Kimmel D B, Slovik D M, Lane N E
Creighton University School of Medicine, Omaha, Nebraska.
Rheum Dis Clin North Am. 1994 Aug;20(3):735-58.
Osteoporosis is a disease of elderly women marked by low bone mass and increased risk of fracture. Though its prevalence can be reduced by timely estrogen replacement at menopause, many persons present with fragility fractures long after much bone has been lost. Osteoporotic subjects have low bone mass and poor structure but few or no metabolic abnormalities, such as ongoing bone loss, for treatment to normalize. The problem is to increase their bone mass and improve their bone structure. Today's major therapeutic approaches are summarized in Table 2. Ironically, they aim at stopping bone loss. Although preventing the skeleton of an osteoporotic person from growing weaker by stopping bone loss is better than allowing the process to continue, raising her to a significantly higher level of bone mass would be a better aim. Existing agents that stop bone loss by reducing turnover also increase bone mass mildly by filling the remodeling space. The result is a rise in bone mass during the first year or two of treatment to a new steady state 2% to 5% higher than baseline that persists throughout treatment. Fluoride increases spinal bone mass markedly. It decreases vertebral, but not hip fractures, but is associated with side effects and a nonresponse rate that makes pursuing other therapies attractive. Agents that upregulate bone mass through regulatory means have been tested in preclinical and a few clinical trials. PGE2 has been thoroughly tested preclinically. By studying PGE2, the field has learned that marked bone mass increases in the estrogen-deplete osteopenic skeleton are possible. The lack of bone specificity for PGE2 will probably limit its use to that of preclinical demonstration agent but leave open the possibility that less potent members of the prostaglandin family with better bone specificity might have promise as osteoporosis treatments. PTH or one of its analogues shows good promise for osteoporosis treatment. The wide availability of cheap PTH or proprietary analogues with similar activity will do much to speed its development. It increases bone formation and cancellous bone mass markedly. If PTH increases bone mass consistently in either large animal or human trials while causing only mild transient cortical bone mass declines, it can be a successful osteoporosis treatment agent. Bone growth factors appear to have much untapped potential for furthering the understanding of local control of bone processes and possibly for treating osteoporosis. Another possibility is biphasic therapy.(ABSTRACT TRUNCATED AT 400 WORDS)
骨质疏松症是一种多见于老年女性的疾病，其特征为骨量低以及骨折风险增加。尽管在绝经后及时进行雌激素替代治疗可降低其患病率，但许多患者在大量骨质流失很久之后才出现脆性骨折。骨质疏松症患者骨量低且结构不佳，但几乎没有或不存在代谢异常，如持续性骨质流失等可供治疗使其恢复正常的情况。问题在于增加他们的骨量并改善其骨结构。当今主要的治疗方法总结于表2中。具有讽刺意味的是，这些方法旨在阻止骨质流失。虽然通过阻止骨质流失来防止骨质疏松症患者的骨骼变弱比任由这一过程继续要好，但将其骨量提高到显著更高的水平会是一个更好的目标。现有的通过减少骨转换来阻止骨质流失的药物，也会通过填充重塑空间而轻度增加骨量。结果是在治疗的头一两年骨量上升至一个比基线高2%至5%的新稳态，并在整个治疗过程中持续保持。氟化物可显著增加脊柱骨量。它能降低椎体骨折的发生率，但对髋部骨折无效，且伴有副作用和无反应率，这使得寻求其他治疗方法颇具吸引力。通过调节手段上调骨量的药物已在临床前和一些临床试验中进行了测试。前列腺素E2（PGE2）已在临床前进行了全面测试。通过对PGE2的研究，该领域了解到在雌激素缺乏的骨质减少的骨骼中显著增加骨量是可能的。PGE2缺乏骨特异性，这可能会限制其仅用作临床前示范药物，但也留下了一种可能性，即前列腺素家族中效力较低但具有更好骨特异性的成员可能有望用于治疗骨质疏松症。甲状旁腺激素（PTH）或其类似物之一在治疗骨质疏松症方面显示出良好的前景。廉价的PTH或具有类似活性的专利类似物的广泛可得性将极大地加速其开发。它能显著增加骨形成和松质骨量。如果PTH在大型动物或人体试验中持续增加骨量，同时仅导致皮质骨量出现轻度短暂下降，那么它可能成为一种成功的骨质疏松症治疗药物。骨生长因子在进一步理解骨过程的局部控制以及可能用于治疗骨质疏松症方面似乎有很大的未开发潜力。另一种可能性是双相治疗。（摘要截取自400字）
