Brittle bones

C04-0026. Cadmium ions are environmental pollutants found in mining waste, metal plating, water pipes, and industrial discharge. Cadmium ions replace zinc ions in biochemistry and cause kidney damage, high blood pressure, and brittle bones. Dissolved Cd " " impurities can be removed from a water sample... 

Reduction of 30% in milk yield rapid decline in plasma copper milk Mo levels of 1.6 mg/L growth reduction in nursing calves (6) Low liver copper, intestinal disturbances, brittle bones prone to fracture (7)... 

The question of whether the variances are not even wider than this and the compositions (including total ash content) stable enough to be distinctive for each individual is particularly interesting and important from the standpoint of the existence of Osteogenests imperfecta (brittle bones) in its various forms and related congenital bone "defects."... 

Otitis media is inflammation or infection of the middle ear and is not usually associated with back pain. Osteoporosis is a condition occurring mostly in postmenopausal women and is characterised by brittle bones caused by reduced bone mass. It is presented with pain. If it occurs in the vertebral structure the condition may be associated with chronic back pain. Pregnancy may be associated with back pain because of an increase in weight and the increased strain. 

Brittle bone disease, or osteogenesis imperfecta (01), is caused by mutations or absence of one of the genes encoding type I collagen chains, which interferes with assembly and function of the triple helix. 

Bone. Although bone is a relatively inert tissue, it can accumulate such substances as tetracyclines, lead, strontium, and the antitumor agent cisplatin. These substances may accumulate in bone by absorption onto the bone crystal surface and eventually be incorporated into the crystal lattice. Tetracycline deposition during odontogenesis may lead to a permanent yellow-brown discoloration of teeth, dysplasia, and poor bone development. Lead can substitute for calcium in the bone crystal lattice, resulting in bone brittleness. Bone may become a reservoir for the slow release of toxic substances, such as lead and cisplatin. 

The active forms of the D vitamins are la,25-dihydroxy-vitamin Dj and 25-hydroxy-vitamin Dj. They are formed by enzymatic hydroxylation in the liver microsomes and then in the kidney mitochondria by a ferredoxin flavoprotein and cytochrome P-450. The 1,25-dihydroxy vitamin is then transported to the bone, intestine, and other target organs (kidneys, parathyroid gland). Consequently, it can be considered a hormone since it is produced in one organ but used elsewhere. It mobilizes calcium and phosphate and also influences the absorption of these ions in the intestine, thus promoting bone mineralization. The hormone is also active in relieving hypoparathyroidism and postmenopausal osteoporosis, which, for example, results in the brittle bones of elderly women. 

After midlife, you begin to lose bone tissue. This can result in porous, brittle bones. Exercise actually encourages the body to keep bone tissue dense and strong. 

The importance of Gly at every third residue is seen when a mutation in the DNA leads to the incorporation of a different amino acid at just one position in the 1000 residue polypeptide chain. For example, if a mutation leads to the incorporation of Cys instead of Gly, the triple helix is disrupted as the -CH2-SH side-chain of Cys is too large to fit in the interior of the triple helix. This leads to a partly unfolded structure that is susceptible to excessive hydroxy-lation and glycosylation and is not efficiently secreted by the fibroblast cells. This, in turn, results in a defective collagen structure that can give rise to brittle bones and skeletal deformities. A whole spectrum of such mutations... 

The richest sources of vitamin C are citrus fruits (e.g., lemon, oranges), tomatoes, potatoes, green chilies, and human milk. Severe deficiency causes scurvy and is prevalent in malnourished infants, children, adults, alcoholics, and drug addicts. Symptoms such as bleeding gums, deformed teeth, brittle bones, impaired wound healing, anemia, and growth retardation are observed. 

Dangerous levels of human exposure from diet have occurred, most notably in Fuchu, in northern Japan where rice was eaten that was contaminated with cadmium derived from an old zinc mine and present in soil and water. Low calcium intake and vitamin D deficiency may also have been factors. The victims suffered from brittle bones, and it became known as itai-itai disease from the Japanese for ouch-ouch (see box). The village of Shipham in Somerset was, similarly, found to have very high levels of cadmium in the soil, which also derived from an old zinc mine. 

In osteogenesis imperfecta, the child has brittle bones , which fracture easily. There may also be blue sclerae, hearing defects, and dental abnormalities. There are a variety of forms of this condition that involve defects in the structure of collagen. 

Congenital diseases (diseases present at birth) of connective tissne (a group of tissues of the body which includes bone) can cause abnormalities of bone structure, and therefore osteoporosis. Such diseases include osteogenesis imperfecta (brittle bone disease) and Marfan syndrome. 

McKenzie, John. Study Depression Causes Brittle Bones. ABC News, January 13, 2007. Available at http //abcnews.go.com/WNT/Depression/ story id= 129893. 

Osteoporosis is a different disease. It can be ttiought of as osteoclast cells removing calcium more quickly that osteoblast cells car lay calcium down The result is porous, brittle bones that break easily. At one time calcitonin some-limes was prescribed to decrease the release of caldum from bone by osteoclast cells. In addition to the bisphosphonates and impact exercise, Lum with D vitamins is currently recom-bended to replace calcium being released from me and excreted through the kidney. 

Mutations that interfere with collagen fiber formation mostly cause lethal or nonlethal osteogenesis imperfecta, also known as brittle bone disease. The bones break easily and apparently spontaneously. The disorder occurs in about one in 50,000 live births in the US. Osteogenesis imperfecta is clinically divided by whether the teeth are also affected. They may appear opalescent blue-gray or yellow-brown because of abnormal dentin calcification. 

When ODAR attaches to the osteoblast surface-bound ODF, the receptor/ligand complex activates a membrane-associated tyrosine-protein kinase to induce synthesis of the ruffled membrane. A tyrosine residue on C1IC-5 (Sect. 10.1.4) is phosphorylated by an activated protein kinase, called c-src, the normal cytosolic homologue of a viral tyrosine kinase which causes a sarcoma (transforms fibroblasts into cancer cells). The phosphorylated C1IC-5 interacts with phospholipids, a chloride channel protein (C1C-7) and two transporter proteins, the ATPase proton transporter, and the proton-dependent phosphate transporter. Mutations that suppress c-src or prevent expression or functioning of C1C-7 or C1IC-5 in mice or humans prevent osteoclast development and cause overly dense, brittle bones (osteopetrosis). 

Mice overexpressing acid phosphatase (Acp5) develop osteoporosis whereas mice lacking this enzyme have decreased bone resorption and develop mild osteopetrosis (overly dense, brittle bones). Fluoride at 0.12 mM (2.3 ppm) inhibits Acp5b and stimulates osteoblast bone deposition in vitro, but fluoride therapy does not inhibit human osteoporosis (Sect. 16.2.2). 

J. C. Marini Osteogenesis imperfecta—managing brittle bones. New England Journal of Medicine 339, 986 (1998). 

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