[New drugs with positive effects on bones].
The paper concerns the nontraditional treatment of osteoporosis using endogenous substances regulating bone metabolism, and also new drugs. NO in high concentrations decreases the activity of osteoclasts, scavenges superoxides which destroy connective tissue, and activates 1 alpha-hydroxylase in kidneys. Bone metabolism is effectively influenced by donors of NO or by modulators of NO synthase. Osteoclastic function is also inhibited by vitamin K. The administration of the vitamin is indicated in osteoporotic patients with proven vitamin K deficiency. Antiestrogens (tamoxifen), ipriflavon and analogues of wortmannin have antiresorptive activity. Under certain conditions parathyroid hormone (PTH) is anabolic for bone. The positive effect on bone was confirmed with the subcutaneous administration of small doses of PTH simulating physiologic pulsatile secretion, as well as the intact somatotropin-IGF-I (insulin like growth factor-I) axis. PTH is extremely useful, especially in osteoporosis induced by hypoestrinism. Somatotropin (GH) also has an anabolic effect on bone. The hormone stimulates bone metabolism with a prevalence of formation due to direct action on bone, as well as by means of IGF-I. Further growth factors with positive osteoprotic effect are TGF-beta (transforming growth factor-beta), FGF (fibroblast growth factor) and calcium conserving dihomogammalinoleic acid. Magnesium influences bone in different ways. It activates osteoblasts, increases bone mineralization, and enhances the sensitivity of target tissues (incl. bone) to PTH and 1,25(OH)2 vitamin D3, Under certain conditions however, magnesium can stimulate bone resorption. A more potent factor than magnesium is stroncium, which not only activates osteoblats but decreases the number of osteoclasts, thus abolishing bone resorption and enhancing formation. Bicarbonates are also favourable for bone. NaHCO3 together with potassium citrate stimulates osteoblasts and enhances bone mineralisation. In the review other prospective substances are also discussed. The osteoprotic effects of most of these factors were confirmed in vitro and in studies in animals, but their use in clinical practice is still a matter for investigation. Mutual interactions with classical osteoprotic drugs remain to be established.
Zofková
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Endokrinologický ústav, Praha.
Kanceva
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RL
D000818:Animals; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism*; D013006:Growth Hormone / Q000494:pharmacology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology; D010024:Osteoporosis / Q000188:drug therapy / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology; D013268:Stimulation, Chemical; D013324:Strontium / Q000494:pharmacology; D014812:Vitamin K / Q000494:pharmacology
D010281:Parathyroid Hormone; D014812:Vitamin K; D009569:Nitric Oxide; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D008274:Magnesium; D013324:Strontium