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。目前治疗骨质疏松症的方法，如膳食钙补充剂、雌激素替代疗法、双磷酸盐和降钙素，都旨在降低骨吸收的速度。在抗吸收治疗中，由于成骨细胞/破骨细胞的偶联作用，骨的形成最终受到限制。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，还与抑制骨吸收的矿化前沿结合。在啮齿动物体内的研究发现，米诺环素可以促进骨形成，并抑制骨吸收。这项研究旨在确定200毫克/天的米诺环素和800毫克/天的钙，以及400IU的维生素D是否可以在毒性最小的情况下增加骨密度。这项研究的结果是基于参与研究的四名女性。进一步的招聘没有成功。在随机调查的四名女性中，所有四人都在服用米诺环素。一名患者在接受药物治疗和再次挑战时，因不明原因的恶心、呕吐和腹痛而在4.5个月后终止研究。在持续到全年的三组中，观察到骨密度损失最小(股骨颈平均为0.016毫克/厘米~2；全脊柱平均为0.012克/厘米~2)。在6个月时，股骨颈的骨密度变化最小，为-0.007，整个脊柱的变化为0.002。血清碱性磷酸酶在6个月和12个月时分别升高3和9.5 mg/dL。总之，这项研究不能证明米诺环素通过改变骨密度或血清碱性磷酸酶来延缓骨丢失的效果。毒性仍然令人担忧，因为每四名患者中就有一人有明显的副作用。

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.