Bone disease osteoporosis

The bone disease osteoporosis results when an imbalance occurs in the normal course of bone remodeling, a dynamic and highly regulated... 

Contraindications Primary or secondary hyperparathyroidism, including hypercalci-uria (renal calcium leak), hypomagnesemic states (serum magnesium less than 1.5 mg/dl), bone disease (osteoporosis, osteomalacia, osteitis), hypocalcemic states (e.g., hypoparathyroidism, intestinal malabsorption), normal or low intestinal absorption and renal excretion of calcium, enteric hyperoxaluria, and patients with high fasting urinary calcium or hypophosphatemia. 

In contrast to these rarer bone diseases, osteoporosis is a very common disease affecting men and women as they age. It is associated with a loss of bone (mainly trabeculae) and an increased risk of fracture. IR has enabled significant differences between normal and osteoporotic tissues to be identified. Osteoporotic animals and humans have fewer trabeculae, but in the trabeculae that are present the mineral content is reduced (Fig. 11.4(a)) while the crystallinity and collagen maturity are increased (Fig. 11.4(b) and (c)). Moreover, there is a distinct difference in the distribution of these parameters as a function of distance from the surface of the trabeculae. This is illustrated for four cases (three osteoporotic and one control) in which a line was drawn across the trabecular width to detect these parameters (Fig. 11.4(d)) but this is seen throughout every biopsy and in all biopsies examined for osteoporotic or normal control patients. 

In contrast to many bone diseases, osteoporosis is often characterized by modest alterations in bone turnover, and thus only small changes may occur during therapy. A period of 1 to 3 years must pass before measurements of bone mass (for example, dual energy x-ray absorptiometry) can identify statistically significant changes in bone mass during therapy. Measurements of bone markers provide earlier assessments of bone resorption and/or formation. Because most current therapies are antiresorptive and resorption markers respond more quickly to these therapies, resorption markers have received the greatest attention. 

HCl-to relieve gaseous distress, stomach pain, and heartburn. The compound can also he used to treat potassium deficiency in the body. Some research suggests that potassium bicarbonate may help restore muscle and bone tissue, particularly in women with the degenerative bone disease osteoporosis. The compound is also used as a food additive, as a leavening agent, to maintain proper acidity in foods, to supply potassium to a diet, and to provide the bubble and fizz in carbonated drinks. 

Exaggerated osteoclast activation leads to another bone disease — osteoporosis. In an ovariectomized rat model, the estrogen deficiency induces osteoporosis, which was reversed by continuous administration of NF-kB decoy using an osmotic pump. The reversal was indicated by attenuation of TRAP activity, significant increase in calcium concentrations in the femur and tibia, and a decrease in urinary deoxypyridinoline. In agreement, NF-kB decoy ODN infusion in an osteoporosis model of vitamin C-deficient rat dramatically improved the bone length, weight, and mineral density, as assessed by DEXA [24]. 

Total synthesis of f-t -deoxypyiTobrine, a potential biochemical marker for diagnosis of osteoporosis, is shown in Eq 10 25 Osteoporosis is a cripphng degenerative bone disease that affects the aged populadon, particularly postmenopausff women... 

Due to its anti-resorptive effects, calcitonin has been widely used to treat a variety of metabolic bone diseases, including osteoporosis. However, the availability of more potent drugs has lead to a decline in the clinical use of calcitonin. 

Furthermore, peptidomimetic SH2 domain inhibitors for Src, such as AP-22408 have been designed that interfere with effector binding and thereby disrupt signal transduction. AP-22408 decreases bone resorption in animal studies and may be a promising drug to treat osteoporosis and other bone diseases, such as Paget s disease and osteolytic bone metastasis. 

Several other inhibitors of nonreceptor PTKs are currently in development but only a few of them are studied in clinical trials. Noteworthy, Dasatinib does not only inhibit c-Abl, but also potently blocks Src activity, a property that may contribute to its beneficial clinical effects in CML. Other kinase inhibitors being developed that inhibit c-Abl and/or Src are AZD-0530, AP-23994, PD-0183805, SU-6656, and Bosutinib (SKI-606). Furthermore, peptidomimetic SH2 domain inhibitors for Src, such as AP-22408 have been designed that decrease bone resorption and may be promising drugs to treat osteoporosis and other bone diseases, such as Paget s disease and osteolytic bone metastasis. 

See Chap. 93, Osteoporosis and Other Metabolic Bone Diseases, authored by Mary Beth O Connell and Sheryl F. Vondracek, for a more detailed discussion of this topic. 

Bone is the main source of calcium in the human body. Osteoporosis, decreased calcium salt reserves in the body, has become the most prevalent bone disease in the U.S., being especially prevalent among post-menopausal women (1). Typical signs of this debilitating condition include backache with spasms, wedge fractures of the dorsal and lumbar vertebrae, and hip fractures (2). 

Rosen, C. J., and Kiel, D. P. (2006). Age-related osteoporosis. In Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism" (M. J. Favus, ed.), American Society for Bone and Mineral Research, Washington, DC. 

Osteoporosis is a metabolic bone disease characterized by low bone mass and micro-architectural deterioration of bone tissue. This will lead to bone fragility and consequent increase in bone fracture risk. Mean bone mineral density (BMD) is measured with dual X-ray absorptiometry (DEXA) and expressed in Tsc (Tscore). WHO standards are a Tsc that is 1 standard deviation (SD) below mean BMD is graded as normal bone, Tsc between 1 and 1.5 SD below mean BMD is graded as osteopenia and a Tsc of more than 2.5 SD below mean BMD is graded as osteoporosis. When the Tsc is below 1.5 SD mean BMD prevention of osteoporosis must be initiated. Primary osteoporosis is caused mainly by hormone deflciency in both women and men. Secondary osteoporosis may result from endocrine, metabolic, nutritional and autoimmune causes or from immobility because of trauma. Also the use of medicaments such as corticosteroids may be contributing. 

A variety of diseases can affect bone and its structure. Paget s disease, for example, is a disorder arising from abnormal osteoclasts, characterized by exeessive bone resorption followed by replacement of the normal mineralized bone with structurally weak, poorly mineralized tissue. However, the most important bone disease is osteoporosis. This is a skeletal bone disease characterized hy microarchitectural deterioration of bony tissue and loss of bone mass, yielding increased susceptibility to bone fracture and bone fragility. In the United States, osteoporosis results in 1.5 million hone fractures annually, with 250,000 of these being hip fractures that sometimes ultimately culminate in patient death. There is a variety of therapies for the prevention and treatment of osteoporosis. 

It is indicated in osteoporosis, hypoparathyroidism, hyperparathyroidism (with bone disease), renal osteodystrophy, nutritional and malabsorptive rickets, hypophosphataemic vitamin D resistant rickets and osteomalacia. 

A number of gastrointestinal and hepatic diseases result in disordered calcium and phosphate homeostasis, which ultimately leads to bone disease. The bones in such patients show a combination of osteoporosis and osteomalacia. 

A number of gastrointestinal and hepatic diseases result in disordered calcium and phosphate homeostasis that ultimately leads to bone disease. The bones in such patients show a combination of osteoporosis and osteomalacia. Osteitis fibrosa does not occur (as it does in renal osteodystrophy). The common features that appear to be important in this group of diseases are malabsorption of calcium and vitamin D. Liver disease may, in addition, reduce the production of 25(OH)D from vitamin D, though the importance of this in all but patients with terminal liver failure remains in dispute. The malabsorption of vitamin D is probably not limited to exogenous vitamin D. The liver secretes into bile a substantial number of vitamin D metabolites and conjugates that are reabsorbed in (presumably) the distal jejunum and ileum. Interference with this process could deplete the body of endogenous vitamin D metabolites as well as limit absorption of dietary vitamin D. 

Osteolytic bone diseases or bone resorption the most important clinical application of BPs is as inhibitors of osteolytic bone diseases, including osteoporosis, tumor-related bone destruction, and Paget s disease. These are discussed in detail in the next section. 

The polypeptide calcitonin is secreted by thyroid C-cells during imminent hypercalcemia. It lowers elevated plasma Ca2+ levels by inhibiting osteoclast activity. Its uses include hypercalcemia and osteoporosis. Remarkably, calcitonin injection may produce a sustained analgesic effect that alleviates pain associated with bone diseases (Paget disease, osteoporosis, neoplastic metastases) or Sudek syndrome. 

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