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Background Information on Bone Health
Bone formation
Bone starts forming in the fetus in the 3rd month of pregnancy from a special type of cell called the mesenchymal cell, which derives from stem cells. This bone forming process is a dynamic, lifelong process in which old bone tissue is removed and new bone tissue is added. Our bone continues to grow bigger and stronger until about the age of 30 when it reaches its peak. From that point on, our bone starts to lose its mineral content (bone mineral density) and structural strength.
Osteoporosis
Osteoporosis is a generalized, progressive diminution of bone mass resulting in bone structure weakness. This is a "silent disease" which progresses without obvious symptoms. Commonly found among older adults, osteoporosis was once thought to be a natural part of aging among women, but as we now know it is not age or gender-dependent.
Causes of osteoporosis
Osteoporosis is caused by an imbalance in the bone remodeling (rebuilding) process. This process is made up of two components: the bone formation and the bone resorption (removal) processes. Usually, the removal and formation of bone are in perfect balance and skeletal strength and integrity is maintained. After approximately
age 30 in women, bone resorption (removal) may begin to outpace bone formation.
When women reach menopause, usually between the age of 45 and 55, bone resorption (removal) significantly exceeds formation. The activity of the osteoblasts (the cells that initiate bone formation) cannot keep up with the activity of the osteoclasts (the cells that initiate bone removal), and women begin to lose bone more rapidly. This places them at increased risk for developing osteoporosis and bone fractures.
Dealing with osteoporosis
Several actions have been employed to slow down the progression of bone loss: a balanced diet rich in calcium and vitamin D3, weight-bearing exercises, a healthy lifestyle with no smoking and moderate consumption of alcohol, and taking prescription drugs.
Osteoporosis medications such as Bisphosphonates, Calcitonin, Estrogen / Hormone replacement (HRT), and selective Estrogen Receptor Modulators are frequently used to combat osteoporosis. Unfortunately, these medications are also associated with serious adverse side effects: increased rate of bone conversion and associated hypercalcaemia and idiopathic hypercalciuria (too much vitamin D intake), increased risk of breast cancer (HRT), and nausea (Phosphonates). Additionally, treatments such as Calcitonin are expensive and are administered by injection.
But more and more people are now embracing the natural alternatives and the limited research in this field has shown that they are just effective in many cases.
Osteoporosis Exercise
Often overlooked is osteoporosis exercise. Along with medication or other forms of osteoporosis treatment, one should not discount the benefits of a basic fitness regimen.
Bone remodeling (rebuilding) process
Bone remodeling is a dynamic, lifelong process in which old bone tissue is removed from the skeleton and new bone tissue is added. It consists of two distinctive stages, resorption (removal) and formation, that involve the activity of special cells called osteoclasts and osteoblasts. Usually, the removal and formation of bone are in balance and bone's skeletal strength and integrity are maintained. But as we grow older, the resorption (removal) activity outpaces the formation
activity and we start losing minerals in the bone and its structural strength is also weaken. It is a natural part of aging. But there are ways we can slow down this progression as you will learn in the following sections when you read on.
Bone formation process
The bone formation process is initiated and affected by many factors, such as estrogen and PTH (parathyroid hormone) levels in human body. The key cell that initiates and proliferates the bone formation activity is the osteoblasts. The process (osteogenesis) itself involves three main steps: 1). production of the extra cellular organic matrix (osteoid); 2). mineralization of the matrix to form bone; 3). and bone remodeling by resorption (removal) and reformation. The cellular activities of osteoblasts, osteocytes, and osteoclasts are essential to the process.
Osteoblasts synthesize the collagenous precursors of bone matrix and also regulate its mineralization. As the process of bone formation progresses, the osteoblasts come to lie in tiny spaces (lacunae) within the surrounding mineralized matrix and are then called osteocytes.
Bone resorption (removal) process
The speed or rate of bone resorption (removal) is controlled by how fast the osteoclasts (cells that break down old bone tissue) are formed and matured. This is because mature osteoclasts release acid to dissolve hydroxypeptide and matrix protein, which hold minerals at the bone area, and result in the release of bone minerals. Consequently bone density becomes lower after resorption.
The endocrine pathway regulates the formation of the osteoclasts, which originate from the heamatopoietic stem cell. In general, osteoblasts, monocytes and T-Lymphocytes release growth factors to stimulate the formation of osteoclasts. Research has indicated that estrogen regulates the monocytes to inhibit the release of IL-1 (Interleukin-1) and TNF (Tumor necrosis factor) and reduces the formation of osteoclasts. Vitamin D3, Parathyroid Hormones (PTH), PTH-related peptide (PTHrP) and prostaglandins of the E series (PGEs) act on osteoblastic stromal cells to release inhibiting cytokines, which would also reduce the formation of osteoclasts.
Osteoclasts are apparently activated by "signals" from osteoblasts. For example, osteoblasts have receptors for PTH whereas osteoclasts do not, and PTH-induced osteoclastic bone resorption is said not to occur in the absence of osteoblasts.
In vitro (test tube) study
This type of research aims at describing the effects of an experimental variable on a subset of an organism's constituent parts. It tends to focus on organs, tissues, cells, cellular components, proteins, and/or biomolecules. Overall, it is better suited for deducing the mechanisms of action. With fewer variables and perceptually amplified reactions to subtle causes, results are, generally, more discernable.
The massive adoption of low-cost in vitro molecular biology techniques has caused a shift away from in vivo research which is more idiosyncratic and expensive in comparison to its molecular counterpart. Currently, in vitro research is both vital and highly productive.
Measuring changes in the bone formation process in a test tube (in vitro) environment
There are many biological indicators in a life form that researchers can use in vitro studies to indirectly measure the activity of osteoblasts, and thus, make an inference on the change in its number and activity. ALP (alkaline phosphate) and OPG (osteoprotegerin) are two of them. There is also a direct way of cultivating the osteoblasts and count the numbers before and after adding the experimental substance of choice. In NuLiv's case, it is the OsteoSine Complex™.
Measuring changes in bone resorption (removal) process in test tube (in vitro) environment
Osteoclasts formation requires the presence of RANKL (Receptor Activator for Nuclear Factor k B Ligand) and M-CSF (Macrophage Colony-stimulating factor). These membrance bound proteins are produced by neighboring stromal cells and osteoblasts; thus requiring direct contact between these cells and osteoclast precursors. M-CSF acts through its receptor on the osteoclast, c-fms (colony stimulating factor 1 receptor), a transmembrance tyrosine kinase-receptor, leading to secondary messenger activation of tyrosine kinase Src. Both of these molecules are necessary for osteoclastogenesis and are widely involved in the differentiation of monocyte cells. RANKL is a member of the tumour necrosis family (TNF), and is essential in osteoclastogenesis.
In vivo (animal) study
This type of research approaches subject experimentation holistically. It is often better suited for observing the overall effects of an experiment on its living subject. In vivo research has an advantage in that: Whether the aim is to discover drugs or to gain knowledge of biological systems, the nature and properties of a chemical tool cannot be considered independently of the system it is to be tested in.
Measuring bone mineral density and bone strength in animal (in vivo)
There are many biochemical substances in animals researchers can utilize to measure changes in their bone mineral density and bone structure. b-ALP (alkaline phosphatase in bone), S-TRAP (tartrate resistant acid phosphatase in serum), and S-BGP (osteocalcin in serum) are some of them. In addition, we can directly measure the bone ash weight, the weights of calcium and phosphate
in bone ash, the weight of lumber spine and femoral head (g/cm2) trabecula surface, the average surface and width of trabecula.
Measuring bone mineral density and bone structural integrity in human
Dual Energy X-ray Absortiometry, or DEXA scanning, is currently the most widely used method to measure bone mineral density. When compared with radiographic absortiometry or single energy x-ray absortiometry, DEXA scanning more precisely documents small changes in bone mass and is also more flexible since it can be used to examine both the spine and the extremities.
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