Copyright 2001 American Academy of Orthopaedic Surgeons What guidelines/algorithms (both operative and nonoperative)are there for the treatment of osteolysis? Osteolysis is the conclusion of a complex particle-induced biologic processresulting in bone loss and in some cases implant loosening.1-5 Early diagnosisof osteolysis requires interval radiographic evaluation of patients with jointreplacements. The success of early treatment underscores the need for con-sistent longitudinal surveillance. The incidence of osteolysis is likely increasing as patients live longer and remain more active. Twenty-five years ago, a total hip replacement in a 65-year-old patient was expected to last for a lifetime. With increased longevity,however, hip replacements remain in service for many years. Significantactivity demands can result in marked wear particle production.
Treatment of osteolysis in asymptomatic patients6 is far different than treatment of patients with symptoms of a loose implant or pain from impend-ing pathologic fracture. The goals of treatment of asymptomatic patients arepreservation of bone stock, reduction of the risk of catastrophic periprostheticfracture, and restoration of the articulation with the best material combina-tions currently available. Any treatment designed to address osteolysis mustaccomplish two key functions—debridement of the lesion, and modificationof the articulation to decrease particle generation.7 These treatment compo-nents are frequently referred to as the osseous lesion and the wear generator.
Although there is no clear consensus on the necessary frequency of radiographs following total hip replacement, most authors agree that imagesshould be obtained 1 year after surgery and then at intervals of 1 to 2 years.
When periprosthetic osteolysis is diagnosed, the radiographic evaluationshould be more frequent in order to quantify the rate of progression and pro-vide a clinical opportunity to question the patient for clues that might indi-cate a loose implant or impending pathologic fracture. The patient can alsobe informed about the process and its treatment. Patients are followed at 3- to 6-month intervals for several visits until a predictable pattern can be deter-mined. If stable clinical and radiographic patterns are identified, then lessfrequent follow-up is acceptable. Each encounter should be used to improvepatient understanding of the disease and its treatment. The addition ofoblique pelvic views increases the sensitivity for the detection of osteolysisin total hip patients.
Acetabular Osteolysis
Several groups have proposed classifications of acetabular osteolysis.
Paprosky and associates8 developed a classification system for cementedimplants that is based on the integrity of the acetabular rim and predicts thetype of bone grafting that will be required to attain a stable implant. Type Idefects involve minimal deformity. These are small, contained defects andare amenable to cancellous bone grafting. A cementless acetabular component,usually larger in diameter than the shell used in the primary arthroplasty, can beused to achieve stable fixation. Type II defects represent distortion of the nor-mal acetabular hemisphere. In these defects, the anterior and posteriorcolumns are intact although the medial wall and superior dome may be defi-cient. The reconstruction options include a high hip center, cancellous bonegraft, femoral head allograft, and a variety of specialized componentsdesigned to replace deficient bone. Type III defects have severe bone lossrequiring the use of structural allograft; examples include severe acetabularprotrusio, column deficiencies, and pelvic discontinuity with associatedglobal deficiency. The American Academy of Orthopaedic Surgeons Committee on the Hip (COTH) classification has two basic categories, segmental and cavitary.
Segmental defects result from complete bone loss in one area of the acetab-ulum and are subclassified into peripheral and central defects. Cavitary bonedeficiencies represent contained bone loss with the acetabular rim remain-ing intact. This system has not been as useful as Paprosky’s because it hasnot been combined with a specific treatment algorithm.
For uncemented acetabular components, a new classification system with treatment algorithm has been created (Fig. 1).7 In the presence ofacetabular osteolysis, type I implants are stable and have intact lockingmechanisms. This combination can be treated with liner exchange, downsiz-ing the femoral head if desirable, and cancellous bone grafting. Becauselesions have been demonstrated to heal without grafting after linerexchange,7 it is not always necessary to place cancellous graft into thelesions. Type II components are also stable; however, the function of the cupis compromised. Examples of Type II include a broken locking mechanism,backside wear of the shell so that the polyethylene liner would be unsup-ported or abraded, or component malposition. Treatment options includeplacement of a new polyethylene liner (possibly even a custom type) andacetabular shell retention with cementation of a new polyethylene liner.
Acetabular shell removal may be necessary. Preoperative planning is criticalif an existing component is to be left in place. Type III implants are loose andmay have migrated. Acetabular screws should be removed at the time ofrevision to allow for stability testing and to permit improved access forlesion debridement. If grafting is to be performed, sufficient access may beachieved through the screw holes but may require a pelvic window. Debridementthrough the shell may be accomplished by curettage. Cancellous bone graftingor placement of bone graft substitutes is done through the same access. It isnot yet known if grafting is required for some of these smaller lesions to heal.
Figure 1 Treatment of acetabular osteolysis. (Adapted with permission from Rubash HE,
Sinha RK, Maloney WJ, Paprosky WG: Osteolysis: Surgical treatment. Instr Course Lect

Removal of the continuous source of particles is necessary. For cementedcups, the treatment depends on whether the implant is loose or stable (Fig. 1).
Femoral Osteolysis
The classification of femoral osteolysis proposed by the COTH has beenuseful. Femoral defects are classified as segmental, cavitary, or combinedlytic. Segmental defects are characterized by erosion of the cortical bone,and are subclassified into complete or partial deficiencies. Cavitary defectsrepresent contained lesions with destruction of endosteal bone. Combineddefects, which include some element of both segmental and cavitary boneloss, are the most common type of femoral bone loss from osteolysis.
Treatment of asymptomatic femoral osteolysis varies with the extent and the progression. The extent of lytic changes should be carefully delineated;extensive radiographic evaluation may be required. Comparison of earlypostoperative radiographs with the most recent images demonstrating lysisis critical. This important comparison has become increasingly difficult,however, because of newer digital film storage and destruction of olderradiographs. The economic demands of the health care environment mustnot lead to destruction of these important early evaluations.
The surgeon must determine if the femoral component is loose, if there is an impending pathologic fracture, and if there is eccentric polyethylenewear, all of which are relative indications for surgical intervention. In thepresence of osteolysis, two special situations suggest more expedient surgicaltreatment–a loose or debonded femoral component with a rough surface tex-ture, and a worn acetabular component with thin polyethylene.
Femoral osteolysis treatment goals are to maximize fixation and overall bone quality and minimize iatrogenic bone loss from revision surgery.
Treatment algorithms can be developed for femoral revision after consider-ing the stability of the implant and its fixation, the need for cancellous andstructural grafting, and the surgical approaches for removal (Fig. 2).
Pharmacologic Treatments
As our understanding of the biologic sequences that lead to osteolysisimproves, nonsurgical treatment of osteolysis may become possible.
Investigators have studied the use of nonsteroidal anti-inflammatory drugsand even gene transfer techniques to inhibit the inflammatory component ofosteolysis.9-11 In addition, newer medical therapies have been developed thatmay interrupt osteolytic progression. Shanbhag and associates12-14 demon-strated in a canine model that bisphosphonates such as alendronate can besuccessfully used to prevent osteolysis. Although the peri-implant boneresorption was prevented in their model, the inflammatory response was notaffected. This finding was not unexpected because bisphosphonates exerttheir effect primarily on the osteoclasts with no known anti-inflammatoryeffects. The efficacy of this drug in treating periprosthetic osteolysis is cur-rently being evaluated in a multicenter placebo-controlled clinical trial. Suchpharmaceutical therapy may be clinically useful in the early stages of osteolysisbefore the lesion has compromised implant stability, or in cases wheresurgery is either too complex or risky.
Periprosthetic osteolysis is a progressive disease that requires careful radio-graphic evaluation. Progression of osteolysis to the level of substantial boneloss, impending pathologic fracture, or to the degree that future reconstruc-tion would be compromised are indications for revision surgery. Limitedrevision surgery that involves exchange of the polyethylene liner, debride-ment of osteolytic lesions, retention of a stable femoral component, and Figure 2 Treatment of femoral osteolysis. (Adapted with permission from Rubash HE, Sinha
RK, Maloney WJ, Paprosky W:, Osteolysis: Surgical treatment. Instr Course Lect

placement of a new femoral head have been successful in appropriate cases.
The indications for bone grafting of acetabular and femoral lesions are notwell defined. Finally, nonsurgical treatment of osteolysis could become aclinical reality.
Future Directions for Research
Will the newer materials (highly elevated cross-linked polyethylenes, ceramic-ceramic, and metal bearings) prevent osteolysis? If lysis does occur, will theclinical manifestations be similar? What modifications can be made toimplant surfaces to prevent periprosthetic osteolysis? Is there an optimalarticulation—lowest wear, least osteolysis, best range of motion and stabili-ty—and how should it be defined? Should advanced imaging techniquessuch as radiostereometric analysis or in-office digitized radiography be rou-tinely used to detect early component wear? Are there low risk, inexpensivemedical therapies for osteolysis? References
1. Goldring SR, Schiller AL, Roelke M, Rourke CM, O’Neil DA, Harris WH: The syn- ovial-like membrane at the bone-cement interface in loose total hip replacements andits proposed role in bone lysis. J Bone Joint Surg Am 1983;65:575-584.
2. Goodman SB, Chin RC, Chiou SS, Schurman DJ, Woolson ST, Masada MP: A clini- cal-pathologic-biochemical study of the membrane surrounding loosened and non-loosened total hip arthroplasties. Clin Orthop 1989;244:182-187.
3. Harris WH: The problem is osteolysis. Clin Orthop 1995;311:46-53.
4. Jiranek WA, Machado M, Jasty M, et al: Production of cytokines around loosened cemented acetabular components: Analysis with immunohistochemical techniquesand in situ hybridization. J Bone Joint Surg Am 1993;75:863-879.
5. Schmalzried TP, Jasty M, Harris WH: Periprosthetic bone loss in total hip arthroplas- ty: Polyethylene wear debris and the concept of the effective joint space. J Bone JointSurg Am 1992;74:849-863.
6. Maloney WJ, Herzwurm P, Paprosky W, Rubash HE, Engh CA: Treatment of pelvic osteolysis associated with a stable acetabular component inserted without cement aspart of a total hip replacement. J Bone Joint Surg Am 1997;79:1628-1634.
7. Rubash HE, Sinha RK, Maloney WJ, Paprosky WG: Osteolysis: Surgical treatment.
Instr Course Lect 1998;47:321-329.
8. Paprosky WG, Perona PG, Lawrence JM: Acetabular defect classification and surgical reconstruction in revision arthroplasty: A 6-year follow-up evaluation. J Arthroplasty1994;9:33-44.
9. Goodman SB, Chin RC, Chiou SS, Lee JS: Suppression of prostaglandin E2 synthesis in the membrane surrounding particulate polymethylmethacrylate in the rabbit tibia.
Clin Orthop 1991;271:300-304. 10. Spector M, Shortkroff S, Hsu HP, Lane N, Sledge CB, Thornhill TS: Tissue changes around loose prostheses: A canine model to investigate the effects of an antiinflamma-tory agent. Clin Orthop 1990;261:140-152. 11. Wooley PH, Sud S, Robbins PD, Whalen JD, Evans CH: Contrasting effects of gene therapy to inhibit interluken-1ß or tumor necrosis factor alpha in the murine inflam-matory response to wear particles. Trans Orthop Res Soc 1998;23:122. 12. Shanbhag AS, Hasselman CT, Rubash HE: The John Charnley Award: Inhibition of wear debris mediated osteolysis in a canine total hip arthroplasty model. Clin Orthop1997;344:33-43.
13. Shanbhag AS, Jacobs JJ, Black J, Galante JO, Glant TT: Macrophage/particle interac- tions: Effect of size, composition and surface area. J Biomed Mater Res 1994;28:81-90. 14. Shanbhag AS, Jacobs JJ, Glant TT, Gilbert JL, Black JM, Galante JO: Composition and morphology of wear debris in failed uncemented total hip replacement. J BoneJoint Surg Br 1994;76:60-67.


Mycologia, 94(1), 2002, pp. 1–5. ᭧ 2002 by The Mycological Society of America, Lawrence, KS 66044-8897Issued 28 January 2002 Formation of conjugates from ciprofloxacin and norfloxacin in cultures of Trichoderma viride desethylene- N -acetyl, and N -formyl metabolites aswell as to metabolites in which an amino group hasreplaced the piperazine ring (Parshikov et al 2001b). Recently

Pharmacology: doses for the examinations

Pharmacology: Doses minations 1st semester Autonomic drugs Epinephrinum, adrenaline (Tonogen inj.) 0.05-0.1-0.2! mg iv Cardiovascular-renal drugs Chinidinium sulfuricum, quinidine, 200-400-500! mg Mexiletin (Mexitil caps., Ritalmex caps.) 200-400 mg Digoxin (Digoxin tabl.) daily maintenance oral dose 0.25-0.5 mg Metoprolol (Betaloc ZOK) daily 1 x 25-100 mg Enalaprilum mal

© 2010-2018 PDF pharmacy articles