Effect exerted by Teriparatide upon Repair Function of β-tricalcium phosphate to ovariectomised rat's femoral metaphysis defect caused by osteoporosis.

In this study, we tested the effect of Teriparatide (PTH) in combination with β-tricalcium phosphate (β-TCP) as a bone void filler in an ovariectomised rat distal femoral metaphysis model.β-TCP is a completely resorbable synthetic calcium phosphate and the Teriparatide is a drug that can promote bone formation in the condition of osteoporosis. A critical size defect of 3mm in diameter, a through-hole bone defect, was drilled into each distal femur of the ovariectomised rats. The hole was filled with β-TCP and the rat was injected PTH Teriparatide (30μg/kg) in peritoneum 5 times per week. After 4and 8 weeks the animals were killed and the degree of bone healing analysed. In total, 60 animals were investigated. When the β-TCP and PTH were used, histological, biochemistry and histomor-phometric evaluations revealed significantly better bone healing in terms of quantity and quality of the newly formed bone. The Ovariectomised rats which suffer from femur metaphysis defect are cured by embedding β-tricalcuim phosphate and intermittently cured by parathyroid hormone (PTH).

[1]  H. Zreiqat,et al.  Beta-tricalcium phosphate exerts osteoconductivity through alpha2beta1 integrin and down-stream MAPK/ERK signaling pathway. , 2010, Biochemical and biophysical research communications.

[2]  R. Morrison Bone Grafts and Bone-Graft Substitutes , 2012 .

[3]  D. Marsh,et al.  Effect of osteoporosis on bone mineral density and fracture repair in a rat femoral fracture model , 2008, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[4]  K. Chihara,et al.  Involvement of calcium-sensing receptor in osteoblastic differentiation of mouse MC3T3-E1 cells. , 2005, American journal of physiology. Endocrinology and metabolism.

[5]  T. Hefferan,et al.  Disuse in adult male rats attenuates the bone anabolic response to a therapeutic dose of parathyroid hormone. , 2006, Journal of applied physiology.

[6]  M. Rudert Histological Evaluation of Osteochondral Defects: Consideration of Animal Models with Emphasis on the Rabbit, Experimental Setup, Follow-Up and Applied Methods , 2002, Cells Tissues Organs.

[7]  U. Wikesjö,et al.  Effect of systemic parathyroid hormone (1-34) and a beta-tricalcium phosphate biomaterial on local bone formation in a critical-size rat calvarial defect model. , 2010, Journal of clinical periodontology.

[8]  Hock Jm Anabolic actions of PTH in the skeletons of animals. , 2001 .

[9]  E. Schwarz,et al.  Teriparatide therapy enhances devitalized femoral allograft osseointegration and biomechanics in a murine model. , 2011, Bone.

[10]  E. Schwarz,et al.  PTH‐enhanced structural allograft healing is associated with decreased angiopoietin‐2–mediated arteriogenesis, mast cell accumulation, and fibrosis , 2013, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[11]  D. Riccardi,et al.  Ca2+ as an extracellular signal in bone. , 2004, Cell calcium.

[12]  G. Daculsi,et al.  OF BIOCERAMICS AND FIBRIN SEALANT , 2004 .

[13]  Dong-Woo Cho,et al.  Efficacy of rhBMP-2 loaded PCL/PLGA/β-TCP guided bone regeneration membrane fabricated by 3D printing technology for reconstruction of calvaria defects in rabbit , 2014, Biomedical materials.

[14]  A. Abzhanov,et al.  Regulation of skeletogenic differentiation in cranial dermal bone , 2007, Development.

[15]  Su‐Li Cheng,et al.  Sustained Activation of the Extracellular Signal-regulated Kinase Pathway Is Required for Extracellular Calcium Stimulation of Human Osteoblast Proliferation* , 2001, The Journal of Biological Chemistry.

[16]  D. Bauer,et al.  Parathyroid hormone and teriparatide for the treatment of osteoporosis: a review of the evidence and suggested guidelines for its use. , 2005, Endocrine reviews.

[17]  R. Sader,et al.  Synthetic, pure-phase beta-tricalcium phosphate ceramic granules (Cerasorb) for bone regeneration in the reconstructive surgery of the jaws. , 2006, International journal of oral and maxillofacial surgery.

[18]  L. Mosekilde,et al.  PTH has a more pronounced effect on vertebral bone mass and biomechanical competence than antiresorptive agents (estrogen and bisphosphonate)--assessed in sexually mature, ovariectomized rats. , 1994, Bone.

[19]  A. Yildiz,et al.  Biomechanical evaluation in osteoporosis: ovariectomized rat model , 2007, Clinical Rheumatology.

[20]  P. Aspenberg,et al.  Implant fixation enhanced by intermittent treatment with parathyroid hormone. , 2001, The Journal of bone and joint surgery. British volume.

[21]  Paul Childress,et al.  Nmp4/CIZ: road block at the intersection of PTH and load. , 2010, Bone.

[22]  H. Weinans,et al.  Mechanical Consequences of Bone Loss in Cancellous Bone , 2001, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[23]  T. Jämsä,et al.  The mechanical strength of bone in different rat models of experimental osteoporosis. , 1994, Bone.

[24]  R. Jilka,et al.  Chronic elevation of parathyroid hormone in mice reduces expression of sclerostin by osteocytes: a novel mechanism for hormonal control of osteoblastogenesis. , 2005, Endocrinology.

[25]  J. Hock Anabolic actions of PTH in the skeletons of animals. , 2001, Journal of musculoskeletal & neuronal interactions.

[26]  J. Granjeiro,et al.  Magnesium incorporation into β-TCP reduced its in vivo resorption by decreasing parathormone production. , 2013, Journal of biomedical materials research. Part A.

[27]  B. Chang,et al.  Fabrication of an rhBMP-2 loaded porous β-TCP microsphere-hyaluronic acid-based powder gel composite and evaluation of implant osseointegration , 2014, Journal of Materials Science: Materials in Medicine.

[28]  W. Tawackoli,et al.  PTH promotes allograft integration in a calvarial bone defect. , 2013, Molecular pharmaceutics.

[29]  P. Esbrit,et al.  C-terminal parathyroid hormone-related protein increases vascular endothelial growth factor in human osteoblastic cells. , 2000, Journal of the American Society of Nephrology : JASN.

[30]  L. Qin,et al.  Impaired bone healing pattern in mice with ovariectomy-induced osteoporosis: A drill-hole defect model. , 2011, Bone.

[31]  B. Mitlak,et al.  Enhancement of experimental fracture-healing by systemic administration of recombinant human parathyroid hormone (PTH 1-34). , 2005, The Journal of bone and joint surgery. American volume.

[32]  Yusuf Khan,et al.  Bone graft substitutes , 2006, Expert review of medical devices.

[33]  A. Díez-Pérez,et al.  The Effect of Teriparatide [Human Parathyroid Hormone (1–34)] Therapy on Bone Density in Men With Osteoporosis , 2003, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[34]  L. Qin,et al.  Changes of microstructure and mineralized tissue in the middle and late phase of osteoporotic fracture healing in rats. , 2007, Bone.

[35]  D. Ward,et al.  Physiological changes in extracellular calcium concentration directly control osteoblast function in the absence of calciotropic hormones. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[36]  Tetsuo Inoue,et al.  Effect of salmon calcitonin on experimental osteoporosis induced by ovariectomy and low-calcium diet in the rat , 2000, Journal of Bone and Mineral Metabolism.

[37]  J. Reginster,et al.  Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. , 2001, The New England journal of medicine.

[38]  J Reeve,et al.  Anabolic effect of human parathyroid hormone fragment on trabecular bone in involutional osteoporosis: a multicentre trial. , 1980, British medical journal.

[39]  B. Boyan,et al.  Characterization of rat calvarial nonunion defects. , 1990, Acta anatomica.

[40]  P. Giannoudis,et al.  Enhancement of fracture healing with parathyroid hormone: preclinical studies and potential clinical applications , 2007, Expert opinion on investigational drugs.

[41]  R. Appleyard,et al.  Osteoporosis influences the early period of fracture healing in a rat osteoporotic model. , 2000, Bone.

[42]  J. Lane,et al.  Clinical applications of bone graft substitutes. , 2000, The Orthopedic clinics of North America.

[43]  J. Williams,et al.  Postoperative Drains at the Donor Sites of Iliac-Crest Bone Grafts. A Prospective, Randomized Study of Morbidity at the Donor Site in Patients Who Had a Traumatic Injury of the Spine* , 1998, The Journal of bone and joint surgery. American volume.

[44]  Chao Wan,et al.  Bone Formation During Distraction Osteogenesis Is Dependent on Both VEGFR1 and VEGFR2 Signaling , 2008, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[45]  P. Aspenberg,et al.  Intermittent parathyroid hormone (1–34) enhances mechanical strength and density of new bone after distraction osteogenesis in rats , 2004, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[46]  T. Wronski,et al.  Long-term effects of ovariectomy and aging on the rat skeleton , 1989, Calcified Tissue International.

[47]  D. Burr,et al.  Treatment with human parathyroid hormone (1-34) for 18 months increases cancellous bone volume and improves trabecular architecture in ovariectomized cynomolgus monkeys (Macaca fascicularis). , 2001, Bone.

[48]  K. Koval,et al.  Bone grafts and bone graft substitutes in orthopaedic trauma surgery. A critical analysis. , 2007, The Journal of bone and joint surgery. American volume.