Intramedullary Lengthening Devices / USA /ISKD -  This update is part of our continued effort to educate those patients seeking long-bone lengthening for limb length discrepancies  due to traumatic, infectious (osteomyelitis), neoplastic and/or congenital etiologies.  Three recent studies examined clinical outcomes using the only currently FDA-approved internal lengthening device, the  Intramedullary Skeletal Kinetic Distractor (ISKD) (Orthofix, Bologna, Italy).  All in all, 180 patients and 242 limb segments were evaluated.   study 1 – 15 ISKDs in 12 patients failed mechanically, including 10 device fractures and unplanned interventions were needed to achieve length [1];  study 2 – 69 patients with 65% complication rate with 90% of femurs and 45% of tibias ultimately achieving desired length [2];  study 3 - insufficient bone regenerate developed in 8/35 (23%) patients undergoing femoral lengthening. Risk factors for poor bone formation were lengthening rate > 1.5 mm/day, age >30 years, smoking and lengthening > 4 cm. Distraction problems were mostly related to internal malfunction of the lengthening mechanism [3].  1.Burghardt, R.D., et al., Mechanical failure of the Intramedullary Skeletal Kinetic Distractor in limb lengthening. Journal of Bone & Joint Surgery – British Volume, 2011. 93(5): p. 639-43.  2. Schiedel, F.M., et al., Intramedullary limb lengthening with the Intramedullary Skeletal Kinetic Distractor in the lower limb. Journal of Bone & Joint Surgery – British Volume, 2011. 93(6): p. 788-92.  3. Kenawey, M., et al., Insufficient bone regenerate after intramedullary femoral lengthening: risk factors and classification system. Clinical Orthopaedics & Related Research, 2011. 469(1): p. 264-73.

Summary: there are new internal distractors on the horizon which may, in time, change the rather dubious performance profile of this particular ”internal method”.   Currently, however, the convenience and “cosmetic” advantages of the ISKD over external fixator protocols (ie; lenghtening over nails (LON) and ex/fix, alone) have been off set by its high rates of mechanical failure, unplanned interventions and unpredictable in situ performance (ie; “runaway nail”).  For further reference, see  1) Kenawey M, Krettek C, Liodakis E, Meller R, Jankemeier S;  Insufficient Bone Regenerate after Intramedullary Femoral Lengthening.  COOR, 2011; 469: 264-273.  2)Cierny G III, DiPasquale D:  Limb lengthening for bone loss due to infection, in Hamdy RC, McCarthy J:  Management of Limb-Length Discrepancy. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2010

Thorough debridement and a two-stage exchange is currently the standard of care for total knee, hip and shoulder arthroplasties complicated by deep infection (peri-prosthetic total joint infections). Both the static and articulating spacers used in these procedures eradicate infection with similar effectiveness. However, using articulating spacers promotes greater range of motion, preserves bone, facilitates reimplantation and may enhance functional recovery.

The treatment of post-debridement, osteomyelitis wounds with residual dead space and the need for prosthetic and/or bony reconstruction follows a standardized algorithm: placement of an antibiotic spacer(depot), intravenous antibiotics, and reimplantation/reconstruction  after the wound has healed and all signs and symptoms of infection have subsided.  The spacers contain high concentrations of antibiotics.  We currently use 35-40cc of finely strained antibiotic powder in every pack of Palecos when using PMMA constructs ; CASO4 antibiotic spacers and beads are used only to supplement antibiotic delivery, not to maintain dead space.  Comparisons of  static and articulating spacers both here (at the San Diego Osteomyelitis Treatment Center) and in the literature of static and articulating spacers show eradication rates of  90%-92%.   However, articulated spacers (essentially fabricated, revision joints loaded with antibiotic) can  enhance rehabilitation in the process.  

Methods for creating an articulating spacer in the hip or knee include using a recycled femoral component, a prosthesis of antibiotic laden acrylic cement (PROSTALAC, Johnson & Johnson) or use of molded, all-cement components; these are articulated with a bare (bony) surface or components made of either polyethylene or PMMA.  The spacer is implanted with intentionally poor cement technique, applied with a small amount of doughy cement into a bloody wound, to reduce adherence and allow for easier removal at time of reimplantation.  Literature supports  infection-control rates of 91% for recycled component spacers, 95% for PROSTALAC spacers and 93% for molded cement spacers.  Fehring, Emerson and Hoffman  reported an increased range of motion using articulating spacers when compared to static and Meek concluded the PROSTALAC system provided functional outcomes for septic revision equal to those of aseptic revision.

Static Spacers(see featured case #15) are used to deliver antibiotics while immobilizing the joint.  This option is preferred when treating extensor or other soft tissue deficiencies, extensive bone loss  or when a post-operative course calls for  immediate mobilization (ie; in the case of a bilateral peri-prosthetic TKA infections where an articulated spacer is used on one side and a static spacer on the other).   References:  *Cierny III, G., DiPasquale,D., Periprosthetic Total Joint Infections; Staging, treatment and outcomes. Clinical Orthopaedics and Related Research, 2002; Number 403, 23-28; *Durbhakula SM, Czajka J, Fuchs MD, Uhl RL. Antibiotic-loaded articulating cement spacer in the 2-stage exchange of infected total knee arthroplasty. J Arthroplasty. 2004;19:768-774;  *Emerson RH Jr, Muncie M, Tarbox TR, Higgins LL. Comparison of a static with a mobile spacer in total knee infection. Clin Orthop Relat Res. 2002;404:132-138. *Evans RP. Successful treatments of total hip and knee infection with articulating antibiotic components: A modified treatment method. Clin Orthop Relat Res. 2004;427:37-46;  *Fehring TK, Odum S, Calton TF, Mason JB. Articulating versus static spacers in revision total knee arthroplasty for sepsis. Clin Orthop Rel Res. 2000;380:9-16. *Goldstein WM, Kopplin M, Wall R, Berland K. Temporary articulating methylmethacrylate antibiotic spacer (TAMMAS). A new method of intraoperative manufacturing of a custom articulating spacer. J Bone Joint Surg. 2001;83-A(Suppl):92-97;  *Hofmann AA, Goldberg T, Tanner AM, Kurtin SM. Treatment of infected total knee arthroplasty using an articulating spacer: 2-12 year experience. Cin Orthop Rel Res. 2005;430:125-131;  *Meek RM, Dunlop D, Garbuz DS, McGraw R, Greidanus NV, Masri BA. Patient satisfaction and functional status after aseptic versus septic revision total knee arthroplasty using the PROSTALAC articulating spacer. J Arthroplasty. 2004;19(7):874-879;  *Lombardi AV Jr. Articulating antibiotic spacers: Standard of Care — Affirms. Paper #98. Presented at Current Concepts in Joint Replacement, Winter 2006 Meeting. Dec. 16, 2006. Orlando, FL.

Researchers, under the direction of Bruce Sangeozan (Univ. Washington, Seattle), have found no significant difference in two year outcomes between total ankle and ankle fusion candidates.  203 patients were entered into the restropective, cohort  study which was neither randomized nor prospective.  Pain and functional levels were the primary parameters studied.  As such, each patient was required to  complete a Musculoskeletal Functional Assessment and the SF:36 at 6 months, 12 months and 24 months.

Voriconazole is a broad-spectrum and highly effective antifungal that has been used in the treatment of resistant fungal pathogens. Voricanazole-containing antibiotic beads were studied in vitro, eluent samples collected over 2 weeks and samples tested against control yeasts. Samples collected out to 2 weeks contained high enough voriconazole concentrations to inhibit growth of the control yeasts. These data demonstrate that voriconazole retains its antifungal activity when mixed into either PMMA or calcium sulfate beads, elutes at biologically effective concentrations over a time period of at least 2 weeks and that its addition to either absorbable or nonabsorbable beads (CASO4) is a reasonable strategy for the local delivery of a potent, broad-spectrum antifungal agent to osteomyelitic wounds.

McLaren and McLemore (Banner Orthopaedics, Phoenix) have also shown excellent release of Amphotericin-B  from PMMA using a lipid encased formulation called Ambisome.  With loaded doses and the use of poragens, the levels appear superior to those found using Amph-B alone.

1) The In Vitro Elution Characteristics of Antifungal-loaded PMMA Bone Cement and Calcium Sulfate Bone Substitute.  Grimsrud C, Raymond Raven R, Fothergill AW, Kim HT; ORTHOPEDICS August 2011;34(8):378.  2) Voriconazole is delivered From Antibiotic Bone Cements.  Miller R, McLaren A, Pauken C, Clarke H, McLemore R;  21st Annual Meeting of the Musculoskeletal Infection Society of North America. Rochester, MN August 5, 2011.  3)  Ambisome Releae From Antibiotic Bone Cement is Limited.  Cunningham B, McLaren A, Yu E, McLemore R; 21st Annual Meeting of the Musculoskeletal Infection Society of North America. Rochester, MN August 5, 2011.

Patients with metal-on-metal THAs and joint-surface replacements must be monitored regularly whether or not they have complications stemming from these implants. There is increasing recognition that in the long term, metal-on-metal bearings may be associated with adverse local and remote tissue responses through metallosis and the known toxicities of these bearings’ metallic constituents. It should be pointed out, however, that these toxicities refer to soluble forms of the bearings’ metallic elements, and may not reflect the toxicity profiles of the specific metal-degradation products of orthopaedic implants.¹  Nevertheless, cobalt toxicity resulting from arthroplastic implants has been linked to tinnitus, vertigo, deafness, blindness, optic nerve atrophy, convulsions, headaches, peripheral neuropathy, cardiomyopathy, hypothyroidism, polycythemia, and carcinogenesis.

There is also evidence that patients with well-positioned, 28-mm metal-on-metal bearings can have very high serum levels of cobalt, although there are indications that the worst problems stemming from THAs with such bearings have occurred with large-diameter head constructs. Patients with these THAs may also develop cobalt toxicity without experiencing sentinel hip pain.

Cutaneous metal sensitivity occurs in 10% to 15% of the general population, but this does not correlate with the incidence of hypersensitivity to orthopaedic implants. The triple assay technique of Hallab and colleagues has been shown to identify individuals potentially susceptible to metal-induced, delayed-type hypersensitivity reactions, but no marker levels are given for ascertaining what constitutes a hypersensitivity reaction. It is also impossible to ascertain whether a prosthesis may trigger a hypersensitivity reaction in a previously unaffected individual. As noted earlier, patch testing of the skin is reliable for investigating whether a patient is experiencing a metal-induced contact dermatitis, but is not so useful in evaluating deep-tissue metal allergy. The true prevalence of metal hypersensitivity to orthopaedic implants is unknown, as are the association between dermal and deep-implant sensitivity and the exact role of hypersensitivity in the pathogenesis of the pain in cases of a painful THA.

More worrisome, however, are cases with significant tissue necrosis, including the necrosis of muscle, such as of the hip abductors, as well as of the joint capsule and other supporting structures, including bone. Cobalt-chromium particles have a high specific surface area, promoting the dissolution of ions of these metal into surrounding tissues. These ions are known to induce apoptosis and necrosis of macrophages, the latter being seen particularly at high ion concentrations.

A finding of necrosis in periprosthetic tissues of a revised metal-on-metal THA, including those cases of such necrosis in which relatively little associated inflammation is evident, indicates that cytotoxicity cannot be discounted as a possible cause of tissue necrosis. Studies have shown that metal particles phagocytosed by macrophages are transported to lysosomes, and that these structures release high concentrations of metal ions, resulting in apoptosis and cell death of the ingesting macrophages, with subsequent release of the phagocytosed metal. The morphology of the necrotic and viable macrophage granulomas seen in pseudotumors, and in some cases of metal-on-metal component loosening of a prosthesis, would be in keeping with this cytotoxic effect, which would lead to a vicious cycle in which the generation of metal-wear particles promotes macrophage recruitment followed by particle phagocytosis, apoptosis, and cell death, with the resultant release of metal particles and further macrophage recruitment, causing repetition of the cycle.  Surface ulceration of the pseudocapsule and pseudomembrane around metal-on-metal articulations may result from a similar process, because the cells lining the pseudocapsule are mainly of macrophage phenotype. Exposure of articular synovial tissue to cobalt-chromium debris is sufficient to provoke surface ulceration and a lymphocytic infiltrate in the absence of a loose prosthesis ²

For the surgeon facing the practical problem of investigating a patient with a painful metal-on-metal THA, differentiating ALTR from infection is difficult because of the lack of a single, consistently reliable test that is generally available at most hospitals. Yet the need to identify the cause of the pain in such cases is crucial in planning their appropriate management through the choice of a single- versus a two-stage revision.

A thorough workup of the patient with a painful metal-on-metal THA or resurfacing arthroplasty requires a systematic approach. The workup should begin with a history that indicates the onset of pain and swelling as occurring shortly after the index surgery. A good physical examination should follow, with an emphasis on detecting synovial irritation and/or a “clunk” with movement. Adequate radiographs must include a cross-table lateral film for evaluating component positioning, loosening, or osteolysis. MARS-MRI imaging can demonstrate characteristic soft-tissue disease in patients in whom conventional radiographs are normal or inconclusive. Additionally, serum or whole blood levels of cobalt and chromium, as well as indices of infection, should be measured. If the diagnosis then still remains equivocal, scintigraphy is an excellent secondary measure for ascertaining the cause of pain.

 1 JJacobs JJ, Skipor AK, Campbell PA, Hallab NJ, Urban RM, Amstutz HC. Can metal levels be used to monitor metal-on-metal hip arthroplasties?  Arthroplasty. 2004 Dec;19(8 Suppl 3):59-65.

2 Howie DW, Vernon-Roberts B: The synovial response to intraarticular cobalt-chrome wear particles. Clin Orthop Relat Res 1988;232:244-254.

C-Reactive Protein(CRP) is secreted by the liver in humans  and can be detected by a routine blood testing to assess patients for signs of inflammation or infection.   For example, CRP testing can help doctors diagnose  inflammatory bowel syndrome, autoimmune diseases, some types of arthritis, lupus erythematosus, lymphomas, osteomyelitis, and pelvic inflammatory diseases.  CRP levels can also provide an early alert that wound care is failing after trauma or surgery or help a doctor distinguish between virus vs. bacterial sources for illness.  Since CRP levels tend to drop as inflammation subsides, doctors can use it to determine if treatment is working or has succeeded, as designed.   More sensitive versions of the test may also serve to alert clinicians as to the presence of significant cardiovascular disease.  What CRP cannot do is pinpoint the exact location of the disease or infection ….. it is only an indicator.

Early industry-sponsored clinical research on rhBMP-2, published in a variety of orthopedic and spine-related medical journals, reported no adverse events or complications in hundreds of patients. However, in recent years, the use of rhBMP-2 has been associated with various early inflammatory reactions, cancer, osteolysis, infection, implant dislodgement and occasional life-threatening complications. In a bold move, the nation’s leading spine journal is shining a critical light on the limitations of industry-sponsored research and is bolstering transparency initiatives to protect the integrity of scientific publishing. The June issue of The Spine Journal is dedicated to a review of recombinant bone morphogenetic protein-2 (rhBMP-2), a controversial synthetic bone growth product often used in spine fusion surgeries.  A separate study also in the June issue of The Spine Journal suggests that rhBMP-2 usage could cause a higher incidence of male sterility than previously described by industry-sponsored researchers.   Despite the growing list of complications associated with this product, rhBMP-2 still may be of great benefit to a small group of patients who have serious problems in healing bone, particular those struggling with control of a recurrent osteomyelitis and/or undergoing concomitant distraction osteogenesis (limb /bone lengthening).   GC

About Metal Hypersenitivity: contact allergy to metals such as nickel, cobalt, and chromium is prevalent in the general population. It is estimated that up to 17% of women and 3% of men are nickel allergic, and that about 1 to 2% are allergic to cobalt, chromium, or both.   Metal allergy is mainly caused by prolonged or repeated skin exposure to consumer items (such as jewelry) and occupational exposure in the metal and construction industries.  Similar reaction to metallic surgical implants may either result in eczematous eruptions on skin overlying the implant or in device failure caused by a delayed-type hypersensitivity(DTH) reaction (ie; a chronic inflammation causing the loosening of joint prostheses).

 Orthopedic implants are most often made from steel (stainless or cobalt-chromium alloys), vitallium, or titanium.  When in contact with biologic fluids, these metals undergo a degree of corrosion, releasing  small ionic compounds which then bind to endogenous proteins to form metal-protein complexes which, in turn, can activate macrophages and a DTH response.

 The most common types of cutaneous allergic reactions associated with metallic implants are eczematous in nature, although urticaria and vasculitis have occasionally been reported. Eruptions may be localized or generalized or both. Localized eruptions present as dermatitis primarily affecting the skin overlying the site of the implant. Generalized eruptions most often present as eczematous reactions and occur equally in association with static and dynamic implants. Noncutaneous complications involving orthopedic implants may occur following total hip or knee arthroplasty as well as following the insertion of other dynamic implants. First-generation metal-on-metal orthopedic hip bearings were introduced in the 1960s and 1970s and were associated with high rates of metal release and sensitization (28–46%).  The prostheses resulted in the excessive release of cobalt, nickel, and chromium into the blood, hair, and urine.  Metal-on-plastic implants, which were increasingly used from the 1970s through the 1990s, are less likely to induce metal sensitization because they release large polyethylene wear particles that prevent the formation of allergenic polymer-protein complexes.

Recently, second-generation metal-on-metal bearings were introduced which have a lower volumetric wear rate, high fracture toughness, and the ability to use large femoral heads to lower the risk of postoperative instability.  However,  studies have documented elevated serum and urine concentrations of cobalt and chromium as seen with first-generation metal-on-metal hip bearings.  Also, clinically serious complications with aseptic lymphocytic vasculitis– associated lesions and pseudotumors have been reported, typically in association with metal-on-metal bearings.   Accumulated reports of metal allergy in total hip arthroplasty patients showed that the prevalence of metal allergy was approximately 25% among patients with a well-functioning hip arthroplastic implant and 60% among patients with a failed or poorly functioning implant.  Despite these prevalences being much higher than general population estimates, it is uncertain whether metal allergy causes device failure or whether device failure causes metal allergy.

In the majority of cases, the removal of the allergenic metal device results in clearing of skin conditions and other adverse tissue responses to the metal ions.  A perfectly functioning dynamic implant causing no pain and without evidence of loosening should not be removed in most cases, despite a positive patch-test result and/or higher levels of metal ions detected in blood or aspiration fluids.

Tobacco  smoking is associated with adverse outcomes after surgery, including wound infection and treatment failure. This is particularly true with reconstructive and aesthetic procedures, but the association is clear with many other types of operations: smokers undergoing aesthetic abdominoplasty were found to have a 12 fold relative risk of of infection (63); patients undergoing breast surgery for cancer, the odds ratio for developing infections in smokers versus nonsmokers was 3x for light smokers and 3.5x for heavy smokers, with an even greater effect on the incidence of skin flap necrosis at 7x for light smokers and 9x for heavy smokers (64); smoking was found to be the only modifiable risk factor for the development of infection in a study of 1505 cases of ventral hernia repair in 13 Veterans Administration Hospitals (66);  the risk of re-amputation was 2.5x higher in smokers than nonsmokers(68); wound infections occurred twice as often in patients undergoing both elective cardiac surgery and all ambulatory surgies (69,70).   Furthermore, infections were significantly fewer in smokers who stopped compared to continued smokers after 4, 8, and 12 weeks of randomization (1.1% vs 21.7%)  in a randomized clinical study involving 78 healthy volunteers in whom small standardized wounds were made on the buttocks and followed for the development of infection (71).  In summary, randomized studies show that the risk of having wound infections in smokers compared to nonsmokers is at least doubled, depending upon the procedure, and is even higher involving procedures, which have associated skin flaps or obesity.  This has proven true in patients undergoing surgery for osteomyelitis at our treatment center, as well.  Although cessation of smoking seems to reverse the increased susceptibility to wound infections, the best length of time for abstinence still remains to be established. From the existing data, it would seem that cessation of 4 weeks might be sufficient (74,75).  References: 63) Araco A, Gravante G, Sorge R, et al.  Wound infections in aesthetic abdomino-plasties:  the role of smoking.  Plast Reconstr Surg 2008; 121:305e-310e.  64) Sørensen LT, Hørby J, Friis E, et al.  Smoking as a risk factor for wound healing and infection in breast cancer surgery.   Eur J Surg Oncol 2002; 28:815-820. 66) Finan KR, Vick CC, Kiefe CI, et al. Predictors of wound infection in vental hernia  repair. Am J Surg 2005; 190:676-681.  68) Lind J, Kramhøft M, Bødtker S.  The influence of smoking on complications after primary amputations of the lower extremity.  Clin Orthop Relat Res 1991; 267:211-217.  69)  Nagachinta T, Stephens M, Reitz B, et al.  Risk factors for surgical-wound infection following cardiac surgery.  J Infect Dis 1987; 156:967-973.  70)  Myles PS, Iacono GA, Hunt JO, Fletcher et al.  Risk of respiratory complications and wound infection in patients undergoing ambulatory surgery.  Anesthesiology 2002; 97:842-847.  71)  Sorensen LT, Kalsmark T, Gottrup F.  Abstinence from smoking reduces incisional wound infection:  A randomized controlled trial.  Ann Surg 2003; 238:1-5.  74)   Lindström D, Sadr Azodi O, Wiadis A, et al.  Effects of a perioperative smoking cessation intervention on postoperative complications:  A randomized trial.  Ann Surg, 2008; 248:739-745.  75)  Jensen  JA, Goodson WH, Hopf HW, et al.  Cigarette smoking decreases tissue oxygen.  Arch Surg 1991; 126:1131-1134