Osteoporosis humans

Human growth hormone, used as a human pharmaceutical, is approved for only one indication in the United States, treatment of growth failure owing to hGH deficiency, a condition known as pituitary dwarfism. However, clinical trials are under way to test its efficacy in Turner s syndrome, bums, wound healing, cachexia, osteoporosis, constitutional growth delay, aging, malnutrition, and obesity. 

In the treatment of diseases where the metaboUtes are not being deUvered to the system, synthetic metaboUtes or active analogues have been successfully adrninistered. Vitamin metaboUtes have been successfully used for treatment of milk fever ia catde, turkey leg weakness, plaque psoriasis, and osteoporosis and renal osteodystrophy ia humans. Many of these clinical studies are outlined ia References 6, 16, 40, 51, and 141. The vitamin D receptor complex is a member of the gene superfamily of transcriptional activators, and 1,25 dihydroxy vitamin D is thus supportive of selective cell differentiation. In addition to mineral homeostasis mediated ia the iatestiae, kidney, and bone, the metaboUte acts on the immune system, P-ceUs of the pancreas (iasulin secretion), cerebellum, and hypothalamus. 

Four of the main-group cations are essential in human nutrition (Table A). Of these, the most important is Ca2+. About 90% of the calcium in the body is found in bones and teeth, largely in the form of hydroxyapatite, CatOH)2 - SCa PO. Calcium ions in bones and teeth exchange readily with those in the blood about 0.6 g of Ca2+ enters and leaves your bones every day. In a normal adult this exchange is in balance, but in elderly people, particularly women, there is sometimes a net loss of bone calcium, leading to the disease known as osteoporosis. 

A peptide hormone rapidly inhibiting osteoclast activity. The relevance of calcitonin in human calcium homeostasis is not well understood. Calcitonin has been used for the treatment of osteoporosis, although due to the availability of more potent drugs with less side effects, and the lack of clear data on the anti-fracture efficacy of calcitonin, its clinical use has been steadily declining. 

Human somatotropin 191 amino acids E. coll Pituitary dwarfism Approved for sale If useful in treatment of osteoporosis then market size will be much larger Has additional methionine residue at N-terminus, but technology for removing this now available... 

In order to get recent advances on the effects of phytoestrogens on hormonal-dependent diseases as well as on human supplementation trials, it might be useful to refer to http //www.venus-ca.org/ (EU-funded project on dietary exposure to phytoestrogens and related compounds and effects on skeletal tissues) http //www.phytos.org (EU-funded project on the prevention of osteoporosis by nutritional phytoestrogens) http //www.phytoprevent.org (EU-funded project on the role of phytoestrogens in the prevention of breast and prostate cancer) and http //www.nutrition.tum.de/isoheart.htm (EU-funded project on cardiovascular health of postmenopausal women). 

An alternative therapeutic approach to osteoporosis is through the use of calcitonin (798), a peptide hormone containing 32 amino acids (the sequence is species dependent) secreted by the thyroid gland, which stimulates the production of new bone. Synthetic calcitonins corresponding to human, eel, and salmon variants, and natural calcitonin extracted from pig thyroid, are all used in medicine - they have slightly different efficacies, side effects, and tolerance levels (799). 

Miproxifene (TAT-59) is a prodrug of 4-hydroxy-tamoxifen that has been developed for tamoxifen-resistant carcinoma, but relatively little information has been published on this drug. Compared with tamoxifen, miproxifene inhibits estradiol-stimulated proliferation of MCF-7 cells at a threefold lower dose than that of tamoxifen, and of dimethyl-benzanthracene (DMBA)-induced rat mammary tumors at a dose tenfold lower than tamoxifen (Toko et al. 1990). In any event, in preclinical castrated rat models, it shows an endometrial stimulation activity that is similar to that of tamoxifen, which means it has limited potential use in the prevention or treatment of osteoporosis or cardiovascular disease (Shibata et al. 2000). Similarly, considering the preclinical findings of endometrial stimulation reported on GW5638 (Willson et al. 1997), it is likely that this new SERM belonging to the triphenylethylene family will be limited in clinical use to the treatment of advanced tamoxifen-resistant breast cancer once its efficacy is demonstrated in human clinical trials. 

Pacifici R, Rifas L, Teitelbaum S, Slatopolsky E, McCracken R, Bergfeld M, Lee W, Avioli LV, Peck WA (1987) Spontaneous release of interleukin 1 from human blood monocytes refiects bone formation in idiopathic osteoporosis. Proc Nad Acad Sci USA 84 4616-4620... 

Research in humans has been mainly focused either in the prevention of osteoporosis in healthy postmenopausal women or in the treatment of already osteoporotic women. Some research programs have extensively used estimates of biochemical markers of bone remodeling, while others have mostly relied on evaluations of BMD, histomorphometry, and fracture incidence. 

Hodgskinson R, Currey JD (1993) Separate effects of osteoporosis and density on the strength and stiffness of human cancellous bone. Clin Biomech 8 262-268... 

The standard model for the preclinical development of anti-osteoporosis therapies is the ovariectomized (OVX) rat. However, Cat K inhibitors developed specifically against the human enzyme are generally significantly less potent ( 2-orders of magnitude) against the rat and mouse enzymes than against human Cat K [9]. This loss of potency towards the rodent enzymes, which is consistent with their low sequence homology, therefore restricts the use of... 

Such acid and calcium excretion may be important in development of osteoporosis. To test diets of meat and vegetable protein upon urinary acid and calcium, nine human adults, aged 22 to 69 years, were fed isonitrogenous diets of chicken or soy beans in seven-day feeding periods. Diets provided daily ... 

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). 

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