Effects of different regimens of sodium fluoride treatment for osteoporosis on the structure, remodeling and mineralization of bone
Effects of different regimens of sodium fluoride treatment for osteoporosis on the structure, remodeling and mineralization of bone
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DOI：
10.1007/s001980050087
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发表时间：
1998-01-01
影响因子：
4
通讯作者：
Parfitt, AM
中科院分区：
文献类型：
--
作者：
Balena, R;Kleerekoper, M;Parfitt, AM
我们比较了 66 名按照三种方案接受氟化钠 (NaF) 治疗的骨质疏松患者和 7 名未接受 NaF 治疗的骨质疏松患者的初始和最终骨组织形态测量结果。 14 名患者连续接受 75 毫克/天（高剂量）NaF 和 1500 毫克/天钙治疗，平均持续 11 个月。 26 名患者接受连续 50 毫克/天（低剂量）NaF 联合 2000 毫克/天钙，平均 15 个月，联合（10 名患者）或不联合（16 名患者）维生素 D。26 名患者接受周期性低剂量 NaF 与维生素 D 交替治疗，平均 15 个月，总治疗持续时间为 28 个月，其中 14 名患者和 12 名患者在第二次活检的时间。忽略治疗方案之间的差异，对照组的总骨量、矿化骨量以及小梁厚度显着增加，而这些测量结果无显着下降。氟化物诱导的骨形成完全是并置的，没有证据表明新骨小梁的形成。当连续或间歇给予相同的总剂量时，以及当患者服用或不服用维生素 D 时，低剂量 NaF 对骨结构的影响是相同的。高剂量 NaF 的总骨量和矿化骨量的增加比低剂量 NaF 的增加更大，但小梁厚度的增加却没有。低剂量 NaF 导致所有类骨指数适度但显着增加，调整后的附着率和类骨成熟率适度但显着下降，但骨形成率没有变化。使用高剂量 NaF 时，BV/TV 的增加更大，但所有类骨质积累指数都高得多，所有成骨细胞功能受损和矿化的指数都低得多，14 名患者中有 12 名患有某种形式的骨软化。在 30 名接受小剂量 NaF 治疗但未服用维生素 D 的患者中，也有 3 名患者出现这种情况；这些患者的类骨厚度平均增加量明显大于 22 名服用维生素 D 的低剂量患者。我们得出的结论是：（1）NaF 在增加骨强度方面的效果不一致，部分原因是严重骨质流失患者未能恢复连接性，部分原因是大量类骨物质积累。 (7) 即使低剂量的 NaF 也会导致成骨细胞功能受损，但高剂量的长期治疗效果会更严重。 (3) 脊柱骨矿物质增加所暗示的骨形成增加与组织形态计量学测量的骨形成缺乏增加之间存在无法解释的差异。 (I) 矿化缺陷与 NaF 的总累积剂量的关系比与治疗持续时间的关系更密切，并且通过低剂量治疗可以通过维生素 D 来预防。 (5) 未来的临床试验应在脊柱水平小梁大量损失之前使用较小剂量的 NaF 进行。
We compared initial and final bone histomorphometric findings in 66 osteoporotic patients treated with sodium fluoride (NaF) according to three regimens, and in 7 osteoporotic patients who did not receive NaF. Fourteen patients received continuous NaF 75 mg/day (high-dose) with calcium 1500 mg/day for a mean of 11 months. Twenty-six patients received continuous NaF 50 mg/day (low-dose) with calcium 2000 mg/day for a mean of 15 months, either with (10 patients) or without (16 patients) vitamin D. Twenty-six patients received cyclical low-dose NaF, alternating with vitamin D, for a mean of 15 months and a total treatment duration of 28 months, of whom 14 were and 12 were not on NaF at the time of the second biopsy. Disregarding differences between regimens, there were significant increases in total and mineralized bone volume and trabecular thickness and nonsignificant decreases in these measurements in the control group. Fluoride-induced bone formation was exclusively appositional with no evidence for the creation of new trabeculae. The effect of low-dose NaF on bone structure was the same when the same total dose was given continuously or intermittently, and when the patient was or was not taking vitamin D. The increases in total and mineralized bone volume but not trabecular thickness were greater with high-dose than with low-dose NaF. Low-dose NaF caused modest but significant increases in all osteoid indices, and modest but significant declines in adjusted apposition rate and osteoid maturation rate and no change in bone formation rate. With high-dose NaF, the increase in BV/TV was greater but all indices of osteoid accumulation were much higher and all indices of impaired osteoblast function and mineralization were much lower, and 12 of 14 patients had some form of osteomalacia. This occurred also in 3 of 30 patients treated with few-dose NaF who were not taking vitamin D; the mean increase in osteoid thickness was significantly greater in these patients than in 22 low-dose patients who were taking vitamin D. We conclude: (1) The inconsistent effect of NaF in increasing bone strength is partly due to failure to restore connectivity in patients with severe bone loss and partly due to substantial osteoid accumulation. (7) Even low-dose NaF causes impaired osteoblast function, but this is much greater with high-dose prolonged therapy. (3) There is an unexplained discrepancy between the increase in bone formation implied by increases in spinal bone mineral and the lack of increase in bone formation measured histomorphometrically. ( I) Defective mineralization is more closely related to the total cumulative dose of NaF than to the duration of treatment, and with low-dose treatment may be preventable by vitamin D. (5) Future clinical trials should be carried out with smaller doses of NaF and before there has been substantial loss of horizontal trabeculae in the spine.