The rhPTH (1–34), But not Elcatonin, Increases Bone Anabolic Efficacy in Postmenopausal Women with Osteoporosis

Abstract

Purpose: Intermittent administration of recombinant human PTH [rhPTH (1?34)] exerts an osteoanabolic effect characterized by direct effects on bone formation, increases bone density, and reduces fracture risk. This study was to investigate the anabolic effects of rhPTH(1?34) on postmenopausal osteoporosis in an Asian population and compare the time course and alteration in bone turnover marker (BTM) during rhPTH(1?34) and elcatonin treatment. Methods: 124 women with postmenopausal osteoporosis were enrolled in this prospective, open-label, active-controlled trial. The patients randomized to subcutaneous rhPTH(1?34) (20?ug, once daily) or elcatonin (200U, once week) injections for 12 months. Biochemical markers of bone formation (bone specific alkaline phosphatase [BSAP]), and bone resorption maker (serum C-telopeptide of type I collagen [CTX-I] were measured at baseline and at 0, 6, and 12 months. Results: At 12 months, rhPTH (1?34) significantly increased lumbar spine BMD significantly compared with baseline, whereas elcatonin was ineffective. BSAP levels were gradually increased in almost all rhPTH(1?34)-treated subjects and at the end of the study, the percentage of subjects with BSAP above the postmenopausal reference interval was gradually increased as high as 91.5% at month 12. Opposite trends in percentages for CTX-I was observed in rhPTH(1?34). With rhPTH(1?34), but not elcatonin, there were significant positive correlations between ratio of BSAP and CTX-I and bone mineral density (BMD) (r=0.318) at the end of month 12. Both treatments were well tolerated and there were no significant differences detected between the 2 groups in the proportion of any adverse events and any serious adverse events. Conclusions: rhPTH (1?34) has more positive effects on bone formation than elcatonin for postmenopausal women with osteoporosis and was proved to be safe and well tolerated. The ratio of BSAP and CTX-I may be a useful indicator for positive bone formation. Registration: Clinical trial registration: ChiCTR-TRC-11001331; Retrospective registered on May 3, 2011. http://apps.who.int/trialsearch/Trial.aspx?TrialID=ChiCTR-TRC-11001313.

Ectopic osteogenesis by type I collagen loaded with a novel synthesized PTH‐related peptide‐1 in vivo

“…This peptide contains 34 amino acids at the N‐terminus of PTH and retains most of the function of PTH, particularly the osteogenic capacity. (Forssmann et al, ; Lindsay et al, ; Lindsay, Krege, Marin, Jin, & Stepan, ; Yewle et al, ; Zhang et al, ). However, teriparatide is expensive, can only be administered through systemic injection for a short period of time, and does not completely expose the active site, leading to hypercalcemia or even osteosarcoma (Culpepper, Phipps, Bonvallet, & Bellis, ; Tashjian Jr & Goltzman, ; Wang, Liu, Fan, & Li, ).…”

“…Osteogenic‐associated proteins consist of bone morphogenetic protein‐2 (BMP‐2; Sun et al, ; Zhan, Liu, & Yu, ), parathyroid hormone (PTH; Khundmiri, Murray, Lederer, & Vitamin, ), and enamel matrix protein derivative (Shahriari, Houshmand, Razavian, Khazaei, & Abbas, ). Some of the modified small molecule active peptides are osteopontin peptide, RADA16‐I peptide (Cormier, Ruiz‐Orta, Alamo, & Paravastu, ), PTH (1‐31), PTH (1‐34; Yewle, Puleo, & Bachas, ; Zhang et al, ), and PTH (1‐37; Forssmann et al, ).…”

Respuesta de preosteoblastos a compuestos de estroncio o calcio: proliferación, diferenciación, mineralización y respuesta génica global

“…The availability of parathyroid hormone (PTH) was a significant advance in the treatment of osteoporosis 8 . The intermittent provision of PTH increases bone formation in patients with osteoporosis, which results in an increase in trabecular bone mass and cortical thickness [8][9][10] . However, this anabolic treatment has some limitations linked to the low half-life and high cost of this molecule.…”