Medial unicompartmental knee arthroplasty in ACL-deficient knees is a viable treatment option: in vivo kinematic evaluation using a moving fluoroscope.

PURPOSE: Unicompartmental knee arthroplasty (UKA), resulting in similar kinematics to native knees, is functionally superior to total knee arthroplasty (TKA). However, ACL deficiency is generally considered to be a contraindication. The main purpose of this study was to investigate if UKA in ACL-deficient knees would result in similar kinematics to conventional UKA with an intact ACL. METHODS: Ten conventional UKA patients were compared to eight ACL-deficient patients with a reduced tibial slope to compensate for instability, resulting from the deficient ACL. Knee kinematics was evaluated with a moving fluoroscope, tracking the knee joint during daily activities. In a standing position (baseline), posterior shift of the femur was observed for ACL-deficient UKA patients, compared to conventional UKA patients. RESULTS: A significant posterior femoral shift in the ACL-deficient group was observed during the first 25% (near extension) of deep knee bend, while there was no difference in kinematic waveforms for all other activities. No significant range of motion differences across different activities between the two UKA groups were detected, except for an increase of medial AP translation in the ACL-deficient group, during deep knee bend and stair descent. CONCLUSION: Despite the posterior femoral shift due to ACL deficiency, both UKA groups showed similar kinematic waveforms, indicating that posterior tibial slope reduction can partially compensate for ACL function. This supported our hypothesis that fixed bearing UKA can be a viable treatment option for selected ACL-deficient patients, allowing patient-specific kinematics. While anteroposterior laxity can be compensated, rotational stability was a prerequisite for this approach. LEVEL OF EVIDENCE: III.

Is ACL deficiency always a contraindication for medial UKA? Kinematic and kinetic analysis of implanted and contralateral knees.

BACKGROUND: Prevalence of knee osteoarthritis increases because life expectancy continues to rise with an active patient population. Hence, the concept of unicompartmental knee arthroplasty (UKA) has regained popularity as a treatment option for unicompartmental knee osteoarthritis. Anterior cruciate ligament (ACL) deficiency is widely considered as a contraindication for UKA, however, there are conflicting reports. If otherwise indicated, some surgeons consider UKA for ACL-deficient patients using a modified surgical technique, with a reduction of posterior tibial slope. RESEARCH QUESTION: The purpose of this study was to evaluate outcomes in UKA patients with ACL deficiency in comparison to a conventional UKA group (intact ACL) by the measurement of knee kinematics and kinetics. METHODS: Ten patients with conventional UKA and an intact ACL and eight patients with an ACL-deficient UKA and a reduced posterior tibial slope relative to the native knee were recruited. Three-dimensional joint kinematics of the knee were measured, using skin markers and an infrared optical motion capture system. Ground reaction forces (GRF) were measured with force plates in all three directions. Level walking, ramp descent and stair descent were analyzed, comparing implanted and contralateral native knees and the two UKA groups. RESULTS: No significant differences in kinetics and kinematics were observed between conventional UKA and ACL-deficient UKA groups for any of the activities. However, some asymmetries in GRF between the implanted and contralateral side were present for the ACL-deficient group, during level walking (unloading rate) and stair descent (stance time). SIGNIFICANCE: Promising outcomes of the ACL-deficient UKA group suggest that ACL deficiency may not always be a contraindication. Therefore, ACL-deficient UKA could be an alternative treatment option to total knee arthroplasty for an appropriate surgeon selected patient population.

Short-term functional advantages after medial unicompartmental versus total knee arthroplasty.

BACKGROUND: There are many uncertainties about the advantages and disadvantages of using unicompartmental (UKA) versus total knee arthroplasty (TKA) to treat patients with knee osteoarthritis. It is important to have sufficient early postoperative quadriceps strength for long-term, self-reported and gait-related outcomes after knee arthroplasty, but very limited comparative data exist regarding UKA and TKA patients. METHODS: This study assessed isometric quadriceps strength, spatio-temporal gait parameters (walking speed, step length, single-limb support phase) and self-reported outcomes (pain, function, stiffness) in 18 TKA and 18 UKA patients six months after surgery, as well as in 18 healthy controls. RESULTS: Quadriceps strength of TKA, but not of UKA patients, was lower than that of controls (P < 0.05). UKA patients demonstrated better gait function in terms of a longer single-limb support phase than TKA patients (P < 0.01), which agreed with better self-reported pain (P < 0.05), function (P < 0.01) and stiffness (P < 0.05) scores compared to TKA patients. CONCLUSIONS: Six months after surgery, UKA patients showed better short-term quadriceps strength and gait function compared to TKA patients, together with less self-reported knee pain and stiffness. Patients eligible for UKA may experience less functional impairments compared to those who require TKA.

Skin crease 'bikini' incision for anterior approach total hip arthroplasty: surgical technique and preliminary results.

BACKGROUND: The direct anterior approach for THA allows implantation through an internervous plane without muscle detachment from bone. However, the classic longitudinal skin incision does not follow the anatomic skin creases and can result in scar widening. We therefore modified our incision technique to a short oblique skin incision following the anatomic skin crease of the groin. QUESTIONS/PURPOSES: We sought to determine whether (1) the oblique incision leads to improved scar results compared with the longitudinal incision, (2) functional and pain scores are similar between the two approaches, and (3) the new incision is safe with respect to complications, blood loss, implant position, and lateral femoral cutaneous nerve (LFCN) symptoms. METHODS: Fifty-nine patients underwent THAs using either the classic (n = 33) or the new oblique incision (n = 26). At 6 months after surgery, we compared objective and subjective scar results, WOMAC, Oxford Hip and UCLA scores, blood loss, cup inclination, and the presence of LFCN symptoms between both groups. RESULTS: Objectively, the modified incision resulted in significantly shorter and narrower scars. Subjectively, patients in the modified incision group were substantially more satisfied with the aesthetic appearance. Functional and pain scores were similar. No complications occurred in either group. Blood loss and cup inclination did not differ between the two groups. There were no differences in LFCN symptoms. CONCLUSIONS: In this series, which selected for thinner patients in the study group, the 'bikini' incision for an anterior approach THA led to improved scar cosmesis and was found to be safe in terms of blood loss, appropriate component placement, and risk for LFCN injury. LEVEL OF EVIDENCE: Level III, retrospective comparative study. See the Guidelines for Authors for a complete description of levels of evidence.

Retention treatment after periprosthetic total hip arthroplasty infection.

PURPOSE: The purpose of this study was to compare infection control rates between implant retention and two-stage revision and assess the effectiveness of retention treatment in THA. METHODS: Twenty-eight debridements with implant retention (retention group) and 65 staged revisions (removal group) were retrospectively analysed and risk factors that can contribute to failure of infection control were explored. RESULTS: For the retention and removal groups, infection control rates were 50% and 78% after initial treatment, and 68% and 82% at latest follow-up, respectively. There were no significant differences in the number of additional operative procedures, total length of hospital stay, and duration of treatment between groups. Infection of revision THA, polybacterial and S. aureus infection were identified as risk factors for infection control. CONCLUSIONS: Retention treatment can be considered an initial treatment option in selected cases of primary THA, with a single organism, non-S. aureus infection with 50% chance of infection control and no disadvantages in terms of additional procedure, hospital stay, and treatment duration.

Can implant retention be recommended for treatment of infected TKA?

BACKGROUND: Retention treatment is reportedly associated with lower infection control rates than two-stage revision. However, the studies on which this presumption are based depend on comparisons of historical rather than concurrent controls. QUESTIONS/PURPOSES: We (1) asked whether the infection control rates, number of additional procedures, length of hospital stay, and treatment duration differed between implant retention and two-stage revision treatment; and (2) identified risk factors that can contribute to failure of infection control. METHODS: We reviewed the records of 60 patients treated for 64 infected TKA from 2002 to 2007. Twenty-eight patients (32 knees) underwent débridement with retention of component, and 32 patients (32 knees) were treated with component removal and two-stage revision surgery. We determined patients' demographics, type of infection, causative organisms, and outcome of treatment. Mean followup was 36 months (range, 12-84 months). RESULTS: Infection control rate was 31% in retention and 59% in the removal group after initial surgical treatment, and 81% and 91% at latest followup, respectively. Treatment duration was shorter in the retention group and there was no difference in number of additional surgeries and length of hospital stay. Type of treatment (retention versus removal) was the only factor associated with infection control; subgroup analysis in the retention group showed Staphylococcus aureus infection and polyethylene nonexchange as contributing factors for failure of infection control. CONCLUSIONS: Although initial infection control rate was substantially lower in the retention group than the removal group, final results were comparable at latest followup. We believe retention treatment can be selectively considered for non-S. aureus infection, and when applied in selected patients, polyethylene exchange should be performed. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Why do we need a national joint replacement registry in the United States?

The continually increasing number of total hip arthroplasties (THAs) being performed, in conjunction with the rapid growth in new surgical techniques and implants related to THA, warrants ongoing and objective monitoring of results. National joint replacement registries have become powerful surveillance systems for monitoring contemporary THAs and improving outcomes. Despite the compelling evidence of their benefits, such a registry has yet to be established in the United States. In this article, we provide a rationale for implementing a national joint replacement registry in the United States.

Association of body mass index and clinical outcome 2 years after unicompartmental knee arthroplasty.

INTRODUCTION: Unicompartmental knee arthroplasty (UKA) has gained in popularity during the last years. However, the body mass index (BMI) of patients undergoing UKA is controversially discussed in the literature. There is, moreover, a paucity of information available concerning the association of BMI with early clinical outcomes after UKA. MATERIALS AND METHODS: We retrospectively reviewed the clinical data of 83 consecutive UKA, 2 years after surgery, and investigated the potential association of BMI and the outcome variables Knee Society Score (KSS), University of California at Los Angeles (UCLA) activity levels, anterior knee pain (AKP), range of motion, and implant failure. RESULTS: The KSS and UCLA significantly increased from 132 and 4.7 preoperatively to 187.5 and 7.1, respectively, after surgery. Knee flexion significantly improved from 123.7 to 128.4 degrees and the prevalence of extension deficiencies significantly decreased from 28.9 to 15.7%. Three knees (3.6%) failed and were converted to total knee arthroplasty. Failures were not associated with increased BMI (P = 0.387). The BMI had no significant association with KSS values, UCLA levels, and implant failure. We found a weak negative correlation between BMI and postoperative knee flexion (r = -0.285, P = 0.009) and a moderate positive correlation between BMI and the intensity of AKP (r = 0.525, P < 0.001). CONCLUSION: The results of the present study suggest that the BMI of patients undergoing UKA has no major impact on the early clinical outcome 2 years after surgery. There was, however, a definite correlation between the BMI and AKP. Longer follow-up is necessary to determine if overweight and obesity may increase revision rates after UKA.

Patellar height before and after unicompartmental knee arthroplasty: association with early clinical outcome?

INTRODUCTION: There is paucity of information available concerning the role of patellar height in unicompartmental knee arthroplasty (UKA). The present study was conducted to determine the patellar height before and after UKA and to assess possible effects on the early clinical outcome. MATERIALS AND METHODS: We measured the patellar height before and after UKA in 83 consecutive knees using the Blackburne-Peel (BP) index and Insall-Salvati (IS) ratio and investigated the impact of the patellar height on the clinical outcome 2 years after surgery. RESULTS: BP values significantly decreased from 0.81 before surgery to 0.76 postoperatively (P < 0.001). IS ratios did not significantly decrease from 1.02 to 1.01 (P = 0.108). Lower preoperative BP values were negatively correlated with the postoperative knee extension (r = -0.357, P = 0.026), while higher preoperative BP values were negatively associated with the postoperative Knee Society Score (r = -0.302, P = 0.046). Lower preoperative IS values were negatively correlated with postoperative Knee Scores (r = -0.394, P = 0.019). CONCLUSION: After UKA, the patellar height decreased significantly according to the BP index, but not significantly according to the IS ratio. We found only weak and inconsistent correlations between the patellar height and clinical outcome parameters. Hence, based on the present results, the patellar height seems not to be a strict separate patient-selection criterion for UKA.

Reliability and validity of the cross-culturally adapted German Oxford hip score.

UNLABELLED: There is currently no German version of the Oxford hip score. Therefore we sought to cross-culturally adapt and validate the Oxford hip score for use with German-speaking patients (OHS-D) with osteoarthritis of the hip using a forward-backward translation procedure. We then assessed the new score in 105 consecutive patients (mean age, 63.4 years; 48 women) undergoing THA. We specifically determined: the number of fully completed questionnaires, reliability, concurrent validity by correlation with the WOMAC, Harris hip score, and SF-12, and distribution of floor and ceiling effects. We received 96.6% fully completed questionnaires. An intraclass correlation coefficient of 0.90 and Cronbach's alpha of 0.87 suggested the OHS-D was reliable. Correlation coefficients between the OHS-D and the WOMAC total score, pain subscale, stiffness subscale, and physical function subscale were 0.82, 0.70, 0.68, and 0.82, respectively. OHS-D correlated with the Harris hip score (r = 0.63) and the physical component scale of the SF-12 (r = 0.58). We observed no ceiling or floor effects. The OHS-D appeared a reliable and valid measurement tool for assessing pain and disability with German-speaking patients with hip osteoarthritis. LEVEL OF EVIDENCE: Level I, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Biomechanical and immunohistochemical properties of meniscal cartilage after high hydrostatic pressure treatment.

Meniscal allograft processing procedures, in particular gamma irradiation, deteriorate the biomechanical and biological properties of the transplanted tissue. High hydrostatic pressure (HHP) treatment, widely used in food technology to inactivate microorganisms while preserving natural compounds, might serve as a gentle alternative to gamma irradiation in the processing of meniscal allografts. We therefore investigated the effects of HHP treatment on the biomechanical and immunohistochemical properties of meniscal cartilage. Specimens of bovine menisci were treated with HHP for 10 min (20 degrees C) at 300 MPa and 600 MPa. Untreated control samples were left at room temperature and ambient pressure. We performed repetitive cycling indentation-tests to assess the biomechanical properties-in particular the viscoelastic behavior-of HHP treated and untreated meniscal specimens. Immunohistochemical analysis for collagens type I, II, and III and for the proteoglycans versican, aggrecan and for link-protein was performed by immunolabeling cross-sections of untreated and at 600 MPa HHP treated specimens. Comparing untreated and HHP treated meniscal specimens there were no significant differences for all tested biomechanical parameters. All cross-sections of untreated and HHP treated specimens stained positive for the collagens and proteoglycans. We demonstrated that meniscal cartilage can be treated by HHP at levels as high as 600 MPa without affection of the biomechanical and immunochistochemical properties. Therefore, HHP treatment might serve as a gentle alternative to gamma irradiation in the processing of meniscal allografts. Further research is necessary to verificate the present results in vivo.

The effects of clindamycin on human osteoblasts in vitro.

INTRODUCTION: Clindamycin is an antibiotic frequently used in different local application forms for the treatment of prosthetic joint infections, chronic osteomyelitis or as infection prophylaxis in bone cement. No information is available regarding its direct effects on bone cells, although very high local effective antibiotic concentrations can be achieved. MATERIALS AND METHODS: We cultured pooled osteoblasts, previously derived from human trabecular bone specimens of four healthy donors, with different concentrations of clindamycin (0-500 microg/ml) for 24, 48 and 72 h. Cell proliferation (MTT), cytotoxicity [lactate dehydrogenase (LDH)-activity], cell metabolism [alkaline phosphatase (ALP)-activity] and extracellular matrix calcification (Alizarin staining) were assessed after antibiotic treatment. RESULTS: Proliferation significantly decreased in a dose-dependent manner and reached 3.5% of control samples at 500 microg/ml at 72 h. LDH-activity was unaffected at lower concentrations but significantly increased at 500 microg/ml at 48 and 72 h. ALP-activity significantly increased at 10 microg/ml at 24 and 48 h and then decreased in a time- and dose-dependent manner. Calcification increased at 10 and 25 microg/ml, while it decreased or no calcification was found at concentrations of 50 microg/ml and above. CONCLUSION: We could demonstrate that clindamycin at lower concentrations stimulated the cell metabolism of human osteoblasts and that higher clindamycin levels of 500 microg/ml had cytotoxic effects. The observed effects of high clindamycin levels on human osteoblasts highlight a potential alteration of bone metabolism in vivo and have to be taken into account in local antibiotic administration, e.g., in clindamycin-impregnated bone cement, where such high antibiotic concentrations can be achieved.

Jumbo cups for revision of acetabular defects after total hip arthroplasty: a retrospective review of a case series.

The treatment of acetabular bone defects presents a great challenge in revision total hip arthroplasty (THA). The purpose of this study was to evaluate the clinical and radiological outcome of revision THA using jumbo cups for acetabular reconstruction after applying the bone-grafting technique. We studied 17 patients with acetabular defects ranging from Type 2A to Type 3A according to Paprosky's classification. According to the AAOS-score twelve patients were classified as Type II and five patients as Type III. Uncemented press-fit cups with an outer diameter larger than 64 mm were used in all cases. Fifteen patients received morselized bone allografts. In eight patients an additional screw fixation was necessary. The mean follow-up period was 82 months (range 33-149). The mean Harris Hip Score was preoperatively 62 and at the time of the last follow-up examination 83 points (p = 0.007). Two acetabular components failed, one due to aseptic loosening and another one due to septic loosening. There was a trend of displacement of the femoral head centre towards the infero-lateral position after using jumbo cups that approached statistical significance (p = 0.065). Closure of acetabular defects of Types 2A to 3A according to Paprosky's classification and type II to III according to the AAOS-score respectively can be satisfactorily accomplished using jumbo cups after applying the bone-grafting technique.

Particle-induced osteolysis in three-dimensional micro-computed tomography.

Small-animal models are useful for the in vivo study of particle-induced osteolysis, the most frequent cause of aseptic loosening after total joint replacement. Microstructural changes associated with particle-induced osteolysis have been extensively explored using two-dimensional (2D) techniques. However, relatively little is known regarding the 3D dynamic microstructure of particle-induced osteolysis. Therefore, we tested micro-computed tomography (micro-CT) as a novel tool for 3D analysis of wear debris-mediated osteolysis in a small-animal model of particle-induced osteolysis. The murine calvarial model based on polyethylene particles was utilized in 14 C57BL/J6 mice randomly divided into two groups. Group 1 received sham surgery, and group 2 was treated with polyethylene particles. We performed 3D micro-CT analysis and histological assessment. Various bone morphometric parameters were assessed. Regression was used to examine the relation between the results achieved by the two methods. Micro-CT analysis provides a fully automated means to quantify bone destruction in a mouse model of particle-induced osteolysis. This method revealed that the osteolytic lesions in calvaria in the experimental group were affected irregularly compared to the rather even distribution of osteolysis in the control group. This is an observation which would have been missed if histomorphometric analysis only had been performed, leading to false assessment of the actual situation. These irregularities seen by micro-CT analysis provide new insight into individual bone changes which might otherwise be overlooked by histological analysis and can be used as baseline information on which future studies can be designed.

Return to sports and recreational activity after unicompartmental knee arthroplasty.

BACKGROUND: There is a lack of detailed information concerning patients' sports and recreational activities after unicompartmental knee arthroplasty. HYPOTHESIS: Patients treated by unicompartmental knee arthroplasty will be able to return to sports and activity. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: The authors surveyed 83 patients by postal questionnaires to determine their sporting and recreational activities at a mean follow-up of 18 +/- 4.6 months (range, 12-28) after unicompartmental knee arthroplasty. For data analysis, patients were divided into groups of women and men, and older and younger patients (those above and below the median age of the group). The authors also assessed the state of general health (SF-36) of the patients at the time of the survey and compared the results with those of a matched (for age and side-diagnoses) reference population. RESULTS: Before surgery, 77 of 83 patients were engaged in an average of 5.0 sports and recreational disciplines; postoperatively, 73 (88%) participated in an average of 3.1 different sports disciplines, resulting in a return to activity rate of 95%. The frequency of activities (sessions per week) was 2.9 preoperatively and remained constant at the time of survey (2.8). The group of older patients (mean age 73.0 y) revealed a significantly higher frequency than the group of younger patients (mean age 57.8 y). The minimum session length decreased from 66 minutes before surgery to 55 minutes after surgery. The most common activities after surgery were hiking, cycling, and swimming. Several high-impact activities, as well as the winter disciplines of downhill- and cross-country skiing had a significant decrease in participating patients. The majority of the patients (90.3%) stated that surgery had maintained or improved their ability to participate in sports or recreational activities. The patients generally scored very high on the SF-36 compared with the matched reference population. Higher SF-36 values in the physical-related domains correlated with an increased level of activity (r = 0.425). The preoperative body mass index showed a weak, negative correlation with the postoperative extent of activities (r = -0.282). CONCLUSION: The majority of patients returned to sports and recreational activity after unicompartmental knee arthroplasty. However, the numbers of different disciplines patients were engaged in decreased as well as the extent of activities. The activities in which most patients participated were primarily low- or midimpact. The patients scored higher on the SF-36 than age-related norms, which might be due to the patient-selection process for unicompartmental knee arthroplasty and geographical differences.

Anabolic effects of bisphosphonates on peri-implant bone stock.

The long-term durability of total joint replacements is critically dependent on adequate peri-implant bone stock, which can be compromised by wear debris-mediated osteolysis. This study investigated the effects of bisphosphonates on enhancing peri-implant bone in the presence of clinically relevant ultra-high molecular weight polyethylene (UHMWPE) wear debris. Fiber-mesh coated titanium-alloy plugs were implanted bilaterally in the femoral condyles of 36 New Zealand white rabbits. Implants in the left femora were covered with submicron UHMWPE particles during surgery. Rabbits were administered either no drug, subcutaneous alendronate weekly (1.0mg/kg/week) or a single dose of intravenous zoledronate (0.015mg/kg). A total of 6/12 rabbits in each group were sacrificed at 6 weeks and the remainder at 12 weeks postoperatively. Peri-implant bone stock was analyzed radiographically and histomorphometrically. Radiographically, both bisphosphonates significantly increased periprosthetic cortical thickness at 6 weeks (p<0.0001; alendronate: +18%; zoledronate: +11%) and at 12 weeks (p=0.001; alendronate: +17%; zoledronate:+19%). Histomorphometrically, alendronate and zoledronate raised peri-implant bone volume (BV/TV) up to 2-fold after 6 weeks without added wear debris and more than 3-fold when wear debris was present. Furthermore a 6-week bisphosphonate treatment increased osteoid thickness in the absence of wear debris (alendronate: +132%, p=0.007; zoledronate: +67%, p=0.51) and in the presence of wear debris (alendronate: +134%, p=0.023; zoledronate: +138%, p=0.016). In summary, alendronate and zoledronate treatment increased periprosthetic bone stock in a rabbit femoral model, particularly in the presence of UHMWPE wear debris. These new findings suggest that bisphosphonates may more than compensate for the well-documented negative effects of wear debris on peri-implant bone stock. The combined antiresorptive and osteoanabolic effects of bisphosphonates on periprosthetic bone stock may have an important role for critically improving the biological fixation and ultimate durability of total joint arthroplasty.

Polyethylene particle-induced bone resorption in alpha-calcitonin gene-related peptide-deficient mice.

UNLABELLED: This study investigates the impact of alpha-CGRP on bone metabolism after implantation of polyethylene particles. alpha-CGRP knockout mice showed less osteolysis compared with wildtype mice. The local neurogenic microenvironment might be a crucial factor in particle-induced osteolysis. INTRODUCTION: Periprosthetic osteolysis is the major reason for aseptic loosening in joint arthroplasty. This study aimed to investigate the potential impact of alpha-calcitonin gene-related peptide (alpha-CGRP) deficiency on bone metabolism under conditions of polyethylene particle-induced osteolysis. MATERIALS AND METHODS: We used the murine calvarial osteolysis model based on polyethylene particles in 14 C57BL 6 mice and 14 alpha-CGRP-deficient mice divided into four groups of 7 mice each. Groups 1 (C57BL/J 6) and 3 (alpha-CGRP knockout) received sham surgery, and groups 2 (C57BL/J 6) and 4 (alpha-CGRP knockout) were treated with polyethylene particles. Qualitative and quantitative 3D analyses were performed using microCT. In addition, bone resorption was measured within the midline suture by histological examination. The number of osteoclasts was determined by counting the TRACP(+) cells. Calvarial bone was tested for RANKL expression by RT-PCR and immunocytochemistry. RESULTS: Bone resorption was significantly reduced in alpha-CGRP-deficient mice compared with their corresponding wildtype C57BL 6 mice as confirmed by histomorphometric data (p < 0.001) and microCT (p < 0.01). Osteoclast numbers were significantly reduced in group 3 and the particle subgroup compared with group 1 (p < 0.001). We observed a >3-fold increase of basal RANKL mRNA levels within group 1 compared with group 3. Additional low RANKL immunochemistry staining was noted in groups 3 and 4. CONCLUSIONS: In conclusion, alpha-CGRP knockout mice did not show the expected extended osteolysis compared with wildtype mice expressing alpha-CGRP. One of the most reasonable explanations for the observed decrease in osteolysis could be linked to the osteoprotegerin (OPG)/RANK/RANKL system in alpha-CGRP-deficient animals. As a consequence, the fine tuning of osteoclasts mediating resorption in alpha-CGRP-null mice may be deregulated.