Bone health

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The human skeletal system is a complex organ in constant equilibrium with the rest of the body. In addition to support and structure of the body, bone is the major reservoir for many minerals and compounds essential for maintaining a healthy pH balance. [1] The deterioration of the body with age renders the elderly particularly susceptible to and affected by poor bone health. Illnesses like osteoporosis, characterized by weakening of the bone's structural matrix, increases the risk of hip-fractures and other life-changing secondary symptoms. In 2010, over 258,000 people aged 65 and older were admitted to the hospital for hip fractures. [2] Incidence of hip fractures is expected to rise by 12% in America, with a projected 289,000 admissions in the year 2030. [3] Other sources estimate up to 1.5 million Americans will have an osteoporotic-related fracture each year. [4] The cost of treating these people is also enormous, in 1991 Medicare spent an estimated $2.9 billion for treatment and out-patient care of hip fractures, this number can only be expected to rise. [5]

Contents

Amino acid metabolism

When more sulfur containing amino acids, methionine and cystine, are consumed than the body can use for growth and repair, they are broken down yielding sulfate, or sulfuric acid among other products. Animal foods such as meat, dairy, and eggs are high in protein and "dietary animal protein intake is highly correlated with renal net acid excretion". [6] Research dating back to the early 1900s has shown correlations between high protein diets and increased acid excretion. [7] One measure of the acidic or basic effects foods have in the body is Potential Renal Acid Load (PRAL). Cheeses with protein content of 15 g protein/100g or higher have a high PRAL value of 23.6 mEq/100 g edible portion. Meats, fish, other cheeses and flour or noodles all have a PRAL around 8.0 mEq/100 g edible portion, where fruits and vegetables actually have a negative PRAL. [1] [8]

Methionine and Cystine Degradation Pathway Met and Cys Degradation Pathway.jpg
Methionine and Cystine Degradation Pathway

In healthy adults, bone is undergoing constant repair and renewal. New bone is deposited by osteoblast cells and resorbed or destroyed by osteoclast cells. This addition and subtraction of bone usually yields no net change in the overall mass of the skeleton, but the turnover process can be significantly affected by pH. [1]

Bone mineral density

Bone mineral density (BMD) is a measure commonly used to quantify bone health. A lower BMD value indicates an increased risk of an osteoporosis or a fracture. [9] There is a large range of factors influencing BMD. Protein consumption has shown to be beneficial for bone density by providing amino acid substrates necessary for bone matrix formation. It is also thought that blood concentration of the bone formation stimulant, Insulin-like Growth Factor-I (IGF-I), is increased from high protein consumption and parathyroid hormone (PTH), a bone resorption stimulant, is decreased. [10] Although protein has shown to be beneficial for increasing bone mass, or bone mineral density, there is no significant association between protein intake and fracture incidence. [11] In other words, a low BMD can be predictive of osteoporosis and increased fracture risk, but a higher BMD does not necessarily mean better bone health. High BMD is also correlated with other health issues. [12] For example, a higher BMD has also been associated with increased risk of breast cancer. [13]

Acid–base homeostasis

PRAL of Common Foods PRAL of common foods.jpg
PRAL of Common Foods

Most metabolic processes have a specific and narrow range of pH where operation is possible, multiple regulatory systems are in place to maintain homeostasis. Fluctuations away from optimal operating pH can slow or impair reactions and possibly cause damage to cellular structures or proteins. To maintain homeostasis the body may excrete excess acid or base through the urine, via gas exchange in the lungs, or buffer it in the blood. [14] The bicarbonate buffering system of blood plasma effectively holds a steady pH and helps to hold extracellular pH around 7.35. [15] The kidneys are responsible for the majority of acid-base regulation but can excrete urine no lower than a pH of 5. This means that a 330mL can of cola, for example, usually ranging in pH from 2.8 to 3.2, would need to be diluted 100 fold before being excreted. Instead of producing 33L of urine from one can of cola, the body relies on buffer to neutralize the acid. [1] Systemic acidosis can be the result of multiple factors, not just diet. Anaerobic exercise, diabetes, AIDS, aging, menopause, inflammation, infections, tumours, and other wounds and fractures all contribute to acidosis. Blood has an average pH of 7.40 but interstitial fluid can vary. Interstitial pH of the skin, for example, is ~7.1. There is no data available for bone. [16]

Homocysteine

Homocysteine, a non-protein amino acid and analogue to the protein amino acid cystine, has been shown to have negative effects on bone health. Higher homocysteine concentrations are likely a result of folate, vitamin B12 B6 deficiencies. In addition, it was found that homocysteine concentration was significantly affected by physical activity. The stimulation of the skeleton through physical activity promotes positive bone remodelling and decreases levels of homocysteine, independently from nutritional intake. Four methods have been proposed regarding the interaction of homocysteine and bone; increase in osteoclast activity, decrease in osteoblast activity, decrease in bone blood flow, and direct action of homocysteine on bone matrix. Homocysteine inhibits lysyl oxidase which is responsible for post-translational modifications of collagen, a key component to bone structure [17]

Osteoclast cells

Light micrograph of an osteoclast displaying typical distinguishing characteristics: a large cell with multiple nuclei and a "foamy" cytosol. Osteoclast.jpg
Light micrograph of an osteoclast displaying typical distinguishing characteristics: a large cell with multiple nuclei and a "foamy" cytosol.

Osteoclasts are located on the surface of bones and form resorption pits by excreting H+ to the bone surface removing hydroxyapatite, multiple bone minerals, and organic components: collagen and dentin. The purpose of bone resorption is to release calcium to the blood stream for various life processes. [17] These resorption pits are visible under electron microscopy and distinctive trails are formed from prolonged resorption. Osteoclasts have shown to be "absolutely dependent on extracellular acidification". [14] A drop in pH of <0.1 units can cause a 100% increase in osteoclast cell activity, this effect persists with prolonged acidosis with no desensitization, "amplifying the effects of modest pH differences". Osteoclast cells show little or no activity at pH 7.4 and are most active at pH 6.8 but can be further stimulated by other factors such as parathyroid hormone. [16]

Osteoblast cells

Osteoblast Cells Bone hypercalcemia - cropped - very high mag.jpg
Osteoblast Cells

Osteoblast are responsible for the mineralization and construction of bone matrix. They are responsible for the formation or production of bone tissue. [18] The origin of the osteoblasts and osteoclasts is from primitive precursor cells found in bone marrow. [18] Like osteoclast cells, osteoblast cell activity is directly related to extracellular pH mirroring of osteoclast activity. At pH 7.4, where osteoclasts are inactive, osteoblast are at peak activity. Likewise, at pH 6.9 osteoblast activity is non-existent. [16] The hormone estrogen is also important for osteoblast regulation. In postmenopausal women estrogen levels are decreased which has negative effects on bone remodeling. Homocysteine further exacerbates this problem by reducing estrogen receptor α mRNA transcription. Thus reducing any beneficial effect that estrogen plays on bone remodeling. [17]

Bone balance

Acidosis inhibits bone osteoblast matrix mineralization with reciprocal effect on osteoclast activation. The combined responses of these cells to acidosis maximizes the availability of hydroxyl ions in solution that can be used to buffer protons. [16] The utilization of bone to buffer even a small percentage of daily acid production can lead to significant loss of bone mass in the course of a decade. [6] Additionally, as the body ages there is a steady decline in renal function. Metabolic acidosis can become more severe as kidney function weakens, and the body will depend more heavily on bone and blood to maintain acid-base homeostasis. [10]

Diet

There is no one food or nutrient capable of providing adequate bone health on its own. Instead, a balanced diet sufficient in fruits and vegetables for their vitamins, minerals, and alkalinizing substrates is thought to be most beneficial. High protein diets supply larger amounts of amino acids that could be degraded to acidic compounds. Protein consumption above the Recommended Dietary Allowance is also known to be beneficial to calcium utilization. Overall it is understood that high-protein diets have a net benefit for bone health because changes in IGF-I and PTH concentrations outweigh the negative effects of metabolic acid production. [10] The source of protein, plant or animal, does not matter in terms of acid produced from amino acid metabolism. Any differences in methionine and cysteine content is not significant to affect the overall potential renal acid load (PRAL) of the food. In addition to their acid precursor protein content, plants also contain significant amounts of base precursors. Potassium bicarbonate, a basic salt, is produced via the metabolism of other organic potassium salts: citrate, malate, and gluconate, which are substantial in plants. The discrepancy observed in PRAL is accounted for by differences in base precursor content. [6] [8]

See also

Related Research Articles

<span class="mw-page-title-main">Bone</span> Rigid organs that constitute part of the endoskeleton of vertebrates

A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, and enable mobility. Bones come in a variety of shapes and sizes and have complex internal and external structures. They are lightweight yet strong and hard and serve multiple functions.

<span class="mw-page-title-main">Osteoporosis</span> Skeletal disorder

Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone sterility, and consequent increase in fracture risk. It is the most common reason for a broken bone among the elderly. Bones that commonly break include the vertebrae in the spine, the bones of the forearm, and the hip. Until a broken bone occurs there are typically no symptoms. Bones may weaken to such a degree that a break may occur with minor stress or spontaneously. After the broken bone heals, the person may have chronic pain and a decreased ability to carry out normal activities.

<span class="mw-page-title-main">Bone healing</span> Healing from bone injury

Bone healing, or fracture healing, is a proliferative physiological process in which the body facilitates the repair of a bone fracture.

<span class="mw-page-title-main">Parathyroid hormone</span> Mammalian protein found in Homo sapiens

Parathyroid hormone (PTH), also called parathormone or parathyrin, is a peptide hormone secreted by the parathyroid glands that regulates the serum calcium concentration through its effects on bone, kidney, and intestine.

<span class="mw-page-title-main">Osteoblast</span> Cells secreting extracellular matrix

Osteoblasts are cells with a single nucleus that synthesize bone. However, in the process of bone formation, osteoblasts function in groups of connected cells. Individual cells cannot make bone. A group of organized osteoblasts together with the bone made by a unit of cells is usually called the osteon.

<span class="mw-page-title-main">Calcitonin</span> Amino acid peptide hormone secreted by the thyroid gland

Calcitonin is a 32 amino acid peptide hormone secreted by parafollicular cells (also known as C cells) of the thyroid (or endostyle) in humans and other chordates in the ultimopharyngeal body. It acts to reduce blood calcium (Ca2+), opposing the effects of parathyroid hormone (PTH).

<span class="mw-page-title-main">Osteoclast</span> Cell that breaks down bone tissue

An osteoclast is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and remodeling of bones of the vertebral skeleton. The osteoclast disassembles and digests the composite of hydrated protein and mineral at a molecular level by secreting acid and a collagenase, a process known as bone resorption. This process also helps regulate the level of blood calcium.

<span class="mw-page-title-main">Alendronic acid</span> Chemical compound

Alendronic acid, sold under the brand name Fosamax among others, is a bisphosphonate medication used to treat osteoporosis and Paget's disease of bone. It is taken by mouth. Use is often recommended together with vitamin D, calcium supplementation, and lifestyle changes.

<span class="mw-page-title-main">Osteoprotegerin</span> Mammalian protein found in Homo sapiens

Osteoprotegerin (OPG), also known as osteoclastogenesis inhibitory factor (OCIF) or tumour necrosis factor receptor superfamily member 11B (TNFRSF11B), is a cytokine receptor of the tumour necrosis factor (TNF) receptor superfamily encoded by the TNFRSF11B gene.

<span class="mw-page-title-main">Osteocyte</span> Mature osteoblasts which helps in communication between cells and also in molecular synthesis

An osteocyte, an oblate shaped type of bone cell with dendritic processes, is the most commonly found cell in mature bone. It can live as long as the organism itself. The adult human body has about 42 billion of them. Osteocytes do not divide and have an average half life of 25 years. They are derived from osteoprogenitor cells, some of which differentiate into active osteoblasts. Osteoblasts/osteocytes develop in mesenchyme.

<span class="mw-page-title-main">Bone resorption</span> Medical condition

Bone resorption is resorption of bone tissue, that is, the process by which osteoclasts break down the tissue in bones and release the minerals, resulting in a transfer of calcium from bone tissue to the blood.

<span class="mw-page-title-main">RANKL</span> Mammalian protein found in Homo sapiens

Receptor activator of nuclear factor kappa-Β ligand (RANKL), also known as tumor necrosis factor ligand superfamily member 11 (TNFSF11), TNF-related activation-induced cytokine (TRANCE), osteoprotegerin ligand (OPGL), and osteoclast differentiation factor (ODF), is a protein that in humans is encoded by the TNFSF11 gene.

<span class="mw-page-title-main">Tartrate-resistant acid phosphatase</span> Protein-coding gene in the species Homo sapiens

Tartrate-resistant acid phosphatase, also called acid phosphatase 5, tartrate resistant (ACP5), is a glycosylated monomeric metalloprotein enzyme expressed in mammals. It has a molecular weight of approximately 35kDa, a basic isoelectric point (7.6–9.5), and optimal activity in acidic conditions. TRAP is synthesized as latent proenzyme and activated by proteolytic cleavage and reduction. It is differentiated from other mammalian acid phosphatases by its resistance to inhibition by tartrate and by its molecular weight.

<span class="mw-page-title-main">Denosumab</span> Human monoclonal antibody

Denosumab is a human monoclonal antibody for the treatment of osteoporosis, treatment-induced bone loss, metastases to bone, and giant cell tumor of bone.

<span class="mw-page-title-main">Strontium ranelate</span> Chemical compound

Strontium ranelate, a strontium(II) salt of ranelic acid, is a medication for osteoporosis marketed as Protelos or Protos by Servier. Studies indicate it can also slow the course of osteoarthritis of the knee. The drug is unusual in that it both increases deposition of new bone by osteoblasts and reduces the resorption of bone by osteoclasts. It is therefore promoted as a "dual action bone agent" (DABA).

Senile osteoporosis has been recently recognized as a geriatric syndrome with a particular pathophysiology. There are different classification of osteoporosis: primary, in which bone loss is a result of aging and secondary, in which bone loss occurs from various clinical and lifestyle factors. Primary, or involuntary osteoporosis, can further be classified into Type I or Type II. Type I refers to postmenopausal osteoporosis and is caused by the deficiency of estrogen. While senile osteoporosis is categorized as an involuntary, Type II, and primary osteoporosis, which affects both men and women over the age of 70 years. It is accompanied by vitamin D deficiency, body's failure to absorb calcium, and increased parathyroid hormone.

An endocrine bone disease is a bone disease associated with a disorder of the endocrine system. An example is osteitis fibrosa cystica.

Milk basic protein (MBP) is a fraction of whey protein found in milk. Separated from milk through the process of fractionation, it is a functional compound and consists of several milk proteins which are biologically active. The composition is approximately 54% lactoferrin and 41% lactoperoxidase, with other active proteins, such as Cyastin C and high mobility group-like proteins, making up the remainder of the fraction. MBP has been evaluated for safety and is intended for use as a dietary ingredient. It is approved in Japan as a functional food ingredient in tofu and nattō.

<span class="mw-page-title-main">Eldecalcitol</span> Chemical compound

Eldecalcitol is an analog of calcitriol, the active form of vitamin D.

A bone growth factor is a growth factor that stimulates the growth of bone tissue.

References

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  2. ↑ "National Hospital Discharge Survey (NHDS)". National Center for Health Statistics. Archived from the original on 30 November 2013. Retrieved 24 November 2013.
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  7. ↑ Sherman, H. C.; Gettler, A. O. (1 May 1911). "The balance of acid-forming and base-forming elements in foods, and its relation to ammonia metabolism". Experimental Biology and Medicine. 8 (5): 119–20. doi:10.3181/00379727-8-71. S2CID   81933816.
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  13. ↑ Lucas, FL; Cauley, JA; Stone, RA; Cummings, SR; Vogt, MT; Weissfeld, JL; Kuller, LH (Jul 1, 1998). "Bone mineral density and risk of breast cancer: differences by family history of breast cancer. Study of Osteoporotic Fractures Research Group". American Journal of Epidemiology. 148 (1): 22–29. doi: 10.1093/oxfordjournals.aje.a009554 . PMID   9663400.
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  15. ↑ Bonjour, JP (October 2013). "Nutritional disturbance in acid-base balance and osteoporosis: a hypothesis that disregards the essential homeostatic role of the kidney". The British Journal of Nutrition. 110 (7): 1168–77. doi:10.1017/S0007114513000962. PMC   3828631 . PMID   23551968.
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  17. 1 2 3 Vacek, TP; Kalani, A; Voor, MJ; Tyagi, SC; Tyagi, N (Mar 1, 2013). "The role of homocysteine in bone remodeling". Clinical Chemistry and Laboratory Medicine. 51 (3): 579–90. doi:10.1515/cclm-2012-0605. PMC   3951268 . PMID   23449525.
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