Battmann A, Resch H, Libanati C R, Ludy D, Fischer M, Farley S, Baylink D J
Institut für Pathologie, Justus Liebig Universität Giessen, Germany.
Osteoporos Int. 1997;7(1):48-51. doi: 10.1007/BF01623460.
In a previous study we found that sustained-release monofluorophosphate (MFP-SR), a novel, sustained-release MFP preparation, acutely maintained the basal therapeutic serum fluoride levels without causing the high serum peak levels associated with plain MFP administration. The objective of the present study was to determine (a) whether chronic MFP-SR administration would provide therapeutic serum fluoride levels, and (b) whether treatment with this new preparation would result in an increase in bone formation similar to that achieved with plain MFP. Bone formation was assessed by serum osteocalcin (OC) determination. We studied 17 postmenopausal women older than 60 years and suffering from primary osteoporosis. All had received a minimum of 6 months of continuous treatment with plain MFP at a dose of 152 mg/day (76 mg b.i.d.). Upon entering the study, the subjects were randomized, in a double-masked protocol, to receive either MFP-SR (76 mg b.i.d.) (n = 9) or placebo (n = 8) for 2 months, after which all subjects returned to the original plain MFP regimen. Serum fluoride and serum OC levels were determined monthly for 3 months. At the beginning of the study serum fluoride levels were in the accepted therapeutic range (5-10 microM) in all patients. Serum fluoride levels were maintained in the patients switched to MFP-SR. In contrast, serum fluoride levels decreased significantly (p < 0.005) in the placebo-treated control subjects and returned to therapeutic levels upon switching back to plain MFP. Similarly, serum OC levels remained elevated in the subjects switched to MFP-SR but dropped significantly (p < 0.001) in the placebo-treated group. Our results demonstrate that chronic MFP-SR administration, at a dose of 152 mg/day, results in maintenance of therapeutic serum fluoride levels and in stimulation of bone formation. Because we have previously reported that high, supratherapeutic post-absorptive serum fluoride levels are avoided by MFP-SR administration, this novel preparation may prevent side effects associated with plain MFP by reducing the amount of fluoride deposited in bone.
在之前的一项研究中，我们发现缓释单氟磷酸酯（MFP-SR），一种新型的缓释MFP制剂，能急性维持基础治疗性血清氟水平，而不会导致与普通MFP给药相关的高血清峰值水平。本研究的目的是确定：（a）长期给予MFP-SR是否能提供治疗性血清氟水平；（b）用这种新制剂治疗是否会导致骨形成增加，类似于普通MFP所达到的效果。通过测定血清骨钙素（OC）评估骨形成。我们研究了17名60岁以上患有原发性骨质疏松症的绝经后妇女。所有人都接受了至少6个月的普通MFP连续治疗，剂量为152毫克/天（76毫克，每日两次）。进入研究后，受试者按照双盲方案随机分组，接受MFP-SR（76毫克，每日两次）（n = 9）或安慰剂（n = 8）治疗2个月，之后所有受试者恢复原来的普通MFP治疗方案。连续3个月每月测定血清氟和血清OC水平。在研究开始时，所有患者的血清氟水平都在公认的治疗范围内（5-10微摩尔）。改用MFP-SR的患者血清氟水平得以维持。相比之下，安慰剂治疗的对照组受试者血清氟水平显著下降（p < 0.005），换回普通MFP后恢复到治疗水平。同样，改用MFP-SR的受试者血清OC水平保持升高，但安慰剂治疗组显著下降（p < 0.001）。我们的结果表明，以152毫克/天的剂量长期给予MFP-SR可维持治疗性血清氟水平并刺激骨形成。因为我们之前报道过，MFP-SR给药可避免吸收后血清氟水平高于治疗水平，这种新型制剂可能通过减少沉积在骨骼中的氟量来预防与普通MFP相关的副作用。
