The Effect of Bovine Bone Graft With or Without Platelet-Rich Plasma on Maxillary Sinus Floor Augmentation

Authors

Fatih Cabbar, Nurhan Güler, Mehmet Kürkcü, Ufuk Is̈eri, Kemal S̈ençift

Abstract

The purpose of this study was to compare Unilab Surgibone (USB) (Mississauga, Ontario, Canada), a bone xenograft (bovine), with platelet-rich plasma (PRP) and USB without PRP to augment the human maxillary sinus in preparation to receive dental implants. Patients who had bilateral pneumatized maxillary sinuses were included. Sinuses on one side were augmented with the USB-PRP combination and formed the study group, whereas the opposite-side sinuses were augmented with USB alone and served as controls. Bone biopsy specimens were taken during implant placement at 6.8 ± 0.9 months after maxillary sinus floor augmentation. Resonance frequency analysis measurements were performed at implant placement (first control) and before the prosthetic stage (second control), at 6.5 ± 0.7 months after implant surgery. There were 10 patients (7 men and 3 women; mean age, 53.7 ± 0.8 years). Integration between new bone and residual grafts was histologically observed in all samples. The volumes of soft tissue were 59.9% ± 7.5% and 57.8% ± 4.4% in the control and study groups, respectively; residual graft, 21.9% ± 6.6% and 23.6% ± 5.9%, respectively; new bone, 15.8% ± 4.8% and 16.0% ± 3.8%, respectively; and trabecular bone, 64.7% ± 22.5% and 69.1% ± 18.6%, respectively. A positive correlation was found between new bone volume and trabecular bone volume (P = .0001). The mean Implant Stability Quotient (ISQ) values were 71.7 ± 4.9 and 70.3 ± 5.7 in the control and study groups, respectively, at first control and 75.4 ± 6.4 and 74.4 ± 6.4, respectively, at second control. The mean ISQ values at second control in both groups were significantly higher than at first control (P = .043 and P = .028, respectively). No statistically significant differences were observed between groups (P > .05). The combination of USB and PRP does not have any effect on new bone formation and implant stabilization.

Link to Article

http://dx.doi.org/10.1016/j.joms.2011.03.040

Different effects on bone strength and cell differentiation in pre pubertal caloric restriction versus hypothalamic suppression

Authors

R.N. Joshi, F.F. Safadi, M. Barbe, Fe Del Carpio-Cano, S. Popoff and V.R. Yingling

Abstract

Hypothalamic amenorrhea and energy restriction during puberty affect peak bone mass accrual. One hypothesis suggests energy restriction alters hypothalamic function resulting in suppressed estradiol levels leading to bone loss. However, both positive and negative results have been reported regarding energy restriction and bone strength. Therefore, the purpose of this study was to investigate energy restriction and hypothalamic suppression during pubertal onset on bone mechanical strength and the osteogenic capacity of bone marrow-derived cells in two models: female rats treated with gonadotropin releasing hormone antagonists (GnRH-a) or 30% energy restriction. At 23 days of age, female Sprague Dawley rats were assigned to three groups: control group (C, n = 10), GnRH-a group (n = 10), and Energy Restriction (ER, n = 12) group. GnRH-a animals received daily injections for 27 days. The animals in the ER group received 70% of the control animals' intake. After sacrifice (50 days of age), body weight, uterine and muscle weights were measured. Bone marrow-derived stromal cells were cultured and assayed for proliferation and differentiation into osteoblasts. Outcome measures included bone strength, bone histomorphometry and architecture, serum IGF-1 and osteocalcin. GnRH-a suppressed uterine weight, decreased osteoblast proliferation, bone strength, trabecular bone volume and architecture compared to control. Elevated serum IGF-1 and osteocalcin levels and body weight were found. The ER model had an increase in osteoblast proliferation compared to the GnRH-a group, similar bone strength relative to body weight and increased trabecular bone volume in the lumbar spine compared to control. The ER animals were smaller but had developed bone strength sufficient for their size. In contrast, suppressed estradiol via hypothalamic suppression resulted in bone strength deficits and trabecular bone volume loss. In summary, our results support the hypothesis that during periods of nutritional stress the increased vertebral bone volume may be an adaptive mechanism to store mineral which differs from suppressed estradiol resulting from hypothalamic suppression.

Link to Article

http://dx.doi.org/10.1016/j.bone.2011.07.019

Conditional Inactivation of the CXCR4 Receptor in Osteoprecursors Reduces Postnatal Bone Formation Due to Impaired Osteoblast Development

Authors

Wei Zhu, Gang Liang, Zhiping Huang, Stephen B. Doty, Adele L. Boskey

Abstract

Cysteine (C)-X-C motif chemokine receptor 4 (CXCR4), the primary receptor for stromal cell-derived factor-1 (SDF-1), is involved in bone morphogenic protein 2 (BMP2)-induced osteogenic differentiation of mesenchymal progenitors. To target the in vivo function of CXCR4 in bone and explore the underlying mechanisms, we conditionally inactivated CXCR4 in osteoprecursors by crossing osterix (Osx)-Cre mice with floxed CXCR4 (CXCR4fl/fl) mice to generate knock-outs with CXCR4 deletion driven by the Osx promoter (Osx::CXCR4fl/fl). The Cre-mediated excision of CXCR4 occurred exclusively in bone of Osx::CXCR4fl/fl mice. When compared with littermate controls, Osx::CXCR4fl/fl mice developed smaller osteopenic skeletons as evidenced by reduced trabecular and cortical bone mass, lower bone mineral density, and a slower mineral apposition rate. In addition, Osx::CXCR4fl/fl mice displayed chondrocyte disorganization in the epiphyseal growth plate associated with decreased proliferation and collagen matrix syntheses. Moreover, mature osteoblast-related expression of type I collagen α1 and osteocalcin was reduced in bone of Osx::CXCR4fl/fl mice versus controls, suggesting that CXCR4 deficiency results in arrested osteoblast progression. Primary cultures for osteoblastic cells derived from Osx::CXCR4fl/fl mice also showed decreased proliferation and impaired osteoblast differentiation in response to BMP2 or BMP6 stimulation, and suppressed activation of intracellular BMP receptor-regulated Smads (R-Smads) and Erk1/2 was identified in CXCR4-deficient cells and bone tissues. These findings provide the first in vivo evidence that CXCR4 functions in postnatal bone development by regulating osteoblast development in cooperation with BMP signaling. Thus, CXCR4 acts as an endogenous signaling component necessary for bone formation.

Link to Article

http://dx.doi.org/10.1074/jbc.M111.250985

Distal tibial fracture repair in a neurofibromatosis type 1-deficient mouse treated with recombinant bone morphogenetic protein and a bisphosphonate

Authors

A. Schindeler, O. Birke, N. Y. C. Yu, A. Morse, A. Ruys, P. A. Baldock, D. G. Little

Abstract

Congenital pseudarthrosis of the tibia is an uncommon manifestation of neurofibromatosis type 1 (NF1), but one that remains difficult to treat due to anabolic deficiency and catabolic excess. Bone grafting and more recently recombinant human bone morphogenetic proteins (rhBMPs) have been identified as pro-anabolic stimuli with the potential to improve the outcome after surgery. As an additional pharmaceutical intervention, we describe the combined use of rhBMP-2 and the bisphosphonate zoledronic acid in a mouse model of NF1-deficient fracture repair. Fractures were generated in the distal tibiae of neurofibromatosis type 1-deficient (Nf1+/–) mice and control mice. Fractures were open and featured periosteal stripping. All mice received 10 µg rhBMP-2 delivered in a carboxymethylcellulose carrier around the fracture as an anabolic stimulus. Bisphosphonate-treated mice also received five doses of 0.02 mg/kg zoledronic acid given by intraperitoneal injection. When only rhBMP but no zoledronic acid was used to promote repair, 75% of fractures in Nf1+/– mice remained ununited at three weeks compared with 7% of controls (p < 0.001). Systemic post-operative administration of zoledronic acid halved the rate of ununited fractures to 37.5% (p < 0.07). These data support the concept that preventing bone loss in combination with anabolic stimulation may improve the outcome following surgical treatment for children with congenital pseudarthoris of the tibia and NF1.

Link to Article

http://dx.doi.org/10.1302/0301-620X.93B8.25940

Mice lacking Nf1 in osteochondroprogenitor cells display skeletal dysplasia similar to patients with neurofibromatosis type I

Authors

Weixi Wang, Jeffrey S. Nyman, Koichiro Ono, David A. Stevenson, Xiangli Yang and Florent Elefteriou

Abstract

Mutations in NF1 cause neurofibromatosis type I (NF1), a disorder characterized, among other clinical manifestations, by generalized and focal bony lesions. Dystrophic scoliosis and tibial pseudoarthrosis are the most severe skeletal manifestations for which treatment is not satisfactory, emphasizing the dearth of knowledge related to the biology of NF1 in bone cells. Using reporter mice, we report here that the mouse Col2α1-Cre promoter is active in chondrocytes but also in adult bone marrow osteoprogenitors giving rise to osteoblasts. Based on this finding, we crossed the Col2α1-Cre transgenic and Nf1flox/flox mice to determine whether loss of Nf1 in axial and appendicular osteochondroprogenitors recapitulates the skeletal abnormalities of NF1 patients. By microtomographic and X-rays studies, we show that Nf1Col2-/- mice display progressive scoliosis and kyphosis, tibial bowing, and abnormalities in skull and anterior chest wall formation. These defects were accompanied by a low bone mass phenotype, high bone cortical porosity, osteoidosis, increased osteoclastogenesis, and decreased osteoblast number, as quantified by histomorphometry and 3D-microtomography. Loss of Nf1 in osteochondroprogenitors also caused severe short stature and intervertebral disc defects. Blockade of the RAS/ERK activation characteristic of Nf1-/- osteoprogenitors by lovastatin during embryonic development could attenuate the increased cortical porosity observed in mutant pups. These data and the skeletal similarities between this mouse model and NF1 patients thus suggest that activation of the RAS/ERK pathway by Nf1 loss-of-function in osteochondroprogenitors is responsible for the vertebral and tibia lesions in NF1 patients, and that this molecular signature may represent a good therapeutic target.

Link to Article

http://dx.doi.org/10.1093/hmg/ddr310

Diabetes mellitus negatively affects peri-implant bone formation in the diabetic domestic pig

Authors

Cornelius von Wilmowsky, Philipp Stockmann, Igor Harsch, Kerstin Amann, Philipp Metzler, Rainer Lutz, Tobias Moest, Friedrich Wilhelm Neukam, Karl Andreas Schlegel

Abstract

Diabetes mellitus is classified as a relative contraindication for implant treatment, and higher failure rates have been seen in diabetic patients. The aim of the present study was to investigate the effect of diabetes on peri-implant bone formation in an animal model of human bone repair. Diabetes was induced by an intravenous application of streptozotocin (90 mg/kg) in 15 domestic pigs. Implants were placed after significant histopathological changes in the hard and soft tissues were verified. The bone–implant contact (BIC), peri-implant bone mineral density (BMD), and expression of collagen type-I and osteocalcin proteins were qualitatively evaluated 4 and 12 weeks after implantation. Fifteen animals served as healthy controls. Diabetes caused pathological changes in the soft and hard tissues. The BIC and BMD were significantly reduced in the diabetic group after 4 and 12 weeks. Collagen type-I was increased in the diabetic group at both time points, whereas osteocalcin was reduced in the diabetic group. Poorly controlled diabetes negatively affects peri-implant bone formation and bone mineralization. These findings have to be taken into consideration for diabetic patients with an indication for implant therapy.

Link to Article

http://dx.doi.org/10.1111/j.1600-051X.2011.01746.x