pearls 3

<body topmargin=0 leftmargin=0 marginheight=0 marginwidth=0> <table cellpadding=0 cellspacing=0 border=0><tr> <td valign="top" colspan=2 height=90 BGCOLOR="#006699" TEXT="#080000" bgproperties="fixed" background="02c285a1erlcgo.png"> <div> <FONT SIZE="5" COLOR="#FFCC66" FACE="Arial" ><B>usmle med 6</B></FONT><B>     |     </B><A HREF="index.htm" TARGET="_top" TITLE="usmle med 6"><U><B>home</B></U></A></div> <div> <A HREF="id23.htm" TARGET="_top" TITLE="pearls 1"><U>pearls 1</U></A>   |   <A HREF="id20.htm" TARGET="_top" TITLE="pearls 2"><U>pearls 2</U></A>   |   <B>pearls 3</B>   |   <A HREF="id22.htm" TARGET="_top" TITLE="pearls 4"><U>pearls 4</U></A>   |   <A HREF="id24.htm" TARGET="_top" TITLE="pearls 5"><U>pearls 5</U></A>   |   <A HREF="id18.htm" TARGET="_top" TITLE="qcm"><U>qcm</U></A>   |   <A HREF="id19.htm" TARGET="_top" TITLE="answers"><U>answers</U></A>   |   <A HREF="id17.htm" TARGET="_top" TITLE="Contact Me"><U>Contact Me</U></A></div> <div> </div> </td> </tr><tr> <td valign="top" width=210 BGCOLOR="#FFCC66" TEXT="#080000" background="02ad2c00dkelyh.png"> <div> <A HREF="id23.htm" TARGET="_top" TITLE="pearls 1"><U>pearls 1</U></A></div> <div> <A HREF="id20.htm" TARGET="_top" TITLE="pearls 2"><U>pearls 2</U></A></div> <div> pearls 3</div> <div> <A HREF="id22.htm" TARGET="_top" TITLE="pearls 4"><U>pearls 4</U></A></div> <div> <A HREF="id24.htm" TARGET="_top" TITLE="pearls 5"><U>pearls 5</U></A></div> <div> <A HREF="id18.htm" TARGET="_top" TITLE="qcm"><U>qcm</U></A></div> <div> <A HREF="id19.htm" TARGET="_top" TITLE="answers"><U>answers</U></A></div> <div> <A HREF="id17.htm" TARGET="_top" TITLE="Contact Me"><U>Contact Me</U></A></div> </td> <td valign="top" height=390 BGCOLOR="#FFFFFF" TEXT="#080000"> <div> <I>pearls 3</I></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">hypercalcemia may develop in children who are immobilized following the fracture of a weight bearing bone</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">complication as hypercalcemia - hypercalciuria :</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">nephrocalciose</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">nephropathy</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">hypertensive encephalopathy</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">convulsions</div> <bR> <div> monitoring:</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">mesure of the serum ionized calcium</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">urinary calcium creatinine ratio </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">a ratio >0.2 = hypercalciuria</div> <bR> <bR> <bR> <bR> <div> <B><U>The Fracture Healing Process</U></B></div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Bone possesses the unique ability to completely heal itself with tissue ultimately undistinguishable from the original structure.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Traditionally, fracture healing has been divided histologically into four descriptive stages: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">stage of inflammation, </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">stage of soft callus, </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">stage of hard callus,</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> and the stage of bone remodeling.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> However, there are two other important aspects of healing which include the stage of impact and the stage of induction.</div> <bR> <bR> <div> <I><U>Stage of Impact</U></I></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">This phase is initiated at the moment of injury and continues through the complete dissipation of energy.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> The amount of energy that can be absorbed by the bone prior to failure is directly proportional to the volume of the bone. </div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The energy amount is also inversely proportional to the modulus of elasticity; therefore, rigid bones allow for less absorption before failure, </B></div> <div> <B><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">whereas the greater organic component in the young tends to allow the bone to bend, a characteristic "'greenstick" incomplete fracture. </B></div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">A direct relation can also be established between the amount of energy absorbed and the rate of force applied: the greater the force applied, the more energy is usually absorbed before failure. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Combining these factors, the fracture pattern can be determined: a simple transverse fracture, comminution, or a segmental fracture. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In turn, the type of fracture dictates the length of time required to heal.</div> <bR> <bR> <div> <I><B><U>Stage of Induction</U></B></I></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The least knowledge regarding the induction stage is known. Although it begins soon after the moment of impact and continues through the stage of inflammation, the duration is indefinite. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The stimulus that causes induction is unknown, but it includes oxygen gradient, bioelectric potentials, bone morphogenic protein, and other noncollagenous proteins. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cells possessing osteogenic potential are stimulated to form bone during the modulation process. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Coincidentally, cells that do not usually possess osteogenic potential may be induced to form bone; their progeny, through differentiation, convert into bone-forming cells.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> In addition, cells that normally produce bone are multiplied and function at maximum potential. It is essential to establish ideal clinical conditions to maximize the inductive forces.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> With time, the influence of these forces seems to diminish, and if the early opportunity for healing is lost, possibilities for delayed union or nonunion are greater.</div> <bR> <bR> <div> <B><U>Stage of Inflammation</U></B></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The stage of inflammation shortly follows impact and endures until the major pain and discomfort abates, about when fibrous union develops between bone ends.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">When the fracture occurs, there is a disruption of the blood supply, hemorrhage, and formation of a fracture hematoma.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> In addition, oxygen and pH drop, and bone necrosis and debris cause the release of lysosomal enzymes.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Inflammation signals restoration processes for damaged tissue.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> There is a rapid ingrowth of vasoformative elements and capillaries (tiny new blood vessels) and an enormous increase in cellular proliferation. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Capillary blood distribution reverses; although there is a tremendous hyperemic response of the edosteal circulation, there is such an enormous proliferation of periosteal vessels that much of the circulation is from the periosteum. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Paradoxically, at the cellular level in a fracture callus so richly invaded with capillaries, the average bone or cartilage cell is in a hypoxic environment. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Although near the capillaries, oxygen tensions are about 90 mmHg, they fall to almost zero just 10 to 15 um away. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Essentially, the proliferation and growth of the cells is even greater than the proliferation of the capillary circulation. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The low oxygen tension and decreasing pH environment encourages growth of the early fibrous or cartilaginous callus. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The callus rapidly and efficiently provides a scaffold for cartilage and endosteal bone production and further circulation.</div> <bR> <div> <I><B><U>Stage of Soft Callus</U></B></I></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The stage of the soft callus begins when pain and swelling in the extremity subside and endures through bony fragment unification with fibrous or cartilaginous tissue. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Characteristic of this period is a substantial increase in vascularity and ingrowth of capillaries into the fracture callus. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">Cellularity experiences an even greater increase.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The hematoma between the fracture ends organizes with fibrous tissue initiating cartilage and bone formation while osteoclasts remove some of the dead bone fragments. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The callus is electronegative relative to the rest of the bone during this period.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Although the PO2 remains low, the pH resumes normality.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> This stage of healing offers possibly the last opportunity to correct alignment relatively easily.</div> <bR> <bR> <div> <I><B><U>Stage of Hard Callus</U></B></I></div> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The stage of the hard callus begins from the soft callus formation through the establishment of fragment unification with new bone, a period that varies with different fractures and the age of the individual.</div> <div> <I><IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> </I>Primary woven bone develops when the callus converts from fibrocartilaginous tissue to fiber bone. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">The amount of movement directly influences the quality of the callus: </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">no motion during healing results in membranous bone formation, </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">and abundant motion leads to primary union, or enchondral bone formation.</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> Although small amounts of movement seem to stimulate callusing,</div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0"> excessive amounts may destroy early bridging and inhibit union. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">In this stage, pH is neutral, the callus is still electronegative, osteoclasts continue removing dead bone, and new bone deposited by osteoblasts is abundant. </div> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">When early callus is visualized radiologically, progressive protected weight bearing provides a useful stimulation for healing.</div> <bR> <bR> <div> <I><B><U>Stage of Remodeling</U></B></I></div> <bR> <bR> <div> <IMG BORDER="0" SRC="Symb075c00b700f000000000.png" HEIGHT="16" WIDTH="24" ALIGN="bottom" HSPACE="0" VSPACE="0">When the fracture is clinically and radiologically judged to be healed, remodeling begins. The complete restoration, including the patency of the medullary canal, signifies the conclusion of the healing process. The fiber bone slowly changes to lamellar bone, and the medullary canal is then reconstituted. The fracture diameter decreases to the original width, oxygen is normal, and the site is no longer electronegative. The remodeling process occurs most efficiently near growth plates and compensates for some deformity or malunion. Growth plates that are more open allow greater potential for remodeling [5]. Once restoration is complete, the new bone is usually thicker and may be even stronger than the old </div> <div> <I><B>Assessing the Fracture</B></I></div> <div> <I><U>Radiography</U></I>, a noninvasive, valuable diagnostic aid in general medicine and dentistry, allows for an early and accurate assessment of bone lesions that requires minimal patient cooperation. </div> <div> Radiographic images depict bone lesions by alterations in the trabecular pattern. These alterations can include the radiographic density related to the amount of absorption of X-rays in the damaged bone tissues or the shape and dimensions of the trabecular pattern. Despite the radiographic capability to provide high resolution images, subtle differences of contrasts in the region of interest and the complicated structure of the trabecular pattern produce difficulties in interpreting bone lesions by human observation. Studies show that minor bone defects in radiographic images escape clinician detection although such information is displayed in the images [8]. In addition, subjectivity is introduced, and investigations have confirmed interobserver and intraobserver variability in the diagnosis [9]. The bias of the observer can have a considerable effect on the interpretation of the radiograph.</div> <div> However, a computer-aided detection technique, <I><U>digital image analysis</U></I>, was proven to provide a more quantitative and reproducible assessment of periapical lesions than conventional interpretation of radiographs. This was concluded through a study which (1) compared the performance of human observers and of the computer-aided method in diagnosing angular periodontal bone defects, (2) ascertained the agreement of the lesion size as determined by the computer and the clinical aspect of the lesion, and (3) determined the reproducibility lesion size as measured by the computer-aided method [8]. The automated lesion detection program assessed periodontal bone lesions with accuracy surpassing or comparable with the results of a group of experienced observers with reduced inter- and intraexaminer variability and decreased time-dependent variability in repeated assessments of a single observer [8,9]. </div> <div> A solution to the problems encountered with the conventional methods of bone fracture diagnosis and its rate of healing lies also in a <I><U>stress wave propagation technique</U></I>. This technique utilizes a simple electromechanical stress wave generator and an electroacoustic transducer that provides for a noninvasive, nondestructive, convenient, reliable, and portable means of assessing both <I>in vivo</I> and <I>in vitro</I> cases. Stress wave propagation provides a useful bone fracture diagnosis on the bed or the emergency site for a qualified general practitioner, avoids the wastage of films and workload on biological departments, and eliminates radiation hazards for patients and staff [10]. </div> <div> <I><B>Accelerating the Fracture Healing Process</B></I></div> <div> <I><U>Ultrasound</U></I></div> <div> At least forty-six various approaches have been employed to stimulate bone repair, including drug treatments, operative procedures, chemical and biochemical agents, and physical methods. After futile attempts to hasten the healing process by pharmacological and hormonal means, a successful technological method of vibration manipulation has been proven to affect the density of solids and other media, otherwise known as ultrasonic therapy. </div> <div> An extremely important mechanism of action of ultrasound is the presence of electrical potentials in bone. In 1968, Friedenberg and Kohanin demonstrated that live, nonstressed bone carries a permanent direct-current polarization that depends on the activity of the bone cells. Accordingly, electronegative areas have high cellular activity in relation to less metabolically active sites. </div> <div> Piezoelectric properties of bone, discovered in 1957 by Fukada and Yasuda, refer to the appearance of electrical potentials in bone when acted upon by mechanical tension, compression, shear stress, or torsion. Two opposite charges develop at the ends of the bone's electrical axis when it is mechanically deformed. Areas under compression and tension become electronegative and electropositive, respectively.</div> <div> Ultrasound describes sound frequencies 20 kHz or higher, beyond the range of human hearing; an ultrasound frequency of 800 kHz has been proven most favorable and is widely used through magnetostrictive or piezoelectric transducers. The first utilizes magnetic energy to generate ultrasound waves by producing a cyclic change in the length of metal rods; the latter generates ultrasound by the transformation of a high-frequency electrical voltage into intense mechanical vibrations. Short ultrasonic wavelengths allow easy, directional, collimated beam emission that is capable of being transmitted at high intensities with a large energy transfer. Tissue is thusly affected at the cellular and molecular level. </div> <div> At a material constant averaging 1500 m/s in human tissue, ultrasound waves propagate in longitudinal vibrations; simultaneously, each particle in the medium vibrates about the center of its resting position. As a result, the alternating pressure states cause a transfer of energy. The <I>amplitude</I> of particle motion within an ultrasound is very small and intensity-dependent. Consequently, matter displacement within a cell does not exceed 1% of the cell diameter. The <I>velocity</I> of the vibrating particles is frequency-independent. The high frequency of ultrasound must accelerate the particles considerably to dictate their direction. Particle acceleration is a significant active force in tissues and contributes significantly to the effects of therapeutic ultrasound.</div> <div> Energy is converted to heat through absorption as it is transported in an ultrasound wave. The absorption coefficient is directly dependent on the frequency and the conducting medium. Generation of excess heat may pose a problem when a higher dose of continuous ultrasound is utilized; however, pulsed ultrasound allows us to minimize this danger and reduce tissue stresses with recovery intervals between pulses [15].</div> <div> The Sonic Accelerated Fracture Healing System (SAFHS) employs such strategy through a portable, noninvasive unit which emanates low-intensity, pulsed ultrasonic waves to promote early healing of fractures by increasing the blood flow to the injured area, thus stimulating bone-forming cells. The SAFHS, which consists of a signal generator connected by a cable to a small, </div> <div> square transducer, is self-administered and applied to the skin over the fracture site approximately 20 minutes per day for a prescribed period of time [11, 12].</div> <div> The ultrasound transducer can also be applied indirectly over the proximal or distal bone fragment, or transarticularly, in which twice the intensity is needed. A slightly warmed, neutral, liquid oil is sometimes used to couple the transducer to the skin as it is slowly moved in a linear, spiral, circular, or sinusoidal pattern. The transducer can also be coupled to the skin by immersing the target and applicator into a water-filled receptacle [15].</div> <div> Early use of low-intensity ultrasound for conservative treatment (cast immobilization) and surgical treatment (intramedullary rods) can result in savings of $14,630, expenses which may include surgery and recovery, outpatient care, workers' compensation, and emergency and disability expenses. Moreover, early use of ultrasound therapy with cast immobilization reduced the average time of disability to 96 days vs. 176 and resulted in saving of $15,000 per case. In conjunction with the surgical treatment of fractures with intramedullary rods, ultrasound reduced disability time to 122 days vs. 154 days without, and resulted in cost savings up to $13,000 per case [13].</div> <div> The results of the experimental and clinical use of therapeutic ultrasound varies according </div> <div> to several factors:</div> <div> * sound intensity (measured in W/cm<FONT SIZE="1" COLOR="#000000" FACE="Arial" >2</FONT>)</div> <div> * the exposure time (minutes)</div> <div> * the sound frequency (in kHz)</div> <div> * the transducer radiating area (cm<FONT SIZE="1" COLOR="#000000" FACE="Arial" >2</FONT>)</div> <div> * the application technique (different sound-transmission properties of water, oils, etc., use of a stationary or moving source)</div> <div> * the reansmission mode (continuous or pulsed beam)</div> <div> * tissue characteristics</div> <div> * reflections at interfaces</div> <div> * the formation of standing waves</div> <div> * temperature</div> <div> * the stage of the disease</div> <div> * the biological properties of the medium [15].</div> <div> <I><U>Electromagnetic Fields</U></I></div> <div> Present knowledge of mechanisms involved in electrical and electromagnetic to speed osteogenesis is derived mostly from cell and tissue culture studies conducted within the last ten years [17, 19].</div> <div> Bone is a framework of mineral crystals built and maintained by living cells within it. Calcium phosphate, the dominant component, is a piezoelectric mineral that generates weak electrical signals with specific waveforms and frequencies in response to mechanical stress. These signals facilitate healing and strengthening by stimulating cell response for calcium fortification [21].</div> <div> Consequently, electromagnetic energy and the human body have an important interrelationship [20]. Transfer of electrical energy to living tissue is achieved through means of an electrical field which is time invariant (electrostatic) or varies with time (electrodynamics). </div> <div> In 1970, Friedenberg et al. tested bone reaction to varying amounts of direct current; optimal current was determined to be within the range 5-20 uA. Currents exceeding 10 uA initiated anode necrosis, and currents that surpassed 100 uA destroyed tissue around the cathode. Optimal results were obtained with the cathode in the fracture gap and the anode positioned in bone or soft tissue away from the fracture. </div> <div> However, the shape of piezoelectric potentials in bone indicates that stimulation with <I>pulsed </I>or <I>alternating </I>current may correspond <I>better </I>to the physiologic potential pattern than to direct current stimulation. To minimize the necrosing effect, Richez et al. used well-defined monophasic current pulses and allowed the tissue to discharge during the time intervals between pulses by short-circuiting the electrodes. In these intervals, approximately 80% of the supplied current appeared in a reverse discharging current. New bone formation was observed around the anode and even greater amounts surrounding the cathode. No osteoclasia was observed. Investigators concluded that strong osteogenesis can be stimulated by a monophasic <I>pulsed</I> current of low frequency, a short duty cycle, i.e., and little ratio between pulse width and period. In addition, pulse frequency and total operating time was postulated more significant for osteogenesis that pulse width or peak output [18]. </div> <div> Stimulation methods can be grouped into four categories:</div> <div> <I>Intraosseous cathodal stimulation</I> (cathode in the fracture site)- Direct or pulsed </div> <div> currents are used. From theoretical analysis, the positive current appears to flow from anode <I>into</I> the fracture through bone and surrounding soft tissue, depending on the location of the anode. </div> <div> b.) <I>Intraosseous current stimulation</I> (anode and cathode in bone adjacent to the fracture site)- Direct, pulsed, or alternating current appears to flow longitudinally across the fracture gap from anode to cathode. </div> <div> c.) <I>Extraosseous current stimulation-</I> Direct, pulsed, or alternating current is driven through the fracture by electrodes conductively coupled to the skin. The positive current appears to flow transversely across the fracture (or obliquely if the electrodes are not directly across from each other).</div> <div> d.) E<I>xtraosseous electromagnetic field stimulation- </I>It is applied by a pair of coils or an electromagnet in physical, but not electrical, contact with the skin over the fracture. The positive current appears to follow a circulating (eddy) current pattern in the fracture. </div> <div> Bioelectric processes such as the alteration of local electric fields and ionic currents is common to all these methods. The current density, in any part of the repair tissue, is related to the electric field through the local electrical conductivity, which may be expected to be heterogeneous and anisotropic throughout the tissue. The current density (J) in a given direction is given by J=oE, where (E) is the local electric field, and (o) is the local electrical conductivity in the same direction. The local current density's magnitude and orientation dictates the amount and orientation of newly formed bone in healing fractures. In the microenvironment of osteogenic cells, the electrophysiological mechanisms in various methods of electrical and electromagnetic stimulation of osteogenesis would depend on J and E. [17]</div> <div> Portable electromagnetic devices, such as the Orthologic 1000 Bone Growth Stimulator, which require a minimum amount of time and administration offer an inexpensive alternative to conventional surgical non-union treatments</div> <div> <I><B>Conventional Methods of Healing</B></I><I>:</I></div> <div> <I><U>Bone Grafting</U></I></div> <div> For centuries, skeletal deficits have been successfully repaired with osseous grafts, as documented by numerous biblical, ecclesiastic, and medical records of varying credibility. The choice of appropriate bone graft substitutes is extensive and should be based upon biological and biomechanical advantages and disadvantages and a clear understanding of the clinical circumstances and goals of the reparative procedure. Bone graft incorporation is an interactive process between the graft and its host bed. Serving as a passive scaffold or template for osteoconduction, the grafts are invaded with blood vessels replete with multipotential cells that differentiate into populations specialized in bone formation or resorption. The graft may also direct active signals to the host for regulating and influencing the incorporation process. </div> <div> Compared with all other bone graft preparations, autografts possess maximal if not superior biological potential and must be highly considered for all circumstances requiring bone graft, especially where failure of unification has occurred. Autografts are histocompatible tissues removed from one place in the body and transferred to another site in the same individual. Fresh autogenous bone contains growth factors and osteoinductive agents including bone morphogenetic proteins that induce cells to proliferate and to differentiate into osteoblasts. Following the formation of the new bone, the normal homeostatic routine of remodeling ensues which is influenced by mechanical and biological physiologic stresses. </div> <div> <I><U>Nonvascularized grafts</U></I><I> </I>are those transferred without an intact blood supply or immediate reestablishment of blood flow by vascular reanastomosis. Hematoma formation begins the histologic pattern followed by a gradual transformation to a fibrovascular response. Inflammation within the contiguous fibrovascular stroma results from the substantial cell necrosis of the graft. However, those cells within approximately 0.1 to 0.3 mm of the graft surface can survive by diffusion.</div> <div> At this point of incorporation, <I>cortical</I> and <I>cancellous</I> grafts exhibit significant qualitative and quantitative differences in the repair process. By virtue of their porous structure, <I>cancellous</I> grafts are rapidly vascularized. Osteoblastic activity follows including osteoid deposition and mineralization which engulfs the initially surface-oriented osteogenic cell population; consequently, cancellous grafts first appear increased in radiographic density. Osteoclastic activity is activated later, and as remodeling ensues, the preexisting acellular graft is eventually resorbed and replaced.</div> <div> <I>Cortical</I> bone revascularizes comparatively slowly, with an initial ingrowth of blood vessels occurring peripherally and through preexistant haversian canals. Increased porosity and reduced mechanical strength in the early stages of incorporation result from a vigorous osteoclastic response. Osteoblastic activity then introduces a "creeping substitution" of the original cortex and increased mechanical strength. A continuous remodeling process follows. Although incorporation is slower and less complete, results are substantial and both biologically and biomechanically effective.</div> <div> The choice to use the cortical or cancellous bone is depends on the specific expectations of the graft material.</div> <div> <I><U>Revascularized grafts</U></I> are tissues transferred limited distances such that their usual blood supply remains intact and tissues transferred with their vascular pedicles to be reanastomosed at the site of implantation. This graft avoids the incorporation process; instead, it unites to the recipient-site skeleton in a way similar to the fracture repair process; substantial distances of segmental loss are bridged with the tissue which rapidly unites at each osteosynthesis site and remains viable rather than experiencing initial cell necrosis. Revascularized grafts continue to remodel and do not undergo matrix resorption or decreased mechanical strength. The host bed is not depended on for success; therefore, grafts can function in locations compromised by irradiation-induced changes, circumstances that may involve infection, or when the patient is more generally impaired (e.g., by chemotherapy). </div> <div> Potential disadvantages include, however, its technically demanding and time-consuming nature, and the limitations imposed by available donor sites, the shape and quantity of the autograft, and the scope of mechanical properties. </div> <div> <I><U>Allografts</U></I><I>, </I>tissues transferred between members of the same species, avoid the need for a donor site and are available in virtually unlimited supply and anatomic shape. Sacrifice of normal structure is unnecessary when graft is removed from cadavers or incidentally from a living donor in an unrelated operative procedure. Furthermore, the second operative site required for an autograft is avoided, and limits in size, shape, and quantity of tissue are circumvented. Clinically used allogenic bone is usually subjected to preservation techniques such as freezing, lyophilization, demineralization, and high-dose irradiation. Statistics suggest 70 to 80 percent of massive frozen osteochondral allografts are associated with successful resolution. However, allografts introduce possibilities of disease transfer and immune responses to foreign tissue dependent on the degree of genetic disparity between donor and recipient, the route of immunization, the dose and time of exposure to antigen, and the general immunocompetence of the recipient.</div> <div> In this regard, the system of bone banking provides adequate quantities of biologically useful tissues at times dictated by clinical circumstance and without concern for transferring disease from donor to recipient. </div> <div> Past experience with <I><U>xenografts</U></I>, tissues transferred between species, has been unsatisfactory due to lack of reliable bone graft incorporation. Nevertheless, efforts to combine xenografts with autogenous marrow and osteogenic factors are being explored.</div> <div> To combat limited availability and potential donor site morbidity associated with autografts and the possibility of disease transmission intrinsic to allografts, a variety of synthetic hydroxyapatite and tricalcium phosphate ceramic preparations are manufactured as bone graft substitutes and supplements. Generally, these products posses only osteoconductive properties and are effectively employed for repairs requiring limited biomechanical strength or as a supplementation of fusion masses [26].</div> <div> <I><U>Internal Fixation</U></I></div> <div> The goals of internal fixation were clearly defined by the Swiss Arbeitgemeinshaft fur Osteosynthesisfragen (AO) group, or the Association for the Study of Internal Fixation (ASIF). Four conditions were deemed prerequisite for "perfect internal fixation": anatomic reduction of the fracture, stable internal fixation (fundamental to all fracture healing), atraumatic surgery, and early active mobilization of the injured limb to prevent stiffness and atrophy caused by cast disease. Fixation methods are measured by this standard criterion. </div> <div> Adequate stabilization can be obtained through the most basic techniques of reapproximation and fracture fixation. For many fracture situations, proper application of splintage techniques yields satisfactory results. </div> <div> <I><U>Pin fixation</U></I> is frequently applied temporarily to maintain fragment alignment while more permanent methods are implemented. It offers several applications as a singular or combination technique. Although one of the simplest and easiest applied methods, it is often misused. Kirschner wires, available in smooth or threaded versions, are usually 0.035, 0.045, or 0.062 inches in diameter and have pointed tips to facilitate bone penetration. Steinmann pins are larger than Kirschner wires and pointed at each end; foot surgery typically requires wire 5/64 inches in diameter. Surgical stainless steel wire is available in numerous sizes that are measured in gauges. The larger the gauge, the smaller the wire diameter; commonly used gauges range from 30 to 18. While thinner gauge provides less tensile strength, it is more flexible and easy to manipulate; </div> <div> thusly, it is reserved for suturing of soft tissues. Thicker gauge renders greater tensile strength but is apt to kink when bent at acute angles.</div> <div> Common complications of wire application in internal fixation are fatigue and failure; minimal wire manipulation during insertion is recommended.</div> <div> Intraosseous wire loops, generally employed to stabilize small fracture fragments, are effectively applied to bones with thick cortical walls. Greater stability is directly related to the greater number of cortices secured by loops that are perpendicularly situated to the fracture in either a horizontal or vertical mattress fashion.</div> <div> However, <I><U>glass fibers</U></I>, nontoxic implants that contain fundamental bone elements such as calcium, phosphorous, and trace amounts of iron oxides, may soon replace more expensive metal pins. The fibers provide strength equal to metal yet dissolve gradually, speeding recovery by supplying necessary nutrients to healing bones [61].</div> <div> Similarly, the use of <I><U>staple fixation</U></I> to treat fractures is somewhat limited to superior methods, although traditional applications include treating elective osteotomies and anchoring detached ligaments and tendons.</div> <div> Almost exclusively designed for use in cancellous bone, the staple form generally includes two or more prongs and an intervening bar or plate. The device is inserted with a specialized driver that grips the staple as it is impacted with a mallet. Consequently, many problems associated with staple fixation are directly related to this method of insertion; the force of impact bears a significant risk of secondary fracture. However, predrilling at insertion sites may prove helpful. Two or more points of fixation, preferably perpendicularly oriented, provide better </div> <div> resistance to rotational, shear, and bending forces that dislodge the staple. Nevertheless, limitations for trauma surgery rest in the lack of precision, finesse, and the crude instrumentation.</div> <div> <I><U>Rigid internal fixation</U></I><I> </I>first demonstrated by Shenk and Willenegger, initiates primary vascular repair, fracture healing <I>without</I> callus formation. The fracture must be stable, anatomically aligned, and surfaces must remain in intimate apposition to obliterate any potential gaps which would hinder capillary and osteogenic cell migration across the osteotomy line, promote fibrous union, and encourage movement at the fracture site [32]. Rigid internal fixation implies that compression exists between fracture fragments. Thusly, interfragmental compression, both static and dynamic, requires the implants to be placed under tension and the bone fragments to be relatively large. Significant advantages of rigid internal fixation include predictable bone healing and decreased convalescence [29]. </div> <div> Although the processes differ, primary repair occurs in cancellous and cortical bone. Charnley & Baker (1952) and Charnley (1953) discovered primary union of cancellous bone under compression during studies on arthrodesis of the knee. Compression is a major application in surgical arthrodesis and has proven more certain and generally more rapid than other knee athrodesis methods. Charnley's view corresponded with subsequent claims concerning the osteo-biological stimulatory effects of compression forces. </div> <div> Primary union of <I>cortical</I> bone is intertwined with the development of plate and screw internal fixation. Observations indicated that increasing the rigidity of the fixation contributed to unification without a radiogically detectable callus (Danis, 1949; Bagby and Janes, 1958; Hicks, 1959, 1961, 1963). However, this does not indicate that primary union, in its true histological sense, has occurred although that is possible. The stability allows a relatively easy and early restoration of the torn medullary circulation across the fracture, which can contribute to cortical union [32]. </div> <div> Rigid internal fixation can also be obtained through <I><U>plate fixation</U></I>. Plate fixation is sometimes manipulated to create interfragmental compression, yet also provides protection of interfragmental compression contributed by lag screws when used as splintage. The type of plate chosen, either straight or shaped, depends on the biomechanical function required and the actual configuration of the fracture and bone fragments. While straight plates are generally designated for diaphyseal fractures, shaped plates are used for irregularly shaped bones and metaphyseal and epiphyseal regions. Internal fixation with metal plates requires major surgical intervention and impairs the blood supply to the fracture fragments [31].</div> <div> <I><U>External fixation</U></I> is primarily applied to fractures associated with soft tissue defects, comminuted or osteoporotic bone, and infection. It can function as a splint to neutralize disruptive forces, maintain the distraction of fragments useful in open comminuted fractures, or create rigid fixation. When a relatively transverse fracture is present, pins are placed percutaneously through the proximal and distal fragments parallel to the fracture line. They then are secured to the frame and simultaneously tightened to create axial compression [29].</div> <div> <I><B>Advanced Methods of Healing</B></I></div> <div> An innovative surgical technique is now being employed to eliminate traction, body casts, and disturbance of traumatized tissues in complex leg fracture sites. Developed in Europe and introduced to the United States in 1982, the <I><U>closed interlocking nailing</U></I> technique offers major advantages over standard methods of treatment eliminating many patient risks and inconveniences. The procedure is monitored by projecting x-ray images of the bone's interior onto a video screen. After a small incision in the buttock, a hole is made at the top of the femur bone some distance from the fracture site. A flexible guidewire is carefully advanced down the entire length of the bone interior, and a reaming device then expands the surrounding area about the guidewire. Afterwards, a hollow, stainless steel nail with holes at each end is inserted over the guidewire until the bottom end reaches just above the knee. </div> <div> In spanning the length of the bone, the nail will provide adequate stability to allow immediate mobility in simple fractures. However, depending on the location and pattern of complex fractures, locking the nail with special screws at either end to prevent telescoping, collapsing, and excessive rotation of the bone is necessary. The screws rigidly maintain the correct length, alignment, and rotation of the bone until the fracture completely heals, and the device is surgically removed about a year later [30].</div> <div> The development of the <I><U>Ilizarov method</U></I> signified the beginning of an innovative and extremely unique scientific and practical concept allowing the enunciation of previously unknown biologic laws regarding bone formation, osteoinduction, and tissue neogenesis. Professor Gavriil Abramovich Ilizarov, director of the Pan-Soviet Scientific Center for Traumatology and Rehabilitation Orthopedics of Kurgan (V.K.N.C.-VTO) and recipient of the 1978 Lenin Prize for Medicine, began his research and experimentation more than thirty-five years ago in Kurgan, Siberia, a small industrial city of 250,000. As an Emeritus Professor and an Inventor Emeritus of the U.S.S.R., Ilizarov recently achieved full membership in the Soviet Science Academy, a rare honor for a doctor of medicine. However, due to language and cultural barriers, political reasons within the Russian orthopaedic community, and the fact that Kurgan was closed for tourism, North American orthopaedic surgeons visiting the Soviet Union were only marginally familiar with his circular apparatus and its possibilities. Amicable relations with Italy allowed the U.S. to invite Ilizarov to the XXII Italian AO Meeting in Bellagio, Italy, in June 1981, for his first western conference. Prophylaxis, bone lengthening, and the treatment of bone infections open fractures, and post-traumatic osteomyelitis were addressed. In a series of European-hosted international conferences, the Ilizarov method diffused beyond U.S.S.R. boundaries [33].</div> <div> The method involves a device that consists of metal rods extended between a series of metal rings externally placed on the arm or leg. Wires are surgically implanted horizontally through the bone and fastened to the Ilizarov device. Through a small incision made between the rings, the hard, outer cortical bone is cut, and the soft, porous cancellous bone is left undamaged. Approximately one week after the frame is applied, tiny knobs are turned a quarter of a millimeter every six hours (1 mm per day) for six to eight months or more, causing distraction between the bone segments and, consequently, new bone formation. Subsequent follow-up assessments are usually administered weekly or bi-weekly [36, 37].</div> <div> This pioneering surgical technique used to eliminate limb length discrepancies and abnormalities caused by birth defects, disease, and injury [32, 35], is so versatile that its assembly is adaptable to treat any skeletal pathology [33]. </div> <div> Treating limb deformities may require a series of stages, correcting one component at a time, or combined stages, remedying components simultaneously. In a kinematic analysis of limb deformities, interactive computer programs coded in FORTRAN were compiled on a Silicon Graphics workstation containing a series of algorithms developed to determine the proper Ilizarov element locations for long deformity correction with angular and lengthening components. With the succcess of the experiment, visualization of specific Ilizarov constructs were graphically represented to reduce the time required for preoperative planning and to determine optimal construct design, thus decreasing overall treatment time. The computational design was validated using bench-top models in which the deformity correction was simulated and documented by photographs. A comparison between the final deformity correction between the bench-top constructions and the computational designs produced errors less than 2.0%, within acceptable physician limits [35]. </div> <div> In addition, incorporating the Ilizarov method with AO internal fixation techniques provides a successful alternative to pilon fracture treatment with minimal complication rate [34]. </div> <div> Perhaps one of the most innovative technological advances in bone healing includes the development of <I><U>bone cement</U></I>, a mineral substitute that provides immediate structural integrity to the fracture site [44, 43]. Monitored on a fluoroscope, the white, putty-like mixture containing recombinant human bone morphogenetic protein (rhBMP-2) is injected into the fracture site, where it hardens partially within ten minutes, and in twelve hours, solidifies and crystallizes largely into carbonated apatite, the dominant component of bone [40,42,43,44,39,45]. Also termed dahllite, carbonated apatite contains small amounts of sodium, magnesium, and other trace components. </div> <div> The most commonly used calcium phosphates for bone defects and trauma application as implant coatings and defect fillers are thermally processed ceramics, hydroxyapatite and tricalcium phosphate. Considerable temperatures are required to produce these preformed, highly crystalline, dense, bioinert ceramics; however, such materials differ from apatites developed <I>in vivo, </I>and their low fatigue properties relative to bone contribute to limited orthopaedic application.</div> <div> Nonetheless, a new process for in situ formation of the mineral phase of bone has been successfully established. Monocalcium phosphate, monohydrate [MCPM, Ca(H<FONT SIZE="1" COLOR="#000000" FACE="Arial" >2</FONT>PO<FONT SIZE="1" COLOR="#000000" FACE="Arial" >4</FONT>)<FONT SIZE="1" COLOR="#000000" FACE="Arial" >2</FONT>*(H<FONT SIZE="1" COLOR="#000000" FACE="Arial" >2</FONT>O)], a-tricalcium phosphate [TCP, Ca<FONT SIZE="1" COLOR="#000000" FACE="Arial" >3</FONT>(PO<FONT SIZE="1" COLOR="#000000" FACE="Arial" >4</FONT>)<FONT SIZE="1" COLOR="#000000" FACE="Arial" >2</FONT>], and calcium carbonate (CC, CaCO<FONT SIZE="1" COLOR="#000000" FACE="Arial" >3</FONT>) are dry mixed then combined with a sodium phosphate solution to form a paste. The paste maintains its pliability for five minutes, is injected, and hardens through dahllite crystallization. Within ten minutes, an initial compressive strength of ~10 MPa is attained; within twelve hours, the material is about eight-five to ninety percent dahllite and attains a final maximum compressive strength of ~55 MPa and a tensile strength of ~2.1 MPa. Compared to cancellous bone, the compressive strength of the new biomaterial is greater, while the tensile strength is about the same. Direct-current plasma spectrometry and carbon coulometry determine the bulk elemental constituents of the dahllite formed; by weight, carbonate constituted ~4.6%, and the calcium-to-phosphate molar ratio measured ~1.67. The stoichiometric formula of the dahllite was therefore obtained:</div> <div> <B>Ca</B><FONT SIZE="1" COLOR="#000000" FACE="Arial" ><B>8.8</B></FONT><B>(HPO</B><FONT SIZE="1" COLOR="#000000" FACE="Arial" ><B>4</B></FONT><B>)</B><FONT SIZE="1" COLOR="#000000" FACE="Arial" ><B>0.7</B></FONT><B>(PO</B><FONT SIZE="1" COLOR="#000000" FACE="Arial" ><B>4</B></FONT><B>)</B><FONT SIZE="1" COLOR="#000000" FACE="Arial" ><B>4.5</B></FONT><B>(CO</B><FONT SIZE="1" COLOR="#000000" FACE="Arial" ><B>3</B></FONT><B>)</B><FONT SIZE="1" COLOR="#000000" FACE="Arial" ><B>0.7</B></FONT><B>(OH)</B><FONT SIZE="1" COLOR="#000000" FACE="Arial" ><B>1.3</B></FONT><B> </B>[46].</div> <div> The recombinant morphogenetic protein signals bone cell proliferation [42] and blood vessel development [45] as the paste is decomposed through resorption and subsequently rebuilt in the body [40, 46].</div> <div> Bone cement contributes to a faster [43], more complete recovery and decreased cast treatment time [39] which ultimately leads to considerable medical care savings [45]. Clinical trials in Sweden, Holland, and the Netherlands have proven successful, although in the United States, approval from the Food and Drug Administration is impending [39, 42]; clinical trials are being conducted in twelve medical centers [46, 40, 45]. </div> <div> In addition, osteogenesis stimulated by <I><U>recombinant human bone morphogenetic protein (rhBMP-2)</U></I> in trials conducted on animals has proven successful. Osseous union in adult rabbits [47] and rats [48, 49] has been observed, and radiographs and mechanical testings revealed healing of large mid femoral segmental defects in sheep treated with rhBMP-2 and inactive bone matrix [50]. <I><U>Demineralized bone matrix</U></I> and bone marrow composite also demonstrate effective induction of bone formation in extraosseos tissue [62], as do demineralized bone matrix combined with rhBMP [63].</div> <div> The remarkable phenomenon of spontaneous osteogenesis in <I><U>porous hydroxyapatite</U></I> when implanted extrskeletally in baboons revealed a novel concept in biomaterial technology, <I>porous bone substitutes with intrinsic osteoinductive activity</I>. This phenomenon suggests the presence of rhBMPs circulating or locally produced [57]. Formed by Porites goniopora conversion, this hydroxyapatite has pores averaging 600 micrometers and pore interconnections averaging 260 micrometers in diameter [58]. Interestingly, the geometry and surface characteristics of the porous substratum are of principal importance to promote bone differentiation, a phenomenon defined as geometric induction of bone formation [57]. </div> <div> A principally new and major advancement within bone biology and reconstructive surgery, the <I><U>osteopromotive e-PTFE</U></I><I> (expanded polytetrafluoroethylene) </I><I><U>membrane techniqu</U></I><I>e </I>provides improved conditions for bone regeneration [52] by preventing fibroblasts and other soft, connective tissue cells from entering the defect and hindering osteogenesis [54]. Several experiments testing this method were executed in the mandible defects of rats. Bone formation and was initiated by combining rhBMP-2 and the e-PTFE membrane technique while maintaining the bone contour [53]. Employing the <I><U>hyperbaric oxygen technique</U></I><I> </I>in conjunction with e-PTFE membranes produced a significant improvement in healing, compared to the osteoinductive properties of either method alone [54]. The hyperbaric oxygen technique involves a highly pressurized chamber that furnishes a completely oxygenated atmosphere; hence, the oxygen-rich blood can minister to injured tissues and, reportedly, speed recovery up to 50% [11]. Furthermore, <I><U>growth hormones</U></I><I> (hGH)</I> also promote bone regeneration and neogenesis by exerting a direct, non-liver mediated effect on bone tissue; e-PTFE used in conjunction with hGH encourages additional bone regeneration [56]. </div> <div> Traditional Chinese herbal treatments, including <I><U>Rehmannia</U></I> (Radix Rehmanniae, Sok-Day-Sang-Day), claim to promote bone healing among other remedying properties [59]. Furthermore, a multiple <I><U>herbal plaster</U></I> prepared according to the dialectic therapeutics of Traditional Chinese Medicine is credited similarly in that, through subcutaneous tissue penetration by external application, it stimulates circulation producing a local analgesic effect and, subsequently, promoting the healing of bone fractures [60].</div> <div> Despite the numerous healing methods for bone defects, there are several factors that increase proclivity to fractures:</div> <div> * Within the last twenty years, a number of research groups have documented slower bone healing among <FONT SIZE="3" COLOR="#000000" FACE="Goudy Old Style" ><I><U>smokers</U></I></FONT>. Twenty-nine men and women who suffered osteomyelitis from a fractured tibia were divided into nonsmokers, former smokers, and current smokers in a clinical study conducted at Emory University in Atlanta by Dr. George Cierny III and his coworkers. The infected bone segment was removed, and patients were treated with the Ilizarov method to initiate bone regeneration. Smokers required more time to heal; the average time for nonsmokers to produce one centimeter of new bone was 69.6 days, compared with 89.4 days for smokers. Accordingly, five centimeters of new bone would require ten months and fifteen months for a nonsmoker and smoker, respectively. Former smokers would need 13.6 months to produce the same amount [64,65].</div> <div> Nicotine contributes to impaired bone regeneration in smokers by reducing the amount of oxygen distributed to body tissues, thus precluding adequate collagen production essential for new bone formation [65]. </div> <div> * Researchers at America’s National Institute of Mental Health (NIMH) recently reported that <I><U>clinical depression</U></I> may be associated with broken bones. Excess cortisal production, a common feature of depression, can result in decreased bone density, and, consequently, a significantly greater fracture risk from weakened bones. Depression may affect as many as nine percent of American women; early treatment can improve physical and mental public health by reducing fracture risk [66].</div> <div> * U.S. soft drink consumption has increased 300 percent within the last three decades. A 1989 epidemiologic study revealed <I><U>carbonated beverage consumption</U></I> is correlated with bone fractures among women over age 40 who had been athletes in college. Lack of adequate calcium absorption resulting from such consumption places women at risk for osteoporosis [67]. </div> <div> * Steven R. Cummings and his colleagues at the University of California conducted a study of 9,515 white women age 65 or older who had never previously broken a hip to determine factors that predisposed women to hip fractures. It was concluded that women whose mothers had suffered hip fractures were twice as likely to sustain the same injury. Elevated risks for tall women, those who had broken any other bone after age 50, and women with an overactive thyroid gland were also observed. Excessive caffeine consumption, inadequate exercise, and weight loss after age 25 contributed to greater fracture risk, as do benzodiazepine and anticonvulsant use [45].</div> <div> Essentially, a proper, well-balanced diet [70], exercise, and adequate nutritional intake are recommended to maintain a healthy life-style, discourage fractures, and hasten fracture recovery. Lack of sunshine, vitamin C and D deficiency, and general malnutrition as a result of inadequate food intake or failure of proper metabolism due to poor digestion, absorption, and assimilation of food are factors to be corrected [68]. Calcium supplements taken with fluoride may be more effective at preventing bone fractures that calcium alone; a moderate increase in spinal density and a decreased fracture rate were observed in an international study of 200 women over a four year period [69]. Estrogen replacement therapy is also recommended to increase bone density </div> <bR> </td> </tr></table></body>