, we can talk a little bit about abnormal bone growth. For example, dwarfism. In this case, we have pituitary growth failure. Not enough growth hormone is being produced to tell the bones to grow. The result is that the bones don’t grow fast enough, so it’s known as pituitary dwarfism.

An individual with this condition would be small all over, not just short arms or legs, but their entire body will be smaller. We don’t see that so much anymore because this is easily treated these days with growth hormone injections.

On the other end of the scale is gigantism. This is a result of the overproduction of growth hormone before puberty. So all the bones grow at really fast rates. After puberty, the bones will start to slow down, but by then we usually have a fairly large individual.

If growth hormone levels are abnormally high, after bone growth is done, you can end up with a condition called acromegaly. Symptoms of acromegaly first present with hands and feet growing larger – enlargement, and if it continues, in most cases, this overproduction of growth hormone is usually due to a pituitary tumor, but if this condition is not medically addressed. Acromegaly can progress to having an overlarge forehead jaw or a nose.

Let’s move on now to some elemental topics.

Normally, bone will be comprised of calcium and phosphate for the most part.

Because of a certain similarity to calcium, heavy metal ions like strontium or cobalt, uranium, plutonium can actually be incorporated into the matrix of your bone. If it’s in the bloodstream, the body will pull it out and deposit it because it has similar properties and this means the heavy metal ions in your blood will land in the bone matrix and be potentially dangerous later on.

Because what were you talking about? Homeostasis. Bone remodeling. You turn over 10% of your bone every year, so as the bone undergoes this turnover, any of these heavy metal ions that were deposited into your bone. Will actually become released later on. So you can have  ongoing problems with these heavy metal ions.

For example, there was the Chernobyl incident in 1986 where radioactive compounds were released. These radioactive compounds ended up in the bones of those people exposed. And over time, the radiation released by the bones during remodeling resulted in some individuals developing leukemia and possibly other fatal cancers.

Replacing bone element minerals was what I did in THE SILVER SKULL. We had calcium phosphate, if you’ll recall, and what I ended up doing was replacing the phosphate with an element called antimony.

Now, if you’ve ever taken a close look at the periodic table, elements are arranged not just into rows, but also into columns and the elements in those particular columns. Tend to share similar properties by virtue of the number of electrons in their outer shell.

Phosphorous, atomic number 15, is a non-metal. It’s highly reactive. It’s important in bone and teeth and animal, as we’ve discussed, but it isn’t a non-metal directly below it at atomic number 33 is arsenic. Arsenic is a metalloid, so it’s not a non-metal. It’s a metalloid. It’s gray. It’s highly toxic. And if you’ve read THE SILVER SKULL, you might’ve run into its name in Chinese. Shen. I may have that pronounced slightly wrong. Gray arsenic can be oxidized to form arsonic oxide, a classic skin purifier – and also a poison.

Phosphorus. Directly below it is arsenic and below arsenic is antimony, atomic number 51, The abbreviation is Sb – capital S, lowercase B. It too is a metalloid. It has a lustrous sort of gray appearance. What is the metalloid? It’s an element with properties that fall in between those of non-metal and metal. We’ll pause here, and I will tell you that China is the largest producer of antimony in the current time period. It produces 77% of all antimony that we mine, which is why the character Wie stepped into my story. Behind China in production is Russia. They also mine it. They come in second place to China at 7%. So we went from China, the largest producer at 77% today to Russia, who only produces 7%.

In large amounts, antimony is a poison. It’s toxic, it’s carcinogenic, and that’s partly why in the story I used the contraption, the osforarre apparatus, to inject it directly. Into the periosteum, that membrane against the bone, and then it wouldn’t have to travel to the bone. It would instead immediately enter into bone metabolism, be deposited in the bone, and hypothetically strengthen it. This is not something we do, so hypothetical, but due to bone remodeling, that antimony would eventually enter the bloodstream and start moving around. That is why the character who appears in chapter one is already sick. He’s got bone tumors.

It’s also why you would never want to try something like this in real life.

Also, workers who are exposed to antimony tend to have it deposit via the lungs. They’ll inhale it in a mining accident or inhaled too much while mining, and it tends to be deposited via that method into red blood cells.

Little artistic license there. So what is antimony used for today? Its main applications are actually industrial, so we need elemental antimony to produce things like semiconductors and diodes. We also use antimony and we mix it into alloys for led storage batteries. For solder, it’s used to make sheet and pipe metal. It’s used in the production of pewter. Also, because it’s toxic, there is a history of antimony being used in medicines as far back as the 14th century, mainly to treat two parasitic diseases, leishmaniasis, and schistosomiasis.

So why was I playing around with the idea of making bone harder anyway. If you’ll recall in THE SILVER SKULL, our hero has a sister that motivated him to develop this osforarre apparatus. This needle like puncture a rotary machine that will deliver specialized cells and antimony right down to the bone surface.

He was trying to cure or at least develop a treatment for his sister’s disease. She has brittle bone disease, which is also known as osteogenesis imperfecta – “bone beginnings are imperfect”. For short, it’s labeled as capital O, capital I, a little bit of creative license here. Again, because osteogenesis imperfecta was not named until 1895. So I dialed that back about 11 years. In any case, osteogenesis imperfecta, or brittle bone disease is a congenital disorder that’s inherited genetically in this disease. The osteoblasts create a malformed matrix, malformed connective tissue, and it’s shaped in a way such that the calcium and phosphate cannot bind to it correctly, making the bone brittle and easily broken. There are other symptoms that go along with brittle bone disease that I didn’t pay much attention to in the book because, like many diseases, brittle bone disease exists on a continuum from mild symptoms all the way to horrifically awful ones.

And partly it depends upon which genetic variant you’ve inherited.

That’s another thing I never addressed in my books is genetics, because genetics comes much, much later in our timeline. What are these other symptoms? If you have brittle bone disease, you might have a bluish tinge to the whites of your eyes.

Patients with brittle bone disease tend to be short. They have loose joints, they can have hearing loss, they can have breathing problems, and they might even have problems with their teeth. Remember scurvy? So if the bone is incompletely mineralized, the teeth may be loose, or perhaps the teeth aren’t formed quite correctly in the first place.

There are eight different types of osteogenesis imperfecta and, again, they have a range of symptoms. Is there a cure? No. Unfortunately, there is no cure. The best that can be done for someone with brittle bone disease is for them to maintain a very healthy lifestyle to avoid accidents where in their bone might get broken.

Now in the story, THE SILVER SKULL, our villain is also interested in removing bone marrow from our hero sister bone marrow is the site of new blood cell production and it’s found in the flare of the hip, in the iliac crest. If you put your hands on your hips, those are the bones that protrude to the side. That’s one of the very few locations where you can get bone marrow from. So, if a doctor suspects that you have, say, leukemia, this is where they might use a large bore needle and drive it into through the bone to collect some of that bone marrow on the inside to collect a sample for analysis to see what’s wrong.

So why am I suddenly talking about bone marrow? Well, bone marrow is where there are undifferentiated cells, sort of baby cells that can grow up and head down a certain pathway and become a multitude of things among which are osteoblasts. In THE SILVER SKULL, our villain is collecting the bone marrow of our hero’s sister, Elizabeth, so that he can take the bone marrow and derive from that, differentiate out osteoblasts. I don’t use the word genetic, exactly, he’s basically going to try to genetically modify Elizabeth’s bone marrow, the osteoblasts, so that he can effect a permanent cure of her disease. That’s his goals, if you’ve read the story, you know, he gets thwarted in that attempt.

Okay. This has been a really fast tear through bone physiology. If you join me next time, I’m going to talk a little bit more about other science stuff that got woven into THE SILVER SKULL and, gasp, we’re going to address some of the physics that crept into the story and how I had to struggle to wrap my resisting brain cells around long forgotten mathematical equations.

If you’ve met me, you might have heard how much I love physics, which is to say, not at all.  I very much enjoy the benefits of physics, but I just don’t do very well with mathematical calculations and such when applied to physics. To that end, I’ve plans to drag my husband onto the show as he has a much better grasp of all things physics.