治療骨質疏鬆症的藥物，在近年來進展得很快。就抑制破骨作用者而言，除各種長效型雙磷酸鹽 之外，抗細胞核因子kB受體活化因子之配體(receptor activator of nuclear factor k-B ligand, RANKL)單株抗 體denosumab已在全球上市。上述兩類均會減少骨組織内之破骨細胞數目及機能。可抑制破骨細胞分泌 之組織蛋白酶K (cathepsin-K)，抑制破骨作用但不減少破骨細胞數者，已有odanocatib。該藥已完成第三 期臨床試驗，結果似乎可接受，或將於2014年内上市。在造骨刺激藥物類中，目前有副曱狀腺素I-34胜 肽及全長之副曱狀腺胜肽製劑，供每日皮下注射使用。新的發展是日本發展的每週一次之治療方式，另 有副曱狀腺素相關胜肽(parathyroid hormone related peptide, PTHrP)及其衍化物，均於初期臨床試驗顯示良 好療效。能同時刺激造骨，抑制破骨作用者，除現有之鍶鹽外，抑硬素(sclerostin)之單株抗體，包括 romosozumab與blosozumab似乎可解除抑硬素對Wnt/ p-catenin/造骨細胞之抑制作用，及細胞核因子kB 受體活化因子之配體(RANKL)/破骨細胞之刺激作用。二者現均在進行臨床試驗，以每日一次之注射方 式，治療骨質疏鬆症患者。近來研究發現餐後小腸黏膜内的細胞可藉製造血清素(serotonin)，經血流到達 骨骼以抑制Wnt/ p-catenin /造骨細胞，所以在動物實驗裡，以不具腸吸收性之口服色胺酸水解酶-I抑 制劑來抑制小腸血清素之產生，而不影響腦部血清素濃度，可以明顯增加去勢動物之骨密度。此外，因 為一氧化氮（nitric oxide, NO)也被證實是骨細胞(osteocyte)的重要產物，可促進造骨細胞和抑制破骨細胞 的功能，最近的臨床試驗經皮給予骨密度較低之停經後婦女硝化甘油膏劑時，可比對照組更能增加造骨 指標，減少破骨指標，並明顯增加骨密度。上述兩類藥物，因具有重大臨床潛力，備受矚目。

Pharmacologic treatment for osteoporosis progressed rapidly in the past decade. Apart from the long acting bisphsosphonates, denosumab, a monoclonal antibody against RANKL/osteoclast is now also a standard semi-annual antiresorptive available globally. Both agents can reduce the numbers and functional activities of osteoclasts in bone. Odanocatib, an inhibitor of the collagen-digesting enzyme cathepsin-K which is secreted by the osteoclasts, can inhibit the bone resorption but nor affecting the numbers of osteoclasts. It just finished its phase 3 clinical trials. The results seem acceptable. It is currently waiting for approval in 2014. The currently available bone forming agents are parathyroid hormone I-34 fragment and the intact 1-84 peptide. Both are for daily injections. The new weekly administered 1-34 fragment of parathyroid hormone is available in Japan. The related drugs under clinical trials included PTHrP and PTHrP analogues, both are promising. Regarding the reagents that can inhibit bone formation and stimulates bone resorption, in addition to strontium ranelate, monoclonal antibodies to sclerostin are major products in the pipelines. Sclerostin is an osteocyte product. At least two products, romosozumab and bloszumab, may counteract the inhibitory effects of sclerostin on the Wnt /p-catenin /osteoblasts, as well as on its stimulatory effect on the receptor activator of nuclear factor k-B ligand, RANKL)/osteoclasts. These agents are undergoing clinical trials, as daily injection form for treatment of osteoporosis. Recent researches revealed that the intestinal serotonin secretary surge after a meal. It can inhibit the Wnt /p-catenin /osteoblasts and bone formation. In animal studies, an orally administered non-absorbable serotonin synthase (tryptophan hydroxylase-I) inhibitor can suppress the secretion of serotonin in intestine but not in the brain. The study showed a remarkable increase of bone mineral density in castrated rats. In addition, nitric oxide (NO) was found to be an important osteocytic product which stimulates osteoblasts and inhibits osteoclasts. A recent clinical trial reported the usage of transdermal nitroglycerin cream on a group of postmenopausal women with low bone mineral density. The results are increased bone formation markers and decreased resorption markers, As well as increased bone mineral density, as compared to the placebo control group. These two categories of new drugs deserve close observation for their good potentials.