EFFECT OF MINOCYCLINE IN POSTMENOPAUSAL OSTEOPOROSIS

米诺环素对绝经后骨质疏松症的作用

• 批准号: 6121421
• 负责人: JAY Robert SHAPIRO
• 金额: $ 6.52万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6121421
• 关键词: bone density; clinical research; human subject; human therapy evaluation; longitudinal human study; osteoblasts; osteoporosis; postmenopause; skeletal disorder chemotherapy; tetracyclines

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.

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，如膳食补钙、雌激素替代疗法、双膦酸盐和降钙素，旨在降低骨吸收率。在抗吸收治疗中，由于成骨细胞/破骨细胞偶联，骨形成最终受到限制。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，还与骨矿化前沿结合，抑制骨吸收。在啮齿类动物体内的研究发现二甲胺四环素增加骨形成，并抑制骨吸收。本研究旨在确定二甲胺四环素200毫克/天、钙800毫克/天、维生素D 400国际单位是否能在毒性最小的情况下增加骨密度。这项研究的结果是基于四位参与研究的女性。进一步的招募没有成功。在随机分配的四名妇女中，四人都服用二甲胺四环素。1例患者在药物治疗和再挑战期间因不明原因的恶心、呕吐和腹痛在4.5个月时停止研究。在持续一整年的3例中，观察到最小的骨矿物质密度损失（股骨颈平均0.016 mg/cm2；全脊柱平均0.012 gm/cm2）。6个月时，股骨颈骨密度变化最小，为-0.007，全脊柱为0.002。血清碱性磷酸酶在6个月和12个月时分别增加3和9.5 mg/dL。总之，本研究无法证明米诺环素通过改变骨密度或血清碱性磷酸酶延缓骨质流失的作用。毒性仍然是一个问题，四分之一的患者有明显的副作用。