EFFECT OF MINOCYCLINE IN POSTMENOPAUSAL OSTEOPOROSIS

骨质疏松症是美国女性和男性的主要健康问题。目前骨质疏松症的治疗方法，如膳食钙补充剂、雌激素替代疗法、双膦酸盐和降钙素，旨在降低骨吸收率。由于成骨细胞/破骨细胞偶联，骨形成在抗吸收治疗期间最终受到限制。已知四环素及其衍生物除了抑制哺乳动物胶原酶和甲状旁腺激素诱导的骨吸收外，还与骨矿化前沿结合，抑制骨吸收。在啮齿动物体内的研究发现米诺环素增加骨形成，以及抑制骨吸收。这项研究旨在确定米诺环素在200毫克/天与800毫克/天的钙，400国际单位的维生素D是否可以增加骨密度，毒性最小。这项研究的结果是基于参加研究的四名妇女。进一步的招聘没有成功。在随机分配的四名女性中，所有四名都服用米诺环素。1例患者在4.5个月时因药物治疗和再激发期间不明原因的恶心、呕吐和腹痛而中止研究。在持续到全年的3例患者中，观察到骨矿物质密度的最小损失（股骨颈平均值为0.016 mg/cm 2;全脊柱为0.012 gm/cm 2）。6个月时，股骨颈骨密度变化最小，为-0.007，全脊柱为0.002。在6个月和12个月时，血清碱性磷酸酶升高3和9.5 mg/dL。总之，本研究无法通过骨密度或血清碱性磷酸酶的变化证明米诺环素在延缓骨丢失方面的作用。毒性仍然是一个令人担忧的问题，因为四分之一的患者有明显的副作用。

Osteoporosis is a major health problem for women and men in the United States. Current treatments for osteoporosis, such as dietary calcium supplements, estrogen replacement therapy, bisphosphonates, and calcitonin, are aimed at decreasing the rate of bone resorption. Bone formation is eventually limited during antiresorptive therapy due to osteoblast/osteoclast coupling. Tetracycline and its derivatives are known to bind to the mineralization front of bone-inhibiting bone resorption, in addiition to inhibiting mammalian collagenase and parathyroid hormone- induced bone resorption. In vivo studies in rodents have found minocycline to increase bone formation, as well as inhibiting bone resorption. This study was designed to determine whether minocycline at 200 mg/day with 800 mg/day of calcium, and 400 IU of vitamin D can increase bone mineral density with minimal toxicity. Results of this study are based on the four women who entered the study. Further recruitment was unsuccessful. Of the four women randomized, all four were on minocycline. One patient discontinued the study at 4.5 months secondary to unexplained nausea, vomiting, and abdominal pain while on drug therapy and with rechallenge. Of the three that continued to the full year, minimal loss of bone mineral density was observed (average 0.016 mg/cm2 at femoral neck; 0.012 gm/cm2 at total spine). At six months, changes in bone mineral density were minimal at -0.007 femoral neck and 0.002 for total spine. Serum alkaline phosphatase demonstrated increases by 3 and 9.5 mg/dL at six and twelve months. In conclusion, this study was unable to demonstrate effects of minocycline in retardation of bone loss either by changes in bone mineral density or in serum alkaline phosphatase. Toxicity remains a concern in that one in four patients had significant side- effects.