Wednesday, January 24, 2018

DX Severe Osteoporosis: Part XII - Could TOO Much Exercise Cause Osteoporosis?



This is Part XII in a multi-part essay chronicling my personal experience with osteoporosis. In this series I have been taking readers through the diagnostic and treatment phases of my care that began over 18 years ago when I was diagnosed with severe osteoporosis. Over the years, the combination of experiencing multiple fragility fractures along with an intense immersion into the study of bone pathophysiology has given me a unique understanding of this disease. If you are just joining the series, I encourage you to skim through the previous DX Severe Osteoporosis essays on my blog (at: www.osteonaturals.com as they provide background to each new installment. It is my hope that this series will provide you with a better understanding of osteoporosis in general, plus a few "pearls" that you may be able to incorporate into your own quest for better bone health. If you have been reading the essays all along...welcome back.    Dr.M


Osteoblasts and osteoclasts have a give-and-take relationship, and their activities are linked. As with any couple, their interactions must stay in balance for marital happiness to be maintained; the harmony of bone depends upon a similar balance. The tricky thing is that resorption, like any form of demolition, is faster than re-building. To offset this, bones produce larger numbers of osteoblasts, and these plentiful cells control the overall activity of osteoclasts.

If the coupling mechanism that balances the activities of osteoblasts and osteoclasts gets out of sync, osteoclasts may begin to resorb more bone than the osteoblasts can replace. Low bone density, and eventually osteoporosis, is the result. On rare occasions it is the osteoclasts that are underactive, resulting in too much bone, a condition called osteopetrosis. It is the balance, and the communication aspects, between the processes that is crucial, as with any relationship.

The communication system between bone cells is a series of linked stimuli and responses. Problems arise when signals are either blocked or amplified. If signals are muffled, the music that coordinates the cells' activities becomes too slow; if they are inappropriately amplified, the notes become distorted and the tempo too fast. In either case the dance between the bone remodeling partners, the osteoblasts and osteoclasts, gets out of step and bone density is lost. The molecules that conduct the music are cytokines, growth factors, and glycoproteins--all of which are woven throughout the bones' collagen foundation to orchestrate the periods of active remodeling.

At the cellular level, the current of our aliveness is carried by metabolic cascades linked through a series of biochemical interactions which adjust the body's state of being to demands being made of it. Cytokines are proteins that are involved in a host of different functions throughout the body, and which can stimulate or inhibit these cascades. They can even direct cells to live or die. It was the cytokines' involvement in mounting the body's immune defenses that caught my interest. Inflammation, as you will remember, is the immune system's response to injury. Whether the injury is the result of chemical, microbial, or physical assault, the body reacts with an increase in blood flow and the release of disease-fighting white blood cells to the area. Heat, redness, pain and swelling are the noticeable consequences of this swift and potent defense.

An athlete's life such as mine is characterized by intense engagements of body and will: inflammation is the mark left by the fires of this passionate encounter. Left to smolder, those hotbeds cause long-term damage to tendons, joints, and even bone. No matter where the inflammation originates—autoimmune problems, toxic gut, glucose imbalances, oxidative stress—the immune system's response will be to flood the body with a deluge of pro-inflammatory cytokines.

Because some of the same cytokines that are active in immune reactions are involved in bone resorption, I looked further into this important link between the inflamed tissues of my hip and the scorching erosion of the bone. One of these cytokines, interleukin-1 (IL-1) stimulates the production of PGE2, a powerful prostaglandin involved in the inflammatory process. Il-1 also happens to be one of the most powerful stimulators of bone resorption.


Another cytokine, interleukin-6 (Il-6), not only stimulates the production of the bone-eating osteoclasts, but it can also increase their destructive potential by extending their normal lifespan. Levels of this cytokine are also high in the inflamed tissues of an injured joint. The link between bone resorption and inflammation was becoming clearer.

And there was more: when Il-6 is elevated it can decrease the synthesis of cartilage proteoglycans, the water-loving molecules in joints whose synthesis depends on glutamine—the same glutamine which is depleted by both Gilbert's syndrome and intense exercise. Combining Gilbert's with elevated Il-6 could severely limit the production of proteoglycans, taking the bounce right out of joint cartilage, and stripping its ability to absorb the compressive forces of exercise. Take the resilience out of cartilage and even low-level activity can be destructive to joints and the surrounding bone.

One of the pro-inflammatory cytokines, tumor necrosis factor (TNF), is from a family of molecules that help regulate bone cell activity. Another important member of that family is receptor activator nuclear kappa-B ligand, or RANKL for short. (I talk A LOT about this molecule in my book, The Whole-Body Approach to Osteoporosis.) A ligand is a communication molecule. This particular communication molecule, RANKL, is released by the osteoblasts and attaches to a special membrane receptor that goes by the acronym RANK, on an osteoclast precursor cell. The
precursor cell of an osteoclast is a type of white blood cell (thus the link to the immune system and bone). By activating this receptor, RANKL has keyed the precursor cell to develop into an osteoclast. So it is through the cytokine RANKL that osteoblasts control osteoclastic activity.

The key, at least for me, is that RANKL-induced aggressive bone resorptin can be stimulated by the over-production of pro-inflammatory cytokines and these same cytokines are capable of blocking osteoprotegerin (OPG). OPG is a "safety net" molecule released by osteoblasts that can prevent excess RANKL from over stimulating osteoclastic activity. With my N-TX (bone resorption marker) spiked so high, excessive osteoclastic activity in my bones was obvious. the linkage between stress, over-production of inflammatory cytokines, and the resulting over stimulation of the RANKL/RANK system suggested a trail to follow—a trail that might reveal the destructive pattern whose effects were showing up in symptoms and lab tests.

The athlete may not always be able to see it but high level competition is stressful. When I was training hard, I didn't think of it as stress, it was just what I did...who I was. But with pro-inflammatory cytokines making a clear link between bone loss and inflammatory states, I began to see my sports life in a different light. Could all of those miles that I ran, biked, and swam actually have contributed to the bone loss instead of stimulating its formation as we generally assume? The impact of healthy amounts of weight-bearing exercise is significantly different than flogging your body for hours upon hours, year upon year—especially if there is insufficient awareness of nutritional needs and an another underlying metabolic disorder (in my case Gilbert's).

Now the words of the acupuncturist began to make more sense. "A constitution dominated by the fire element, and the smell of being scorched." Had I done more than just bruise my wings? maybe I had been literally "scorched" by an unrelenting inflammatory cascade within me. An inability to limit the activity of the pro-inflammatory cytokines would  continually fuel smoldering fires and steadily sap the bones' strength. Now I saw that I had never given the time or the extra nutrients necessary for my body to recover between the intensity of workouts. When the heat is kept up non-stop and the furnace is never allowed to cool between engagements, the walls can crack...and the bones will break.

Saturday, January 6, 2018



This is Part XI of a multi-part essay chronicling my personal experience with osteoporosis. In this series I have been taking readers through the diagnostic and treatment phases of my care that began over 18 years ago when I was diagnosed with severe osteoporosis. Over the years, the combination of experiencing multiple fragility fractures along with an intense immersion into the study of bone pathophysiology has given me a unique understanding of this disease. If you are just joining the series, I encourage you to skim through the previous DX Severe Osteoporosis essays on my blog as they provide background to each new installment. It is my hope that this series will provide you with a better understanding of osteoporosis in general, plus a few "pearls" that you may be able to incorporate into your own quest for better bone health. If you have been reading the essays all along...welcome back.    Dr.M



                                          "And now here is my secret, a very simple
                                            secret: It is only with the heart that one can
                                            see rightly; what is essential is invisible
                                            to the eye." 

                                                                         The Little Prince
                                                                         Antoine de Saint-Exupery



Not only was I beginning to discover ways to improve my skeletal and overall health but I was also starting to see osteoporosis through a much different lens—and this lens was projecting multiple images from seemingly divergent rays of medical and biochemical data. For example, exercise signals the body to form bone. Well, I had certainly engaged in enough exercise in my life to build several skeletons if this was the case. So why was my skeleton, or at least its density, so paltry?

Concussive forces and the shear strain (an engineering term for the application of force at a specific angle) from muscular activity send waves of vibration rippling through the body and into bone. Here, cells called osteocytes detect and respond to these mechanical signals, translating them into biochemical signals that stimulate bone-building. Osteocytes start off as osteoblasts, the very cells that build bone. When osteoblasts have finished forming the collagen matrix foundation of bone, each osteoblast then builds a small chamber around itself. This chamber is like a cocoon offering a protected site for the osteoblast's transformation into an osteocyte while the matrix around it is being flooded with solidifying minerals such as calcium, phosphorous, and magnesium. Once the bone is calcified, the now chambered (in an elongated cartilage sac called a lacuna) osteocyte is in place and able to receive those vibrating wave forces—the signals necessary to activate future bone remodeling activity.

Osteocytes in lacunae
Osteocytes have a star-like configuration with appendages reaching out through bony tunnels that radiate from them. These tunnels are fluid-filled corridors extending to neighboring osteocytes, and along them the vibrating mechanical signal is communicated from one osteocyte to the next. Thus, from every movement of the body, there comes the potential to alter the shape of each osteocyte's cell membrane. It is at this point that the signal changes from a mechanical one to a biochemical one. Receivers in the cell's membrane transmit the signal (if the membrane is healthy enough) into the cell where substances that promote bone formation are then released.

Because of this link between physical activity and osteogenic (bone forming) signaling, it makes sense that athletes generally have better bone density than non-athletes. But for athletes who have pushed themselves to excess for years...decades...this positive response to exercise may indeed turn into a negative response. Over stressing the body regularly with excessive, adrenal cortisol-releasing stress, coupled with neglecting to sufficiently refuel the body with important nutrients, puts the active aging athlete at considerable addition risk for osteoporosis. In addition, exercise alone does not necessarily make for better bones. Young adults who take up an exercise program will only gain a small amount of bone density. A post-menopausal woman who starts working out in a gym won't typically gain any density. Her low estrogen causes a continued loss of bone, although her rate of loss will not be as rapid as a post-menopausal woman who does not exercise. So exercise helps to stimulate osteogenic signaling, and it is vitally important for both bone and overall health, but it will not result in increased bone density beyond a certain age—and it is not the primary determinant of bone density at any age.

I was not only seeing that bone was very much alive and amazingly complex but I was beginning to sense that it had a hidden dynamic life. Bone is amazing in that it can undergo change both by remodeling its architecture in response to external mechanical demands, and to internal physiological needs. A hefty percentage of bone is fairly quiescent at any given time. It is just there, doing its job of supporting the body and providing a reservoir for minerals. But in areas in need of repair or when the body is desperate for mineral reserves, metabolic and remodeling activity increases dramatically. Continuous cycles of remodeling are necessary to maintain skeletal health for normal, everyday activity—but when the stresses of life (both physical and emotional) increase, or when the concussive forces of weight-bearing activity are particularly high, micro-fracturing of bone and the need for
repair increases. Weakened bone must be replaced with new, resilient bone. This renewal process is accomplished by coordinated cell groups called basic multicellular units (BMUs).

At any given time there can be millions of BMUs, areas where osteoclasts are actively tearing down old micro-fractured bone and new bone is being formed in its place. Osteoclasts move like predators on the prowl for injured prey. They feast on old microfractured bone, leaving gouged out tunnels and troughs, and then move on. The osteoblasts come in behind, filling the stripped out areas with strong, new collagen matrix. This bone-like substance, called "osteoid," is then mineralized over the next several weeks by osteoblasts. These cells deposit crystalline mineral salts (hydroxyapatite, such as in OsteoMineralBoost) between the collagen fibers to make them rigid and increase their overall strength. Once this biomineralization has occurred and the hydroxyapatite crystals are in place, the bone formation process is complete.

My job was to try and find out if this process was going on in my body and if not...why? Intermittently, as I learned more about bone biology and it hidden physiology, I would scan the slide from the biopsy of my pelvis looking for clues. I could see the BMUs very clearly in their lit-up red tetracycline "ink." Instead of the uniform mineralized bone formation typically seen in "normal"
Zebra-striping: red is new mineralized bone
bone, my BMUs were filled with alternating layers of mineralized bone and un-mineralized matrix, giving it a zebra-striped look.

To me, this suggested there may be a mineralization defect of some kind that was involved in my osteoporosis. It really looked like my severe bone loss—bone weakness—wasn't just from over-activity of the osteoclasts breaking down excessive amounts of bone, but that there was something else going on in addition. It looked as though the crystalline mineral salts weren't "sticking" to the osteoid matrix after it was formed. Or that maybe there was something intermittently inhibiting mineralization. Maybe there was a mineral missing?...or a toxin infiltrating and preventing the hydroxyapatite crystal from forming? Maybe the levels of my testosterone and estrogen hormones were fluctuating every few days? Could the vitamin D and parathyroid hormones which are responsible for pulling in calcium from the gut and kidneys, and maintaining its optimal levels in bone and blood somehow be ineffective? Their levels, after all, had been tested several times over the past year and shown to be normal which meant that the calcium should be there in high enough quantities. Maybe my low level of essential fatty acids (that I discovered through lab testing) was involved? Fatty acids are needed for absorption and deposition of calcium into bone. But if the fatty acids were keeping me from bringing in enough calcium, then shouldn't my parathyroid hormone have been elevated in response to low levels of calcium? My questions seemed endless, and my dearth of information was evident and discouraging. I was seeing that this last question, that of parathyroid function, was of prime importance when evaluating the causes of bone loss, and that is where I placed my next investigatory lens.


                                                    "I need to put up with two or three
                                                       caterpillars if I want to get to
                                                      know the butterflies."

                                                                                The Little Prince
                                                                                Antoine de Saint-Exupery



Stay tuned for DX Severe Osteoporosis - Part XII



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