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In rat models looking at the effect of malnutrition on fracture healing, amino acid supplementation in a nutritionally deprived rat increases all of the following EXCEPT
Quadriceps total protein content
Fracture callus mineralization
Insulin-like growth factor 1 (IGF-1) mRNA expression
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The study by Hughes et al found that essential amino acid supplementation (glutamine, arginine, and taurine) following femoral fracture in a protein-malnourished rat model increases serum albumin, body mass, quadriceps total protein content, and fracture callus mineralization. Expression of IGF-1 and IGF-2, myosin, actin, and VEGF mRNA were all significantly decreased in the amino acid supplemented group compared to the malnourished group. The malnourished group is thought to have upregulation of mRNA expression in attempt to increase the amount of protein product that is translated, however the lack of amino acid building blocks in the malnutrition group was a barrier to appropriate protein synthesis.
The study by Day et al created a malnourished rat femur fracture model by administering a 6% protein diet. They found that administering a 20% protein diet in the post-fracture period yielded a greater cross-sectional area of the fracture callus and callus stiffness compared to the 6% protein malnourished group.
Hughes MS, Kazmier P, Burd TA, Anglen J, Stoker AM, Kuroki K, Carson WL, Cook JL.
J Bone Joint Surg Am. 2006 Nov;88(11):2386-94. PMID: 17079395 (Link to Abstract)
Day SM, DeHeer DH.
J Orthop Trauma. 2001 Jan;15(1):47-53. PMID: 11147687 (Link to Abstract)
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Average 1.0 of 99 Ratings
Level 1 evidence has shown Low-intensity Pulsed Ultrasound Stimulation (LIPUS) decreased the time to fracture union in all of the the following injuries EXCEPT?
Radius shaft fracture
Distal radius fracture
Tibia shaft fracture treated with casting
Tibia shaft fracture treated with reamed intramedullary nailing
Tibia shaft fractures treated with reamed intramedullary nailing do not have Level 1 evidence supporting adjunctive LIPUS treatment. Low-intensity pulsed ultrasound (LIPUS) "bone stimulators" deliver 30mW/cm2 pulsed-waves via an external device over the fracture site.
The meta-analysis by Busse et al found 6 randomized, controlled trials evaluating LIPUS. They concluded that low-intensity pulsed ultrasound treatment may significantly reduce the time to fracture healing for fractures treated nonoperatively.
The metanalysis cites that Emami et al found no benefit to LIPUS treatment on intramedullary fixed tibial fractures. Injuries described in the metaanalysis as having positive benefits from LIPUS include radius shaft(Cook et al), distal radius(Kristiansen et al), scaphoid(Mayr et al), and tibia treated with casting (Heckman et al).
The Level 1 study by Heckman et al of 67 patients found a significant decrease in the time to clinical healing in tibia fractures treated with casting and no serious complications with its use.
Busse JW, Bhandari M, Kulkarni AV, Tunks E.
CMAJ. 2002 Feb 19;166(4):437-41. PMID: 11873920 (Link to Abstract)
Heckman JD, Ryaby JP, McCabe J, Frey JJ, Kilcoyne RF.
J Bone Joint Surg Am. 1994 Jan;76(1):26-34. PMID: 8288661 (Link to Abstract)
Average 1.0 of 60 Ratings
What is the mechanism of action of capacitive coupling (CC) stimulation when used as an adjunctive therapy for bone healing?
Reduces oxygen concentration and increases local tissue pH
Stimulates transmembrane calcium translocation via voltage-gated calcium channels
Upregulates TNF alpha
Transmits mechanical energy to stimulate bone formation
Upregulates osteoclast activity
Adjunctive therapies for bone healing are widely used and the mechanism of action is slowly being elucidated. Capacitive coupling involves externally placed electrodes with an alternating current which creates an electrical field. This stimulates calcium translocation which then activates calmodulin and upregulates many factors involved in bone healing (BMP, cyclic adenosine monophosphate (cAMP), and TGF-beta1).
Direct current(DC) stimulates an inflammatory-like response during fracture repair while . Pulsed electromagnetic fields (PEMFs) cause calcification of fibrocartilage but not calcification of fibrous tissue.
Answer 1 describes the mechanism of action of direct current stimulation. Answer 4 describes ultrasound stimulation. Otter et al present a nice review of electromagnetic fields and their influence of fracture healing.
Otter MW, McLeod KJ, Rubin CT.
Clin Orthop Relat Res. 1998 Oct;(355 Suppl):S90-104. PMID: 9917630 (Link to Abstract)
Average 2.0 of 30 Ratings
Which of the following statements regarding COX-2 is FALSE?
It causes mesenchymal stem cells to differentiate into osteoblasts
COX-2 knockout mice heal fractures more quickly than control mice
COX-2 is an enzyme which converts arachidonic acid to prostaglandin endoperoxide H2
Most NSAIDS non-specifically inhibit both COX-1 and COX-2 enzymes
The expression of COX-2 is upregulated in several human cancers
Cycloxygenase-2 (COX-2,aka prostaglandin-endoperoxide synthase 2) is an enzyme which converts arachidonic acid to prostaglandin endoperoxide H2. COX-2 is not expressed under normal conditions, but elevated levels are found during general states of inflammation. Zhang et al and Simon et al have both studied the role of COX-2 with regard to fracture healing. Zhang et al created a COX-2 knockout mouse (one which does not express the COX-2 gene). This COX-2 knockout mouse has been shown to heal fractures more slowly than COX-1 knockout mice or normal controls, thus identifying the role of COX-2 in general inflammation and bone repair. Zhang et al hypothesize that COX-2 causes mesenchymal progenitor cells to differentiate into osteoblasts, thus promoting new bone formation. Simon et al showed the delayed effects of fracture healing when animals were treated with COX-2 inhibitors. Gerstenfeld et al. studied the reversibility of COX-2 inhibition on the short term bone healing in an animal model. They found that COX-2 inhibitors block fracture healing more than NSAIDS and the magnitude of this effect is related to the duration of treatment. While specific inhibitors of COX-2 exist, traditional NSAIDs non-specifically inhibit both COX-1 and COX-2 enzymes. In addition to its role in inflammation, COX-2 has been shown to be upregulated in many human cancers such as gallbladder carcinoma.
Gerstenfeld LC, Al-Ghawas M, Alkhiary YM, Cullinane DM, Krall EA, Fitch JL, Webb EG, Thiede MA, Einhorn TA
J Bone Joint Surg Am. 2007 Jan;89(1):114-25. PMID: 17200318 (Link to Abstract)
Simon AM, Manigrasso MB, O'Connor JP.
J Bone Miner Res. 2002 Jun;17(6):963-76. PMID: 12054171 (Link to Abstract)
Zhang X, Schwarz EM, Young DA, Puzas JE, Rosier RN, O'Keefe RJ.
J Clin Invest. 2002 Jun;109(11):1405-15. PMID: 12045254 (Link to Abstract)
Average 3.0 of 34 Ratings
The nonunion as seen in Figure A will most likely unite by what intervention?
Increased mechanical stability
Decreased mechanical stability
Increased biology at the fracture site
Decreased biology at the fracture site
Antibiotics and resection of pseudoarthrosis
As described in the review by Rodriguez-Merchan and Forriol, hypertrophic nonunions result from motion at the fracture site and generally unite once the mechanical stability is increased. Atrophic and oligotrophic nonunions, while multi-factorial, result from poor biology at the fracture site (poor vascularity, lack of mesenchymal stem cells, bone loss). Treatment of atrophic nonunions then entails takedown of the nonunion and bone grafting (to improve the biology) with stabilization to initiate a healing response.
Rodriguez-Merchan EC, Forriol F.
Clin Orthop Relat Res. 2004 Feb;(419):4-12. PMID: 15021125 (Link to Abstract)
Average 3.0 of 19 Ratings
Which of the following is a mechanism by which low-intensity pulsed ultrasound is reported to stimulate fracture healing?
decreasing intracellular calcium concentration
produces nanomotion at the fracture site
decreases proteoglycan synthesis
Despite various reports documenting effects of low intensity ultrasound on living tissues, the exact mechanism of ultrasound on biological tissues remains largely unknown. It is most likely due to the mechanical energy of the sound waves that are transferred to tissues. Low frequency ultrasound in the region of 1.0 kHz may be capable of producing vibration and therefore strain across the cell wall (aka nanomotion at the fracture site).
The study by Parvizi et al observed that rat chondrocytes were stimulated by an ultrasound signal. They found that intracellular Ca++ concentration increased and proteoglycansynthesis increased in response to stimulation. When intracellular calcium was chelated in their experiment, the increase in proteoglycan synthesis reduced significantly, indicating that the rising intracellular Ca++ concentration as a result of ultrasound stimulation functioned as an intracellular signal to increase proteoglycan synthesis.
Parvizi J, Parpura V, Greenleaf JF, Bolander ME.
J Orthop Res. 2002 Jan;20(1):51-7. PMID: 11853090 (Link to Abstract)
Leung KS, Lee WS, Cheung WH, Qin L.
Clin Orthop Relat Res. 2004 Oct;(427):234-40. PMID: 15552163 (Link to Abstract)
Average 2.0 of 18 Ratings
What type of fracture healing occurs in a femoral shaft fracture treated with an intramedullary nail?
Primary fracture healing
Secondary fracture healing
"Cutting cone" remodelling
Intramedullary nails function as internal splints that allow for secondary fracture healing.
Secondary bone healing involves responses in the periosteum and external soft tissues. Here both committed osteoprogenitor cells and uncommitted undifferentiated mesenchymal cells contribute to the process of fracture healing by recapitulation of embryonic intramembranous ossification and endochondral bone formation. The response from the periosteum is a fundamental reaction to bone injury and is enhanced by motion and inhibited by rigid fixation.
Bong et al. reviewed the biomechanics and biology of long bone fracture healing with Intrameduallary nailing. They showed that reaming and the insertion of intramedullary nails can have early deleterious effects on endosteal and cortical blood flow initially. However, the canal reaming appears to have an overall positive effect at the fracture site as it increases extra osseous circulation and applies bone graft to the fracture site.
Illustration A shows a series of radiographs of a fracture healed by secondary intention with an IM nail.
Answer 1,4,5: Primary fracture healing (aka haversian remodelling or cutting cone remodelling) involves a direct attempt by the cortex to reestablish itself. In order for a fracture to become united, bone on one side of the cortex must unite with bone on the other to reestablish mechanical continuity. This process seems to occur only when there is anatomic restoration of the fracture fragments and when stability of the fracture reduction is ensured by rigid internal fixation and a substantial decrease in interfragmentary strain.
Answer 3: Secondary bone healing involves the ecapitulation of embryonic INTRAmembranous ossification and endochondral bone formation. EXTRAmembranous ossification is not believed to be a process involved in the healing of bone.
Bong MR, Kummer FJ, Koval KJ, Egol KA
J Am Acad Orthop Surg. 2007 Feb;15(2):97-106. PMID: 17277256 (Link to Abstract)
Average 3.0 of 28 Ratings
Which of the following is most often implicated as an etiology for a hypertrophic nonunion?
Malreduction with open plating
Inadequate mechanical stability
Open injury with significant soft tissue stripping
Hypertrophic nonunions are caused by inadequate stability, with callus formation by an appropriate biological response. Lack of biology leads to an atrophic nonunion. Hypertrophic nonunions should be treated with a fixation construct that lends appropriate stability without creating a poor biological environment.
Average 4.0 of 17 Ratings
Type X collagen expression by hypertrophic chondrocytes is characteristic of which of the following aspects of fracture healing?
Granulation tissue formation
Cartilage callus formation and calcification
There are three phases to fracture healing: 1) Reactive, 2) Reparative, and 3) Remodeling. The reactive phase is characterized by inflammation and granulation tissue formation. The reparative phase is marked by cartilage callus formation and bone deposition. Finally, the bone deposited during the reparative phase is remodeled during the remodeling phase. Type X collagen is a homotrimeric collagen found in hypertrophic cartilage expressed during the cartilage callus calcification phase of fracture healing. After fracture, inflammation and clot formation occurs where type I and II collagen are found. Type III collagen is expressed by fibroblasts and type V is found in areas of fibrous tissue formation. In the soft tissue callus/chondroid phase, types II and IX predominate, with type II being deposited in areas of mature cartilage production and type IX stabilizing the fibrils of type II. In the callus calcification phase type X collagen is expressed by proliferating chondrocytes as the extracellular matrix undergoes calcification. In the osteogenic bone deposition phase, there is a progressive shift from primary to secondary spongiosa and type I collagen predominates.
Average 3.0 of 31 Ratings
HPI - case of fracture femur sustained 6 months ago .fixed with interlockin nail.now comes with occasional pain very minimal.patient is walking full weight bearing without any support
has the fracture healed completely or is this delayed healing
A brief overview of the principles of fracture fixation, this video provides bas...
does somebody know the definition about the topic above ? i wounld like to...