Article

Occurrence of substance P in bone repair under different load comparison of straight and angulated fracture in rat tibia

Section of Orthopaedics and Sports Medicine, Institution of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Journal of Orthopaedic Research (Impact Factor: 2.97). 12/2010; 28(12):1643-50. DOI: 10.1002/jor.21169
Source: PubMed

ABSTRACT Substance P (SP) has been shown in vitro to stimulate both formation and resorption of bone. This seemingly contradictory observation could be explained by in vivo variations in skeletal loading and rate of bone turnover, features which may be explored during different phases of fracture healing. In 50 SD rats, the right tibia was fractured and fixed with an intramedullary pin in straight alignment and in anterior angulation resulting in a convex and concave side under different load. Fracture repair was assessed by radiography, histology, and semi-quantitative immunohistochemistry of SP nerve fiber occurrence at days 7, 21, 35, 56, and 84 post-fracture. During regeneration, days 7-35, abundant SP-nerve ingrowth was observed in the fracture callus reaching a side-symmetrical peak at day 21 in straight fractures. In angulated fractures, the SP peak was also observed at day 21 on the concave loaded side, but not until day 35 on the convex unloaded side. Each SP-peak coincided with cortical bridging. During remodeling, days 35-84, a side-symmetrical disappearance of SP-positive fibers was seen in straight fractures. The same pattern was seen on the concave loaded side of angulated fractures. However, on the convex unloaded side, where resorption now took place, SP-fibers remained until the end of the experiment. Our study suggests that neuronal SP during bone regeneration has a stimulatory role on bone formation, while during remodeling increased SP fiber density in unloaded areas may be related to bone resorption.

Download full-text

Full-text

Available from: Paul Ackermann, Jul 29, 2015
0 Followers
 · 
141 Views
  • Source
    • "(a) locking plate [80] [85] (c) locking nail [86] (b) pin clip device [80] [81] (iii) Closed fracture by 3-point bending system [26] [80] [82] [87] [88] (c) external fixator [80] [89] [90] Rat (i) Anesthesia (i) Anesthesia (i) Anesthesia (ii) Lateral exposure of femoral bone [91] [92] (ii) Initial stabilization: (ii) Closed fracture model [93] [94]: (iii) Medial exposure of femoral bone [91] [92] (a) intramedullary steel pin [95] [96] [97] (a) 3-point bending system (iv) Fracture performance by osteotomy [98] [99] (b) intramedullary K-wire [95] [96] [97] (b) 300 g weight from 20 cm height (v) Fracture stabilization: (iii) Closed fracture by blunt guillotine: (iii) Open fracture model [100] [101]: (a) intramedullary pin or K-wire [95, 96, 102–104] (a) 500–650 g steel weight [87] [97] [102] [105] (a) lateral exposure of tibia (b) combination of K-wire and 2 screws [99] (b) 14 cm drop height [87] [97] [102] [105] (b) fracture performance by osteotomy (c) plate osteosynthesis [106] [107] (iv) Fracture stabilization: (d) external fixator [91] [108] [109] (a) K-wire or modified needle [93] [101] (b) plate fixation [100] [110] (c) external fixator [111] Pig (i) Complex anesthesia "
    [Show abstract] [Hide abstract]
    ABSTRACT: Treatment of polytrauma patients remains a medical as well as socioeconomic challenge. Although diagnostics and therapy improved during the last decades, multiple injuries are still the major cause of fatalities in patients below 45 years of age. Organ dysfunction and organ failure are major complications in patients with major injuries and contribute to mortality during the clinical course. Profound understanding of the systemic pathophysiological response is crucial for innovative therapeutic approaches. Therefore, experimental studies in various animal models are necessary. This review is aimed at providing detailed information of common trauma models in small as well as in large animals.
    BioMed Research International 01/2011; 2011:797383. DOI:10.1155/2011/797383 · 2.71 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Infection is a major clinical complication of orthopaedic implants and prosthetic devices, and patients with traumatic open fractures have a high risk of infection that may exceed 30%. Surgical trauma, burns, and major injuries such as traumatic open fractures induce immunosuppression, decrease resistance to infection, and decrease production of T helper type 1 (Th1) cytokines. QUESTIONS/HYPOTHESES: Exogenous interleukin-12 p70 (IL-12p70 or IL-12), a natural cytokine that plays a central role in Th1 response and bridges innate and adaptive immunities, will reduce open fracture-associated infection. We propose using exogenous IL-12 nanocoating to restore or enhance the body's natural defense system to combat pathogens. Rats will have a femur fractured, inoculated with Staphylococcus aureus or injected with phosphate buffered saline, left open for 1 hour, and then fixed with an intramedullary Kirschner wire with or without IL-12 nanocoating. Animals will be euthanized at postoperative Day 21; samples of blood, soft tissue, bone, and draining lymph nodes will be collected. Infection, bone healing, and local and systemic responses will be determined. IL-12 nanocoating is a promising prophylactic means to modulate the host immune response to help prevent open fracture-associated infections and to avoid the problem of antibiotic resistance.
    Clinical Orthopaedics and Related Research 11/2010; 469(11):3262-5. DOI:10.1007/s11999-010-1690-0 · 2.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Osteoporosis drugs are prescribed to prevent fragility fractures, which is the principal aim of the management of osteoporosis. However, if fracture does occur, then it is also important to promote a fast and uneventful healing process. Despite this, little is known about the effect of osteoporosis drugs on bone healing in humans. Strontium ranelate is an osteoporosis agent that increases bone formation and reduces bone resorption and may therefore be beneficial in fracture healing. We report four cases of fracture non-union for up to 20 months. Treatment with strontium ranelate (2 g/day) for between 6 weeks and 6 months appeared to contribute to bone consolidation in the four cases. Animal studies support beneficial effects of strontium ranelate on bone healing via improvement of bone material properties and microarchitecture in the vicinity of the fracture. The clinical cases described herein provide new information on these effects, in the absence of randomized controlled studies on the clinical efficacy of pharmacological treatments in osteoporosis in fracture repair. Further studies are necessary. Fracture healing is an important topic in orthopedic research and is also a concern for patients with postmenopausal osteoporosis. Evidence from case reports and animal studies suggests that strontium ranelate improves bone microarchitecture and accelerates fracture healing. A positive effect of osteoporosis treatments on bone healing is an interesting possibility and merits further clinical research.
    Rheumatology International 12/2010; 32(2):439-43. DOI:10.1007/s00296-010-1687-8 · 1.63 Impact Factor
Show more