Bicycling and Bone Density in the NYTimes

The WellBlog in the NYTimes Health Section recently had an post about low bone density in competitive cyclists.  The author of the post points out that high speed, high impact accidents are obviously the source of some bone breaks that occur, but also that bone mineral density is actually lower in competitive male cyclists than is average for men in their age range.  In the study cited, the cyclists were leaner, consumed more calcium, and showed no difference in testosterone levels- all things that are supposed to be good for bone health- but were still more likely to have a lower Bone Minderal Density (BMD).

This is strange because endurance athletes usually have much better BMDs than the rest of the population.  As the famous tennis player examples illustrate, performing weight-bearing exercise protects your bones from atrophy- especially when you start young.  New bone will always deposit itself on the outer surface of a bone (the perichondrium) which is why, as we get older, our bones get wider and have a larger cross-section.  This is a phenomenon known as “cortical drift.”  When you exercise, your bones aren’t getting denser- you’re just adding more bone along the outside, like everyone does.  What is different with exercise is that you aren’t losing bone from the inside as would happen if you were a couch potato.  Bone is an expensive tissue, so if you don’t use it, your body is going to want to lose it.  It’ll send osteocytes out to eat the bone away from the inside out so it doesn’t have to worry about it anymore.  But, if your body can justify the cost of continued maintenance of that tissue, osteocytes, osteoclasts, and osteoblasts will happily work at detecting microfractures, cleaning the “wounds,” and repairing them.

So why isn’t this happening with competitive cyclists?  Nobody’s quite sure yet, but there are a few clues.  The lightest cyclists have the lowest BMD, and we know that cycling is a relatively low-impact activity.  It builds lots of muscle without the continuous, repetitive stress of slamming your feet against hard pavement that happens when you run.  This could result in a lot fewer of the little microfractures in bone that kick the bone remodeling sequence into gear.  Without microfractures, maybe the bone doesn’t know that it’s being stressed.

Competitive cyclists also have very little body fat.  Bone has recently been discovered to be an endocrine organ that communicates with adipose tissue via leptin.  The adipose tissue secretes leptin, which binds to receptors in bone cell precursors and upregulates their differentiation into osteoblasts (the cells that deposit new bone).  At the same time, it downregulates differentiation of osteoclasts (the cells that “eat” old bone).  Of all of the negative health risks associated with obesity, it is actually very good for your skeleton, whether the person is active or not.  So maybe this lack of body fat is negatively affecting competitive cyclists as well.

The article mentions something about calcium intake and sweat, but I’m not sure if that really has anything to do with it.  Runners sweat a lot, too, but they seem to be okay.  They don’t provide a link or any names with the blurb about calcium and it’s not research that I’m familiar with,  so maybe I’m missing an important detail, but this avenue doesn’t sound very promising to me.

At any rate, most of us don’t have to worry about biking away our bone.  The casual bicyclist, and even the average person who uses bicycling as exercise, is not in danger of losing BMD because they don’t spend 8 hours a day burning calories and avoiding microfractures.  And those of us who spend 8+ hours in front of a computer screen per day usually have a little bit of adipose tissue protecting us!

Vitamin D in Furry Primates

In my last post, I talked about how Vitamin D works in the body to regulate calcium digestion and absorption.  The process is a little different in our furry little monkey cousins, though, and understanding their mechanisms of vitamin D absorption can give us a little perspective on the evolutionary history of our own vitamin D use.

Most primates, if not all of them, live at altitudes where sunlight levels are high enough to synthesize previtamin D all year long.  We know that it’s important to their bone health because many captive monkeys living at high latitudes develop rickets, and need high doses of Vitamin D in their monkey chow.

In my last post, I discussed how the human synthesizes vitamin D and then directly absorb it.  In non-human, furry primates, vitamin D is synthesized in the skin and then secreted into the fur.  It is then digested orally through the process of grooming themselves and others.  Each one of those little bugs and skin flakes carries with it some vitamin D.  Given that humans are the “hairless ape,” but we no doubt evolved from a hairy ape, we can be pretty sure that this method of ingestion is in our evolutionary history.  But what happened as we lost our hair?  Did we get it from licking ourselves and others?  Is this where kissing comes from?!  That’s probably a little out there…

Anyway, regardless of how humans ingested vitamin D during the period between when we lost our hair and when we evolved to be able to absorb it directly through our skin, we’ve steadily been decreasing the amount of time we spend outside and the amount of our skin that we expose to sunlight.  This has proven to be a very important selective agent in human history, and has resulted in a lot of the phenotypic variation that we see today.

Up next:  Vitamin D as a selective agent

Vitamin D- How does it work?

We all know that calcium is good for you because it helps us grow big, strong, bones.  Vitamin D isn’t talked about quite as often, but it’s also really important for healthy bones.  When you go to the grocery store, you’ll often see milk with added Vitamin D, and I’ve noticed that my favorite yogurt has started to advertise its high levels of Vitamin D as well.  So what is Vitamin D, and what does it do?

We call it Vitamin D because we’ve evolved the need to acquire it nutritionally, but in its natural form, vitamin D is actually a hormone produced and secreted by the kidney.  Most plants, animals, and even fungi produce provitamin D, which is converted to previtamin D by exposure to sunlight- particularly UV-B rays between 215 and 240 nanometers.  This suggests that it may be an important hormone which originally evolved to signal sunlight exposure.  Previtamin D is then metabolized into 1,25 dihydroxyvitamin D by the kidney in order to be biologically active.  The kidney is able to monitor circulating levels of calcium and synthesize vitamin D accordingly.  When UV exposure is sustained, previtamin D and vitamin D deteriorate before they can be used to make hormonal vitamin D.  This reaction prevents the substance from reaching toxic levels in our bodies.

But what about the Vitamin D that we ingest through milk, yogurt, and supplements?  Most of that Vitamin D is obtained from sheep’s wool, during the defatting process.  Sheep produce Vitamin D in the same manner as we do, but instead of absorbing it directly, they secrete it through skin oils and fur.  The oils and fat obtained from the wool is exposed to UV radiation and then purified for use in supplements.  The wool goes into our sweaters and sportcoats.

When exposed to enough sunlight to generate Vitamin D, the body absorbs Vitamin D by way of Vitamin D-binding protein, or DBP.  Our absorption of the vitamin D we ingest from the diet is a little more complicated, however.  The body uses dietary Vitamin D by absorbing it in the same manner as we absorb cholesterol.  Bile breaks up the lipids in which it is hidden into tiny droplets which deliver the vitamin D to the adipose tissue, or fat.  The liver then clears it and makes it available for metabolism.  It regulates the level of calcium in the blood by increasing how much is absorbed in the intestine, and then how much is then reabsorbed in the kidney during urine formation.

Next up:  Vitmain D in furry monkeys!

Bone formation

Bone formation is some convoluted stuff. Our bones start out as cartilage models, or anlage (from the German word for foundation or preparatory framework). The cartilage cells, or chondrocytes, express a certain transcription factor, Sox9, and produce an extracellular matrix which is rich in Type II collagen, the basis for hyaline cartilage. Hyaline cartilage, for all you carnivores out there, is better known as “gristle.”  This cartilage is covered in a very fibrous membrane called the perichodrium.

As our bones begin to mature, those chondrocytes begin to hypertrophy, or increase in size. The perichondrium begins to differentiate into the periosteum. The periosteum is similar to the fibrous perichondrium in its outside layer, but the inside layer contains progenitor cells which develop into osteoblasts (bone forming cells). As the chondrocytes hypertrophy, they begin to secrete Type X collagen, which promotes mineralization of the extracellular matrix. The hypertrophic chondrocytes also synthesize transcription factors (VEGF and MMP9) which encourage the invasion of blood vessels, osteloblasts, and osteoclasts into the forming bone.

These hypertrophic chondrocytes are, in effect, building a mineralized wall around themselves by encouraging the extracellular matrix to mineralize. Once the matrix is sufficiently mineralized, there is no way for the cell to grow or receive nutrients, and it will die. This can be thought of as an apoptosis of sorts, but is a little different from traditional apoptosis. The cell is programmed to secrete matrix, which kills it, but it’s not programmed to die at a certain point.

But wait, there’s more!

While the chondrocytes are in their hypotrophic stage, they synthesize a gene called Indian hedgehog (Ihh), which in turn upregulates the expression of Parathyroid Hormone-related Peptide (PTHrP). The PTHrP diffuses through the chondrocytes and binds to receptors in the proliferating chondrocytes. By binding to the receptors, the PTHrP keeps the chondrocytes from entering the hypertrophic stage. In this manner, cell maturation is limited. Ihh also directly increases the rate of mitosis in the proliferating chondrocytes. Through these mechanisms, we get limited maturation along with increased mitosing during the development of the animal.

In addition to that, there are also Bone Morphogenic Proteins (BMP). BMPs increase the rate of mitosis in the proliferating chondrocytes as well. BMP also upregulates the expression of Ihh, which serves to enlarge the proliferative zone of chondrocytes, while also delaying chondrocyte death, thereby enlarging the hypertrophic zone. (It took all of my resolve to resist using the word “embiggening” in this paragraph.)

The presence of Fibroblast Growth Factors (FGF) results in an opposite effect. FGF downregulates Ihh, slowing the rate of mitosis in the proliferating chondrocytes and speeding up the rate of maturation to apoptosis.

And that, dear bloggy readers, is how we get boned.

Dinosaur Dads

A male ostrich with chicks. Art Wolfe- Stone/Getty Images

90% of bird species today receive care from their fathers.  This care can be the result of a two-parent model, with both mother and father contributing food and care to the offspring, or it can be the result of a father-only model.  When rare, seemingly disadvantageous strategies like this are adopted by so many species, it is probably wise to look for an adaptive reason for that behavior.  In the case of paternal care for offspring, the adaptation is for increased parental care of the young.  Instead of spreading their genetic material around, the male will invest in one set of his genetic material in order to insure that they survive into adulthood, hopefully to pass on his genes to subsequent generations.  It is the “quality over quantity” approach to parenthood.  So, when did this behavioral trait evolve?

One of the phrases that I find myself repeating a lot is “behavior doesn’t fossilize.”  It doesn’t, but sometimes there are clues in the biology that do fossilize, and can allow us to infer certain aspects of behavior.  Two clues that we can look at with regard to parental behavior in the ancestors of modern birds is the size of the clutches, and the structure of maternal bone.  A single clutch of eggs is usually laid over a period of time instead of contemporaneously.  A female can lay more or bigger eggs if she is allowed to go out and hunt and obtain nutrition than if she is stuck next to the clutch guarding her eggs.  We can look at the size of a clutch of eggs compared with adult body mass to see if the mother was more likely to be the brooding parent, or if she left the care of eggs with the father.  In extant crocodiles, the mother alone is responsible for protecting the eggs.  In one clade of modern birds, the neognathes (ducks, geese, finches, etc.), a two-parent model predominates.  In the other modern bird clade, the paleognathes (ostriches, emus, kiwis), paternal care is the predominant mode.

David Varricchio and his colleagues examined specimens of three different species of theropod dinosaurs to see what kinds of patterns were visible.  In these species, belonging to the geni Troodon, Oviraptor, and Citipati, adults have been found in association with nests.  The nests contained between 22-30 eggs each, and when compared with the clutch size/body mass ratio of 433 extant animals, matched most closely with modern birds exhibiting paternal care.

In order to form an eggshell and fetal skeleteon, females of many species have to extract phosphorus and calcium from their own skeletons.  Most of this bone comes from the inside of the long bones, next to the long, hollow medullary cavity where bone marrow is stored.  When this resorption happens, it leaves scars in the bone that can be observed when the bone is seen in cross-section.  Varricchio and his colleagues looked at cross-sections of the long bones of the dinosaurs found in association with the nests, and observed very little evidence of remodeling or resporption, indicating that these skeletons were not the ones who had laid the eggs.

This is a rather clever way to observe behavior in fossil species.  The clutch size/body mass ratio is consistent with birds that offer paternal care, like ostriches and rheas, and the bone histology is consistent with paternal care as well.  The authors suggest that this type of reproductive strategy may have evolved concurrently with larger eggs that were laid sequentially instead of all at once, along with the increased thermal needs that such large eggs would require.  By allowing the female to focus on her nutritional needs, the father ensures that his eggs will be bigger and his offspring stronger.  Paternal-only care in birds is thus the ancestral condition, with two-parent and maternal care being secondarily derived.

Citation:

Avian Paternal Care Had Dinosaur Origin. David J. Varricchio, Jason R. Moore, Gregory M. Erickson, Mark A. Norell, Frankie D. Jackson, and John J. Borkowski (19 December 2008)

Science 322 (5909), 1826. [DOI: 10.1126/science.1163245]