Lindsay Robert, Zhou Hua, Cosman Felicia, Nieves Jeri, Dempster David W, Hodsman Anthony B
Clinical Research Center, Helen Hayes Hospital, West Haverstraw, NY 10993, USA.
J Bone Miner Res. 2007 Apr;22(4):495-502. doi: 10.1359/jbmr.070104.
Using bone histomorphometry, we found that a 1-month treatment with PTH(1-34) [hPTH(1-34)] stimulated new bone formation on cancellous, endocortical, and periosteal bone surfaces. Enhanced bone formation was associated with an increase in osteoblast apoptosis.
The precise mechanisms by which hPTH(1-34) increases bone mass and improves bone structure are unclear. Using bone histomorphometry, we studied the early effects of treating postmenopausal women with osteoporosis with hPTH(1-34).
Tetracycline-labeled iliac crest bone biopsies were obtained from 27 postmenopausal women with osteoporosis who were treated for 1 month with hPTH(1-34), 50 microg daily subcutaneously. The results were compared with tetracycline-labeled biopsies from a representative control group of 13 postmenopausal women with osteoporosis.
The bone formation rate on the cancellous and endocortical surfaces was higher in hPTH(1-34)-treated women than in control women by factors of 4.5 and 5.0, respectively. We also showed a 4-fold increase in bone formation rate on the periosteal surface, suggesting that hPTH(1-34) has the potential to increase bone diameter in humans. On the cancellous and endocortical surfaces, the increased bone formation rate was primarily caused by stimulation of formation in ongoing remodeling units, with a modest amount of increased formation on previously quiescent surfaces. hPTH(1-34)-stimulated bone formation was associated with an increase in osteoblast apoptosis, which may reflect enhanced turnover of the osteoblast population and may contribute to the anabolic action of hPTH(1-34).
These findings provide new insight into the cellular basis by which hPTH(1-34) improves cancellous and cortical bone architecture and geometry in patients with osteoporosis.
通过骨组织形态计量学,我们发现用甲状旁腺激素(1-34)[hPTH(1-34)]治疗1个月可刺激松质骨、骨内膜和骨膜表面的新骨形成。骨形成增强与成骨细胞凋亡增加有关。
hPTH(1-34)增加骨量和改善骨结构的确切机制尚不清楚。我们通过骨组织形态计量学研究了用hPTH(1-34)治疗绝经后骨质疏松症妇女的早期效果。
从27名绝经后骨质疏松症妇女中获取四环素标记的髂嵴骨活检样本,这些妇女每天皮下注射50微克hPTH(1-34),治疗1个月。将结果与来自13名绝经后骨质疏松症代表性对照组妇女的四环素标记活检样本进行比较。
接受hPTH(1-34)治疗的妇女松质骨和骨内膜表面的骨形成率分别比对照妇女高4.5倍和5.0倍。我们还发现骨膜表面的骨形成率增加了4倍,这表明hPTH(1-34)有可能增加人类的骨直径。在松质骨和骨内膜表面,骨形成率增加主要是由于正在进行重塑的单位中形成受到刺激,先前静止的表面上形成也有少量增加。hPTH(1-34)刺激的骨形成与成骨细胞凋亡增加有关,这可能反映了成骨细胞群体更新的增强,并可能有助于hPTH(1-34)的合成代谢作用。
这些发现为hPTH(1-34)改善骨质疏松症患者的松质骨和皮质骨结构及几何形状的细胞基础提供了新的见解。