INTRODUCTION: The study was designed to compare the bone anabolic effects of basic fibroblast growth factor (bFGF), a selective agonist for prostaglandin E receptor subtype EP4, and parathyroid hormone (PTH) in aged ovariectomized (OVX) rats with severe cancellous osteopenia. METHODS: Groups of aged OVX rats were maintained untreated for 1 year postovariectomy (15 months of age) to develop severe tibial cancellous osteopenia. These animals were then treated with bFGF or the EP4 agonist (EP4) for 3 weeks. Other groups of aged OVX rats were treated with EP4 or PTH alone for 11 weeks, or sequentially with bFGF or EP4 for 3 weeks followed by PTH for 8 weeks. Cancellous and cortical bone histomorphometry were performed in the right proximal tibial metaphysis and tibial diaphysis respectively. RESULTS: Treatment with bFGF for 3 weeks markedly increased serum osteocalcin, osteoid volume, and osteoblast and osteoid surfaces to a greater extent than EP4. Basic FGF, but not EP4 or PTH, induced formation of osteoid islands within bone marrow. EP4 stimulated cancellous bone turnover, but failed to restore lost cancellous bone in the severely osteopenic proximal tibia after 11 weeks of treatment. In contrast, EP4, much like PTH, increased cortical bone mass in the tibial diaphysis by stimulating both periosteal and endocortical bone formation. Treatment of aged OVX rats with PTH alone tended to partially reverse the severe tibial cancellous osteopenia, whereas sequential treatment with bFGF and PTH increased tibial cancellous bone mass to near the level of vehicle-treated control rats. These findings indicate that bFGF had the strongest stimulatory effect on cancellous bone formation, and was the only anabolic agent to induce formation of osteoid islands within the bone marrow of the severely osteopenic proximal tibia. Therefore, bFGF may be more effective for the reversal of severe cancellous osteopenia. PTH and EP4 increased cortical bone mass to nearly the same extent, but cancellous bone mass was greater by two-fold in PTH-treated OVX rats than in EP4-treated OVX rats. CONCLUSION: These findings in aged OVX rats suggest that PTH is more efficacious than EP4 for augmentation of cancellous bone in the severely osteopenic, estrogen-deplete skeleton.
INTRODUCTION: The study was designed to compare the bone anabolic effects of basic fibroblast growth factor (bFGF), a selective agonist for prostaglandin E receptor subtype EP4, and parathyroid hormone (PTH) in aged ovariectomized (OVX) rats with severe cancellous osteopenia. METHODS: Groups of aged OVX rats were maintained untreated for 1 year postovariectomy (15 months of age) to develop severe tibial cancellous osteopenia. These animals were then treated with bFGF or the EP4 agonist (EP4) for 3 weeks. Other groups of aged OVX rats were treated with EP4 or PTH alone for 11 weeks, or sequentially with bFGF or EP4 for 3 weeks followed by PTH for 8 weeks. Cancellous and cortical bone histomorphometry were performed in the right proximal tibial metaphysis and tibial diaphysis respectively. RESULTS: Treatment with bFGF for 3 weeks markedly increased serum osteocalcin, osteoid volume, and osteoblast and osteoid surfaces to a greater extent than EP4. Basic FGF, but not EP4 or PTH, induced formation of osteoid islands within bone marrow. EP4 stimulated cancellous bone turnover, but failed to restore lost cancellous bone in the severely osteopenic proximal tibia after 11 weeks of treatment. In contrast, EP4, much like PTH, increased cortical bone mass in the tibial diaphysis by stimulating both periosteal and endocortical bone formation. Treatment of aged OVX rats with PTH alone tended to partially reverse the severe tibial cancellous osteopenia, whereas sequential treatment with bFGF and PTH increased tibial cancellous bone mass to near the level of vehicle-treated control rats. These findings indicate that bFGF had the strongest stimulatory effect on cancellous bone formation, and was the only anabolic agent to induce formation of osteoid islands within the bone marrow of the severely osteopenic proximal tibia. Therefore, bFGF may be more effective for the reversal of severe cancellous osteopenia. PTH and EP4 increased cortical bone mass to nearly the same extent, but cancellous bone mass was greater by two-fold in PTH-treated OVX rats than in EP4-treated OVX rats. CONCLUSION: These findings in aged OVX rats suggest that PTH is more efficacious than EP4 for augmentation of cancellous bone in the severely osteopenic, estrogen-deplete skeleton.
Authors: Mei Li; Hua Zhu Ke; Hong Qi; David R Healy; Yan Li; D Todd Crawford; Vishwas M Paralkar; Thomas A Owen; Kimberly O Cameron; Bruce A Lefker; Thomas A Brown; David D Thompson Journal: J Bone Miner Res Date: 2003-11 Impact factor: 6.741
Authors: Fawad Javed; Mohammad D Al Amri; Sergio Varela Kellesarian; Abdulaziz A Al-Kheraif; Fahim Vohra; José Luis Calvo-Guirado; Hans Malmstrom; Georgios E Romanos Journal: Clin Oral Investig Date: 2015-12-22 Impact factor: 3.573
Authors: E K Stuermer; S Sehmisch; T Rack; E Wenda; D Seidlova-Wuttke; M Tezval; W Wuttke; K H Frosch; K M Stuermer Journal: Langenbecks Arch Surg Date: 2008-12-02 Impact factor: 3.445
Authors: L Kolios; M Hitzler; A Moghaddam; C Takur; H Schmidt-Gayk; B Höner; M Lehnhardt; P Grützner; C Wölfl Journal: Eur J Trauma Emerg Surg Date: 2012-04-25 Impact factor: 3.693