This piece is the middle portion of Chapter 7 of Stones in the Body: More Frightening Than Cancer (Yoon Jong-won). It is a narrative containing the author's academic hypothesis, and the body, figures, and citations follow the manuscript as written.
The Pathway by Which Calcium Dissolves Out of the Bone: The Double Strike of Inflammation
When the I (inflammation) trigger is pulled, in our body calcium dissolves out of the bone through two different pathways. One is indirect, and one is direct.
The problem is that these two pathways operate simultaneously and amplify each other.
1. The First Pathway: Indirect Action Through Calcium Consumption
The inflammatory response requires an enormous amount of calcium. Calcium is consumed in every process in which immune cells are activated, attack pathogens, and regenerate damaged tissue.
Because this calcium is supplied from the blood, the more severe and prolonged the inflammation, the more the blood calcium concentration falls.
When blood calcium falls to the lower limit of the normal range, the calcium-sensing receptors of the parathyroid gland immediately detect this. And PTH is secreted and the D trigger operates.
PTH activates the osteoclasts of the bone, breaking down bone and releasing calcium into the blood. This is the body's automatic response to replenish the calcium consumed because of inflammation.
2. The Second Pathway: The Direct Action of Inflammatory Substances
When inflammation occurs, immune cells secrete inflammatory substances such as IL-1, IL-6, and TNF-α. These substances circulate through the whole body via the blood, and when they reach the bone they directly stimulate the osteoclasts.
The specific mechanism operates through the RANKL system. Inflammatory substances stimulate the osteoblasts and immune cells around the bone to make more of a protein called RANKL.
RANKL is a kind of 'permit for breakdown' that binds to the receptors on the surface of osteoclasts and activates them. In the normal state, a protein called osteoprotegerin (OPG, Osteoprotegerin) neutralizes RANKL and prevents excessive bone breakdown.
But in the inflammatory state, RANKL production increases and osteoprotegerin production decreases, so the balance tilts completely toward bone breakdown.
It is just as if the brake were broken and only the accelerator were working.
3. The Synergy Effect of the Two Pathways
The problem is that these two pathways are not independent. When inflammatory substances directly stimulate osteoclasts and dissolve bone, blood calcium can temporarily rise in that process.
But this calcium is immediately consumed by the inflammatory response, and as blood calcium falls again, PTH is additionally secreted.
As a result, while inflammation persists, the bone is attacked doubly through the two pathways. The direct stimulation of inflammatory substances and the command of PTH operate simultaneously, and the bone dissolves away at a far faster rate than normal.
This is why patients with rheumatoid arthritis or chronic inflammatory bowel disease progress rapidly to osteoporosis.
The Modern Causes of Chronic Inflammation
Modern people live in the era of chronic inflammation. Acute inflammation resolves within a few days, but chronic inflammation persists for months, years, and even a lifetime, quietly destroying our body.
1. Periodontitis
The most common source of chronic inflammation is inside the mouth.
According to domestic oral health surveys, a considerable number of Korean adults suffer from periodontal disease of varying degrees. Periodontitis is not simply a problem of the gums alone.
It has been revealed through numerous studies that the inflammatory substances made by the bacteria in the mouth spread through the whole body via the blood and raise the risk of cardiovascular disease, diabetes, and rheumatoid arthritis.
More directly, as the alveolar bone resorption caused by periodontitis progresses, calcium leaks out of the bone. This is the I-FI (infectious inflammation) trigger.
2. Gut Health
Increased intestinal barrier permeability (intestinal permeability) or an imbalance of the gut microbiota is being studied as a major cause of chronic inflammation. When the intestinal barrier is damaged, bacteria or toxins that should originally remain only inside the gut can leak into the blood and cause systemic inflammation.
Processed foods, excessive antibiotic use, stress, and so on are major factors that harm gut health. This too corresponds to the I-FI (infectious inflammation) trigger.
3. Obesity
Fat cells, especially visceral fat cells, are not a mere energy storehouse but an endocrine organ that secretes inflammatory substances.
The research finding that as the body mass index increases the blood concentrations of IL-6 and TNF-α rise proportionally shows that obesity is itself a state of chronic inflammation.
This is the I-MT (metabolic inflammation) trigger.
4. Chronic Stress
Another major cause that provokes chronic inflammation in modern people is stress. When one is under stress, cortisol is secreted from the adrenal gland.
In acute stress, cortisol actually plays the role of suppressing inflammation, but in a state of chronic stress it paradoxically promotes inflammation.
Continuous exposure to cortisol makes the cortisol receptors of immune cells insensitive, and as a result the secretion of inflammatory cytokines increases.
At the same time, cortisol suppresses calcium absorption in the gut and increases calcium excretion in the kidney, thereby operating the D trigger together as well. This is the I-ST (stress inflammation) trigger.
How the I Trigger Operates the D Trigger
When inflammation occurs, calcium is consumed in large amounts. This is because calcium is needed for immune cell activation, signal transmission, and tissue regeneration all alike. Because this calcium is supplied from the blood, the more severe and prolonged the inflammation, the more the blood calcium concentration falls.
When blood calcium falls, the D trigger operates. PTH is secreted, and it draws calcium out of the bone. Inflammation itself also directly activates osteoclasts through inflammatory substances, but at the same time it operates PTH as well through the decrease in blood calcium. This is a double attack.
The bigger problem is what becomes of the calcium that has left the bone after the inflammation is resolved. Normally, when the inflammation subsides, the calcium should return to the bone again or be excreted through the kidney.
But in a state of chronic inflammation, calcium is continuously consumed, continuously comes out of the bone, and some of the calcium that has come out fails to find its place and begins to pile up in the tissues. This is the beginning of 'calcification.'
Here the more decisive variable is D (deficiency). Because the blood calcium concentration is a lifeline that the body defends to the last, when intake is insufficient or absorption declines, the body, in order to put out the urgent fire, opens once again the emergency warehouse that is the bone and draws out the shortfall to use,
when blood calcium falls, parathyroid hormone responds and mobilizes calcium from the bone, and in the kidney the regulation shifts toward holding onto more calcium.
That is, in a state where efflux has once begun through inflammation, when deficiency overlaps, repeated efflux recurs, and the possibility that the calcium that has come out remains in the tissues without being recovered and precipitates also grows together.
The I trigger too is divided into 7 according to cause. They are inflammation due to stress (I-ST), inflammation due to metabolic problems such as obesity or diabetes (I-MT), chronic infection such as gingivitis or gastritis (I-CH), acute infection such as pneumonia or sepsis (I-AC), latent infection (I-FI), inflammation that arises with age (I-AG), and environmental factors such as fine dust or heavy metals (I-EN).
If it is stress inflammation, stress management is needed, and if it is metabolic inflammation, weight control is needed. Only when the cause is known can the direction of treatment be determined.
■ I (Inflammation) Subclassification
| Code | Name | Core Mechanism |
|---|---|---|
| I-EN | Environmental Amplifier / Environmental Amplifier | Increased inflammatory burden from pollution, chemicals, dust, electromagnetic waves (under study), and so on - fine dust and air pollution, chemicals and endocrine disruptors, occupational exposure (solvents/dust/metals), electromagnetic/radiofrequency exposure (E), and so on |
| I-MT | Metabolic Inflammation / Metabolic Inflammation | Inflammatory substances or metabolic waste generated within the body such as obesity, glucotoxicity, insulin resistance - obesity and visceral fat, insulin resistance, glucotoxicity (AGEs), ultra-processed-food-centered eating habits, dyslipidemia and fatty liver, and so on |
| I-CH | Chronic Infection / Chronic Infection | Persistent infection such as periodontitis, leaky gut, chronic bronchitis - periodontitis and sinusitis (oral/upper respiratory tract), leaky gut and gut dysbiosis (gut), chronic bronchitis (lower respiratory tract), urinary tract infection/chronic cystitis (urinary tract), and so on |
| I-AG | Age-related Inflammation / Age-related Inflammation | Chronic inflammation following immune aging) - base: immune aging (inflammaging), accumulation of cellular waste, decline in antioxidant capacity, sarcopenia and reduced activity (lack of exercise ↔ aging inflammation vicious cycle), and so on |
| I-ST | Stress-induced Inflammation / Stress-induced | Inflammation from the collapse of cortisol rhythm · chronic stress (D-LF/I-ST - recovery↓ + inflammation↑), sleep deprivation and apnea (inflammation↑ + acidosis↑ + hypoxia↑), autonomic imbalance, and so on |
| I-AI | Autoimmune Inflammation / Autoimmune Inflammation | Chronic inflammation from an autoimmune reaction - rheumatoid arthritis, lupus (SLE), ankylosing spondylitis, psoriasis, inflammatory bowel disease (Crohn's disease, ulcerative colitis), multiple sclerosis, Sjogren's syndrome, and so on |
The connection between hormone excess and inflammation: cortisol excess (chronic stress) suppresses inflammation in the short term, but when it becomes prolonged it results in a failure of inflammation regulation (I-ST).
Also, glucocorticoid drugs (steroids) suppress osteoblasts and prolong the lifespan of osteoclasts, thereby provoking D-MD and I-ST at the same time. Therefore "hormone excess" is interpreted not as an independent trigger but as a higher-order cause that provokes I.
I-AI (Autoimmune Inflammation / Autoimmune Inflammation): autoimmune diseases provoke chronic inflammation as the immune system attacks its own tissue. In rheumatoid arthritis, lupus, ankylosing spondylitis, and so on, inflammatory cytokines (TNF-α, IL-1, IL-6) activate osteoclasts and promote bone calcium efflux.
Unlike I-CH (chronic infection), this is inflammation caused by an internal immune abnormality without an external pathogen.
A Trigger: Acidosis - The Bone Is Sacrificed to Acid Neutralization
pH Balance: Life's Narrow Tightrope Walk
Our body ceaselessly produces acid. In every process of digesting food, producing energy, and cells being active, acidic substances are generated as byproducts.
In particular, when protein is broken down, strong acids such as sulfuric acid and phosphoric acid are made, and when glucose is converted into energy, lactic acid is generated.
The acid generated in our body is divided into two kinds. The volatile acid removed through respiration in the form of CO2 is about 15,000 to 20,000 mmol per day, and the nonvolatile metabolic acid excreted through the kidney is about 50 to 100 mEq per day.
But the pH of our body must be maintained within the very narrow range of 7.35 to 7.45. This is managed as strictly as the blood calcium concentration. If the pH falls below 7.35, acidosis occurs, and if it rises above 7.45, alkalosis occurs.
If the pH deviates greatly from this range, enzyme function is paralyzed and cells begin to die, and life is threatened.
Then how does our body maintain a constant pH while making an enormous amount of acid every day? Three buffer systems operate. The first is the bicarbonate buffer system in the blood, the second is carbon dioxide expulsion through the lungs, and the third is acid excretion through the kidney.
But when acid is excessive beyond what these systems can handle or persists for a long time, our body uses the last bastion. It is precisely the bone.
The Bone: The Body's Enormous Alkali Storehouse
The bone is not only a calcium storehouse but also the largest storehouse of alkaline substances in our body. Hydroxyapatite, the main component of bone, is a strongly alkaline substance.
In the bone, along with about 1kg or more of calcium, about 600g of phosphate is stored, and these all have a buffering capacity that can neutralize acid.
A classic study published in the American journal of nephrology showed how the bone operates in a state of metabolic acidosis. When a state of acidosis was induced in the experiment, calcium and phosphate were released from the bone and neutralized the acid.
The interesting point is that in the early stage physical and chemical dissolution can appear relatively quickly, and when it becomes prolonged the cell-mediated (osteoclast) pathway is strengthened.
That is, in the acute phase the calcium carbonate on the bone surface directly dissolves and neutralizes the acid, and when it becomes chronic the osteoclasts break down the bone in earnest.
This shows that the bone is not a passive storehouse that merely receives the command of PTH, but an active buffer system that directly senses and responds to pH changes. Bone cells exposed to an acidic environment send signals that stimulate osteoclasts, and at the same time release calcium and phosphate directly from the bone surface to neutralize the acid.
In a healthy person, the blood pH itself remains within the normal range (7.35 to 7.45) thanks to the buffer system. But in order to maintain that normal range, the bone, kidney, and respiratory systems can overwork. There is an important point here.
The 'acidosis' we speak of is not a disease in which the blood becomes acidic. Even though the blood pH is normal, it is a situation in which the bone pays the price to maintain that normal state. This is the 'invisible sacrifice,' and the problem arises when this sacrifice accumulates over a long period.
The Pathway by Which Calcium Dissolves Out of the Bone: The Price of Acid Neutralization
When the A (acidosis) trigger is pulled, the pathway by which calcium dissolves out of the bone proceeds in two stages.
1. The first stage: the rapid dissolution of the bone surface (within a few hours)
When exposed to an acidic environment, the hydroxyapatite crystals that are the outermost layer of the bone begin to dissolve chemically. This is a pure chemical reaction. When acid meets the alkaline components of the bone, a neutralization reaction occurs, and in that process calcium and phosphate are released into the blood.
This process is the same principle as when you pour vinegar (acid) onto calcium carbonate (limestone) and it dissolves while producing bubbles. Because the surface area of the bone is very large (about several thousand square meters), this chemical dissolution occurs quickly and efficiently. In fact, when the blood of an acute acidosis patient is analyzed, one can confirm that the calcium and phosphate concentrations rise within a few hours.
2. The second stage: the activation of osteoclasts (several days to several weeks)
An acidic environment directly stimulates osteoclasts. According to a paper published by the bone biology research team of Oxford University in the United Kingdom, when the pH falls from 7.4 to 7.1 (becomes more acidic), the activity of osteoclasts can increase more than twofold. Conversely, when the pH rises (becomes alkaline), osteoclast activity decreases and osteoblast activity increases.
The mechanism by which osteoclasts are activated in an acidic environment is very elaborate. On the surface of osteoclasts there are receptors that sense acid, and when the surrounding pH falls, these receptors are activated and send a signal for the osteoclasts to break down the bone more actively.
Osteoclasts dissolve the bone with the local acidic environment (around pH 4.5) that they themselves create, and when the whole body is acidified this task becomes much easier.
3. Long-term Result: Chronic Acidosis and Osteoporosis
Short-term acidosis is temporarily borrowing calcium from the bone, but chronic acidosis is different. Although the intensity differs from study to study, it is repeatedly reported that the higher the dietary acid load, the faster the rate of bone density decrease and the greater the risk of fracture. This tendency was especially pronounced in people who have a high-protein diet, a grain-centered diet, or a diet high in processed foods.
The Acidified Lifestyle of Modern People
The diet of modern people tends to have a high PRAL (Potential Renal Acid Load) compared to that of our ancestors. The diet of humanity in the hunter-gatherer era was rich in fruits, vegetables, and nuts and so was alkaline, but the modern diet is dominated by grains, meat, and processed foods and has a high dietary acid load. This is the A-DT (dietary acid load) trigger.
A high dietary acid load means that it can place a burden on the kidney and the bone. However, in a healthy person the blood pH itself is maintained within the normal range (7.35 to 7.45) by the buffer system. The problem is that the bone can be sacrificed in order to maintain this normal range.
1. Animal Protein
When meat, fish, eggs, and dairy products are digested, sulfuric acid and phosphoric acid are generated. In particular, the sulfur-containing amino acids abundant in meat are converted into sulfuric acid in the metabolic process. If you eat 100g of meat a day, about 10 to 15 mEq of acid is generated.
2. Refined Grains
White rice, white flour, bread, and noodles generate acid in the digestion process. Moreover, such refined grains have had their alkaline minerals (potassium, magnesium) removed and so have no ability to neutralize acid.
3. Processed Foods
Processed meat with added phosphate, soft drinks (about 50mg of phosphoric acid in one can of cola), processed cheese, and so on increase the acid load. In particular, the phosphoric acid in soft drinks binds with calcium and exerts a double adverse effect that hinders calcium absorption.
4. Sugar
Sugar itself is neutral, but in the metabolic process it makes acidic substances such as lactic acid and ketone bodies. In particular, fructose generates uric acid in the metabolic process, becoming a cause of gout and kidney stones, and increases systemic inflammation.
5. The Shortage of Alkaline Foods
On the other hand, the intake of alkaline foods that can neutralize acid has decreased. Alkaline minerals such as potassium, magnesium, and calcium abundant in vegetables and fruits neutralize acid, but modern people's vegetable intake often falls short of the recommended amount.
In particular, the younger the generation, the less the vegetable intake and the more the intake of processed foods and meat, so the risk of chronic acidosis is high.
How the A (Acidosis) Trigger Operates the D (Deficiency) Trigger
It is not only that acidosis directly dissolves calcium out of the bone that is the problem. The bigger problem is that this process eventually operates the D (deficiency) trigger.
When calcium is released from the bone to neutralize acid, the blood calcium concentration temporarily rises. But this calcium is soon consumed or excreted through the kidney.
In particular, in a state of acidosis, the kidney tends to send calcium out into the urine together in order to excrete acid. According to several studies, the higher the dietary acid load, the more the amount of calcium excreted into the urine increased.
As a result, in a state of chronic acidosis, even though calcium comes out of the bone, it is not properly maintained in the blood, and rather a situation occurs in which the blood calcium concentration falls.
This is precisely what operates the D (deficiency) trigger. PTH is additionally secreted, and a vicious cycle begins in which more calcium is drawn out of the bone.
Moreover, acidosis hinders vitamin D activation and thereby decreases calcium absorption in the gut. A triple hardship occurs in which calcium does not come in, the calcium that has gone out escapes into the urine, and the bone continuously dissolves.
This is why chronic acidosis patients progress rapidly to osteoporosis.
The A trigger is divided into 4.
Acidosis in which the kidney function declines so that acid cannot be excreted (A-FN), acidosis that arises from drinking a lot of carbonated drinks or alcohol or from overeating protein (A-DT),
acidosis in which breathing is shallow so that carbon dioxide piles up (A-RS), and acidosis in which a lot of acid is made through vigorous exercise or metabolic hyperactivity (A-HM). If it is dietary acidosis, the diet must be adjusted, and if it is respiratory acidosis, breathing training is needed.
A-HM (Hypermetabolic Acidosis / Hypermetabolic Acidosis): hyperthyroidism excessively promotes metabolism and thereby increases acid production.
By the pathway of a rise in basal metabolic rate → increased oxygen consumption → increased metabolites (acid) → mobilization of alkali (calcium) from the bone, it contributes to bone calcium efflux through the A trigger.